Inhibitory Effect of Crizotinib on Creatinine Uptake by Renal Secretory Transporter OCT2.

PubMed

Arakawa, Hiroshi; Omote, Saki; Tamai, Ikumi

2017-09-01

Crizotinib, a tyrosine kinase inhibitor, exhibits some cases of an increase in serum creatinine levels. Creatinine is excreted by not only glomerular filtration but also active secretion by organic cation transporters such as organic cation transporter 2 (OCT2). In the present study, we evaluated in vitro inhibitory effect of crizotinib on OCT2 by directly measuring creatinine uptake by OCT2. Coincubation of crizotinib reduced uptake of [ 14 C]creatinine by cultured HEK293 cells expressing OCT2 (HEK293/OCT2) in a concentration-dependent manner with IC 50 values of 1.58 ± 0.24 μM. Preincubation or both preincubation and coincubation (preincubation/coincubation) with crizotinib showed stronger inhibitory effect on [ 14 C]creatinine uptake compared with that in coincubation alone with IC 50 values of 0.499 ± 0.076 and 0.347 ± 0.040 μM, respectively. These IC 50 values of crizotinib on [ 3 H]N-methyl-4-phenylpyridinium acetate uptake by OCT2 were 10-20 times higher than those of [ 14 C]creatinine uptake. Furthermore, preincubation of crizotinib inhibited creatinine uptake by OCT2 in an apparently competitive manner. In conclusion, crizotinib at a clinically relevant concentration has the potential to inhibit creatinine transport by OCT2, suggesting an increase of serum creatinine levels in clinical use. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Analysis of factors causing hyperkalemia.

PubMed

Takaichi, Kenmei; Takemoto, Fumi; Ubara, Yoshifumi; Mori, Yasumichi

2007-01-01

Patients with impaired renal function or diabetes are considered to be prone to hyperkalemia. Furthermore, hyperkalemia is an adverse drug reaction of inhibitors of the renin-angiotensin system (RAS) that are established to be efficacious in these patients. However, the current status of hyperkalemia in the clinical setting remains obscure. A total of 9,117 patients treated at Toranomon Hospital between January and October 2005, who had serum creatinine levels below 5 mg/dL were studied. Patients on dialysis and patients using cation exchange resin or diuretics that lower serum potassium were excluded. Serum potassium increased significantly accompanying the increase in serum creatinine, and was significantly elevated in diabetic patients compared to non-diabetic patients. Serum potassium also increased significantly with the administration of angiotensin-II receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEI) or beta-blockers. A combination of diabetes and RAS inhibitor administration significantly increased serum potassium compared to each factor alone in patients with a serum creatinine level below 1.5 mg/dL but not in those with a higher serum creatinine level. According to step-wise multiple regression analyses, an elevated serum creatinine level had the strongest positive correlation with the serum potassium level, followed by diabetes, ACEI use, ARB use, and age. Lowered renal function, diabetes, use of RAS inhibitors and old age are independent factors that increase the serum potassium level. Caution should be exercised when using RAS inhibitors in diabetic patients even if their renal function is relatively preserved. In selected patients with diabetes or impaired renal function, however, RAS inhibitors can be used without hyperkalemia.

Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

PubMed

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S; Benedict, Sheela; Pathan, Javed Y; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K; Yandle, Tim G; Nicholls, Gary M; Frampton, Chris M; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System

PubMed Central

Ali, Mahmoud Alhaj; Adem, Abdu; Chandranath, Irwin S.; Benedict, Sheela; Pathan, Javed Y.; Nagelkerke, Nicolas; Nyberg, Fred; Lewis, Lynley K.; Yandle, Tim G.; Nicholls, Gary M.; Frampton, Chris M.; Kazzam, Elsadig

2012-01-01

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP. PMID:22624009

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models.

PubMed

Wada, Yusuke; Abe, Masaki; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-10-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. © 2016 by the Society for Experimental Biology and Medicine.

Classifying AKI by Urine Output versus Serum Creatinine Level.

PubMed

Kellum, John A; Sileanu, Florentina E; Murugan, Raghavan; Lucko, Nicole; Shaw, Andrew D; Clermont, Gilles

2015-09-01

Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist. Copyright © 2015 by the American Society of Nephrology.

Classifying AKI by Urine Output versus Serum Creatinine Level

PubMed Central

Sileanu, Florentina E.; Murugan, Raghavan; Lucko, Nicole; Shaw, Andrew D.; Clermont, Gilles

2015-01-01

Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist. PMID:25568178

Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

PubMed

McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

2016-11-01

The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.

PubMed

Hoeksma, Dane; Rebolledo, Rolando A; Hottenrott, Maximilia; Bodar, Yves S; Wiersema-Buist, Janneke J; Van Goor, Harry; Leuvenink, Henri G D

2017-04-01

Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.

Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women.

PubMed

Pringle, Kirsty G; de Meaultsart, Celine Corbisier; Sykes, Shane D; Weatherall, Loretta J; Keogh, Lyniece; Clausen, Don C; Dekker, Gus A; Smith, Roger; Roberts, Claire T; Rae, Kym M; Lumbers, Eugenie R

2018-04-01

The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preeclampsia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preeclampsia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preeclampsia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease. Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Shrunken Pore Syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting.

PubMed

Dardashti, Alain; Nozohoor, Shahab; Grubb, Anders; Bjursten, Henrik

2016-01-01

Shrunken Pore Syndrome was recently suggested for the pathophysiologic state in patients characterized by an estimation of their glomerular filtration rate (GFR) based upon cystatin  C, which is lower or equal to 60% of their estimated GFR based upon creatinine, i.e. when eGFR cystatin  C ≤ 60% of eGFR creatinine. Not only the cystatin C level, but also the levels of other low molecular mass proteins are increased in this condition. The preoperative plasma levels of cystatin C and creatinine were measured in 1638 patients undergoing elective coronary artery bypass grafting. eGFR cystatin C and eGFR creatinine were calculated using two pairs of estimating equations, CAPA and LMrev, and CKD-EPI cystatin  C and CKD-EPI creatinine, respectively. The Shrunken Pore Syndrome was present in 2.1% of the patients as defined by the CAPA and LMrev equations and in 5.7% of the patients as defined by the CKD-EPI cystatin C and CKD-EPI creatinine equations. The patients were studied over a median follow-up time of 3.5 years (2.0-5.0 years) and the mortality determined. Shrunken Pore Syndrome defined by both pairs of equations was a strong, independent, predictor of long-term mortality as evaluated by Cox analysis and as illustrated by Kaplan-Meier curves. Increased mortality was observed also for the subgroups of patients with GFR above or below 60 mL/min/1.73 m(2). Changing the cut-off level from 60 to 70% for the CAPA and LMrev equations increased the number of patients with Shrunken Pore Syndrome to 6.5%, still displaying increased mortality.

Serum Uric Acid Levels and Uric Acid/Creatinine Ratios in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients: Are These Parameters Efficient Predictors of Patients at Risk for Exacerbation and/or Severity of Disease?

PubMed

Durmus Kocak, Nagihan; Sasak, Gulsah; Aka Akturk, Ulku; Akgun, Metin; Boga, Sibel; Sengul, Aysun; Gungor, Sinem; Arinc, Sibel

2016-11-03

BACKGROUND Serum uric acid (sUA) levels were previously found to be correlated with hypoxic states. We aimed to determine the levels of sUA and sUA/creatinine ratios in stable COPD patients and to evaluate whether sUA level and sUA/creatinine ratio can be used as predictors of exacerbation risk and disease severity. MATERIAL AND METHODS This cross-sectional study included stable COPD patients and healthy controls. The sUA levels and sUA/creatinine ratios in each group were evaluated and their correlations with the study parameters were investigated. ROC analyses for exacerbation risk and disease severity were reported. RESULTS The study included 110 stable COPD patients and 52 healthy controls. The mean sUA levels and sUA/creatinine ratios were significantly higher in patients with COPD compared to healthy controls. The most common comorbidities in COPD patients were hypertension, diabetes, and coronary artery disease. While sUA levels were significantly higher in patients with hypertension (p=0.002) and malignancy (p=0.033), sUA/creatinine ratios was higher in patients with malignancy (p=0.004). The ROC analyses indicated that sUA/creatinine ratios can be more useful than sUA levels in predicting exacerbation risk (AUC, 0.586 vs. 0.426) and disease severity (AUC, 0.560 vs. 0.475) especially at higher cut-off values, but with low specificity. CONCLUSIONS Our study suggested that sUA levels and sUA/creatinine ratios increased in patients with stable COPD, especially among patients with certain comorbidities compared to healthy controls. At higher cut-off values, sUA levels and especially sUA/creatinine ratios, might be useful in predicting COPD exacerbation risk and disease severity. Also, their association with comorbidities, especially with malignancy and hypertension, may benefit from further investigation.

[The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].

PubMed

Arrabal-Polo, Miguel Ángel; del Carmen Cano-García, María; Arrabal-Martín, Miguel

2016-04-01

To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.

Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function.

PubMed

Svensson, Anders S; Kvitting, John-Peder Escobar; Kovesdy, Csaba P; Cederholm, Ingemar; Szabó, Zoltán

2016-06-01

The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB. This was a prospective study at an academic medical centre between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP. Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, P = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, P = 0.012) decreased significantly in the first 8 h postoperatively compared to preoperatively, as a result of haemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 h post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, P = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C. Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. © 2015 Asian Pacific Society of Nephrology.

Does elevation of serum creatinine in patients with chronic hepatitis C under therapy of telaprevir mean renal impairment?

PubMed

Matsui, Katsuomi; Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Ikeda, Hiroki; Okuse, Chiaki; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

2015-11-01

Treatment with telaprevir (TVR) entails adverse side-effects including anaemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C. Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (i) patients with an increase in SCr during the treatment (n = 8), and (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were evaluated. Although there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase-in-SCr group during the triple therapy. The SCr level returned to the pre-treatment level after cessation of TVR. There were no differences in urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre-treatment tended to be higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR. Elevation of SCr levels with TVR therapy may not suggest renal impairment. © 2015 Asian Pacific Society of Nephrology.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

PubMed

Kwon, H-M; Moon, Y-J; Jung, K-W; Jun, I-G; Song, J-G; Hwang, G-S

2018-05-01

The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease.

PubMed

Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-06-30

Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

PubMed Central

Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

2016-01-01

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

Renal function in the fetus and neonate - the creatinine enigma.

PubMed

Kastl, Justin T

2017-04-01

The use of serum creatinine levels to estimate glomerular function in infants is admittedly fraught with inherent inaccuracies which are both physiological and methodological in nature. This characteristic can understandably reduce the neonatal clinician's confidence in the ability of serum creatinine levels to provide useful information relevant to their patients' medical care. The aim of this review is to provide further insight into the peculiarities of serum creatinine trends in both premature and term infants with special focus on the maturational and developmental changes occurring in the kidney during this crucial time-period. Though newer markers of glomerular function are gaining increasing traction in the clinical realm, the most prominent of which is currently cystatin C, creatinine nonetheless remains an important player in the scientific evolution of glomerular filtration rate (GFR) estimation. Not only do its limitations provide a level of distinction for newer markers of GFR, but its advantages persist in refining the precision of newer GFR formulae which incorporate multiple patient characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Separation methods applicable to urinary creatine and creatinine.

PubMed

Smith-Palmer, Truis

2002-12-05

Urinary creatinine has been analyzed for many years as an indicator of glomerular filtration rate. More recently, interest in studying the uptake of creatine as a result of creatine supplementation, a practice increasingly common among bodybuilders and athletes, has lead to a need to measure urinary creatine concentrations. Creatine levels are of the same order of magnitude as creatinine levels when subjects have recently ingested creatine, while somewhat elevated urinary creatine concentrations in non-supplementing subjects can be an indication of a degenerative disease of the muscle. Urinary creatine and creatinine can be analyzed by HPLC using a variety of columns. Detection methods include absorption, fluorescence after post-column derivatization, and mass spectrometry, and some methods have been automated. Capillary zone electrophoresis and micellar electrokinetic capillary chromatography have also been used to analyze urinary creatine and creatinine. Creatine and creatinine have also been analyzed in serum and tissue using HPLC and CE, and many of these separations could also be applicable to urinary analysis.

Kocher-Debré-Semelaigne syndrome with rhabdomyolysis and increased creatinine.

PubMed

Cimbek, Emine Ayça; Şen, Yaşar; Yuca, Sevil Arı; Çam, Demet; Gür, Celal; Peru, Harun

2015-11-01

Association of Kocher-Debré-Semelaigne syndrome-a myopathy of hypothyroidism in childhood characterized by muscular hypertrophy, with rhabdomyolysis is very rare. We present a case of Kocher-Debré-Semelaigne syndrome with rhabdomyolysis secondary to Hashimoto's thyroiditis. He had muscular symptoms simulating poly/dermatomyositis, massively elevated creatine kinase (CK) levels and high creatinine levels. All of the findings reversed on treatment of hypothyroidism. The response to the therapy strongly suggested that Kocher-Debré-Semelaigne (KDS) syndrome was the underlying etiology. Serum thyroid- stimulating hormone levels should be routinely determined in all patients with muscular symptoms and/or elevation of CK and creatinine, keeping KDS syndrome in mind.

Relationship between body mass index and proteinuria in hypertensive nephrosclerosis: results from the African American Study of Kidney Disease and Hypertension (AASK) cohort.

PubMed

Toto, Robert D; Greene, Tom; Hebert, Lee A; Hiremath, Leena; Lea, Janice P; Lewis, Julia B; Pogue, Velvie; Sika, Mohammed; Wang, Xuelei

2010-11-01

Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression. Observational cross-sectional analysis. Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK). Obesity, determined using body mass index (BMI). Urine total protein-creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections. AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m(2). Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m(2) increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein-creatinine and urine albumin-creatinine ratios, respectively. In multivariable models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m(2) increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants. May not generalize to other populations; cross-sectional analysis precludes statements regarding causality. BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients. Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Relationship Between Body Mass Index and Proteinuria in Hypertensive Nephrosclerosis: Results From the African American Study of Kidney Disease and Hypertension (AASK) Cohort

PubMed Central

Toto, Robert D.; Greene, Tom; Hebert, Lee A.; Hiremath, Leena; Lea, Janice P.; Lewis, Julia B.; Pogue, Velvie; Sika, Mohammed; Wang, Xuelei

2011-01-01

Background Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression. Study Design Observational cross-sectional analysis. Setting & Participants Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK). Predictors Obesity, determined using body mass index (BMI). Measurements & Outcomes Urine total protein–creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections. Results AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m2. Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m2 increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein–creatinine and urine albumin-creatinine ratios, respectively. In multivari-able models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m2 increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants. Limitations May not generalize to other populations; cross-sectional analysis precludes statements regarding causality. Conclusions BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients. PMID:20801567

Renal failure in a patient with postpolio syndrome and a normal creatinine level.

PubMed

Leming, Melissa K; Breyer, Michael J

2012-01-01

Patients with renal failure who are taking trimethoprim have an increased risk of developing hyperkalemia, which can cause muscle weakness. In patients with postpolio syndrome, a normal creatinine level could be abnormally high, renal failure is possible because of lack of creatinine production, and the muscle weakness from resultant hyperkalemia could be more severe because of their underlying condition. This abnormally high creatinine level has been termed from this point relative renal failure. The objective of the study was to review a case in which relative renal failure and hyperkalemia caused muscle weakness that manifested as shortness of breath and confusion with electrocardiographic changes. A dehydrated patient with relative renal failure and postpolio syndrome had taken trimethoprim-sulfamethoxazole that caused symptomatic hyperkalemia. The patient presented with muscle weakness, shortness of breath, and confusion, with her postpolio syndrome compounding the situation and likely making the muscle weakness more severe. A patient on trimethoprim with renal failure is at an increased risk of developing hyperkalemia. Patients with postpolio syndrome could have severe muscle weakness from the hyperkalemia and could have renal failure even with a normal creatinine level. This case report will remind treating physicians to evaluate such patients for hyperkalemia if they present with muscle weakness, especially if the patient has renal failure and is on trimethoprim. Copyright © 2012 Elsevier Inc. All rights reserved.

Blood pressure and serum creatinine in obese female.

PubMed

Asrin, M; Nessa, A; Hasan, M I; Das, R K

2015-01-01

Obesity is increasing in developed as well as in developing countries. This analytical cross sectional study was carried out to document the relation between blood pressure, serum creatinine and body mass index in female and to assess potential health differences among obese female and normal weight female. This study was done in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2012 to June 2013. Seventy female persons volunteered as subjects. Among them 35 were within normal weight (BMI 18.5-24.9kg/m²) and 35 were obese (BMI≥30kg/m²). Non probability purposive type of sampling technique was used to select the subjects. Measurement of body mass index and blood pressure were done as per procedure. Serum creatinine level was estimated by enzymatic colorimetric method. The results were calculated and analyzed by using SPSS (statistical package for social science, version 17.0), scientific electronic calculator and simultaneously with a computer assisted program like Microsoft excel. Unpaired 't' test was applied to find the significance of difference regarding serum creatinine and blood pressure levels in obese female. The value of p was 1% to indicate highly significant and 5% to indicate simply significant or statistically significant. The mean±SE of systolic blood pressure, diastolic blood pressure and serum creatinine levels were 135.71±1.58mmHg, 88.74±0.95mmHg and 1.03±0.01mg/dl respectively; significant at 1% level for obese group of BMI (p<0.0001). The examinations and biochemical investigations revealed that high BMI is significantly related to increased levels of serum creatinine & blood pressure in obese female which indicate the obese subjects are prone to cardiovascular & metabolic risk.

Renal function improves with the treatment of hypothyroidism.

PubMed

Bulur, Oktay; Dal, Kursat; Ertugrul, Derun Taner; Eser, Murat; Kaplan Efe, Fatma; Karakaya, Serdar; Şahin, Kubilay; Baser, Salih; Ata, Naim; Aybal Kutlugun, Aysun; Beyan, Esin

2017-08-01

It has been known that thyroid hormones may affect renal function. In this study, we aimed to investigate the effect of levothyroxine replacement on renal function in hypothyroid patients before and after treatment. We retrospectively investigated free T3 (fT3), free T4 (fT4), TSH, creatinine, and eGFR measurements during both hypothyroid and euthyroid states of hypothyroid patients. The eGFR was calculated using the simplified Modification of Diet in Renal Disease formula. fT3, fT4, and eGFR measurements increased, meanwhile creatinine and TSH levels decreased significantly after euthyroidism was achieved with levothyroxine treatment (p < 0.0001 for all). The correlation analyses revealed that ∆creatinine and ∆TSH levels were significantly correlated before and after levothyroxine treatment (r: 0.288, p < 0.0001). ∆eGFR and ∆TSH levels were significantly correlated before and after LT4 treatment (r: -0.272, p < 0.0001). In this study, we evaluated creatinine and eGFR levels in patients with hypothyroidism and found out that renal function improved in most patients after euthyroidism was achieved. In some patients, above-normal creatinine levels completely returned to normal once the patients became euthyroid.

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

PubMed

Bonds, D E; Craven, T E; Buse, J; Crouse, J R; Cuddihy, R; Elam, M; Ginsberg, H N; Kirchner, K; Marcovina, S; Mychaleckyj, J C; O'Connor, P J; Sperl-Hillen, J-A

2012-06-01

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. ClincalTrials.gov: NCT00000620. The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

[Risk for hyperkalemia during long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetics in relation to the glomerular filtration rate].

PubMed

Raml, A; Schmekal, B; Grafinger, P; Biesenbach, G

2001-11-23

The risk for hyperkalaemia during therapy with angiotensin-converting enzyme inhibitors is especially increased in the elderly diabetic because of a decrease in glomerular filtration rate (GFR), as well as the occurrence of hyporeninaemic hypoaldosteronism. We evaluated the risk for hyperkalaemia under long-term angiotensin-converting enyzme inhibition in 86 insulin-dependent type 2 diabetic patients in relation to their GFR. We compared the influence of a 3 to 6 months long treatment with angiotensin-converting enzyme inhibitors on the serum potassium levels, the creatinine clearance and the urinary albumin excretion in insulin-dependent type 2 diabetic patients with an initial creatinine clearance < 50 ml/min/1.73m(2) (n = 15, age 66 +/- 6 years) and >/= 50 ml/min/1.73m(2) respectively (n = 71, age 61 +/- 10 years). In addition, we also investigated the influence on the metabolic control and the blood pressure values in both groups of patients. In the patients with creatinine clearance >/= 50 ml/min/1,73m(2) the mean potassium level increased from 4.3 +/- 0.2 to 4.6 +/- 0.4 mmol/l (P < 0,01), while the incidence of a potassium level > 5 mmol/l was 17 %. In the group with a creatinine clearance < 50 ml/min/1.73m(2) the potassium level rose from 4.5 +/- 0.2 to 5.0 +/- 0.4 mmol/l (P < 0.01). The incidence of potassium levels > 5 mmol/l was 66 % (P < 0,01). In both patient groups the creatinine clearances did not change significantly during angiotensin-converting enzyme inhibition, and the urinary albumin excretion as well as the HbA(1c) values and blood pressure showed only a tendency towards a decrease. Long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetic patients leads to a significant increase in serum potassium. The incidence of hyperkalaemia with potassium levels > 5 mmol/l is significantly higher in the patients with initial creatinine clearance < 50 ml/min/1.73m(2). Severe hyperkalaemia with potassium levels > 6 mmol/l was not observed.

Environmental tobacco smoke exposure among casino dealers.

PubMed

Achutan, Chandran; West, Christine; Mueller, Charles; Bernert, John T; Bernard, Bruce

2011-04-01

This study quantified casino dealers' occupational exposure to environmental tobacco smoke (ETS). We measured casino dealers' exposure to ETS components by analyzing full-shift air and preshift and postshift urine samples. Casino dealers were exposed to nicotine, 4-vinyl pyridine, benzene, toluene, naphthalene, formaldehyde, acetaldehyde, solanesol, and respirable suspended particulates. Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine increased significantly during an 8-hour work shift both with and without adjustment for creatinine clearance. Creatinine-unadjusted cotinine significantly increased during the 8-hour shift, but creatinine-adjusted cotinine did not increase significantly. Casino dealers at the three casinos were exposed to airborne ETS components and absorbed an ETS-specific component into their bodies, as demonstrated by detectable levels of urinary NNAL. The casinos should ban smoking on their premises and offer employee smoking cessation programs.

Adherence to guidelines for creatinine and potassium monitoring and discontinuation following renin–angiotensin system blockade: a UK general practice-based cohort study

PubMed Central

Schmidt, Morten; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A

2017-01-01

Objectives To examine adherence to serum creatinine and potassium monitoring and discontinuation guidelines following initiation of treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs); and whether high-risk patients are monitored. Design A general practice-based cohort study using electronic health records from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. Setting UK primary care, 2004–2014. Subjects 223 814 new ACEI/ARB users. Main outcome measures Proportion of patients with renal function monitoring before and after ACEI/ARB initiation; creatinine increase ≥30% or potassium levels >6 mmol/L at first follow-up monitoring; and treatment discontinuation after such changes. Using logistic regression models, we also examined patient characteristics associated with these biochemical changes, and with follow-up monitoring within the guideline recommendation of 2 weeks after treatment initiation. Results 10% of patients had neither baseline nor follow-up monitoring of creatinine within 12 months before and 2 months after initiation of an ACEI/ARB, 28% had monitoring only at baseline, 15% only at follow-up, and 47% both at baseline and follow-up. The median period between the most recent baseline monitoring and drug initiation was 40 days (IQR 12–125 days). 34% of patients had baseline creatinine monitoring within 1 month before initiating therapy, but <10% also had the guideline-recommended follow-up test recorded within 2 weeks. Among patients experiencing a creatinine increase ≥30% (n=567, 1.2%) or potassium level >6 mmol/L (n=191, 0.4%), 80% continued treatment. Although patients with prior myocardial infarction, hypertension or baseline potassium >5 mmol/L were at high risk of ≥30% increase in creatinine after ACEI/ARB initiation, there was no evidence that they were more frequently monitored. Conclusions Only one-tenth of patients initiating ACEI/ARB therapy receive the guideline-recommended creatinine monitoring. Moreover, the vast majority of the patients fulfilling postinitiation discontinuation criteria for creatinine and potassium increases continue on treatment. PMID:28069618

Glomerular Filtration Rate is Unchanged By Ultramarathon.

PubMed

Wołyniec, Wojciech; Ratkowski, Wojciech; Kasprowicz, Katarzyna; Jastrzębski, Zbigniew; Małgorzewicz, Sylwia; Witek, Konrad; Grzywacz, Tomasz; Żmijewski, Piotr; Renke, Marcin

2017-12-27

Acute kidney injury (AKI) is reported as a common complication of marathon and ultramarathon running. In previous studies AKI was diagnosed on the basis of the creatinine level in serum and estimated glomerular filtration rate (eGFR). In the present study we calculated eGFR and also measured creatinine clearance after every 25 km of a 100 km run. 20 healthy, amateur runners (males, mean age 40.75 ± 7.15 years, mean weight 76.87 ± 8.39 kg) took part in a 100 km run on a track. Blood and urine were collected before the run, after every 25 km and 12 hours after the run. 17 runners completed the study. There was increase in creatinine, urea and uric acid observed after 100 km (p < 0.05). The mean increase in creatinine was 0.21 mg/dl (24.53%). 5 runners fulfilled the Acute Kidney Injury Network (AKIN) criteria of AKI. The eGFR according to the MDRD (modification of diet in renal disease), CKD-EPI (chronic kidney disease epidemiology collaboration) and Cockcroft-Gault formulas was significantly decreased after the run (p < 0.05). Otherwise, creatinine clearance calculated from creatinine level in both serum and urine remained stable. In contrast to the majority of previous studies, we did not observe any decrease in the kidney function during an ultramarathon. In this study the creatinine clearance, which is the best routine laboratory method to determine glomerular filtration rate was used. There is no evidence that long running is harmful for kidney.

Distribution pattern of urine albumin creatinine ratio and the prevalence of high-normal levels in untreated asymptomatic non-diabetic hypertensive patients.

PubMed

Ohmaru, Natsuki; Nakatsu, Takaaki; Izumi, Reishi; Mashima, Keiichi; Toki, Misako; Kobayashi, Asako; Ogawa, Hiroko; Hirohata, Satoshi; Ikeda, Satoru; Kusachi, Shozo

2011-01-01

Even high-normal albuminuria is reportedly associated with cardiovascular events. We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and <300 µg/mg·creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to <30 µg/mg·creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

Effects of Endurance and Endurance-strength Exercise on Renal Function in Abdominally Obese Women with Renal Hyperfiltration: A Prospective Randomized Trial.

PubMed

Szulińska, Monika; Skrypnik, Damian; Ratajczak, Marzena; Karolkiewicz, Joanna; Madry, Edyta; Musialik, Katarzyna; Walkowiak, Jaroslaw; Jakubowski, Hieronim; Bogdański, Pawel

2016-10-01

Obesity is associated with kidney defects. Physical activity is a key element in the treatment of obesity. The aim of this study was to compare the effect of endurance and endurance-strength training on kidney function in abdominally obese women. Forty-four abdominally obese women were randomized to endurance training or endurance-strength training, three times a week for 3 months. Before and after the intervention, kidney function was assessed by measuring blood creatinine, urine creatinine, and urine albumin levels, and the albumin-to-creatinine ratio and glomerular filtration rate (GFR) were calculated. Renal hyperperfusion was present in both groups before the study. Following both types of physical activity, similar modifications of the investigated parameters were observed, but with no significant between-group differences. Both courses of training led to a significant increase in blood creatinine and a subsequent decrease in the GFR. A significant increase in urine creatinine and album levels, though not exceeding the range for microalbuminuria, was not accompanied by any difference in the albumin-to-creatinine ratio after endurance-strength training alone. Three months of either endurance or endurance-strength training has a favorable and comparable effect on renal function in abdominally obese women with renal hyperfiltration. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Influence of the 6-month physical activity programs on renal function in obese boys.

PubMed

Lousa, Irina; Nascimento, Henrique; Rocha, Susana; Catarino, Cristina; Reis, Flávio; Rêgo, Carla; Santos-Silva, Alice; Seabra, André; Ribeiro, Sandra; Belo, Luís

2018-05-01

BackgroundWe intended to evaluate the effects of physical activity (PA) programs on renal function in obese boys.MethodsThirty-nine boys participated in one of the following three groups: soccer (SG, n=13), traditional PA (AG, n=13), and sedentary control (CG, n=13). SG and AG were involved in 6-month PA programs, involving three sessions/week for 60-90 min. Anthropometric measurements, body composition, creatinine and cystatin C plasmatic levels, and estimated glomerular filtration rate (eGFR) were evaluated.ResultsAt baseline (n=39), age and lean mass index (LMI) were positively correlated with creatinine levels. After 6 months, both intervention groups decreased the BMI z-score and waist circumference, while the CG increased the body fat percentage (BFP). LMI increased in all the groups. SG presented a small increment in plasma creatinine and a decrease in the eGFR values, using the Schwartz formula. Concerning the cystatin C levels and eGFR values using Filler (cystatin C-based) or Combined Zappitelli (creatinine/cystatin C-based) formulas, no significant changes were observed in any group.ConclusionThe combined Zappitelli formula showed no significant impact of PA on eGFR in obese boys. Although plasma creatinine is significantly influenced by lean body mass, cystatin C is likely to be a more accurate marker of renal function in this population.

Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats.

PubMed

Ehsani, Vahid; Amirteimoury, Morteza; Taghipour, Zahra; Shamsizadeh, Ali; Bazmandegan, Gholamreza; Rahnama, Amir; Khajehasani, Fatemeh; Fatemi, Iman

2017-11-01

Pistacia vera is a plant of the family Anacardiaceae found in Central and West Asia. P. vera nut (Pistachio) possess multiple pharmacological effects such as antimicrobial, anti-hyperlipidemia, antioxidant and anti-inflammatory. This study is designed to evaluate the protective effect of the hydroalcoholic extract of pistachio on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin (100 mg/kg/day for 7 days). Hydroalcoholic extract of pistachio (10, 50 and 100 mg/kg/p.o) was administered for 7 days. The nephroprotective activity was evaluated by determining creatinine clearance, serum creatinine, urine volume, urine glucose and blood urea nitrogen (BUN) levels. The kidneys were processed for histopathological examinations and all specimens were examined for morphologic parameters involving tubular degeneration, tubular necrosis and tubule interstitial nephritis. Results showed a significant increase in the levels of serum creatinine, urine volume, urine glucose and BUN and decrease of creatinine clearance by gentamicin (GA) administration. Co-administration with pistachio extract showed reduction in the levels of serum creatinine, urine volume, urine glucose and BUN and increase of creatinine clearance in all doses but the most significant alteration was observed in doses of 100 mg/kg. Also, the nephroprotective effect of the GA was confirmed by the histological examination of the kidneys. The study revealed the nephroprotective effect of the hydroalcoholic extract of pistachio. These findings suggest that pistachio treatment may attenuate renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in the kidney.

Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats

PubMed Central

Ehsani, Vahid; Amirteimoury, Morteza; Taghipour, Zahra; Shamsizadeh, Ali; Bazmandegan, Gholamreza; Rahnama, Amir; Khajehasani, Fatemeh; Fatemi, Iman

2017-01-01

Abstract Purpose:Pistacia vera is a plant of the family Anacardiaceae found in Central and West Asia. P. vera nut (Pistachio) possess multiple pharmacological effects such as antimicrobial, anti-hyperlipidemia, antioxidant and anti-inflammatory. This study is designed to evaluate the protective effect of the hydroalcoholic extract of pistachio on gentamicin-induced nephrotoxicity in rats. Methods: Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin (100 mg/kg/day for 7 days). Hydroalcoholic extract of pistachio (10, 50 and 100 mg/kg/p.o) was administered for 7 days. The nephroprotective activity was evaluated by determining creatinine clearance, serum creatinine, urine volume, urine glucose and blood urea nitrogen (BUN) levels. The kidneys were processed for histopathological examinations and all specimens were examined for morphologic parameters involving tubular degeneration, tubular necrosis and tubule interstitial nephritis. Results: Results showed a significant increase in the levels of serum creatinine, urine volume, urine glucose and BUN and decrease of creatinine clearance by gentamicin (GA) administration. Co-administration with pistachio extract showed reduction in the levels of serum creatinine, urine volume, urine glucose and BUN and increase of creatinine clearance in all doses but the most significant alteration was observed in doses of 100 mg/kg. Also, the nephroprotective effect of the GA was confirmed by the histological examination of the kidneys. Conclusion: The study revealed the nephroprotective effect of the hydroalcoholic extract of pistachio. These findings suggest that pistachio treatment may attenuate renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in the kidney. PMID:28558475

Coronary disease risk curve of serum creatinine is linear in Turkish men, U-shaped in women.

PubMed

Onat, Altan; Can, Günay; Ademoğlu, Evin; Çelik, Etem; Karagöz, Ahmet; Örnek, Ender

2013-01-01

The highest levels of glomerular filtration rate are associated with increased coronary heart disease (CHD) risk, an issue we investigated in separate sexes in a population prone to metabolic syndrome. In total, 1948 participants of the Turkish Adult Risk Factor study with available creatinine determinations were studied at a mean 3.4 years' follow-up. Using quartiles of creatinine, risk in Cox models of incident CHD or the likelihood of combined prevalent and incident CHD was assessed. Women in the lowest creatinine quartile demonstrated the lowest risk profile across diverse variables, except showing low high-density lipoprotein cholesterol and average apolipoprotein A-I and lipoprotein (a) concentrations implicating impaired atheroprotective properties. Whereas serum creatinine in men was not significantly associated with 6 proinflammatory variables comprised in linear regression analysis, apolipoprotein A-I and lipoprotein (a) were significant positive covariates in women, the latter tending to negative association in women without metabolic syndrome. In men, the highest (>1.10 mg/dL), compared with the lowest, creatinine quartile significantly predicted CHD risk, at 1.85-fold relative risks, after adjustment for established risk factors. The risk curve in women was U-shaped, the top and bottom quartiles tending to display higher risk (odds ratio, 1.28 [95% confidence interval, 0.91-1.80]) compared with the 2 intermediate quartiles. Increasing serum creatinine values are associated strongly and independently with CHD risk in men but not in women in whom the risk curve is U-shaped. The phenomenon of low creatinine levels underlies some hitherto unexplained relevant observations, and low measurements may be attributed to inassayability secondary to involvement in autoimmune activation.

Underestimation of urinary albumin to creatinine ratio in morbidly obese subjects due to high urinary creatinine excretion.

PubMed

Guidone, Caterina; Gniuli, Donatella; Castagneto-Gissey, Lidia; Leccesi, Laura; Arrighi, Eugenio; Iaconelli, Amerigo; Mingrone, Geltrude

2012-04-01

Albuminuria, a chronic kidney and/or cardiovascular disease biomarker, is currently measured as albumin-to-creatinine ratio (ACR). We hypothesize that in severely obese individuals ACR might be abnormally low in spite of relatively high levels of urinary albumin due to increased creatininuria. One-hundred-eighty-four subjects were divided into tertiles based on their BMI. Fat-free mass (FFM) and fat-mass were assessed by DEXA; 24-h creatinine and albumin excretion, ACR, lipid profile and blood pressure were measured. Twenty-four-hour creatinine highly correlated (R = 0.75) with FFM. Since both creatininuria and albuminuria increased with the BMI, being the increase in creatininuria preponderant in subjects with BMI>35, their ratio (AC-ratio) did not change significantly from that of subjects in the lower BMI tertile. ACR only correlated with the systolic blood pressure, while both albuminuria and cretininuria correlated (P = 0.01) with the absolute 10-year CHD risk. In subjects with BMI>35, 100 mg of albumin excreted with urine increased the CHD risk of 2%. Albumin-to-creatinine ratio is underestimated in severely obese individuals as a consequence of the large creatininuria, which is proportional to the increased FFM. Therefore, at least in this population 24-h albuminuria should be more reliable than ACR. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

PubMed

Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

2015-01-01

Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

Can salivary creatinine and urea levels be used to diagnose chronic kidney disease in children as accurately as serum creatinine and urea levels? A case-control study.

PubMed

Renda, Rahime

2017-11-01

Children with chronic kidney disease (CKD) develop many metabolic changes in blood that often necessitate frequent biochemical analysis. Serum analysis is an invasive and painful procedure. It would be highly beneficial if a noninvasive alternative process to serum analysis in children were identified. Saliva can be collected noninvasively, repeatedly, and without the use of healthcare personnel. The aims of this study were to compare serum and salivary urea and creatinine levels in children with CKD and healthy controls, and to determine if salivary creatinine and urea levels can be used to diagnose CKD in children as accurately as serum creatinine and urea levels. This case-control study included 35 children with CKD and 28 healthy children as controls. Saliva and blood samples were collected for measurement of urea and creatinine levels. The urea and creatinine levels in serum and saliva in the CKD and control groups were compared using the independent samples Mann-Whitney U test. Correlations between the serum and salivary urea and creatinine levels were determined using Pearson's correlation coefficient. Receiver operating characteristic analysis was used to assess the diagnostic performance of salivary creatinine and cutoff values were identified. In the CKD group, the mean salivary creatinine level was 0.45 mg/dL and the mean salivary urea level was 0.11 mg/dL, versus 28.83 mg/dL and 21.78 mg/dL, respectively, in the control group. Stage 4 and 5 CKD patients had a mean salivary urea level of 31.35 mg/dL, as compared to 17.78 mg/dL in the control group. Serum urea and creatinine, and salivary creatinine were significantly higher in the CKD patients (regardless of disease stage) than in the controls (p < .05). The salivary urea level was significantly higher in the stage 4 and 5 CKD patients than in the controls (p < .05). There was a positive correlation between serum and salivary creatinine. The area under the curve for salivary creatinine was 0.805. The cutoff value for salivary creatinine was 0.125 mg/dL, with a sensitivity of 82.9% and specificity of 78.6%. Based on the positive correlation between the serum and saliva creatinine levels observed in the present study, we think saliva analysis could be used as a noninvasive alternative to blood analysis for diagnosing CKD in children.

Serum creatinine and alkaline phosphatase levels are associated with severe chronic periodontitis.

PubMed

Caúla, A L; Lira-Junior, R; Tinoco, E M B; Fischer, R G

2015-12-01

Periodontitis may alter systemic homeostasis and influence creatinine and alkaline phosphatase levels. Therefore, the aim of this study was to evaluate the relationship between severe chronic periodontitis and serum creatinine and alkaline phosphatase levels. One hundred patients were evaluated, 66 with severe chronic periodontitis (test group) and 34 periodontally healthy controls (control group). Medical, demographic and periodontal parameters were registered. Blood sample was collected after an overnight fast and serum creatinine and alkaline phosphatase levels were determined. There were significant differences between test and control groups in ethnicity, gender and educational level (p < 0.05). Patients with periodontitis showed a lower mean creatinine level (p < 0.05) and higher mean alkaline phosphatase level (p < 0.001) than the control group. There were significant correlations between periodontal parameters and serum creatinine and alkaline phosphatase levels. Severe chronic periodontitis was associated to lower creatinine and higher alkaline phosphatase levels. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic Importance of Low Admission Serum Creatinine Concentration for Mortality in Hospitalized Patients.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Kittanamongkolchai, Wonngarm; Harrison, Andrew M; Kashani, Kianoush

2017-05-01

The study objective was to assess the association between low serum creatinine value at admission and in-hospital mortality in hospitalized patients. This was a retrospective single-center cohort study conducted at a tertiary referral hospital. All hospitalized adult patients between 2011 and 2013 who had an admission creatinine value available were identified for inclusion in this study. Admission creatinine value was categorized into 7 groups: ≤0.4, 0.5 to 0.6, 0.7 to 0.8, 0.9 to 1.0, 1.1 to 1.2, 1.3 to 1.4, and ≥1.5 mg/dL. The primary outcome was in-hospital mortality. Logistic regression analysis was performed to obtain the odds ratio of in-hospital mortality for the various admission creatinine levels, using a creatinine value of 0.7 to 0.8 mg/dL as the reference group in the analysis of all patients and female patients and of 0.9 to 1.0 mg/dL in the analysis of male patients because it was associated with the lowest in-hospital mortality. Of 73,994 included patients, 973 (1.3%) died in the hospital. The association between different categories of admission creatinine value and in-hospital mortality assumed a U-shaped distribution, with both low and high creatinine values associated with higher in-hospital mortality. After adjustment for age, sex, ethnicity, principal diagnosis, and comorbid conditions, very low creatinine value (≤0.4 mg/dL) was significantly associated with increased mortality (odds ratio, 3.29; 95% confidence interval, 2.08-5.00), exceeding the risk related to a markedly increased creatinine value of ≥1.5 mg/dL (odds ratio, 2.56; 95% confidence interval, 2.07-3.17). The association remained significant in the subgroup analysis of male and female patients. Low creatinine value at admission is independently associated with increased in-hospital mortality in hospitalized patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Adherence to guidelines for creatinine and potassium monitoring and discontinuation following renin-angiotensin system blockade: a UK general practice-based cohort study.

PubMed

Schmidt, Morten; Mansfield, Kathryn E; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A

2017-01-09

To examine adherence to serum creatinine and potassium monitoring and discontinuation guidelines following initiation of treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs); and whether high-risk patients are monitored. A general practice-based cohort study using electronic health records from the UK Clinical Practice Research Datalink and Hospital Episode Statistics. UK primary care, 2004-2014. 223 814 new ACEI/ARB users. Proportion of patients with renal function monitoring before and after ACEI/ARB initiation; creatinine increase ≥30% or potassium levels >6 mmol/L at first follow-up monitoring; and treatment discontinuation after such changes. Using logistic regression models, we also examined patient characteristics associated with these biochemical changes, and with follow-up monitoring within the guideline recommendation of 2 weeks after treatment initiation. 10% of patients had neither baseline nor follow-up monitoring of creatinine within 12 months before and 2 months after initiation of an ACEI/ARB, 28% had monitoring only at baseline, 15% only at follow-up, and 47% both at baseline and follow-up. The median period between the most recent baseline monitoring and drug initiation was 40 days (IQR 12-125 days). 34% of patients had baseline creatinine monitoring within 1 month before initiating therapy, but <10% also had the guideline-recommended follow-up test recorded within 2 weeks. Among patients experiencing a creatinine increase ≥30% (n=567, 1.2%) or potassium level >6 mmol/L (n=191, 0.4%), 80% continued treatment. Although patients with prior myocardial infarction, hypertension or baseline potassium >5 mmol/L were at high risk of ≥30% increase in creatinine after ACEI/ARB initiation, there was no evidence that they were more frequently monitored. Only one-tenth of patients initiating ACEI/ARB therapy receive the guideline-recommended creatinine monitoring. Moreover, the vast majority of the patients fulfilling postinitiation discontinuation criteria for creatinine and potassium increases continue on treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Changes in Serum Electrolytes, Urea, and Creatinine in Aloe Vera-treated Rats

PubMed Central

Saka, WA; Akhigbe, RE; Popoola, OT; Oyekunle, OS

2012-01-01

This study was carried out to investigate the effect of Aloe vera extract (AvE) on serum electrolytes, urea, and creatinine as indices of renal function in Sprague-Dawley rats. Twelve male Sprague-Dawley rats weighing between 80 and 130 g were used. Rats were divided into two groups: The control and the test groups (n=6). The test group received 1 ml of AvE daily for 28 days. Both the groups fed on standard rat chow and water ad libitum. The results showed a decrease in serum levels of sodium, and potassium, but an increase in the serum levels of bicarbonate, urea, and creatinine in the test group. The changes seen were, however, statistically insignificant, except for the serum levels of sodium and creatinine (P<0.05). It is thus concluded that AvE impairs renal handling of electrolytes with consequent hyponatremia and hypercreatinemia. However, this might be of therapeutic value in conditions associated with hypernatremia. PMID:22754258

The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum creatinine rats: Can creatinine predict renal tubular elimination?

PubMed

Ma, Yan-Rong; Zhou, Yan; Huang, Jing; Qin, Hong-Yan; Wang, Pei; Wu, Xin-An

2018-03-01

The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Renal Allograft Function Is a Risk Factor of Left Ventricular Remodeling After Kidney Transplantation.

PubMed

Koo, T Y; Ahn, C; Yang, J

2017-06-01

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplantation (KT) patients. The prevalence of left ventricular hypertrophy increases with the progression of renal insufficiency. We investigated the association between the progression of renal insufficiency and left ventricular hypertrophy after KT. We reviewed KT patients at Seoul National University Hospital from January 1973 to December 2009. The creatinine elevation ratio (CER, the percentage change in the creatinine level from 1 month to 5 years after transplant) was calculated as follows: (creatinine level at 5 years minus creatinine level at 1 month)/creatinine level at 1 month × 100. The study population was classified into a high-CER group (CER ≥25%) and low-CER group (CER <25%). Mean left ventricular mass index (LVMI) values were 135.7 and 134.7 g/m 2 before KT and 101.7 and 123.7 g/m 2 at 5 years after KT in the low-CER and high-CER groups, respectively. The LVMI before or 1 year after KT was not different between the 2 groups, but the LVMI at 5 years post-transplant was higher in the high-CER group than in the low-CER group. The LVMI increased after its initial decrease in the high-CER group, whereas its reduction was maintained in the low-CER group during the 5 years after KT (P = .009, repeated-measures analysis of variance). These data suggest that deterioration of renal allograft function is associated with left ventricular remodeling after KT. Copyright © 2017 Elsevier Inc. All rights reserved.

A creatinine biosensor based on admittance measurement

NASA Astrophysics Data System (ADS)

Ching, Congo Tak-Shing; Sun, Tai-Ping; Jheng, Deng-Yun; Tsai, Hou-Wei; Shieh, Hsiu-Li

2015-08-01

Regular check of blood creatinine level is very important as it is a measurement of renal function. Therefore, the objective of this study is to develop a simple and reliable creatinine biosensor based on admittance measurement for precise determination of creatinine. The creatinine biosensor was fabricated with creatinine deiminase immobilized on screen-printed carbon electrodes. Admittance measurement at a specific frequency ranges (22.80 - 84.71 Hz) showed that the biosensor has an excellent linear (r2 > 0.95) response range (50 - 250 uM), which covers the normal physiological and pathological ranges of blood creatinine levels. Intraclass correlation coefficient (ICC) showed that the biosensor has excellent reliability and validity (ICC = 0.98). In conclusion, a simple and reliable creatinine biosensor was developed and it is capable of precisely determining blood creatinine levels in both the normal physiological and pathological ranges.

Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

PubMed

Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

2017-09-01

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Salivary creatinine and urea analysis in patients with chronic kidney disease: a case control study.

PubMed

Lasisi, Taye Jemilat; Raji, Yemi Raheem; Salako, Babatunde Lawal

2016-01-16

Many metabolic changes develop in patients with chronic kidney disease which often necessitate frequent biochemical analysis of blood. Saliva analysis as an alternative to blood has many advantages. The aims of this study were to evaluate levels of salivary creatinine and urea in patients with chronic kidney disease in comparison to healthy individuals; to determine correlation between salivary creatinine/urea and blood creatinine/urea and to evaluate the diagnostic potential of saliva. A case control study, involving 50 patients with late stage chronic kidney disease and 49 healthy individuals as control. Blood and saliva samples were analyzed for urea and creatinine levels. Data are presented as median with interquartile range and compared using Independent Samples Mann Whitney U test. Correlation between plasma and salivary creatinine as well as urea was determined using Spearman's correlation test. Receiver operating characteristics (ROC) analysis was done to determine the diagnostic ability of salivary creatinine and urea and cut-off values were established. Median salivary creatinine levels were 2.60 mg/dl and 0.20 mg/dl while median salivary urea levels were 92.00 mg/dl and 20.50 mg/dl in patients with chronic kidney disease and controls respectively. Salivary levels of creatinine and urea were significantly elevated in chronic kidney disease patients (p < 0.001). In addition, there was positive correlation between blood and salivary creatinine as well as urea levels. Total areas under the curve for salivary creatinine and urea were 0.97 and 0.89 respectively. Cut-off values for salivary creatinine and urea were 0.55 mg/dl and 27.50 mg/dl respectively which gave sensitivity and specificity of 94 % and 85 % for creatinine; as well as 86 % and 93 % for urea. Findings of this study suggest that analysis of salivary creatinine and urea in patients with chronic kidney disease reflects their levels in blood. Hence, salivary creatinine and urea could be used as diagnostic biomarkers of chronic kidney disease.

Body Mass Index Is Associated with Increased Creatinine Clearance by a Mechanism Independent of Body Fat Distribution

PubMed Central

Gerchman, Fernando; Tong, Jenny; Utzschneider, Kristina M.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; McNeely, Marguerite J.; Carr, Darcy B.; Leonetti, Donna L.; Young, Bessie A.; de Boer, Ian H.; Boyko, Edward J.; Fujimoto, Wilfred Y.; Kahn, Steven E.

2009-01-01

Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration. Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration. Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington. Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington. Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan. Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P < 0.001), fasting glucose (r = 0.198; P = 0.001), and insulin levels (r = 0.125; P = 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P < 0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF areas were not independently associated with creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r = 0.471; P < 0.001). Conclusions: BMI rather than body fat distribution is an independent determinant of creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association. PMID:19584179

Measurement of creatinine in human plasma using a functional porous polymer structure sensing motif

PubMed Central

Nanda, Sitansu Sekhar; An, Seong Soo A; Yi, Dong Kee

2015-01-01

In this study, a new method for detecting creatinine was developed. This novel sensor comprised of two ionic liquids, poly-lactic-co-glycolic acid (PLGA) and 1-butyl-3-methylimidazolium (BMIM) chloride, in the presence of 2′,7′-dichlorofluorescein diacetate (DCFH-DA). PLGA and BMIM chloride formed a functional porous polymer structure (FPPS)-like structure. Creatinine within the FPPS rapidly hydrolyzed and released OH−, which in turn converted DCFH-DA to DCFH, developing an intense green color or green fluorescence. The conversion of DCFH to DCF+ resulted in swelling of FPPS and increased solubility. This DCF+-based sensor could detect creatinine levels with detection limit of 5 µM and also measure the creatinine in blood. This novel method could be used in diagnostic applications for monitoring individuals with renal dysfunction. PMID:26347475

Risk Stratification of Acute Kidney Injury Using the Blood Urea Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.

PubMed

Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei

2015-01-01

Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality. In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine. The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.

Elevated serum creatinine at baseline predicts poor outcome in patients receiving cardiac resynchronization therapy.

PubMed

Shalaby, Alaa; El-Saed, Aiman; Voigt, Andrew; Albany, Constantine; Saba, Samir

2008-05-01

Renal insufficiency is recognized as a predictor of mortality and poor outcome in heart failure patients. We sought to study the impact of baseline serum creatinine on subsequent outcome in cardiac resynchronization therapy (CRT) recipients. We retrospectively reviewed hospital records of all CRT recipients at Pittsburgh Veterans Affairs (VA) Healthcare System (2003-2005) and University of Pittsburgh Medical Center (2004). We recorded clinical characteristics at the time of implantation including demographics, New York Heart Association (NYHA) functional class, ejection fraction, QRS duration, cardiomyopathy etiology, medical history, medication use, and serum creatinine. Mortality alone and mortality combined with heart failure hospitalization were the study endpoints. Out of the 330 patients studied, a total of 66 (20.0%) patients died over a mean follow-up duration of 19.7 +/- 9.0 months (range 1-44). The cohort was studied by three creatinine tertiles (0.6-1.0, 1.1-1.3, 1.4-3.0 mg/dL). Both study endpoints were observed more frequently in patients in the highest creatinine tertile compared to others (28.7% vs 14.0%, P = 0.008 for death and 41.6% vs 21.5%, P = 0.001 for the combined endpoint). High creatinine remained an independent predictor of mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.06-3.39, P = 0.032) and the combined endpoint (HR 1.94, 95% CI 1.20-3.13, P = 0.007) in multivariate adjusted models. Studied as a continuous variable, increase in creatinine level by 0.1 mg/dL was associated with an 11% increase in mortality risk and a 7% increase in the combined endpoint. In an unselected cohort of CRT recipients, the baseline creatinine was found to predict worse survival and poor outcome over a modest follow-up duration.

Is elevated creatinine a reliable marker for methanol toxicity in nitromethane-containing model fuel ingestions in children?

PubMed

Padmanabhan, Pradeep; Spiller, Henry A; Ross, Mitchell P; Bosse, George M

2011-01-01

In the absence of a rapid serum methanol level estimation, it is difficult to assess the risk from unintentional childhood ingestion of model fuels containing methanol and nitromethane (MFNM). Previous reports have documented false elevations of serum creatinine from the nitromethane in these fuels, suggesting its utility as a readily available marker of significant methanol ingestion. We performed a 2-year retrospective chart review of cases of ingestion of MFNM in children, with both a methanol level and measured creatinine level. Seven children, ages 19 months to 3 years, ingested MFNM. All seven children were seen in a hospital and had measured methanol and creatinine levels. All blood samples for methanol and creatinine were drawn within 3 hours of ingestion with methanol estimation delayed up to 24 hours. Creatinine ranged from 0.39 (0.034 mmol/l) to 10.7 mg/dl (0.95 mmol/l). All methanol levels were <10 mg/dl (0.31 mmol/l) or reported as negative. Fomepizole was initiated empirically in two patients due to delay in obtaining methanol analysis results. Transient elevations of creatinine occurred in five of the seven children. Blood urea nitrogen was within normal limits, and there was no history of renal impairment in these children, suggesting the elevated creatinine was mostly related to nitromethane ingestion. No child had a significantly elevated methanol level. Elevated creatinine level, as measured by Jaffe colorimetric method, is not a reliable marker for elevated methanol levels after unintentional ingestion of MFNM.

Four hour creatinine clearance is better than plasma creatinine for monitoring renal function in critically ill patients

PubMed Central

2012-01-01

Introduction Acute kidney injury (AKI) diagnosis is based on an increase in plasma creatinine, which is a slowly changing surrogate of decreased glomerular filtration rate. We investigated whether serial creatinine clearance, a direct measure of the glomerular filtration rate, provided more timely and accurate information on renal function than serial plasma creatinine in critically ill patients. Methods Serial plasma creatinine and 4-hour creatinine clearance were measured 12-hourly for 24 hours and then daily in 484 patients. AKI was defined either as > 50% increase in plasma creatinine from baseline, or > 33.3% decrease in creatinine clearance. The diagnostic and predictive performance of the two AKI definitions were compared. Results Creatinine clearance decrease diagnosed AKI in 24% of those not diagnosed by plasma creatinine increase on entry. These patients entered the ICU sooner after insult than those diagnosed with AKI by plasma creatinine elevation (P = 0.0041). Mortality and dialysis requirement increased with the change in creatinine clearance-acute kidney injury severity class (P = 0.0021). Amongst patients with plasma creatinine < 1.24 mg/dl on entry, creatinine clearance improved the prediction of AKI considerably (Net Reclassification Improvement 83%, Integrated Discrimination Improvement 0.29). On-entry, creatinine clearance associated with AKI severity and duration (P < 0.0001) predicted dialysis need (area under the curve: 0.75) and death (0.61). A > 33.3% decrease in creatinine clearance over the first 12 hours was associated with a 2.0-fold increased relative risk of dialysis or death. Conclusions Repeated 4-hour creatinine clearance measurements in critically ill patients allow earlier detection of AKI, as well as progression and recovery compared to plasma creatinine. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN012606000032550. PMID:22713519

Acute Urinary Obstruction in a Tetraplegic Patient from Misplacement of Catheter in Urethra.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Hughes, Peter L; Soni, Bakul M

2016-01-01

A male tetraplegic patient attended accident and emergency with a blocked catheter; on removing the catheter, he passed bloody urine. After three unsuccessful attempts were made to insert a catheter by nursing staff, a junior doctor inserted a three-way Foley catheter with a 30-mL balloon but inflated the balloon with 10 mL of water to commence the bladder irrigation. The creatinine level was mostly 19 µmol/L (range: 0-135 µmol/L) but increased to 46 µmol/L on day 7. Computerized tomography urogram revealed that the bilateral hydronephrosis with hydroureter was extended down to urinary bladder, the bladder was distended, prostatic urethra was dilated and filled with urine, and although the balloon of Foley catheter was not seen in the bladder, the tip of the catheter was seen lying in the urethra. Following the re-catheterization, the creatinine level decreased to 21 µmol/L. A follow-up ultrasound scan revealed no evidence of hydronephrosis in both kidneys. Flexible cystoscopy revealed inflamed bladder mucosa, catheter reaction, and tiny stones. There was no bladder tumor. This case report concludes that the cause of bilateral hydronephrosis, hydroureter, and distended bladder was inadequate drainage of urinary bladder as the Foley balloon that was under-filled slipped into the urethra resulting in an obstruction to urine flow. Urethral catheterization in tetraplegic patients should be performed by senior, experienced staff in order to avoid trauma and incorrect positioning. Tetraplegic subjects with decreased muscle mass have low creatinine level. Increase in creatinine level (>1.5 times the basal level) indicates acute kidney injury, although peak creatinine level may still be within laboratory reference range. While scanning the urinary tract of spinal cord injury patients with indwelling urinary catheter, if Foley balloon is not seen within the bladder, urethra should be scanned to locate the Foley balloon.

Four-week effects of allopurinol and febuxostat treatments on blood pressure and serum creatinine level in gouty men.

PubMed

Kim, Hyun Ah; Seo, Young-Il; Song, Yeong W

2014-08-01

The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4-week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men.

Validation of the salivary urea and creatinine tests as screening methods of chronic kidney disease in Vietnamese patients.

PubMed

Pham, Thuy Anh Vu

2017-11-01

The aims of this case control study were to correlate the serum and salivary urea as well as creatinine levels; and to evaluate salivary urea and creatinine as noninvasive alternatives to serum for creatinine estimation in chronic kidney disease (CKD) patients. Blood and saliva samples were collected from 112 CKD patients and 108 subjects without CKD for quantitative analysis of urea and creatinine. Spearman's correlation coefficients between salivary and serum urea as well as creatinine were obtained. Receiver operating characteristic analysis was done to assess the diagnostic tests of salivary urea and creatinine. Cut-off values were determined based on the best trade-off between the sensitivity and specificity for both salivary urea and creatinine. Salivary urea and creatinine concentrations were significantly higher in CKD patients than those in control subjects; and increased by the stages of the severity of the disease. The positive correlation was significantly found between salivary and serum creatinine (r  =  0.90) and between salivary and serum urea (r  =  0.73). Area under the curve for salivary urea was 0.76 and a cut-off value of 14.25 mmol/L gave a sensitivity of 82.9% and specificity of 57.8%. Area under the curve for salivary creatinine was 0.92 and a cut-off value of 0.24 mg/dL gave a sensitivity of 86.5% and specificity of 87.2%. Both salivary urea and creatinine have a high capacity for serum creatinine estimation. Salivary urea and creatinine tests can be used as low-cost, easily accessible and noninvasive tools for screening, diagnosing, monitoring treatment outcomes and ascertaining prognosis of chronic kidney disease.

Mechanisms Underlying Early Rapid Increases in Creatinine in Paraquat Poisoning

PubMed Central

Mohamed, Fahim; Endre, Zoltan; Jayamanne, Shaluka; Pianta, Timothy; Peake, Philip; Palangasinghe, Chathura; Chathuranga, Umesh; Jayasekera, Kithsiri; Wunnapuk, Klintean; Shihana, Fathima; Shahmy, Seyed; Buckley, Nicholas

2015-01-01

Background Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR). Methods and Findings This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied. Results Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days. Conclusion Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury. PMID:25815837

Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.

PubMed

Mohamed, Fahim; Endre, Zoltan; Jayamanne, Shaluka; Pianta, Timothy; Peake, Philip; Palangasinghe, Chathura; Chathuranga, Umesh; Jayasekera, Kithsiri; Wunnapuk, Klintean; Shihana, Fathima; Shahmy, Seyed; Buckley, Nicholas

2015-01-01

Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR). This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied. Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days. Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury.

Serum creatinine is associated with the prevalence but not disease progression of multiple system atrophy in Chinese population.

PubMed

Cao, Bei; Guo, XiaoYan; Chen, Ke; Song, Wei; Huang, Rui; Wei, QianQian; Zhao, Bi; Shang, Hui-Fang

2016-03-01

Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). Creatine, which is converted to creatinine, has an anti-oxidative effect. Our aim is to clarify the correlations between creatinine and the occurrence as well as the progression of MSA. A total of 115 patients with probable MSA and 115 age- and gender-matched healthy controls were included in the study. The serum creatinine level of all patients and controls were evaluated and compared. The mean age of MSA patients was 58.18 ± 8.67 years and the mean disease duration was 2.85 ± 1.71 years. The creatinine level of MSA patients was significantly lower than that of healthy controls (P < 0.0001). The occurrence of MSA was decreased in the highest creatinine quartiles compared with the lowest creatinine quartiles. In a gender-specific analysis, patients with the highest quartiles and second quartiles of creatinine level had decreased occurrence than patients with the lowest quartile in females, but not in males. The serum level of creatinine was not found correlated with the mean rate of annualised changes, neither with other independent factors, such as age, body mass index (BMI), sex, Unified MSA Rating Scale (UMSARS) scores and disease duration at the initial visit in patients with MSA. High level of serum creatinine may be associated with a low occurrence of MSA in Chinese population, especially in female. However, serum creatinine does not deteriorate or ameliorate the progression of MSA.

Determining the relationship between atherosclerosis and periodontopathogenic microorganisms in chronic periodontitis patients.

PubMed

Bozoglan, Alihan; Ertugrul, Abdullah Seckin; Taspınar, Mehmet; Yuzbasioglu, Betul

2017-05-01

The aim of this study is to determine the relationship between atherosclerosis and periodontopathogenic microorganisms in chronic periodontitis patients following periodontal treatment. A total of 40 patients were included in the study. 20 of these patients diagnosed with atherosclerosis and chronic periodontitis formed the test group. The remaining 20 patients were systemically healthy patients diagnosed with chronic periodontitis and formed the control group. All patients had nonsurgical periodontal treatment. The periodontopathogenic microorganism levels were determined at baseline and at 6 months in microbial dental plaque samples and WBC, LDL, HDL, PLT, fibrinogen, creatinine and hs-CRP levels were determined by blood samples. Statistically significant reduction has been achieved in clinical periodontal parameters following non-surgical periodontal treatment in test and control groups. Following periodontal treatment, WBC, LDL, PLT, fibrinogen, creatinine and hs-CRP levels significantly decreased and HDL levels significantly increased in both test and control groups. Similarly, the periodontopathogenic microorganism levels significantly decreased following periodontal treatment in the test and control groups. A statistically significant positive correlation has been determined between the periodontopathogenic microorganism levels and WBC, LDL, PLT, fibrinogen, creatinine, and hs-CRP levels in the test group. The association between hs-CRP, WBC, LDL, PLT, fibrinogen, creatinine, and the amount of periodontopathogenic microorganisms indicates the possibility that periodontal treatment could decrease the risk atherosclerosis. More studies must be conducted in order for these results to be supported.

Cystatin C as an early marker of acute kidney injury in septic shock.

PubMed

Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

2015-03-01

To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children.

PubMed

Övünç Hacıhamdioğlu, Duygu; Hacıhamdioğlu, Bülent; Altun, Demet; Müftüoğlu, Tuba; Karademir, Ferhan; Süleymanoğlu, Selami

2016-09-01

Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

Creatinine as predictor value of mortality and acute kidney injury in rhabdomyolysis.

PubMed

Baeza-Trinidad, R; Brea-Hernando, A; Morera-Rodriguez, S; Brito-Diaz, Y; Sanchez-Hernandez, S; El Bikri, L; Ramalle-Gomara, E; Garcia-Alvarez, J L

2015-11-01

Rhabdomyolysis (RB) is a syndrome characterised by decomposition of skeletal muscle that could be life threatening, so the identification of biomarkers of its severity could help us in its treatment. Creatine kinase (CK) is usually taken as a reference in patients with RB in order to stratify prognosis, however that is not probably the most effective parameter. The present study was designed to analyse the specific features and mortality of patients with RB and the relation between creatinine, CK and mortality. Retrospective cohort analysis among patients admitted to San Pedro Hospital in Logroño (Spain) with RB (CK levels higher than 2000 U/L) diagnosed since 1 January 2009 until 31 December 2; 013 522 patients with RB patients diagnosed of RB were collected. The aetiology and the analytical feature (creatinine, CK, calcium, phosphorus, pH and bicarbonate), as well as 30-year mortality, were investigated. Among the 522 patients, there were 138 deaths. Four patients required renal replacement therapy. The most common cause of RB was trauma (29%). Infectious aetiology had the highest mortality (41.2%). The median CK was 3451 u/L (interquartile range 3348), and the mean creatinine at admission was 132.6 umol/L (±110.5). Initial CK levels do not have predictive ability on mortality or renal dysfunction in contrast to initial creatinine values. Each state of acute kidney injury (AKI) increased mortality compared with those who have not presented this renal dysfunction (P < 0.0001). Age, calcium, phosphorus, bicarbonate and pH are associated with AKI. Despite being a diagnostic marker for RB, initial CK levels do not predict mortality. However, creatinine initial levels are related to progression to acute renal injury and mortality at 30 days. © 2015 Royal Australasian College of Physicians.

Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

PubMed

Satarug, Soisungwan; Vesey, David A; Gobe, Glenda C

2017-03-01

Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer's disease. We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection. Staple foods constitute 40-60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70-1.85 μg/g creatinine in men and 0.95-3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16-31.5 μg/day was associated with 25-94% increase in risk of estrogen receptor-positive breast cancer. Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal. Citation: Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284-288; http://dx.doi.org/10.1289/EHP108.

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

PubMed

Yamada, Shunsuke; Taniguchi, Masatomo; Tokumoto, Masanori; Yoshitomi, Ryota; Yoshida, Hisako; Tatsumoto, Narihito; Hirakata, Hideki; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. Cross-sectional study and prospective longitudinal cohort study. An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. Bone fracture at any site. In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Pantoprazole-induced acute kidney injury: A case report.

PubMed

Peng, Tao; Hu, Zhao; Zheng, Hongnan; Zhen, Junhui; Ma, Chengjun; Yang, Xiangdong

2018-06-01

The present study reports a case of pantoprazole-induced acute kidney disease. The patient was diagnosed with acute kidney injury with wide interstitial inflammation and eosinophil infiltration. Following 1 month of glucocorticoid therapy, the patient's serum creatinine and urea nitrogen decreased to within normal ranges. The presentation, clinical course, diagnosis and prognosis of pantoprazole-induced acute kidney injury are discussed herein to highlight the importance of early and correct diagnosis for good prognosis. Disease characteristics include short-term increased serum creatinine levels that respond to glucocorticoid treatment. The patient had no history of chronic kidney disease or proteinuria and presented with increased serum creatinine following treatment with pantoprazole. Following the end of pantoprazole treatment, short-term RRT and long-term prednisolone was administered, then serum creatinine returned to normal. Pantoprazole-induced acute kidney injury is commonly misdiagnosed and late diagnosis results in poor patient prognoses. Misdiagnosis leads to the administration of treatments that may exacerbate the condition, so appropriate diagnosis and treatment for pantoprazole-induced acute kidney injury is necessary.

Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin-angiotensin-aldosterone system activity and the efficacy of renin-angiotensin-aldosterone system blockade in the kidney.

PubMed

van den Heuvel, Mieke; Batenburg, Wendy W; Jainandunsing, Sjaam; Garrelds, Ingrid M; van Gool, Jeanette M G; Feelders, Richard A; van den Meiracker, Anton H; Danser, A H Jan

2011-11-01

To study which renin-angiotensin-aldosterone system (RAAS) component best reflects renal RAAS activity. We measured urinary and plasma renin, prorenin, angiotensinogen, aldosterone, albumin and creatinine in 101 diabetic and nondiabetic patients with or without hypertension. Plasma prorenin was elevated in diabetic patients. Urinary prorenin was undetectable. Urinary albumin and renin were higher in diabetic patients. Men had higher plasma renin/prorenin levels, and lower plasma angiotensinogen levels than women. Plasma creatinine and albumin were also higher in men. Urinary RAAS components showed no sexual dimorphism, whereas urinary creatinine and albumin were higher in men. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers increased plasma renin and decreased plasma angiotensinogen, without altering plasma aldosterone. In contrast, in urine, these drugs decreased renin and aldosterone without affecting angiotensinogen. When analyzing all patients together, urinary angiotensinogen excretion closely mimicked that of albumin, whereas urinary angiotensinogen and albumin levels both were 0.05% or less of their concomitant plasma levels. This may reflect the identical glomerular filtration and tubular handling of both proteins, which have a comparable molecular weight. In contrast, urinary renin excretion did not correlate with urinary albumin excretion, and the urinary/plasma concentration ratio of renin was more than 200 times the ratio of albumin, despite its comparable molecular weight. Urinary aldosterone excretion closely followed urinary creatinine excretion. The increased urinary renin levels in diabetes and the decreased urinary renin levels following RAAS blockade, occurring independently of changes in plasma renin, reflect the activated renal RAAS in diabetes and the success of RAAS blockade in the kidney, respectively. Urinary renin, therefore, more closely reflects renal RAAS activity than urinary angiotensinogen or aldosterone.

Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.

2008-01-01

Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 {+-} 2.98 {mu}g/g creatinine, for UC patients thanmore » for healthy controls of 21.10 {+-} 0.79 {mu}g/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 {+-} 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 {+-} 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 {+-} 0.75 than those of males at 5.76 {+-} 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic.« less

Elevated Levels of Urinary 8-Hydroxy-2′-deoxyguanosine, Lymphocytic Micronuclei, and Serum Glutathione S-Transferase in Workers Exposed to Coke Oven Emissions

PubMed Central

Liu, Ai-Lin; Lu, Wen-Qing; Wang, Zeng-Zhen; Chen, Wei-Hong; Lu, Wen-Hong; Yuan, Jing; Nan, Pei-Hong; Sun, Jian-Ya; Zou, Ya-Lin; Zhou, Li-Hong; Zhang, Chi; Wu, Tang-Chun

2006-01-01

To investigate associations among occupational exposure to coke oven emissions (COEs), oxidative stress, cytogenotoxic effects, change in the metabolizing enzyme glutathione S-transferase (GST), and internal levels of polycyclic aromatic hydrocarbons (PAHs) in coke oven workers, we recruited 47 male coke oven workers and 31 male control subjects from a coke oven plant in northern China. We measured the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine, micronucleated binucleated cells (BNMNs) in peripheral blood lymphocyte, and GST in serum. Our results showed that the group exposed to COEs had significantly increased levels of 1-OHP [median 5.7; interquartile range (IQR), 1.4–12.0 μmol/mol creatinine] compared with the control group (3; 0.5–6.4 μmol/mol creatinine). In addition, the median levels (IQR) of 8-OHdG, BNMNs, and GST were markedly increased in the exposed [1.9 (1.4–15.4) μmol/mol creatinine; 6 (2–8) per thousand; 22.1 (14.9–31.2) U/L, respectively] compared with controls [1.3 (1.0–4.0) μmol/mol creatinine, 2 (0–4) per thousand; and 13.1 (9.5–16.7) U/L, respectively]. These results appeared to be modified by smoking. However, multivariate logistic regression analysis revealed that exposure to COEs had the highest odds ratio among variables analyzed and that smoking was not a significant confounder of the levels of studied biomarkers. Overall, the present findings suggest that COE exposure led to increased internal PAH burden, genetic damage, oxidative stress, and GST activity. The consequences of the changes in these biomarkers, such as risk of cancer, warrant further investigations. PMID:16675419

Serum creatinine detection by a conducting-polymer-based electrochemical sensor to identify allograft dysfunction.

PubMed

Wei, Fang; Cheng, Scott; Korin, Yael; Reed, Elaine F; Gjertson, David; Ho, Chih-ming; Gritsch, H Albin; Veale, Jeffrey

2012-09-18

Kidney transplant recipients who have abnormally high creatinine levels in their blood often have allograft dysfunction secondary to rejection. Creatinine has become the preferred marker for renal dysfunction and is readily available in hospital clinical settings. We developed a rapid and accurate polymer-based electrochemical point-of-care (POC) assay for creatinine detection from whole blood to identify allograft dysfunction. The creatinine concentrations of 19 blood samples from transplant recipients were measured directly from clinical serum samples by the conducting polymer-based electrochemical (EC) sensor arrays. These measurements were compared to the traditional clinical laboratory assay. The time required for detection was <5 min from sample loading. Sensitivity of the detection was found to be 0.46 mg/dL of creatinine with only 40 μL sample in the creatinine concentration range of 0 mg/dL to 11.33 mg/dL. Signal levels that were detected electrochemically correlated closely with the creatinine blood concentration detected by the UCLA Ronald Reagan Medical Center traditional clinical laboratory assay (correlation coefficient = 0.94). This work is encouraging for the development of a rapid and accurate POC device for measuring creatinine levels in whole blood.

Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

PubMed

Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Mazzei, Bruno; Di Iorio, Angelo; Carbonin, Pierugo; Incalzi, Raffaele Antonelli

2005-09-01

In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.

A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease

PubMed Central

Laucho-Contreras, Maria E.; Petersen, Hans; Bijol, Vanesa; Sholl, Lynette M.; Choi, Mary E.; Divo, Miguel; Pinto-Plata, Victor; Chetta, Alfredo; Tesfaigzi, Yohannes; Celli, Bartolomé R.

2017-01-01

Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. Objectives: To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress–advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs–RAGE pathway in endothelial cells in both organs. Methods: In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice. Measurements and Main Results: Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions. Conclusions: Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury. PMID:28085500

A study of the prevalence of significant increases in serum creatinine following angiotension-converting enzyme inhibitor administration.

PubMed

Thorp, M L; Ditmer, D G; Nash, M K; Wise, R; Jaderholm, P L; Smith, J D; Chan, W

2005-05-01

Angiontension-converting enzyme inhibitors (ACEIs) are beneficial in the treatment of diabetic and nondiabetic kidney disease, coronary artery disease and congestive heart failure. One adverse effect of ACEIs use is a rise in serum creatinine and potential renal failure. This paper attempts to quantify this risk and assess the need for pre- and post-ACEI serum creatinine measurements. A computerized search of Kaiser Permanente Northwest's electronic medical record was conducted to find patients over the age of 40 years taking lisinopril between July 1, 2000 and June 30, 2002. Patient demographic information and presence in diabetes and coronary artery disease registries was collected. A subsequent search for pre- and postlisinopril serum creatinine levels within 6 months of initial lisinopril prescription was conducted. Patients with prelisinopril creatinine < or = 1.2 mg/dl and postlisinopril creatinine > 2.5 mg/dl underwent chart review to discern adverse events associated with the rise in serum creatinine. A total of 18,977 patients were prescribed lisinopril between July 1, 2000 and June 30, 2002. In all 13 166 patients had a pre- and postlisinopril creatinine checked. In all, 31 patients had a rise in creatinine from < or = 1.2 mg/dl to > 2.5 mg/dl (0.2%). Possible contributors to rise in creatinine included congestive heart failure, dehydration and infection. No patients developed end-stage renal disease, although three died. In conclusion, end-stage renal disease is an unlikely outcome among patients prescribed lisinopril and is most likely associated with other events.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: A five-year follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Limpatanachote, Pisit; Mahasakpan, Pranee

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels {>=}5 {mu}g/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of {beta}{sub 2}-microglobulin ({beta}{sub 2}-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmiummore » statistically significantly reduced from 9.5{+-}1.6 {mu}g/g creatinine in 2005 to 8.8{+-}1.6 {mu}g/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary {beta}{sub 2}-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.« less

Utility of Serum Creatinine, Creatine Kinase and Urinary Myoglobin in Detecting Acute Renal Failure due to Rhabdomyolysis in Trauma and Electrical Burns Patients.

PubMed

Bhavsar, Preetish; Rathod, Kirtikumar Jagdish; Rathod, Darshana; Chamania, C S

2013-02-01

Rhabdomyolysis due to trauma and burns is an important cause of acute renal failure (ARF) secondary to myoglobinuria. To prevent morbidity and mortality from ARF due to rhabdomyolysis, early detection of ARF by monitoring the biochemical parameters such as serum creatinine, serum creatine kinase (CK), and urinary myoglobin (UM) can be helpful. The aims of the study were (1) to detect ARF due to rhabdomyolysis using serum creatinine, serum CK, and UM in trauma and electrical burn patients (2) to compare utility of these parameters in early prediction of ARF in patients of rhabdomyolysis. A total of 50 patients with trauma and electrical burns were included in the study. Serum creatinine, serum CK, and UM measurements were done at the time of admission and after 48 h. Diagnosis of ARF was made in the patients by Rifle's criteria. The presence of significant elevation of creatinine, serum CK, and UM at the time of admission and after 48 h was compared in patients developing ARF by Fisher's exact test. Fifteen of the 50 patients developed ARF as per the defined criteria. Of these, 9 patients (60 %) had raised level of serum creatinine above 1.4 mg% at admission and 14 patients (93.33 %) had CK level >1250 U/L at admission, whereas UM was positive in 6 (40 %) patients. Serum creatinine was significantly raised in all of the 15 ARF patients (100 %) after 48 h of admission and serum CK was raised in 14 of the 15 ARF patients (93.33 %). UM was negative in all the patients after 48 h of admission. Statistical analysis showed that rise in serum CK on admission was significantly increased in patients developing ARF as compared with serum creatinine and UM (P < 0.0001). On admission, CK is a better predictor of ARF due to rhabdomyolysis than creatinine and UM. Initial creatinine is a better predictor of ARF due to rhabdomyolysis than UM. UM assay is not a good investigation for early prediction of ARF in rhabdomyolysis.

Trends in the levels of urine and serum creatinine: data from NHANES 2001-2014.

PubMed

Jain, Ram B

2017-04-01

Data from the National Health and Nutrition Examination Survey were used to study trends for urine and serum creatinine over 2001-2014 for those aged ≥20 years. In the absence of chronic kidney disease, levels of urine creatinine decreased for the total population, for those aged 20-29, 50-59, and ≥70 years, for males, and for Mexican Americans and other race/ethnicities. Levels of serum cotinine also exhibited a decreasing trend over 2001-2014 for the total population, for those aged 20-29 and 40-49 years, for females, and for non-Hispanic whites and Mexican Americans. In general, levels of serum creatinine and urine creatinine were positively correlated for chronic kidney disease stages 1-3 and negatively correlated for chronic kidney disease stages 4 and 5.

Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates.

PubMed

Kimura, Toshimi; Sunakawa, Keisuke; Matsuura, Nobuo; Kubo, Hiroaki; Shimada, Shigehiko; Yago, Kazuo

2004-04-01

Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CL(arbekacin) = 0.0238 x BW/serum creatinine level for PCAs of <33 weeks and CL(arbekacin) = 0.0367 x BW/serum creatinine level for PCAs of > or = 33 weeks, V(arbekacin) = 0.54 liters/kg, CL(vancomycin) = 0.0250 x BW/serum creatinine level for PCAs of <34 weeks and CL(vancomycin) = 0.0323 x BW/serum creatinine level for PCAs of > or = 34 weeks, V(vancomycin) = 0.66 liters/kg, CL(panipenem) = 0.0832 for PCAs of <33 weeks and CL(panipenem) = 0.179 x BW for PCAs of > or = 33 weeks, and V(panipenem) = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of > or = 33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates.

Cystatin C a marker for renal function after exercise.

PubMed

Mingels, A; Jacobs, L; Kleijnen, V; Wodzig, W; Dieijen-Visser, M van

2009-09-01

Renal impairment is common during and after severe exercise. In clinical practice, renal function is evaluated using serum creatinine, urine parameters, and equations to estimate the Glomular Filtration Rate (GFR). However, creatinine levels may be biased by skeletal muscle damage and the GFR equations, requiring age, gender and body weight, are shown to be inadequate in normals. In the present study, we show that serum cystatin C and creatinine concentrations were elevated after marathon running in 26% and 46% of the 70 recreational male runners, respectively, possibly because of reduction in renal blood flow. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively), suggesting that cystatin C is indeed less biased by muscle damage. Future research has to reveal whether training diminishes the elevation in renal markers. Overall, cystatin C seems a more reliable method to establish renal function during and after extensive exercise. Georg Thieme Verlag KG Stuttgart.

Inflammatory response and postoperative kidney failure in patients with diabetes type 2 or impaired glucose tolerance undergoing heart valve surgery.

PubMed

Zakrzewski, Dariusz; Janas, Jadwiga; Heretyk, Hanna; Stepińska, Janina

2010-05-01

Diabetes type 2 (DM) or impaired glucose tolerance (IGT) are linked with a 3-fold increased risk of renal failure after heart valve surgery. The increase of proinflammatory cytokines is detected in patients with DM or IGT, moreover cardiac surgery promotes the proinflammatory response, which may be responsible for the development of postoperative kidney failure. To assess the impact of perioperative pro- and antiinflammatory reaction after heart valve surgery and other clinical parameters on the risk of postoperative acute kidney injury in patients with DM or IGT. Thirty patients with DM or IGT, without fibrate or statin treatment, with a mean LDL-cholesterol below 129 mg/dL, ejection fraction > 45%, in NYHA class II and III, referred for surgery due to acquired heart valve disease entered the study. Patients with acute or chronic inflammatory conditions, coronary artery disease or creatinine clearance below 50 mL/min were excluded. Serum creatinine, glycosylated hemoglobin, LDL-cholesterol and interleukin-10 as well as TNF-alpha were assessed before surgery. Interleukin-10 and TNF-alpha were also measured 4 hours after weaning from cardiopulmonary bypass. Moreover, serum creatinine and hemoglobin were measured 18 +/- 2 hours after surgery. The relationship between postoperative creatinine clearance, its postoperative change and other parameters was assessed. These parameters included: age, weight and body mass index, pre- and postoperative serum level of TNF-alpha and interleukin-10, preoperative concentration of LDL-cholesterol and glycosylated hemoglobin, duration of cardiopulmonary bypass and postoperative hemoglobin. The significant postoperative decrease of creatinine clearance was noted in the study group. Eight (27%) patients developed postoperative kidney failure, of them 2 (6.5%) patients required hemodialysis. The level of TNF-alpha and interleukin-10 increased significantly postoperatively. A significant correlation between duration of cardiopulmonary bypass and postoperative decrease of creatinine clearance was noted (R = 0.43, p = 0.02). A non-significant trend towards correlation between preoperative TNF-alpha and postoperative decrease of creatinine clearance was observed (R = -0.36, p = 0.05). Postoperative kidney failure with the incidence of 27% is a frequent finding in patients with DM or IGT operated due to acquired heart valve disease. The postoperative proinflammatory response is not involved in the development of this complication. The correlation between postoperative decrease of creatinine clearance and duration of cardiopulmonary bypass was noted. The trend toward the link between postoperative kidney failure and preoperative proinflammatory status was seen.

Association between serum soluble CD30 and serum creatinine before and after renal transplantation.

PubMed

López-Hoyos, M; San Segundo, D; Benito, M J; Fernández-Fresnedo, G; Ruiz, J C; Rodrigo, E; Gómez-Alamillo, C; Benito, A; Arias, M

2008-11-01

There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.

The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist?

PubMed

Chu, Xiaoyan; Bleasby, Kelly; Chan, Grace Hoyee; Nunes, Irene; Evers, Raymond

2016-09-01

In humans, creatinine is formed by a multistep process in liver and muscle and eliminated via the kidney by a combination of glomerular filtration and active transport. Based on current evidence, creatinine can be taken up into renal proximal tubule cells by the basolaterally localized organic cation transporter 2 (OCT2) and the organic anion transporter 2, and effluxed into the urine by the apically localized multidrug and toxin extrusion protein 1 (MATE1) and MATE2K. Drug-induced elevation of serum creatinine (SCr) and/or reduced creatinine renal clearance is routinely used as a marker for acute kidney injury. Interpretation of elevated SCr can be complex, because such increases can be reversible and explained by inhibition of renal transporters involved in active secretion of creatinine or other secondary factors, such as diet and disease state. Distinction between these possibilities is important from a drug development perspective, as increases in SCr can result in the termination of otherwise efficacious drug candidates. In this review, we discuss the challenges associated with using creatinine as a marker for kidney damage. Furthermore, to evaluate whether reversible changes in SCr can be predicted prospectively based on in vitro transporter inhibition data, an in-depth in vitro-in vivo correlation (IVIVC) analysis was conducted for 16 drugs with in-house and literature in vitro transporter inhibition data for OCT2, MATE1, and MATE2K, as well as total and unbound maximum plasma concentration (Cmax and Cmax,u) data measured in the clinic. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

How to use… serum creatinine, cystatin C and GFR.

PubMed

Pasala, Swetha; Carmody, J Bryan

2017-02-01

Glomerular filtration rate (GFR) is the best overall measure of kidney function. The GFR is relatively low at birth but increases through infancy and early childhood to reach adult levels of approximately 120 mL/min/1.73 m 2 by age 2. While GFR can be measured most accurately by the urinary clearance of an exogenous ideal filtration marker such as inulin, it is more clinically useful to estimate GFR using a single serum measurement of an endogenous biomarker such as creatinine or cystatin C. When in steady state, there is an inverse relationship between creatinine/cystatin C and GFR, allowing GFR to be estimated from either using simple equations. Because of the non-linear relationship between creatinine/cystatin C and GFR, relatively small initial increases in these markers represent significant decreases in GFR. While cystatin C is produced by all nucleated cells, creatinine is a waste product of muscle metabolism and is therefore influenced by diet and muscle mass/body habitus. Decreased GFR is used to diagnose and stage chronic kidney disease (CKD) using the Kidney Disease: Improving Global Outcomes system. A diagnosis of CKD requires GFR <60 mL/min/1.73 m 2 for more than 3 months; higher GFR also represents CKD if evidence of kidney damage (such as albuminuria or abnormal imaging) is present. Changes in serum creatinine and urine output are used to diagnose acute kidney injury. It is possible to calculate a kinetic GFR when the creatinine is changing rapidly, though more complex calculations are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Serum creatinine levels and risk of incident type 2 diabetes mellitus or dysglycemia in middle-aged Japanese men: a retrospective cohort study.

PubMed

Takeuchi, Mamoru; Imano, Hironori; Muraki, Isao; Shimizu, Yuji; Hayama-Terada, Mina; Kitamura, Akihiko; Okada, Takeo; Kiyama, Masahiko; Iso, Hiroyasu

2018-02-26

To assess the association between low serum creatinine levels and an increased risk of type 2 diabetes mellitus and dysglycemia. We conducted a retrospective cohort study of 3313 Japanese male workers aged 30-55 years, who underwent annual health check-ups during 2001-2008 and showed no type 2 diabetes mellitus, and underwent follow-up examinations until March 2013. Dysglycemia was defined as a fasting plasma glucose concentration of ≥ 110 mg/dL (6.1 mmol/L), or a non-fasting plasma glucose concentration of ≥ 140 mg/dL (7.8 mmol/L). A Cox proportional model was used to calculate HRs and 95% CIs for developing type 2 diabetes mellitus or dysglycemia. During the median 6.7-year follow-up, there were 207 cases of incident type 2 diabetes mellitus and 596 cases of incident dysglycemia, including 115 cases of type 2 diabetes mellitus among the subjects with normal glucose concentrations at baseline. After adjustment for age, body mass index and known diabetes risk factors, the multivariable HR of type 2 diabetes mellitus for the lowest category of serum creatinine (<0.7 mg/dL) vs the highest category (0.9-1.1 mg/dL) was 1.9 (95% CI 1.2 to 2.9; P for trend 0.03). The multivariable HRs of dysglycemia for the lowest category of serum creatinine versus the highest category was 1.5 (95% CI 1.1 to 1.9; P for trend 0.01). Low serum creatinine levels were associated with an increased risk of type 2 diabetes mellitus and dysglycemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association of plasma manganese levels with chronic renal failure.

PubMed

Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

2015-01-01

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn. Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: a five-year follow-up.

PubMed

Swaddiwudhipong, Witaya; Limpatanachote, Pisit; Mahasakpan, Pranee; Krintratun, Somyot; Punta, Boonyarat; Funkhiew, Thippawan

2012-01-01

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels ≥5 μg/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of β(2)-microglobulin (β(2)-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5±1.6 μg/g creatinine in 2005 to 8.8±1.6 μg/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary β(2)-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy. Copyright © 2011 Elsevier Inc. All rights reserved.

Does maternal hydronephrosis have an impact on urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels?

PubMed

Pabuccu, Emre G; Caglar, Gamze Sinem; Kiseli, Mine; Yarci Gursoy, Asli; Candar, Tuba; Tangal, Semih; Ergun, İhsan

2017-03-01

To determine urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels and creatinine clearance values in women with different degrees of asymptomatic hydronephrosis during pregnancy. A total of 44 pregnant women with different degrees of hydronephrosis and 46 without hydronephrosis were consecutively enrolled in this prospective study. Basic serum and urine parameters, uNGAL levels, and creatinine clearance values were evaluated. All results were compared between the two groups. Regression analysis was used to determine independent predictors, which were mostly related to hydronephrosis. Demographic data, basal laboratory parameters, and creatinine clearance values were similar, whereas significantly higher uNGAL levels were detected in women with hydronephrosis compared to those without hydronephrosis (45.3 versus 33.2 ng/mL, respectively) (p = 0.004). An increasing trend in uNGAL levels was detected with increasing degrees of hydronephrosis; as it was not statistically significant (p = 0.163). Linear regression analysis revealed that the parameter of "pelvic diameter" was found as a significant independent factor influencing uNGAL concentrations (β = 0.289; 95% CI: 0.522-3.061; p = 0.006). Other independent variables were not found to influence uNGAL concentrations (p > 0.05). The results obtained from this study indicate a significant increase of urinary concentration of NGAL in the presence of asymptomatic maternal hydronephrosis. This impact is likely to be more profound in those with severe hydronephrosis although this has not been specifically investigated. This theory needs to be validated in larger populations.

Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study.

PubMed

Sonu, Yeldose; Avinash, S S; Sreekantha; Arun Kumar, K; Malathi, M; Shivashankara, A R

2016-07-01

Given the paucity of studies conducted to know the effect of suddenness and earlier onset of endocrinological changes associated with hysterectomy, on the serum and urinary levels of calcium, magnesium and phosphate the present study was conducted to compare the levels of calcium, magnesium and phosphate in serum and urine of hysterectomised and natural menopausal south Indian women. This is a cross-sectional observational study. The study included three groups of 30 healthy premenopausal, 30 early surgical menopausal and 30 natural post menopausal women. Women suffering from any endocrine disease were excluded. Analysis was performed in serum and urine sample. The levels of calcium, magnesium and phosphate in serum and calcium/creatinine, magnesium/creatinine and phosphate/creatinine ratio were estimated in urine by spectrophotometric method. Hysterectomised women (serum calcium: 8.7 ± 0.09 mg/dl; urine calcium/creatinine: 0.16 ± 0.02) have significantly low serum calcium (p < 0.001) and high urinary calcium/creatinine (p = 0.002) ratio and post menopausal women (serum magnesium: 2.1 ± 0.03; serum phosphate: 4.4 ± 0.16; urinary calcium/creatinine: 0.17 ± 0.02; urinary magnesium/creatinine: 0.09 ± 0.01) have significantly high serum magnesium (p = 0.016), serum phosphate (p = 0.043) and high urinary calcium/creatinine (p = 0.002), magnesium/creatinine ratio (p = 0.025) compared to healthy pre menopausal women. Post menopausal women (serum calcium: 9.1 ± 0.08) have significantly high serum calcium and phosphate compared to hysterectomised women (serum phosphate: 3.93 ± 0.11). Hysterectomised women have significantly low serum calcium, oestrogen and high urinary calcium/creatinine ratio compared to healthy premenopausal women and low serum calcium and low serum phosphate compared to natural postmenopausal women. Natural postmenopausal women had low serum oestrogen and high serum magnesium, serum phosphate, urinary calcium creatinine ratio and urinary magnesium creatinine ratio compared to healthy premenopausal women.

Mercury concentrations in urine of amerindian populations near oil fields in the peruvian and ecuadorian amazon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, Jena, E-mail: jena.webb@mail.mcgill.ca

Background: Mercury is a global contaminant with toxic, persistent effects on human health. Petroleum extraction is an important source of elemental mercury; little is known about human exposure levels near oil fields in the Amazon basin. Objectives: To characterize mercury levels in people living near oil production sites in the Peruvian and Ecuadorian Amazon, controlling for fish consumption, occupation, source of water and socio-demographic characteristics. Methods: Analyze mercury levels in urine samples using cold vapour atomic fluorescence spectrometry from 76 indigenous men and women in eight riverine communities situated near oil wells or pipelines. Subjects answered a questionnaire soliciting socio-demographic,more » occupational and dietary information. Data were analyzed using multiple linear regression modeling. Results: The mean value of U-Hg was 2.61 μg/g creatinine (95% CI: 2.14–3.08), with 7% of the sample recording values above the global background standard suggested by The World Health Organization (5 μg/g creatinine). Women who used water from a surface source had two and a half times the amount of mercury in their urine (mean=3.70 μg/g creatinine, 95% CI: 2.26–5.15) compared with women who used other water sources (mean =1.39 μg/g creatinine, 95% CI: 0.51–2.25). Men who were involved in an oil clean-up operation had twice as much mercury in their urine (mean =3.07 μg/g creatinine, 95% CI: 1.97–4.16) as did those who worked on other tasks (mean =1.56 μg/g creatinine, 95% CI: 1.48–2.65). Mercury levels were not associated with the number of fish meals per week. Conclusions: Indigenous peoples of the Peruvian and Ecuadorian Amazon living near oil production sites generally had urine mercury levels within the global background standard suggested by the World Health Organization. Increased levels of mercury in urine were detected for men involved in oil spill remediation and for women who relied on surface water for household needs. These findings signal the need for strict safety measures to limit the amount of oil entering the waterways in Andean Amazonia so as to protect the health of indigenous people. - Highlights: • 7% of participants had levels of inorganic mercury at or exceeding levels suggested by WHO (5 μg/g creatinine). • U-Hg levels were 2.5 times higher among women using surface water than those who drew on water from a well, spring or rain. • Men who had worked cleaning up an oil spill had more than twice the amount of mercury in their urine as men who did not.« less

Urinary dialkylphosphate metabolites and health symptoms among farmers in Thailand.

PubMed

Sapbamrer, Ratana; Hongsibsong, Surat; Kerdnoi, Tanyaporn

2017-05-04

Using a cross-sectional study, we investigated urinary DAPs levels and health symptoms related to the type of crop cultivation and farm tasks among 84 farmers in Phayao Province of northern Thailand. The results showed that the average of ∑DAPs levels was 10.93 ± 19.64 μg/g creatinine (range 1.48-163.90 μg/g creatinine). The compound found the most was DEP, followed by DETP, DEDTP, DMP, DMTP, and DMDTP, respectively. The type of crop cultivation may be associated with an increasing prevalence of respiratory tract, muscle system, and skin irritation. Farm tasks were associated with an increasing prevalence of muscle system and skin irritation. It was difficult to assess adverse health symptoms associated with urinary DAPs in low levels of exposure; therefore, further investigation is needed using more sensitive biomarkers and more sensitive health symptom measurement.

Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice.

PubMed

Chashmi, Nooshin Ahmadian; Emadi, Sarvenaz; Khastar, Hossein

2017-01-22

Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice. Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected. Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen. Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT. Copyright © 2016 Elsevier Inc. All rights reserved.

Leukotriene E(4) in urine in patients with asthma and COPD--the effect of smoking habit.

PubMed

Gaki, E; Papatheodorou, G; Ischaki, E; Grammenou, V; Papa, I; Loukides, S

2007-04-01

Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.

The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

2011-04-01

In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.

Interdialytic creatinine change versus predialysis creatinine as indicators of nutritional status in maintenance hemodialysis

PubMed Central

Walther, Carl P.; Carter, Caitlin Wise; Low, Chai L.; Williams, Peter; Rifkin, Dena E.; Steiner, Robert W.

2012-01-01

Background. Protein–energy wasting is common in patients on maintenance hemodialysis and is strongly associated with poor quality of life and mortality. However, clinical assessment of protein–energy wasting remains difficult. Predialysis creatinine levels are associated with mortality risk but may be influenced by both muscle mass and dialysis dose. This might be overcome by examining the rate of rise in creatinine between dialysis sessions. Methods. We conducted an observational cohort study among 81 patients on maintenance hemodialysis at our Veterans Affairs unit. Predialysis serum creatinine and change in serum creatinine between midweek dialysis sessions served as the predictor variables of interest and clinically available proxies of nutritional status and time to mortality served as the outcome variables. Linear regression and Cox proportional hazards models evaluated relationships, respectively. Results. The mean age of the study participants was 63 ± 10 years, 77 (95%) were male, mean body mass index was 27 ± 6 kg/m2 and 69% had diabetes. Median follow-up time was 13 months, during which 12 patients (15%) died. Interdialytic change in serum creatinine showed a strong direct correlation with predialysis serum creatinine (R = 0.96). Higher levels of both markers were associated with younger age, less residual urine volume and higher serum albumin, serum phosphorus and normalized protein catabolic rate (P < 0.05 for all). Both markers were approximately equally strongly associated with mortality. For example, compared to the highest predialysis creatinine tertile, participants in the lowest tertile (<6 mg/dL) had 5.5-fold [95% confidence interval (CI) 1.1, 26.6] higher risk of death. Similarly, participants in the lowest tertile of interdialytic change in creatinine (change <3.7 mg/dL/48 h), had 5.0-fold (95% CI 1.0, 24.4) higher death risk. Conclusions. Predialysis creatinine and interdialytic change in creatinine are both strongly associated with proxies of nutritional status and mortality in hemodialysis patients and are highly correlated. Interdialytic change in creatinine provided little additional information about nutritional status or mortality risk above and beyond predialysis creatinine levels alone. PMID:21775764

Perioperative change in creatinine following cardiac surgery with cardiopulmonary bypass is useful in predicting acute kidney injury: a single-centre retrospective cohort study.

PubMed

Takaki, Shunsuke; Shehabi, Yahya; Pickering, John W; Endre, Zoltan; Miyashita, Tetsuya; Goto, Takahisa

2015-10-01

Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24-48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypass. We hypothesized that, following cardiopulmonary bypass, creatinine reduction ratios would correlate with haematocrit reduction ratios and would be associated with the incidence of acute kidney injury. We collected demographic and blood test data from consecutive patients (n = 1137) who had undergone cardiac surgery with cardiopulmonary bypass. The creatinine reduction ratio was calculated as follows: (preoperative creatinine-postoperative creatinine)/preoperative creatinine. Patients were assigned to either of two groups. The first group (Group 1) was used to determine the threshold for acute kidney injury, and the second group (Group 2) was used to assess diagnostic performance. Acute kidney injury was defined as an increase in serum creatinine level >0.3 mg/dl or >150% from baseline. The incidence of acute kidney injury was 14.5% (79/545) in Group 1 and 15.5% (92/592) in Group 2. Postoperatively, creatinine concentration correlated strongly with haematocrit concentration (Pearson's r(2): 0.91). In Group 1, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.71, 64.1 and 66.4%, respectively, for creatinine reduction ratios of <20%. In Group 2, the odds ratio, positive predictive value, negative predictive value and relative risk for creatinine reduction ratio performance were 4.3 (95% confidence interval 2.6-7.0), 0.27 (0.21-0.32), 0.92 (0.89-0.95) and 3.42 (2.22-5.27), respectively. The creatinine reduction ratio may be associated with perioperative renal injury. Therefore, it is a good diagnostic indicator with high performance, and may be useful in detecting acute kidney injury at an earlier stage relative to conventional means. In addition, using creatinine reduction ratios in this manner is financially feasible. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Influence of zeolite shape and particle size on their capacity to adsorb uremic toxin as powders and as fillers in membranes.

PubMed

Lu, Limin; Chen, Chen; Samarasekera, Champika; Yeow, John T W

2017-08-01

Membranes with zeolites are promising for performing blood dialysis because zeolites can eliminate uremic toxins through molecular sieving. Although the size and the shape of zeolite particles can potentially influence the performance of the membranes with respect of creatinine uptake level, it is not clear what sizes and shapes lead to better performance. In this paper, we carry out experiments to answer this question. Spherical microparticle 840, spherical nanoparticle P-87 and rod-like nanoparticle P-371 zeolites were chosen to be used in all the experiments. Their creatinine uptake levels were first measured as powders in creatinine solutions with different concentrations, volumes and adsorption times. Then, nanofibrous membranes with zeolites were electrospun and their ability to adsorb creatinine was measured and compared against their respective powders' creatinine uptake level. The experiment shows that the zeolites have similar creatinine uptake ability as powders. However, they have significantly different creatinine uptake ability after being incorporated inside the membranes. Spherical microparticle 840 in the membrane presented the best creatinine uptake ability, at 8957 µg g -1 , which was half of its powders'. On the other hand, P-87 presented largely decreased, while P-371 presented even lower creatinine uptake ability in membranes when compared to respective powders'. The results shows that microparticle and sphere shaped particles perform better inside the membranes. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1594-1601, 2017. © 2016 Wiley Periodicals, Inc.

Urinary trans,trans-muconic acid as an indicator of exposure to benzene in cigarette smokers.

PubMed

Melikian, A A; Prahalad, A K; Hoffmann, D

1993-01-01

Epidemiological studies have shown an association between cigarette smoking and increased risk of myeloid leukemia in smokers. In evaluating this link it is important to note that cigarette smoke contains benzene, among other carcinogens. Since chronic benzene, among other carcinogens. Since chronic benzene exposure causes acute myeloid leukemia in humans, we aimed to determine the uptake and metabolic activation of benzene from cigarette smoke in smokers by measuring the levels of the urinary benzene metabolite, trans,trans-muconic acid (t,t-MA). The method used involved a clean-up procedure, followed by high-performance liquid chromatography with UV detection. The levels of urinary t,t-MA ranged from 0.02 to 1.3 mg/g creatinine, resulting in a mean of 0.29 +/- 0.04 mg/g creatinine in 42 male smokers, and corresponding values in nonsmokers ranged from "nondetectable" to 0.52 mg/g creatinine with an average of 0.09 +/- 0.02 mg/g creatinine. In the current study, the levels of t,t-MA in smokers were about 3 times higher than those in nonsmokers (P = 0.0001), and a significant correlation between concentration of t,t-MA and levels of cotinine in smokers was observed (r = 0.55; P = 0.0001; 95% confidence interval, 0.30-0.93), suggesting that urinary t,t-MA can be utilized as a biochemical marker to quantitate benzene exposure due to cigarette smoking.

Factors Other than GFR Affecting Serum Cystatin C Levels

PubMed Central

Stevens, Lesley A; Schmid, Christopher H.; Greene, Tom; Li, Liang; Beck, Gerald J; Joffe, Marshall; Froissart, Marc; Kusek, John; Zhang, Yaping (Lucy); Coresh, Josef; Levey, Andrew S

2015-01-01

Cystatin C is gaining acceptance as an endogenous filtration marker. Factors other than glomerular filtration rate (GFR) that affect the serum level have not been carefully studied. In a cross-sectional analysis of a pooled dataset of participants from clinical trials and a clinical population with chronic kidney disease (N=3418), we related serum levels of cystatin C and creatinine to clinical and biochemical variables after adjustment for GFR using errors-in-variables models to account for GFR measurement error. GFR was measured as urinary clearance of 125I-iothalamate and 15Cr-EDTA. Cystatin C was assayed at a single laboratory and creatinine was standardized to reference methods. Mean (SD) creatinine and cystatin C were 2.1 (1.1) mg/dL and 1.8 (0.8) mg/L, respectively. After adjustment for GFR, cystatin C was 4.3% lower for every 20 years of age, 9.2% lower for female sex but only 1.9% lower in blacks. Diabetes was associated with 8.5% higher levels of cystatin C and 3.9% lower levels of creatinine. Higher C-reactive protein and white blood cell count and lower serum albumin were associated with higher levels of cystatin C and lower levels of creatinine. Adjustment for age, sex and race had a greater effect on association of factors with creatinine than cystatin C. In conclusion, cystatin C is affected by factors other than GFR. Clinicians should consider these factors when interpreting the serum levels or GFR estimates from cystatin C. PMID:19119287

Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis.

PubMed

Yang, Dehao; Su, Zhongqian; Wu, Shengjie; Bi, Yong; Li, Xiang; Li, Jia; Lou, Kangliang; Zhang, Hongyu; Zhang, Xu

2016-12-01

Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine. We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls. We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America. Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.

Effect of lemongrass tea consumption on estimated glomerular filtration rate and creatinine clearance rate.

PubMed

Ekpenyong, Christopher E; Daniel, Nyebuk E; Antai, Atim B

2015-01-01

The existing research findings regarding the effects of lemongrass (Cymbopogon citratus) tea on renal function indices are conflicting and inconclusive. In the present study, we investigated the effects of infusions prepared from C citratus leaves on creatinine clearance rate (CCr) and estimated glomerular filtration rate (eGFR) in humans. One hundred five subjects (55 men and 50 women) aged 18 to 35 years were randomly assigned to groups set to orally receive infusions prepared from 2, 4, or 8 g of C citratus leaf powder once daily, for 30 days. Serum and urinary levels of urea, creatinine, pH, specific gravity, uric acid, electrolytes, diuretic indices, and eGFR were assessed at days 0, 10, and 30 after the initiation of treatment. Results obtained on days10 and 30 were compared with baseline values. CCr and eGFR decreased significantly at day 30 in both male and female subjects in all the groups and in females treated with infusion prepared from 8 g of C citratus leaf powder for 10 days. At day 10, CCr and eGFR were unchanged in those treated with infusions prepared from 2 or 4 g of the leaf powder, whereas diuretic indices (urine volume, urination frequency, diuretic action, and saliuretic indices) increased above the baseline levels. Serum and urinary creatinine levels significantly increased (P < .05) in both male and female subjects in all the groups. Serum urea significantly increased in the groups treated with infusions prepared from 4 or 8 g of the leaf powder (P < .05) for 30 days. Serum electrolytes remained unchanged, but their urinary levels increased. We observed dose- and time-dependent adverse effects of C citratus on CCr and eGFR. At a high dose or with prolonged treatment with a low dose, eGFR decrease may be followed by a decline in the other renal function indices. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

PubMed

Awodele, Olufunsho; Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

2015-12-01

There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl(-), urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats

PubMed Central

Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

2015-01-01

There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl−, HCO3−), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl−, urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MDA. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology. PMID:27486379

Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia.

PubMed

Zhang, Yi; Jin, Lijun; Liu, Jinchang; Wang, Wei; Yu, Haiyang; Li, Jian; Chen, Qian; Wang, Tao

2018-03-25

Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity. After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells. In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100μM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2). Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2. Copyright © 2017 Elsevier B.V. All rights reserved.

Mercury concentrations in urine of amerindian populations near oil fields in the peruvian and ecuadorian amazon.

PubMed

Webb, Jena; Coomes, Oliver T; Ross, Nancy; Mergler, Donna

2016-11-01

Mercury is a global contaminant with toxic, persistent effects on human health. Petroleum extraction is an important source of elemental mercury; little is known about human exposure levels near oil fields in the Amazon basin. To characterize mercury levels in people living near oil production sites in the Peruvian and Ecuadorian Amazon, controlling for fish consumption, occupation, source of water and socio-demographic characteristics. Analyze mercury levels in urine samples using cold vapour atomic fluorescence spectrometry from 76 indigenous men and women in eight riverine communities situated near oil wells or pipelines. Subjects answered a questionnaire soliciting socio-demographic, occupational and dietary information. Data were analyzed using multiple linear regression modeling. The mean value of U-Hg was 2.61μg/g creatinine (95% CI: 2.14-3.08), with 7% of the sample recording values above the global background standard suggested by The World Health Organization (5μg/g creatinine). Women who used water from a surface source had two and a half times the amount of mercury in their urine (mean=3.70μg/g creatinine, 95% CI: 2.26-5.15) compared with women who used other water sources (mean =1.39μg/g creatinine, 95% CI: 0.51-2.25). Men who were involved in an oil clean-up operation had twice as much mercury in their urine (mean =3.07μg/g creatinine, 95% CI: 1.97-4.16) as did those who worked on other tasks (mean =1.56μg/g creatinine, 95% CI: 1.48-2.65). Mercury levels were not associated with the number of fish meals per week. Indigenous peoples of the Peruvian and Ecuadorian Amazon living near oil production sites generally had urine mercury levels within the global background standard suggested by the World Health Organization. Increased levels of mercury in urine were detected for men involved in oil spill remediation and for women who relied on surface water for household needs. These findings signal the need for strict safety measures to limit the amount of oil entering the waterways in Andean Amazonia so as to protect the health of indigenous people. Copyright © 2016 Elsevier Inc. All rights reserved.

Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia.

PubMed

Vidal-Petiot, Emmanuelle; Rea, Delphine; Serrano, Fidéline; Stehlé, Thomas; Gardin, Claude; Rousselot, Philippe; Peraldi, Marie-Noëlle; Flamant, Martin

2016-03-01

Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated. We retrospectively analyzed data from imatinib-treated patients explored in our renal physiology unit with measurement of glomerular filtration rate (urinary clearance of (51)CrEDTA) and of urinary clearance and tubular secretion of creatinine. Results were compared with those of controls matched for measured glomerular filtration rate, age, gender, and ethnicity. We also analyzed variations of serum creatinine before and during imatinib cessation and after imatinib resumption in patients enrolled in imatinib discontinuation studies. In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, -1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P < .001). In 1 patient, exploration was repeated after imatinib discontinuation and evidenced a recovery of creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%. Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Chronic kidney disease in the source documentation of the outpatient clinic Department of Nephrology. Part I. Causes of renal failure and characteristics of the studied population].

PubMed

Kopeć, Jerzy; Januszek, Rafał; Wieczorek-Surdacka, Ewa; Sułowicz, Władysław

2009-01-01

During the last years the incidence of chronic kidney disease (CKD) is permanently increasing and has become a global social and economical problem in the world as well as in Poland. The aim of the study was the retrospective analysis of medical records of patients with renal failure under supervision at the outpatient clinic, Department of Nephrology, University Hospital in Cracow. The study population enclosed 1183 patients (640 men and 543 women) aged between 17 and 98 years (mean 64.7) with creatinine concentration >120 micromol/l and/or creatinine clearance <90 ml/min/1.73 m2. Hemoglobin, iron, creatinine, urea, sodium, potasium, calcium, phosphate, magnesium, PTH, uric acid, albumin, total protein, bilirubin, glucose, total cholesterol, LDL and HDL cholesterol, triglicerydes concentration and values of hematocrite, MCV, HbA1, as well as alkaline phosphatase, AspAT, AIAT activity were estimated based on standard laboratory methods. Creatinine clearances were evaluated based on 3 different methods: simplified MDRD formula, Cockcroft-Gault formula and 24-h urine collection. Mean creatinine concentration in the studied population was 172.8 micromol/l (1.95 mg/dl). Hypertension was diagnosed in 65% of patients. In spite of treatment, more than half of the patients (51.9%) have increased systolic blood pressure and above 1/3 (35%) increased diastolic blood pressure. Mean hemoglobin concentration was 13.02 g/dl; more than 12% of patients had decreased hemoglobin below 11 g/dl. Mean values of parameters discovering calcium-phosphate metabolism were: calcium--2.33 mmol/l, phosphate--1.23 mmol/l and parathormon--169.3 pg/ml. Increased value of total serum cholesterol level was noted more than half of the patients (56.5%). Significant positive correlations were found between GFR calculated based on Cockcroft-Gault formula and BMI, hemoglobin, hematocrite, serum iron, diastolic blood pressure, total and LDL serum cholesterol, triglicerydes level, as well as AIAT activity and % values of HbA1c and negative with age, serum potassium, phosphorus, PTH and uric acid.

Comparison of the Protective Effects of Melatonin and Silymarin Against Gentamicin-Induced Nephrotoxicity in Rats.

PubMed

Ghaznavi, Habib; Mehrzadi, Saeed; Dormanesh, Banafshe; Tabatabaei, Seyyed Mohammad Taghi Hosseini; Vahedi, Habib; Hosseinzadeh, Azam; Pazoki-Toroudi, HamidReza; Rashidian, Amir

2016-10-01

This study compared the possible protective effects of silymarin and melatonin against gentamicin (GEN)-induced nephrotoxicity in rats. Rats were allocated to 6 groups: Group I, control group; Groups II and III, administered with silymarin or melatonin; Group IV, injected with GEN; and Groups V and VI, administered with silymarin or melatonin, and then injected with GEN. Compared with the rats in the control group, all rats injected with GEN significantly presented elevated levels of serum creatinine and urea that was accompanied by an increase in relative kidney weight, increase in renal reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and reduction in renal glutathione (GSH) level and superoxide dismutase (SOD) activity. Silymarin and melatonin pretreatment significantly lowered the elevated serum urea and creatinine concentration, kidney weight, and renal ROS and MDA levels. In addition, silymarin and melatonin significantly enhanced renal GSH level and SOD activity. This study indicates that silymarin and melatonin can attenuate renal injury in rats treated with GEN possibly by reducing the ROS level. © The Author(s) 2015.

Serum Creatinine: Not So Simple!

PubMed

Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

2017-01-01

Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU.

PubMed

Ravn, Bo; Prowle, John R; Mårtensson, Johan; Martling, Claes-Roland; Bell, Max

2017-09-01

Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness. Retrospective observational cohort study. In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease. None. During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality. In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Biomonitoring of polycyclic aromatic hydrocarbon exposure in pregnant women in Trujillo, Peru — Comparison of different fuel types used for cooking☆

PubMed Central

Adetona, Olorunfemi; Li, Zheng; Sjödin, Andreas; Romanoff, Lovisa C.; Aguilar-Villalobos, Manuel; Needham, Larry L.; Hall, Daniel B.; Cassidy, Brandon E.; Naeher, Luke P.

2016-01-01

Women and children in developing countries are often exposed to high levels of air pollution including polycyclic aromatic hydrocarbons (PAHs), which may negatively impact their health, due to household combustion of biomass fuel for cooking and heating. We compared creatinine adjusted hydroxy-PAH (OH-PAH) concentrations in pregnant women in Trujillo, Peru who cook with wood to levels measured in those who cook with kerosene, liquefied petroleum gas or a combination of fuels. Seventy-nine women were recruited for the study between May and July 2004 in the first trimester of their pregnancy. Urine samples were collected from the subjects in the first, second and third trimesters for OH-PAH analyses. The concentrations of the OH-PAHs were compared across the type of fuel used for cooking and pregnancy trimesters. The relationships between OH-PAHs levels in the first trimester and concurrently measured personal exposures to PM2.5, carbon monoxide and nitrogen dioxide together with their indoor and outdoor air concentrations were also investigated. Women cooking with wood or kerosene had the highest creatinine adjusted OH-PAH concentrations compared with those using gas, coal briquette or a combination of fuels. Concentrations of creatinine adjusted 2-hydroxy-fluorene, 3-hydroxy-fluorene, 1-hydroxy-fluorene, 2-hydroxy-phenanthrene and 4-hydroxy-phenanthrene were significantly higher (p<0.05) in women who used wood or kerosene alone compared with women who used liquefied petroleum gas (LPG), coal briquette or a combination of fuels. An increase in the concentrations of creatinine adjusted 9-hydroxy-fluorene, 1-hydroxy-phenanthrene, 2-hydroxy-phenanthrene, 4-hydroxy-phenanthrene and 1-hydroxy-pyrene in the third trimesters was also observed. Weak positive correlation (Spearman correlation coefficient, ρ<0.4; p<0.05) was observed between all first trimester creatinine adjusted OH-PAHs and indoor (kitchen and living room), and personal 48-h TWA PM2.5. Women who cooked exclusively with wood or kerosene had higher creatinine adjusted OH-PAH levels in their urine samples compared to women who cooked with LPG or coal briquette. PMID:23314038

[Diagnostic value of PTH total kit for estimation of bone turnover in children with chronic renal failure].

PubMed

Ziółkowska, Helena; Roszkowska-Blaim, Maria

2006-01-01

The aim of the study was to estimate the usefulness of total PTH and 1-84 molecule (CAP) assay in clinical practice. 118 children with chronic renal failure aged 13.8 +/- 4.5 years were examined: 69 on conservative treatment with creatinine clearance 40.7 +/- 20 ml/min/1.73 m2, 31 on peritoneal dialysis and 16 on hemodialysis. In all patients the following parameters were assessed: serum levels of calcium (sCa), phosphorus (sP), PTH intact (PTHs) by chemiluminescence method (Immulite analyzer), total PTH (PTHc) and CAP with Duo PTH Assay (Scantibodies Laboratories, USA). The value of CIP as the difference between total PTH and CAP was calculated. For the evaluation of bone turnover the serum level of osteocalcin (OC) with IRMA, (OsteoRiact, CIS, F) and activity of serum alkaline phosphatase (AP) were determined. The correlations between parameters were calculated by Pearson's correlation coefficient (r). Significant correlation were found between PTHs and PTHc (r=0.84, p=0.0000), CAP (r=0.79, p=0.0000) and CIP. The increase of PTHs, PTHc, CAP, CIP, sP, OC and percentage of CIP were noticed, when parallel increase of creatinine level was found. The negative correlation between creatinine level and CAP/CIP was observed. The similar correlations between level of PTHs, PTHc, CAP and OC level were observed (r=0.55, 0.49 and 0.50 respectively). The assay of total PTH and CAP fragment is not usefull in clinical practice for estimation of bone turnover in children with chronic renal failure.

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry.

PubMed

Zou, Ying; Zhu, Fu-Fan; Fang, Chao-Ying; Xiong, Xi-Yue; Li, Hong-Yun

2018-04-20

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS. This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups. In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers. This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.

Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers

PubMed Central

Siwinska, E; Mielzynska, D; Kapka, L

2004-01-01

Methods: Blood and urine samples were collected immediately after a shift at the end of a working week from 50 coke oven workers and 50 control workers not exposed to PAHs. Methods included: (1) biomarkers of exposure: urinary 1-hydroxypyrene (HpU), urinary mutagenicity by the plate Salmonella test with strains TA98 and YG1024 after metabolic activation, expressed as mutagenic rate (MR98 and MR1024, respectively), urinary cotinine; and (2) biomarkers of biological effects in peripheral blood lymphocytes (PBL): sister chromatid exchanges (SCE/cell), cells of high frequency of SCE (% HFC), micronuclei (MN/1000 cells), chromosomal aberrations (CA/100 cells), and DNA damage by the Comet assay. Results: Occupational exposure to PAH resulted in significantly increased levels of HpU and mutagenic effect of urine. Median values of these biomarkers in coke oven workers were: 9.0 µmol/mol creatinine for HpU, 2.7 for MR98, and 8.2 for MR1024, compared to the controls: HpU = 0.6 µmol/mol creatinine, MR98 = 1.2, and MR1024 = 5.5. Occupational exposure caused significant induction of SCE, HFC, and MN in coke oven workers: median SCE = 5.9, HFC = 12.0%, MN = 6.0 compared to the controls: 3.9, 5.0%, and 3.0, respectively. No effect of occupational exposure was found in relation to CA and DNA damage measured with the Comet assay. HpU concentration was positively associated with SCE and HFC. The concentration of urinary 1-hydroxypyrene corresponding to a 5% probability of increased SCE was 1.0 µmol/mol creatinine. Conclusions: The occupational exposure to PAHs resulted in measurable biological effects (SCE, HFC, MN). In coke oven workers an increased level of SCE was not observed below the level of 1.0 µmol HpU/mol creatinine. PMID:14985527

Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

PubMed

Arenas, Ivan A; Navas-Acien, Ana; Ergui, Ian; Lamas, Gervasio A

2017-10-01

Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects

PubMed Central

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

Objective: The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. Methods: This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. Results: A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. Conclusion: The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol. PMID:26430445

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects.

PubMed

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol.

The relationship of nitric oxide synthesis capacity, oxidative stress, and albumin-to-creatinine ratio in black and white men: the SABPA study.

PubMed

Mels, Catharina M C; Huisman, Hugo W; Smith, Wayne; Schutte, Rudolph; Schwedhelm, Edzard; Atzler, Dorothee; Böger, Rainer H; Ware, Lisa J; Schutte, Aletta E

2016-02-01

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R (2) = 0.15; β = -0.20; p = 0.050) and GPx/SOD ratio (R (2) = 0.24; β = -0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R (2) = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R (2) = 0.26; β = -0.29; p = 0.002) and GR/GPx ratio (R (2) = 0.25; β = -0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.

Serum cystatin C: a surrogate marker for the characteristics of peritoneal membrane in dialysis patients.

PubMed

Al-Wakeel, Jamal S; Hammad, Durdana; Memon, Nawaz Ali; Tarif, Nauman; Shah, Iqbal; Chaudhary, Abdulrauf

2009-03-01

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 +/- 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 +/- 0.67 and 73.3 +/- 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > or = 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.

PubMed

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-11-01

In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5 th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution-liquid chromatography mass spectrometry.

PubMed

Nah, Hyunjin; Lee, Sang-Guk; Lee, Kyeong-Seob; Won, Jae-Hee; Kim, Hyun Ok; Kim, Jeong-Ho

2016-02-01

The aim of this study was to estimate bilirubin interference and accuracy of six routine methods for measuring creatinine compared with isotope dilution-liquid chromatography mass spectrometry (ID-LC/MS). A total of 40 clinical serum samples from 31 patients with serum total bilirubin concentration >68.4μmol/L were collected. Serum creatinine was measured using two enzymatic reagents and four Jaffe reagents as well as ID-LC/MS. Correlations between bilirubin concentration and percent difference in creatinine compared with ID-LC/MS were analyzed to investigate bilirubin interference. Bias estimations between the six reagents and ID-LC/MS were performed. Recovery tests using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 967a were also performed. Both the enzymatic methods showed no bilirubin interference. However, three of the four Jaffe methods demonstrated significant bilirubin concentration-dependent interference in samples with creatinine levels <53μmol/L, and two of them showed significant bilirubin interference in samples with creatinine levels ranging from 53.0 to 97.2μmol/L. Comparison of these methods with ID-LC/MS using patients' samples with elevated bilirubin revealed that the tested methods failed to achieve the bias goal at especially low levels of creatinine. In addition, recovery test using NIST SRM 967a showed that bias in one Jaffe method and two enzymatic methods did not achieve the bias goal at either low or high level of creatinine, indicating they had calibration bias. One enzymatic method failed to achieve all the bias goals in both comparison experiment and recovery test. It is important to understand that both bilirubin interference and calibration traceability to ID-LC/MS should be considered to improve the accuracy of creatinine measurement. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose.

PubMed

Brvar, Miran; Stajer, Dusan; Kozelj, Gordana; Osredkar, Josko; Mozina, Martin; Bunc, Matjaz

2007-01-01

Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

GFR estimated from cystatin C versus creatinine in children born small for gestational age.

PubMed

Franco, Maria C P; Nishida, Sônia K; Sesso, Ricardo

2008-06-01

Low birth weight caused by intrauterine growth restriction may be a risk factor for renal impairment in the adult life. A cross-sectional study. 71 children aged 8 to 13 years living in the community of São Paulo, Brazil, were included in the study. Gestational age was within the normal range. Birth weight (range, 2,052 to 3,560 g) divided into quartiles: 2,500 g or less; 2,501 to 2,740 g; 2,741 to 3,000 g; and greater than 3,000 g. Birth weight ascertained by birth records in 43 and by recall in 28 participants. Cystatin C, creatinine, and glomerular filtration rate (GFR) estimated by equations using cystatin C (eGFR(cys)) or creatinine (eGFR(cr)). Overall, mean serum creatinine level was 0.8 +/- 0.01 (SE) mg/dL (range, 0.7 to 1.1 mg/dL); mean plasma cystatin C level was 0.9 +/- 0.02 mg/L (range, 0.5 to 1.6 mg/L), and eGFR(cr) and eGFR(cys) were 102.4 +/- 2.16 (range, 66 to 140) and 91.8 +/- 2.46 mL/min/1.73 m(2) (range, 49 to 139 mL/min/1.73 m(2)), respectively. No differences were found for serum creatinine or eGFR(cr) values among the birth-weight quartiles. There was a significant linear trend of increasing cystatin C levels (decreasing eGFR(cys)) in the lower birth-weight quartile groups (P = 0.002 and P = 0.02, respectively). Systolic blood pressure correlated with plasma cystatin C level (r = 0.31; P = 0.008) and eGFR(cys) (r = -0.26; P = 0.028). Covariance analysis adjusting for age, sex, body mass index for age compared with standards of the National Center for Health Statistics and expressed as a z score, and systolic blood pressure showed that cystatin C values remained greater in the lowest than highest birth-weight quartile (1.01 +/- 0.05 versus 0.83 +/- 0.05 mg/L; P = 0.02). Ascertainment of birth weight by recall in some participants. Lack of measurement of microalbuminuria, absence of direct GFR measurement, and small sample size. Lower birth weight is associated with higher levels of cystatin C but not creatinine in 8-13 yr. old children born full-term.

Long-term effects of steroid withdrawal in kidney transplantation.

PubMed

Offermann, G; Schwarz, A; Krause, P H

1993-01-01

The long-term graft function after withdrawal of steroids from maintenance immunosuppression was analyzed in 98 kidney recipients (59 on cyclosporin monotherapy, 39 on cyclosporin plus azathioprine) who had not developed an early rejection episode when prednisolone was discontinued. Seven years after steroid withdrawal the probability of an increase in serum creatinine (> 20% of baseline levels) was 51%. The increase in creatinine was associated with sclerosing arteriopathy as a marker of chronic rejection in 29 of 43 graft biopsies. The addition of azathioprine had no effect on the stability of long-term graft function and did not influence the 7-year graft survival rate in this highly selected group of patients.

Detection of ingested nitromethane and reliable creatinine assessment using multiple common analytical methods.

PubMed

Murphy, Christine M; Devlin, John J; Beuhler, Michael C; Cheifetz, Paul; Maynard, Susan; Schwartz, Michael D; Kacinko, Sherri

2018-04-01

Nitromethane, found in fuels used for short distance racing, model cars, and model airplanes, produces a falsely elevated serum creatinine with standard creatinine analysis via the Jaffé method. Erroneous creatinine elevation often triggers extensive testing, leads to inaccurate diagnoses, and delayed or inappropriate medical interventions. Multiple reports in the literature identify "enzymatic assays" as an alternative method to detect the true value of creatinine, but this ambiguity does not help providers translate what type of enzymatic assay testing can be done in real time to determine if there is indeed false elevation. We report seven cases of ingested nitromethane where creatinine was determined via Beckman Coulter ® analyser using the Jaffé method, Vitros ® analyser, or i-Stat ® point-of-care testing. Nitromethane was detected and semi-quantified using a common clinical toxic alcohol analysis method, and quantified by headspace-gas chromatography-mass spectrometry. When creatinine was determined using i-Stat ® point-of-care testing or a Vitros ® analyser, levels were within the normal range. Comparatively, all initial creatinine levels obtained via the Jaffé method were elevated. Nitromethane concentrations ranged from 42 to 310 μg/mL. These cases demonstrate reliable assessment of creatinine through other enzymatic methods using a Vitros ® analyser or i-STAT ® . Additionally, nitromethane is detectable and quantifiable using routine alcohols gas chromatography analysis and by headspace-gas chromatography-mass spectrometry.

Uranium Associations with Kidney Outcomes Vary by Urine Concentration Adjustment Method

PubMed Central

Shelley, Rebecca; Kim, Nam-Soo; Parsons, Patrick J.; Lee, Byung-Kook; Agnew, Jacqueline; Jaar, Bernard G.; Steuerwald, Amy J.; Matanoski, Genevieve; Fadrowski, Jeffrey; Schwartz, Brian S.; Todd, Andrew C.; Simon, David; Weaver, Virginia M.

2017-01-01

Uranium is a ubiquitous metal that is nephrotoxic at high doses. Few epidemiologic studies have examined the kidney filtration impact of chronic environmental exposure. In 684 lead workers environmentally exposed to uranium, multiple linear regression was used to examine associations of uranium measured in a four-hour urine collection with measured creatinine clearance, serum creatinine- and cystatin-C-based estimated glomerular filtration rates, and N-acetyl-β-D-glucosaminidase (NAG). Three methods were utilized, in separate models, to adjust uranium levels for urine concentration - μg uranium/g creatinine; μg uranium/L and urine creatinine as separate covariates; and μg uranium/4 hr. Median urine uranium levels were 0.07 μg/g creatinine and 0.02 μg/4 hr and were highly correlated (rs =0.95). After adjustment, higher ln-urine uranium was associated with lower measured creatinine clearance and higher NAG in models that used urine creatinine to adjust for urine concentration but not in models that used total uranium excreted (μg/4 hr). These results suggest that, in some instances, associations between urine toxicants and kidney outcomes may be statistical, due to the use of urine creatinine in both exposure and outcome metrics, rather than nephrotoxic. These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research. PMID:23591699

Elevated plasma creatinine due to creatine ethyl ester use.

PubMed

Velema, M S; de Ronde, W

2011-02-01

Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure.

A validated LC-MS/MS method for the quantitative measurement of creatinine as an endogenous biomarker in human plasma.

PubMed

Zhao, Yue; Liu, Guowen; Angeles, Aida; Christopher, Lisa J; Wang, Zhaoqing; Arnold, Mark E; Shen, Jim X

2016-10-01

Creatinine is an endogenous compound generated from creatine by normal muscular metabolism. It is an important indicator of renal function and the serum level is routinely monitored in clinical labs. Results & methodology: Surrogate analyte (d3-creatinine) was used for calibration standard and quality control preparation and the relative instrument response ratio between creatinine and d3-creatinine was used to calculate the endogenous creatinine concentrations. A fit-for-purpose strategy of using a surrogate analyte and authentic matrix was adopted for this validation. The assay was the first human plasma assay using such strategy and was successfully applied to a clinical study to confirm a transient elevation of creatinine observed using an existing clinical assay.

Deceiving proteins! A case of lymphoma and high creatinine.

PubMed

Metraiah, El Hakem Abdelkarim; Regan, Helen; Louw, Johanna; Kidder, Dana

2017-01-23

Estimation of kidney function by measuring serum creatinine is one the commonest laboratory tests conducted in clinical practice. Enzymatic methods are often used to measure serum creatinine. Clinicians should be aware of the limitations of these methods, such as test interference with paraproteins.We present a case of falsely elevated serum creatinine in a patient referred for renal biopsy. The combination of fluctuating creatinine and normal blood urea level was unusual. Serum protein electrophoresis revealed the presence of an IgM paraprotein. Further investigations confirmed an underlying diagnosis of lymphoplasmacytoid lymphoma. This case highlights how IgM paraprotein can interfere with creatinine estimation by enzymatic assay and the utility of alternative methods of estimating serum creatinine. 2017 BMJ Publishing Group Ltd.

[Acute physical exercise increases homocysteine concentrations in young trained male subjects].

PubMed

Maroto-Sánchez, Beatriz; Valtueña, Jara; Albers, Ulrike; Benito, Pedro J; González-Gross, Marcela

2013-01-01

High levels of homocysteine (Hcy) have been identified as a cardiovascular risk factor. Regarding physical exercise, the results are contradictory. The aim of this study was to determine the influence of maximal intensity exercise and submaximal constant exercise on total serum homocysteine concentrations (tHcy) and other related parameters. Ten physically active male subjects (mean age: 23.51 ± 1.84), performed two treadmill tests, a maximal test and a stable submaximal test at an intensity of 65% of maximal oxygen uptake (VO2max). Serum concentrations of tHcy, Folate, Vitamin B12 and creatinine were analysed before and after each test. Significant increase in serum tHcy concentrations after the maximal (p < 0.05) and submaximal (p < 0.01) tests were observed. Folate and vitamin B12 concentrations also increased significantly after both tests (p < 0.05). Creatinine levels increased only after the maximal test (p < 0.001). A statistically significant inverse relationship was found between folate and tHcy concentrations (p < 0.05) at all the measurement points. THcy levels increased significantly after acute exercise in both maximum and submaximal intensity exercises. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Renal Dysfunction in Streptozotocin-Induced Diabetic Rats.

PubMed

Iroaganachi, Mercy; Eleazu, Chinedum; Okafor, Polycarp

2015-03-20

Although unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) are used as single plants to manage diabetes mellitus in Nigeria, the possibility of combining them in a typical diabetic diet and the glycemic response elicited as a result of such combination has not been investigated. To determine the effect of unripe plantain and ginger on serum total proteins, albumin, creatinine and urea levels of streptozotocin induced diabetic rats. Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) received standard rat feeds; Group 2 (diabetic) received standard rat feeds; Group 3 received unripe plantain pellets and Group 4 received unripe plantain+ginger pellets. There were significant increases (P=0.045) of both serum urea and creatinine, but significant decreases (P=0.045) of both serum total protein and albumin levels, in Group 2 rats compared with Group 1. There were significant decreases (P=0.033) of both serum urea and creatinine levels of Group 3 and 4 rats compared with Group 2. In addition, there were significant increases of both serum total protein and albumin levels (P=0.033) in Group 3 rats compared with Group 2, but the comparison of serum total protein and albumin levels between Group 4 and Group 2 did not reach the significant level (P=0.056 and P=0.065 for serum total protein and albumin levels, respectively. Combination of unripe plantain and ginger at the ratio used in the management of renal dysfunction in diabetics was not very effective compared with unripe plantain alone.

Gender differences in cadmium and cotinine levels in prepubertal children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fucic, A., E-mail: afucic@imi.hr; Plavec, D; Casteleyn, L.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age–sex groups: boys (6–8 years, 9–10 years and 11 years old), and girls (6–7 years, 8–9 years, 10–11 years). The number of subjects permore » group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10–0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80–39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6–7 year old girls, 11 year old boys and 10–11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation. - Highlights: • In 216 children from 6 to 11 years old the median level of Cd was 0.18 µg/L. • The median level of cotinine was 1.50 µg/L. • Correlation between levels of Cd and creatinine in all children was detected. • Cd levels were different between 6–7 year old, 10–11 year old girls vs. 11 year old boys.« less

Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial

PubMed Central

Carpenter, Myra A.; Weiner, Daniel E.; Levey, Andrew S.; Pfeffer, Marc; Kusek, John W.; Cai, Jianwen; Hunsicker, Lawrence G.; Park, Meyeon; Bennett, Michael; Liu, Kathleen D.; Hsu, Chi-yuan

2016-01-01

Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver–type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes. PMID:26538631

Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture.

PubMed

Gezer, Cenk; Ekin, Atalay; Golbasi, Ceren; Kocahakimoglu, Ceysu; Bozkurt, Umit; Dogan, Askin; Solmaz, Ulaş; Golbasi, Hakan; Taner, Cuneyt Eftal

2017-04-01

To determine whether urea and creatinine measurements in vaginal fluid could be used to diagnose preterm premature rupture of membranes (PPROM) and predict delivery interval after PPROM. A prospective study conducted with 100 pregnant women with PPROM and 100 healthy pregnant women between 24 + 0 and 36 + 6 gestational weeks. All patients underwent sampling for urea and creatinine concentrations in vaginal fluid at the time of admission. Receiver operator curve analysis was used to determine the cutoff values for the presence of PPROM and delivery within 48 h after PPROM. In multivariate logistic regression analysis, vaginal fluid urea and creatinine levels were found to be significant predictors of PPROM (p < 0.001 and p < 0.001, respectively) and delivery within 48 h after PPROM (p = 0.012 and p = 0.017, respectively). The optimal cutoff values for the diagnosis of PPROM were >6.7 mg/dl for urea and >0.12 mg/dl for creatinine. The optimal cutoff values for the detection of delivery within 48 h were >19.4 mg/dl for urea and >0.23 mg/dl for creatinine. Measurement of urea and creatinine levels in vaginal fluid is a rapid and reliable test for diagnosing and also for predicting delivery interval after PPROM.

Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine < 1.5 mg/dL) and having renal dysfunction (serum creatinine ≤ 1.5 mg/dL). For the processing of data, SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic aqueous extract in rat.

PubMed

Ahmed, Walaa; Zaki, Amr; Nabil, Taghred

2015-01-01

Methotrexate (MTX) has been widely used for treatment of cancer and rheumatoid arthritis, but its use has been limited by its nephrotoxicity. This study was carried out to determine whether garlic exerts a protective effect against MTX-induced nephrotoxicity. Nephrotoxicity was induced in rats after a single i.p. injection of MTX (20 mg/kg). Garlic extract (1 mL/100 g b.w.) was given orally for 7 days before and after MTX administration. Serum samples were collected to evaluate urea, creatinine, sodium, phosphorous, potassium, and calcium. Reduced glutathione, catalase, adenosine deaminase, nitric oxide, and malondialdehyde were measured in renal tissue. Tubular injury was evaluated by histopathological examination. MTX increased urea and creatinine levels and led to imbalances in some electrolytes. It also depleted renal antioxidant enzyme levels and increased malondialdehyde, adenosine deaminase, and nitric oxide levels. Histopathological examination showed glomerular and tubular alterations. Pretreatment with garlic significantly improved renal function and increased renal antioxidant enzyme activities. Furthermore, garlic reduced renal oxidative stress and prevented alterations in renal morphology. Garlic treatment has a reversible biochemical and histological effect upon MTX-induced nephrotoxicity.

Renal creatinine handling in very old patients with chronic renal disease.

PubMed

Musso, Carlos G; Michelángelo, Hernán; Vilas, Manuel; Martinez, Bernardo; Bonetto, Alberto; Jauregui, Ricardo; Algranati, Luis

2011-09-01

Renal creatinine handling is basically the result of its glomerular filtration and proximal tubular secretion. However, creatinine reabsorption has been documented in certain conditions, such as premature babies, newborns, and healthy elderly people. Additionally, it is known that there is an increase in the proportion of secreted creatinine in chronic renal disease. In this paper, we report our studies on the characteristic reabsorption pattern of creatinine in the elderly with chronic renal disease. We studied twenty-seven volunteers with chronic kidney disease, eleven of whom were young and the rest were very old (age > 75 years old). We measured creatinine clearance without (Ccr) and with cimetidine (CcrWC) and Ccr/CcrWC ratio from each volunteer, in timed urine samples. Then, Ccr, CcrWC, and Ccr/CcrWC ratio were compared between young and very old people in two chronic kidney disease subgroups: stages II-III and stages IV-V. Statistical analysis was performed applying a non-parametric test (Wilcoxon). We observed a tendency towards a lower Ccr/CcrWC ratio in the very old stage II-III group compared with the young one: 1 (0.96-1.26) (very old) vs 1.3 (1.1-1.5) (young), P = 0.09, on the contrary, there was no significant difference in Ccr/CcrWC ratio between very old and young person with stage IV-V CKD: 1.66 (1.41-2.21) (young) vs 1.77 (1.1-2.7) (young), P = NS. Creatinine secretion pattern in very old patients with advanced chronic renal disease is similar to that observed in young ones with similar level of CKD.

Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study

PubMed Central

Mansfield, Kathryn E; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A

2017-01-01

Objective To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment. Design Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics. Setting UK primary care, 1997-2014. Participants Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363). Main outcome measures Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs. Results Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (<10%, 10-19%, 20-29%, 30-39%, and ≥40%) showed a graduated relation for all outcomes (all P values for trends <0.001). Notably, creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using <10% as reference). Results were consistent across calendar periods, across subgroups of patients, and among continuing users. Conclusions Increases in creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment. PMID:28279964

Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report.

PubMed

Kazama, Itsuro; Nakajima, Toshiyuki

2017-10-01

In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.

Outcomes of tubeless percutaneous nephrolithotomy in patients with chronic renal insufficiency.

PubMed

Etemadian, Masoud; Maghsoudi, Robab; Shadpour, Pejman; Ghasemi, Hadi; Shati, Mohsen

2012-05-01

We evaluated the outcomes of percutaneous nephrolithotomy in patients with chronic renal insufficiency. A total of 60 patients with a creatinine level greater than 1.5 mg/dL who underwent PCNL were included. Serum creatinine level, as a kidney function index, was assessed before and after the operation. The mean calculus size was 31.13 ± 9.38 mm. The mean pre-operative and 2-week postoperative serum creatinine levels were 2.43 ± 0.75 mg/dL and 2.08 ± 0.78 mg/dL, respectively. There was a significant difference between the pre-operative and postoperative creatinine levels in all postoperative days (days 1, 2, and 14). Fifty of the 60 patients (83.3%) were stone free. Ten patients (16.6%) developed postoperative fever. We can conclude that percutaneous nephrolithotomy seems to be a safe and effective therapeutic option for kidney calculi in patients with chronic kidney disease.

Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110.

PubMed

Zhang, Yan; Warren, Mark S; Zhang, Xuexiang; Diamond, Sharon; Williams, Bill; Punwani, Naresh; Huang, Jane; Huang, Yong; Yeleswaram, Swamy

2015-04-01

Serum creatinine is commonly used as a marker of renal function, but increases in serum creatinine might not represent changes in glomerular filtration rate (GFR). INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine was observed after treatment with INCB039110. However, a dedicated renal function study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy volunteers indicated no change in GFR. In vitro studies were therefore conducted to investigate the interaction of INCB039110 with five transporters that are likely involved in the renal clearance of creatinine. Cell systems expressing individual or multiple transporters were used, including a novel quintuple-transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of creatinine. Given the interactions of INCB039110 with multiple transporters affecting creatinine uptake and efflux, an integrated system expressing all five transporters was sought; in that system, INCB039110 caused a dose-dependent decrease in transcellular transport of creatinine with weaker net inhibition compared with the effects on individual transporters. In summary, a molecular mechanism for the increase in serum creatinine by INCB039110 has been established. These studies also underline the limitations of using serum creatinine as a marker of renal function. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Biomonitoring of organophosphate exposure of pesticide sprayers and comparison of exposure levels with other population groups in Thessaly (Greece).

PubMed

Koureas, Michalis; Tsakalof, Andreas; Tzatzarakis, Manolis; Vakonaki, Elena; Tsatsakis, Aristidis; Hadjichristodoulou, Christos

2014-02-01

To evaluate the exposure of different population groups in Thessaly (Greece) to organophosphate pesticides (OPs) and investigate the dependence of exposure levels on pesticide application practices, personal protective and hygienic measures taken. For the exposure assessment, four dialkyl phosphate (DAP) metabolites of organophosphate pesticides were quantified in spot urine samples of 77 pesticide sprayers, 75 residents of the studied agricultural area non-involved in agricultural activities and 112 urban residents who served as a control group. Structured questionnaires were used to record demographic characteristics, pesticide application parameters and protective measures taken. Univariate and multivariate analysis of the obtained cross-sectional data was performed to identify potential risk factors associated with biomarker levels. It was found that total DAP median level in the sprayers' group was 24.9 μg/g creatinine (IQR: 13.0-42.1), while the rural and urban residents had significantly lower (p<0.001) levels of 11.3 μg/g creatinine (IQR: 5.3-18.7) and 11.9 μg/g creatinine (IQR: 6.3-20.3), respectively. In sprayers who had recently applied an OP pesticide (n=28), the median levels of DAP metabolites were 31.8 μg/g creatinine (IQR: 22.3-117.2). Logistic regression analysis showed that the use of full body coveralls while handling and spraying pesticides was significantly associated with lower DAP levels (OR 4.05, 95% CI 1.22 to 13.46). Also, changing clothes immediately after accidental contamination of clothing with pesticide amounts was found to be significantly associated with lower exposure levels (OR 4.04, CI 1.05 to 15.57). Our study findings confirm the increased exposure to OPs in pesticide sprayers and underline the importance of protective measures especially those that focus on dermal exposure mitigation.

High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.

PubMed

Joannon, Pilar; Oviedo, Iris; Campbell, Myriam; Tordecilla, Juan

2004-07-01

The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity. Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance. Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed. These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable. Copyright 2004 Wiley-Liss, Inc.

TNF-α, IL-6 and IL-10 expressions, responsible for disparity in action of curcumin against cisplatin-induced nephrotoxicity in rats.

PubMed

Kumar, Parveen; Sulakhiya, Kunjbihari; Barua, Chandana C; Mundhe, Nitin

2017-07-01

Cisplatin is a regularly employed effective chemotherapeutic agent for the treatment of many types of cancer. The main drawback of cisplatin treatment is kidney toxicity which affects 25-35% of treated patients. Many mechanisms are believed to be involved in this kidney damage, but inflammation plays a significant role in this event. Curcumin is a polyphenol and has antioxidant and anti-inflammatory effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Female rats were randomly divided into 5 groups: control, curcumin, cisplatin, curcumin plus cisplatin (pre-treatment group) and cisplatin plus curcumin (post-treatment group). Rats were given cisplatin (7.5 mg/kg body weight) with or without curcumin treatment (120 mg/kg body weight). Blood urea nitrogen (BUN), creatinine, albumin, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 expressions and histological changes were determined on the 5th day after cisplatin injection. Acute kidney damage was evident by increased BUN and creatinine levels. In addition, cisplatin showed a marked pro-inflammatory response as revealed by a significant increase in the tissue levels of TNF-α, IL-6, IL-8 and decrease in the IL-10 level. Pre-treatment of curcumin reduced cisplatin-induced nephrotoxicity which was clearly evident from the reduced BUN, creatinine, TNF-α, IL-6 and IL-8 levels and increased albumin and IL-10 levels. Additionally, these findings were also supported by histopathology of the kidneys. In contrast, post-treatment of curcumin failed to cut down the expression of inflammatory markers substantially and also neglected to increase the expression of IL-10. The disparity in the action of curcumin after pre- and post-treatment with cisplatin-induced nephrotoxicity was due to the inability of post-treatment to reduce TNF-α & IL-6, besides to show a concurrent rise in IL-10 expression in renal tissues.

Personal exposure and health effect relationship for NO2 with urinary hydroxyproline to creatinine ratio as indicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanagisawa, Y.; Nishimura, H.; Matsuki, H.

Establishment of an exposure-effect relationship was attempted between personal nitrogen dioxide (NO/sub 2/) exposure and urinary hydroxyproline to creatinine ratio of approximately 800 adult women, who were mothers of primary schoolchildren living in two communities around Tokyo. Daily average of the personal NO/sub 2/ exposure (ENO/sub 2/) was measured during wintertime by a newly developed personal monitor exposed for 24 hours. The hydroxyproline to creatinine ratio (HOP:C) in the urine sample collected early in the morning of the day for ENO/sub 2/ measurement was used as a biochemical indicator of the health effect of NO/sub 2/ exposure. The HOP:C wasmore » found to have significant correlation with ENO/sub 2/ and number of cigarettes smoked actively and passively. ENO/sub 2/, however, had no correlation with the intensity of the smoking levels; they might affect HOP:C independently. Stepwise multiple regression analysis revealed that HOP:C could be predicted by ENO/sub 2/ and smoking habits at a high confidence level. The regression analysis of the active smokers group indicated that a few cigarettes was enough to increase the HOP:C, while in the case of passive smoking, HOP:C increased proportionally to the number of cigarettes.« less

Early Acute Kidney Injury in Military Casualties

DTIC Science & Technology

2015-05-01

days, because of the high rates of amputations in this patient popu- lation, which may lower creatinine independent of renal func- tion.26 Data on...combat support hospi- tal in Afghanistan. Levels of serum creatinine were collected for up to 14 days and were available in both Afghanistan and...patient did not have a baseline creatinine , then a baseline creatinine was derived using theModification of Diet in Renal Disease (MDRD) study equation

Predictivity and fate of metal ion release from metal-on-metal total hip prostheses.

PubMed

Nicolli, Annamaria; Bisinella, Gianluca; Padovani, Giovanni; Vitella, Antonio; Chiara, Federica; Trevisan, Andrea

2014-09-01

Blood metal ion levels in 72 patients with large head metal-on-metal hip arthroplasty were studied to determine the correlation between the values measured in whole blood and urine. Urinary cobalt and chromium levels of 30μg and 21μg, respectively, adjusted to creatinine were found to correspond to the 7μg/l cut-off value that has been accepted in whole blood. Cobalt and chromium levels in whole blood and urine both significantly correlated with increased acetabular component inclination angle over 50 degrees and pain scores. There was no correlation with socket anteversion angle or femoral head diameter. The data support the use of urinary measurement of metal ions adjusted to creatinine to monitor patients with large head metal-on-metal total hip arthroplasty. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of body mass index status on urinary creatinine and specific gravity for epidemiological study of children.

PubMed

Wang, Bin; Tang, Chuanxi; Wang, Hexing; Zhou, Wei; Chen, Yue; Zhou, Ying; Jiang, Qingwu

2015-11-01

In epidemiological studies, urinary biomonitoring is a valid approach to assess the association between environmental chemical exposure and children's health. Many clinical biomarkers (e.g., endogenous metabolites) are also based on analysis of urine. Considering the variability in urinary output, urinary concentrations of chemicals are commonly adjusted by creatinine and specific gravity (SG). However, there is a lack of systematic evaluation of their appropriateness for children. Furthermore, urinary SG and creatinine excretion could be influenced by body mass index (BMI), but the effect of BMI status on the two correction factors is unknown. We measured SG and creatinine concentrations of repeated first morning urine samples collected from 243 primary school children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher temporal consistency compared with creatinine. Urinary SG was associated with sex (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with urinary creatinine levels. Inter-day collection time was not associated with SG or creatinine after excluding the effect of Monday as a confounder. When stratified by BMI status, none of the factors were associated with creatinine among the overweight and obese children. Generally, SG is preferable for correcting the variability in urinary output for children although creatinine correction may also perform well in overweight and obese children. SG correction is recommended for epidemiological exposure analysis in children based on urinary levels of exogenous or endogenous metabolites.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

PubMed

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Serum Cystatin C– Versus Creatinine-Based Definitions of Acute Kidney Injury Following Cardiac Surgery: A Prospective Cohort Study

PubMed Central

Spahillari, Aferdita; Parikh, Chirag R.; Sint, Kyaw; Koyner, Jay L.; Patel, Uptal D.; Edelstein, Charles L.; Passik, Cary S.; Thiessen-Philbrook, Heather; Swaminathan, Madhav; Shlipak, Michael G.

2012-01-01

Background The primary aim of this study was to compare the sensitivity and rapidity of AKI detection by cystatin C relative to creatinine following cardiac surgery. Study Design Prospective cohort study Settings and Participants 1,150 high-risk, adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. Predictor Changes in serum creatinine and cystatin C Outcome Post-surgical incidence of AKI Measurements Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1–5. To allow comparisons between changes in creatinine and cystatin C, AKI endpoints were defined by the relative increases in each marker from baseline (25, 50 and 100%) and the incidence of AKI was compared based upon each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine. Results Overall, serum creatinine detected more cases of AKI than cystatin C: 35% developed a ≥25% increase in serum creatinine, whereas only 23% had ≥25% increase in cystatin C (p < 0.001). Creatinine also had higher proportions meeting the 50% (14% and 8%, p<0.001) and 100% (4% and 2%, p=0.005) thresholds for AKI diagnosis. Clinical outcomes were generally not statistically different for AKI cases detected by creatinine or cystatin C. However, for each AKI threshold, patients with AKI confirmed by both markers had significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine alone (p=0.002). Limitations There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based upon their definitions of AKI. Conclusion In this large multicenter study, we found that cystatin C was less sensitive for AKI detection compared with creatinine. However, confirmation by cystatin C appeared to identify a subset of AKI patients with substantially higher risk of adverse outcomes. PMID:22809763

Diagnostic value of potassium level in a spot urine sample as an index of 24-hour urinary potassium excretion in unselected patients hospitalized in a hypertension unit

PubMed Central

Symonides, Bartosz; Wojciechowska, Ewa; Gryglas, Adam; Gaciong, Zbigniew

2017-01-01

Background Primary hyperaldosteronism may be associated with elevated 24-hour urinary potassium excretion. We evaluated the diagnostic value of spot urine (SU) potassium as an index of 24-hour urinary potassium excretion. Methods We measured SU and 24-hour urinary collection potassium and creatinine in 382 patients. Correlations between SU and 24-hour collections were assessed for potassium levels and potassium/creatinine ratios. We used the PAHO formula to estimate 24-hour urinary potassium excretion based on SU potassium level. The agreement between estimated and measured 24-hour urinary potassium excretion was evaluated using the Bland-Altman method. To evaluate diagnostic performance of SU potassium, we calculated areas under the curve (AUC) for SU potassium/creatinine ratio and 24-hour urinary potassium excretion estimated using the PAHO formula. Results Strongest correlation between SU and 24-hour collection was found for potassium/creatinine ratio (r = 0.69, P<0.001). The PAHO formula underestimated 24-hour urinary potassium excretion by mean 8.3±18 mmol/d (95% limits of agreement -28 to +44 mmol/d). Diagnostic performance of SU potassium/creatinine ratio was borderline good only if 24-hour urinary potassium excretion was largely elevated (AUC 0.802 for 120 mmol K+/24 h) but poor with lower values (AUC 0.696 for 100 mmol K+/24 h, 0.636 for 80 mmol K+/24 h, 0.675 for 40 mmol K+/24 h). Diagnostic performance of 24-hour urinary potassium excretion estimated by the PAHO formula was excellent with values above 120 mmol/d and good with lower values (AUC 0.941 for 120 mmol K+/24 h, 0.819 for 100 mmol K+/24 h, 0.823 for 80 mmol K+/24 h, 0.836 for 40 mmol K+/24 h). Conclusions Spot urine potassium/creatinine ratio might be a marker of increased 24-hour urinary potassium excretion and a potentially useful screening test when reliable 24-hour urine collection is not available. The PAHO formula allowed estimation of the 24-hour urinary potassium excretion based on SU measurements with reasonable clinical accuracy. PMID:28662194

Empirical relationships among oliguria, creatinine, mortality, and renal replacement therapy in the critically ill.

PubMed

Mandelbaum, Tal; Lee, Joon; Scott, Daniel J; Mark, Roger G; Malhotra, Atul; Howell, Michael D; Talmor, Daniel

2013-03-01

The observation periods and thresholds of serum creatinine and urine output defined in the Acute Kidney Injury Network (AKIN) criteria were not empirically derived. By continuously varying creatinine/urine output thresholds as well as the observation period, we sought to investigate the empirical relationships among creatinine, oliguria, in-hospital mortality, and receipt of renal replacement therapy (RRT). Using a high-resolution database (Multiparameter Intelligent Monitoring in Intensive Care II), we extracted data from 17,227 critically ill patients with an in-hospital mortality rate of 10.9 %. The 14,526 patients had urine output measurements. Various combinations of creatinine/urine output thresholds and observation periods were investigated by building multivariate logistic regression models for in-hospital mortality and RRT predictions. For creatinine, both absolute and percentage increases were analyzed. To visualize the dependence of adjusted mortality and RRT rate on creatinine, the urine output, and the observation period, we generated contour plots. Mortality risk was high when absolute creatinine increase was high regardless of the observation period, when percentage creatinine increase was high and the observation period was long, and when oliguria was sustained for a long period of time. Similar contour patterns emerged for RRT. The variability in predictive accuracy was small across different combinations of thresholds and observation periods. The contour plots presented in this article complement the AKIN definition. A multi-center study should confirm the universal validity of the results presented in this article.

Serum creatinine is independently associated with angiographic extent of coronary artery disease in patients with stable angina pectoris.

PubMed

Korkmaz, Şule; Demirkan, Burcu; Altay, Hakan; Refiker Ege, Meltem; Çaldır, Vedat; Yılmaz, Mehmet Birhan; Güray, Yeşim; Güray, Ümit; Şaşmaz, Hatice

2011-08-01

Renal dysfunction has been shown to be linked to high risk for cardiovascular events. Even milder forms of creatinine elevation are associated with poor cardiovascular outcomes. We designed a retrospective study and searched the association of angiographic extent of coronary artery disease and creatinine levels in patients without overt renal dysfunction. We retrospectively reviewed 892 consecutive patients with typical stable angina pectoris (311 female with mean age of 62 ± 10 years, 581 male with mean age of 56 ± 11 years) at Türkiye Yüksek İhtisas Hospital and creatinine level ≤ 3 mg/dl without history of hemodialysis. Patients without overt renal disease were divided into 3 groups according to level of creatinine (Group A: Cr level <1.2 mg/dl, Group B: Cr level ≥ 1.2 and <1.5 mg/dl and Group C: Cr level ≥ 1.5 -≤ 3 mg/dl). Additionally after evaluation of coronary angiograms, patients were also classified according to those with high stenosis (stenosis score ≥ 16) and high extension scores (extension score >50%) versus low stenosis and low extension scores. Logistic regression analysis was performed to establish the clinical predictors of high total stenosis and high extension scores. Each group of patients according to level of creatinine showed marked difference in terms of angiographic extent of coronary artery disease (p<0.001). Those in the highest creatinine group (≥ 1.5 mg/dl, but not above 3 mg/dl) had the highest total stenosis (17 ± 6, p<0.001) and extension (78 ± 25, p<0.001) scores irrespective of age and gender. Creatinine was shown to be significantly correlated with both stenosis and extension scores. Age (OR:1.035, 95% CI:1.016-1.054, p<0.0001), being male (OR:1.746, 95% CI: 1.135-2.685, p=0.011), presence of hypertension (OR:1.507, 95%CI: 1.005-2.25 p=0.047), presence of diabetes mellitus (OR: 1.865, 95%: 1.250-2.783, p=0.002), previous history of myocardial infarction (OR: 1.624, 95%CI: 1.094-2.413, p=0.016), wall motion score index (OR:1.203, 95%CI: 1.108-1.305, p<0.0001) and creatinine (OR:4.037, 95%CI: 2.530-6.443, p<0.0001) level were found to be independent predictors of high total stenosis score. Furthermore, age (OR:1.042, 95%CI: 1.026-1.059, p<0.0001), being male (OR:2.587, 95%CI: 1.794-3.731, p<0.0001), presence of hypertension (OR:1.536, 95% CI:1.100-2.147, p=0.012), previous myocardial infarction (OR:6.183, 95%CI: 4.340-8.807, p<0.0001), total cholesterol/HDL ratio (OR:1.215, 95%CI: 1.114-1.327, p<0.0001) and creatinine (OR:3.814, 95%CI: 2.149-6.768, p<0.0001) were found to be independent predictors of high extension score. Serum creatinine seems to denote severity of angiographic extent of coronary artery disease in patients with typical chest pain.

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures.

PubMed

O'Brien, Katie M; Upson, Kristen; Buckley, Jessie P

2017-03-01

Urine- and serum-based biomarkers are useful for assessing individuals' exposure to environmental factors. However, variations in urinary creatinine (a measure of dilution) or serum lipid levels, if not adequately corrected for, can directly impact biomarker concentrations and bias exposure-disease association measures. Recent methodological literature has considered the complex relationships between creatinine or serum lipid levels, exposure biomarkers, outcomes, and other potentially relevant factors using directed acyclic graphs and simulation studies. The optimal measures of urinary dilution and serum lipids have also been investigated. Existing evidence supports the use of covariate-adjusted standardization plus creatinine adjustment for urinary biomarkers and standardization plus serum lipid adjustment for lipophilic, serum-based biomarkers. It is unclear which urinary dilution measure is best, but all serum lipid measures performed similarly. Future research should assess methods for pooled biomarkers and for studying diseases and exposures that affect creatinine or serum lipids directly.

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures

PubMed Central

O’Brien, Katie M.; Upson, Kristen; Buckley, Jessie P.

2017-01-01

Purpose of review Urine- and serum-based biomarkers are useful for assessing individuals’ exposure to environmental factors. However, variations in urinary creatinine (a measure of dilution) or serum lipid levels, if not adequately corrected for, can directly impact biomarker concentrations and bias exposure-disease association measures. Recent findings Recent methodological literature has considered the complex relationships between creatinine or serum lipid levels, exposure biomarkers, outcomes, and other potentially relevant factors using directed acyclic graphs and simulation studies. The optimal measures of urinary dilution and serum lipids have also been investigated. Summary Existing evidence supports the use of covariate-adjusted standardization plus creatinine adjustment for urinary biomarkers and standardization plus serum lipid adjustment for lipophilic, serum-based biomarkers. It is unclear which urinary dilution measure is best, but all serum lipid measures performed similarly. Future research should assess methods for pooled biomarkers and for studying diseases and exposures that affect creatinine or serum lipids directly. PMID:28097619

Anti-smoking legislation and its effects on urinary cotinine and cadmium levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sánchez-Rodríguez, Jinny E., E-mail: jinnysanchez@isciii.es; Bartolomé, Mónica, E-mail: mbj@isciii.es; Cañas, Ana I, E-mail: acanas@isciii.es

Anti-smoking legislation has been associated with an improvement in health indicators. Since the cadmium (Cd) body burden in the general population is markedly increased by smoke exposure, we analyzed the impact of the more restrictive legislation that came into force in Spain in 2011 by measuring Cd and cotinine in first morning urine samples from 83 adults in Madrid (Spain) before (2010) and after (2011) introduction of this law. Individual pair-wise comparisons showed a reduction of creatinine corrected Cotinine and Cd levels for non-active smokers, i. e. those which urinary cotinine levels are below 50 μg/L. After the application ofmore » the stricter law, cotinine levels in urine only decreased in non-active smokers who self-reported not to be exposed to second-hand smoke. The reduction in second hand smoke exposure was significantly higher in weekends (Friday to Sunday) than in working days (Monday to Thursday). The decrease in U-Cd was highly significant in non-active smokers and, in general, correlated with lower creatinine excretion. Therefore correction by creatinine could bias urinary Cd results, at least for cotinine levels higher than 500 μg/L. The biochemical/toxicological benefits detected herein support the stricter application of anti-smoking legislation and emphasize the need to raise the awareness of the population as regards exposure at home.« less

Urinary cotinine levels of electronic cigarette (e-cigarette) users.

PubMed

Göney, Gülşen; Çok, İsmet; Tamer, Uğur; Burgaz, Sema; Şengezer, Tijen

2016-07-01

The popularity of electronic cigarettes (e-cigarettes) is rapidly increasing in many countries. These devices are designed to imitate regular cigarettes, delivering nicotine via inhalation without combusting tobacco but currently, there is a lack of scientific evidence on the presence or absence of nicotine exposure. Such research relies on evidence from e-cigarette users urine samples. In this study, we aimed to determine the levels and compare the amount of nicotine to which e-cigarette users, cigarette smokers and passive smokers are exposed. Therefore, urine samples were collected from e-cigarette users, cigarette smokers, passive smokers, and healthy nonsmokers. The urinary cotinine levels of the subjects were determined using gas chromatography-mass spectrometry. The mean (±SD) urinary cotinine levels were determined as 1755 ± 1848 ng/g creatinine for 32 e-cigarette users, 1720 ± 1335 ng/g creatinine for 33 cigarette smokers and 81.42 ± 97.90 ng/g creatinine for 33 passive smokers. A significant difference has been found between cotinine levels of e-cigarette users and passive smokers (p < 0.05). There were no statistically significant differences between e-cigarette users and cigarette smokers (p > 0.05). This is a seminal study to demonstrate the e-cigarette users are exposed to nicotine as much as cigarette smokers.

Gender-Specific Differences in Baseline, Peak, and Delta Serum Creatinine: The NACSELD Experience.

PubMed

O'Leary, Jacqueline G; Wong, Florence; Reddy, K Rajender; Garcia-Tsao, Guadalupe; Kamath, Patrick S; Biggins, Scott W; Fallon, Michael B; Subramanian, Ram M; Maliakkal, B; Thacker, Leroy; Bajaj, Jasmohan S

2017-03-01

Women have lower serum creatinine values than men for similar renal function. We aimed to determine the differential effect of baseline, peak, and delta creatinine between genders on outcomes in infected hospitalized cirrhotic patients. North American Consortium for the Study of End-Stage Liver Disease is a 15-center consortium of tertiary care hepatology centers prospectively enrolling infected cirrhotic inpatients. Baseline, peak, and delta creatinine during hospitalization were compared between genders, and their impact on overall survival, transplant-free survival, probability of transplantation, and need for renal replacement therapy (RRT) was analyzed. In total, 532 patients with cirrhosis (males = 59% median admission MELD = 20) had significantly lower median baseline (1.07 vs. 1.30 mg/dL, p < 0.0001) and peak creatinine (1.47 vs. 1.59 mg/dL, p = 0.024) in women than men during hospitalization for an infection, but both genders had similar delta creatinine levels (0.30 vs. 0.30 mg/dL, p = 0.957). Thirty-day mortality was similar between genders. RRT was not used more often in women (19 vs. 12%, p = 0.050), and women were 1.8 times more likely than men to receive RRT at the same creatinine (p = 0.028). Both peak and delta creatinine significantly predicted 6-month overall and transplant-free survival (p < 0.0001), but the probability of liver transplantation was affected by the interaction between gender and both peak and delta creatinine. Infected hospitalized cirrhotic women are significantly more likely than men to receive RRT at similar creatinine levels. Gender-specific differences in baseline, peak, and delta creatinine need further investigation to determine whether women need acute kidney injury treatment at lower creatinine thresholds than men.

Urinary level of nickel and acute leukaemia in Chinese children.

PubMed

Yang, Y; Jin, X M; Yan, C H; Tian, Y; Tang, J Y; Shen, X M

2008-10-01

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage but might also be a risk factor for many diseases including cancer. Metal exposure may play an important role in oxidative DNA damage among children. However, few studies on urinary 8-OHdG and metals have been conducted in children with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in 116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/- 76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/- 124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36 ng/mg creatinine) was significantly elevated compared with controls (11.92 +/- 15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and urinary Ni showed a weak but significant association with increased risk of childhood leukaemia. The present study suggests that Ni may be an etiologic factor for childhood acute leukaemia by oxidative DNA damage.

Assessment of 1H NMR-based metabolomics analysis for normalization of urinary metals against creatinine.

PubMed

Cassiède, Marc; Nair, Sindhu; Dueck, Meghan; Mino, James; McKay, Ryan; Mercier, Pascal; Quémerais, Bernadette; Lacy, Paige

2017-01-01

Proton nuclear magnetic resonance ( 1 H NMR, or NMR) spectroscopy and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for metabolomics and metal analysis in urine samples. However, creatinine quantification by NMR for the purpose of normalization of urinary metals has not been validated. We assessed the validity of using NMR analysis for creatinine quantification in human urine samples in order to allow normalization of urinary metal concentrations. NMR and ICP-MS techniques were used to measure metabolite and metal concentrations in urine samples from 10 healthy subjects. For metabolite analysis, two magnetic field strengths (600 and 700MHz) were utilized. In addition, creatinine concentrations were determined by using the Jaffe method. Creatinine levels were strongly correlated (R 2 =0.99) between NMR and Jaffe methods. The NMR spectra were deconvoluted with a target database containing 151 metabolites that are present in urine. A total of 50 metabolites showed good correlation (R 2 =0.7-1.0) at 600 and 700MHz. Metal concentrations determined after NMR-measured creatinine normalization were comparable to previous reports. NMR analysis provided robust urinary creatinine quantification, and was sufficient for normalization of urinary metal concentrations. We found that NMR-measured creatinine-normalized urinary metal concentrations in our control subjects were similar to general population levels in Canada and the United Kingdom. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective but Non-Synergistic Effects of Nigella Sativa and Vitamin E against Cisplatin-Induced Renal Toxicity and Oxidative Stress in Wistar Rats.

PubMed

Busari, Abdulwasiu A; Adejare, Abdullahi A; Shodipe, Abiodun F; Oduniyi, Oludaisi A; Ismail-Badmus, Khadijah B; Oreagba, Ibrahim A

2018-06-26

Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress. 48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis. Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects. These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative. © Georg Thieme Verlag KG Stuttgart · New York.

Levels of 1-hydroxypyrene in urine of people living in an oil producing region of the Andean Amazon (Ecuador and Peru).

PubMed

Webb, Jena; Coomes, Oliver T; Mergler, Donna; Ross, Nancy A

2018-01-01

Polycyclic aromatic hydrocarbons (PAHs) are contaminants with carcinogenic effects but little is known about their presence in environments surrounding oil drilling operations and spills or exposure levels in nearby communities. The objective of this study was to characterize PAH levels in people living near oil drilling operations in relation to fish consumption, occupation, source of water and other socio-demographic characteristics. This pilot study examined PAH exposure by measuring 1-hydroxypyrene (1-OHP) in urine samples using high-performance liquid chromatography and fluorescence detection from 75 women and men in the Ecuadorian and Peruvian Amazon living near oil drilling operations and who answered a questionnaire collecting socio-demographic, occupational and dietary information. Data were analyzed using multiple linear regression models. The mean value of 1-OHP was 0.40 μmol/mol creatinine, 95% CI 0.32-0.46 μmol/mol creatinine. Women who used water from a surface source (for washing clothes or bathing) had almost twice the amount of 1-OHP in their urine (mean 1-OHP = 0.41 μmol/mol creatinine, 95% CI 0.28-0.54 μmol/mol creatinine, n = 23) as women who used water from either a well, a spring or rain (mean 1-OHP = 0.22 μmol/mol creatinine, 95% CI 0.11-0.34 μmol/mol creatinine, n = 6). Men who reported eating a bottom-dwelling species as their most commonly consumed fish (mean 1-OHP = 0.50 μmol/mol creatinine, 95% CI 0.36-0.64 μmol/mol creatinine, n = 31) had twice as much 1-OHP in their urine as men who reported a pelagic fish (mean 1-OHP = 0.25 μmol/mol creatinine, 95% CI 0.15-0.35 μmol/mol creatinine, n = 15), signaling either oral (fish consumption) or dermal (while standing in water fishing benthic species) exposure. More contact with surface water and benthic fish may result in higher levels of 1-OHP in human urine among the study population. Reducing the amount of oil and wastes entering the waterways in Andean Amazonia would be one way to reduce exposure.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

Cardiac troponin increases among marathon runners in the Perth Marathon: the Troponin in Marathons (TRIM) study.

PubMed

Hubble, Kelley M; Fatovich, Daniel M; Grasko, Jonathon M; Vasikaran, Samuel D

2009-01-19

To determine the prevalence of elevated troponin levels after a marathon, and test for an association with reduced renal clearance. Prospective observational study of entrants running the full (42 km) 2007 Perth Marathon, Western Australia. Elevated troponin levels (> or = 0.1 microg/L) after the race; pre- and post-race survey data, and biochemical parameters. 27% of runners (92/346) enrolled in the study, of whom 88 (96%) completed it. Most were men (71%; 65/92); mean age was 43.1 years (SD, 9.8 years; range, 25-64 years) and mean body mass index (BMI) was 24.1 kg/m(2). Raised troponin levels were seen in 32% of participants (28/88), the highest being 1.4 microg/L. The strongest predictor for developing elevated troponin levels was a decrease in weight (odds ratio [OR], 2.15; 95% CI, 1.27-3.65). Creatinine increase was also associated with elevated troponin levels (OR, 1.03; 95% CI, 1.01-1.06), but pre-race estimated glomerular filtration rate, age, sex, BMI, training factors, marathon experience and race time were not. Most runners (99%; 87/88) had elevated levels of ischaemia-modified albumin after the race. Troponin level increases were common among marathon finishers. The strongest predictors were weight loss and an increase in creatinine levels, suggesting that reduced renal clearance is an associated factor. Further study is needed to determine the clinical significance of these findings, and to understand the mechanism.

Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

PubMed Central

Sudjarwo, Sri Agus; Eraiko, Koerniasari; Sudjarwo, Giftania Wardani; Koerniasari

2017-01-01

Objective(s): In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats. PMID:29299200

Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study.

PubMed

Schmidt, Morten; Mansfield, Kathryn E; Bhaskaran, Krishnan; Nitsch, Dorothea; Sørensen, Henrik Toft; Smeeth, Liam; Tomlinson, Laurie A

2017-03-09

Objective  To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment. Design  Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics. Setting  UK primary care, 1997-2014. Participants  Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363). Main outcome measures  Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs. Results  Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (<10%, 10-19%, 20-29%, 30-39%, and ≥40%) showed a graduated relation for all outcomes (all P values for trends <0.001). Notably, creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using <10% as reference). Results were consistent across calendar periods, across subgroups of patients, and among continuing users. Conclusions  Increases in creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial

PubMed Central

Nadkarni, Girish N.; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A.; Shah, Sudhir V.; Simonson, Michael S.; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R.

2016-01-01

Background and objectives Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. Design, setting, participants, & measurements We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m2), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Results Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Conclusions Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. PMID:27189318

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

PubMed

Nadkarni, Girish N; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A; Shah, Sudhir V; Simonson, Michael S; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R; Coca, Steven G

2016-08-08

Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. Copyright © 2016 by the American Society of Nephrology.

Reduction of Slit Diaphragm-associated Molecules by Sirolimus: Is it Enough to Induce Proteinuria?

PubMed

Kim, B S; Lee, J G; Cho, Y; Song, S H; Huh, K H; Kim, M S; Kim, Y S

2017-06-01

Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer. The mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the SRL-treated mice, but serum creatinine levels were found to increase dose-dependently and were significantly higher in the animals treated with 30 mg/kg of SRL than in untreated controls. Glomerular mRNA expression profiling showed down-regulations of podocyte-related genes (Wilms tumor 1, synaptopodin, nephrin, CD2-associated protein, and podocin) and of transforming growth factor-beta (a marker of fibrosis) in sirolimus-treated mice. In addition, expressions of the antiapoptotic genes Bcl-2 and Bcl-xL were also down-regulated. Furthermore, the protein levels of these genes in mice kidney were also decreased by sirolimus. Although sirolimus treatment reduced the expressions of slit diaphragm-associated molecules and increased serum creatinine levels, it failed to induce proteinuria. Our findings indicate that proteinuria is not induced by isolated SRL treatment. Further studies are required to identify conditions in which sirolimus induces proteinuria. Copyright © 2017 Elsevier Inc. All rights reserved.

Nephrology consultations incorporated into HIV care - non-compliance is an important issue.

PubMed

Matłosz, Bartłomiej; Firląg-Burkacka, Ewa; Horban, Andrzej; Kowalska, Justyna D

2017-02-01

Although infrequent, kidney disease is a potentially serious co-morbidity among human immunodeficiency virus (HIV)-infected patients. The spectrum of renal impairment is very wide from clinically insignificant to end stage renal disease and often requires nephrologist's consultation. Therefore, we established combined renal and HIV care in the HIV Out-Patient Clinic in Warsaw. Medical records of patients consulted by nephrologist from March 2014 to March 2015 were included in analyses. Patients changing medication without consulting the physician or persistently not coming for follow-up visits were defined as non-compliant. In statistical analyses, non-parametric tests and logistic regression models were used as appropriate. In total, 100 patients were consulted by a nephrologist during the study period. All patients were white Europeans, 88 (88%) male, 42 (42%) infected through men having sex with men and 16 (16%) through intravenous drug users. Fifteen (15%) patients had hepatitis C virus (HCV) infections and 11 (11%) confirmed with positive HCV RNA. The most common reasons for referral were proteinuria and increased serum creatinine. In 6 out of 31 patients (19.3% of those referred for increased creatinine level) elevated serum creatinine was due to illegal substances or diet supplements use. Fifty-seven (57%) of patients were non-compliant. In univariate logistic regression models, all tested factors were non-significant. In most cases, patients were referred to nephrologist due to possible link between laboratory abnormalities and antiretroviral treatment. In one out of five cases, elevated creatinine level was linked with substance/dietary abuse. Poor compliance is an important problem in integrated nephrological care, however we were not able to identify any factors associated with non-compliance.

Mineral water administration may increase kidney elimination of urea, creatinine and folic acid in a concentration-dependent fashion.

PubMed

Calomino, Francesco; Di Paolo, Nicola; Nicolai, Giulia; Miglio, Antonio

2010-05-01

In a previous experimental study we showed that the administration of a large water load in a short time increases the urinary flow and the transport capacity in the excretory tract of the rabbit ureter. In human subjects drinking a water load of 25 ml/kg(BW) in 30 minutes, diuresis, creatinine and urea clearance increase more than in those drinking the same load in 24 hours. The aim of the present study was to investigate possible correlations between percent reduction and baseline values of serum urea, creatinine, folic acid, and magnesium in humans. 20 volunteers were divided in two groups. Subjects in group 1 received a water load of 25 ml/kg(BW) in 24 hours followed by the same load in 30 minutes. Subjects in group 2 received the same water load but in inverse order. Before and after each water administration, the following variables were measured and compared: diuresis, serum urea, creatinine, folic acid and magnesium concentration, and urea and creatinine clearance. Serum urea and folic acid concentration decreased up to 40% after administration of the water load in 24 hours. Serum creatinine concentration decreased up to 20% after administration of the water load in 30 minutes. The concentration drop of these metabolites increased with increasing baseline metabolite concentrations.

Efficacy of lycopene on modulation of renal antioxidant enzymes, ACE and ACE gene expression in hyperlipidaemic rats.

PubMed

Khan, Nazish Iqbal; Noori, Shafaq; Mahboob, Tabassum

2016-07-01

We aimed to evaluate the efficacy of lycopene on renal tissue antioxidant enzymes and angiotensin converting enzyme (ACE) gene expression and serum activity in diet-induced hyperlipidaemia. Thirty-two female Wistar albino rats (200-250 g weight), 5-6 months of age, were randomly selected and divided into four groups. Group I received normal diet; group II received 24 g high fat diet/100 g of daily diet; group III received 24 g high fat diet/100 g daily diet and 200 ml of lycopene extract (twice a week) for 8 weeks; and group IV received 200 ml oral lycopene extract twice a week for 8 weeks. A marked increase was observed in plasma urea and creatinine levels, serum C-reactive protein, kidney weight, tissue renal malonyldialdehyde level, ACE gene expression and serum level, while a decrease catalase level among hyperlipidaemic rats was observed. Histologically, interstitial inflammation and proliferation was seen. Lycopene supplementation significantly decreased plasma urea and creatinine, serum ACE, renal tissue malonyldialdehyde level and C-reactive protein level, while it increased tissue antioxidant enzymes level and total protein. Tissue inflammation and proliferation was improved. This finding suggests that supplementation of lycopene is effective for renal antioxidant enzymes, ACE gene expression and ACE serum level in hyperlipidaemic rats. © The Author(s) 2016.

A determination of the current causes of hyperkalaemia and whether they have changed over the past 25 years.

PubMed

Muschart, X; Boulouffe, C; Jamart, J; Nougon, G; Gérard, V; de Cannière, L; Vanpee, D

2014-08-01

Hyperkalaemia is a potentially lethal electrolyte disorder. The objective of this study was to determine if the causes of hyperkalaemia-related visits to the emergency department (ED) have changed since 25 years. All patients presenting to the ED with hyperkalaemia between January 2009 and August 2011 were included in this retrospective, single-centre study. Patients were divided into one of these three categories: mild (5·2≤ K(+)<5·8 mEq/l), moderate (5·8≤K(+)<7·0 mEq/l) or severe hyperkalaemia (K(+)≥7·0 mEq/l). The causes of hyperkalaemia were divided into three groups: renal failure (RF), potassium-increasing drugs (PIDs) or others. Overall, 139 patients with hyperkalaemia were included in the study (mean K(+) of 6·2 mEq/l): 35% with mild, 49% with moderate and 16% with severe hyperkalaemia. Eighty-three per cent of patients (n = 115) had RF with creatinine levels ≥1·25 mg/dl or estimated glomerular filtration rate (eGFR) levels ≤60 ml/min/1·73 m(2). Serum potassium levels were significantly related with creatinine and eGFR values (P<0·001). The severity of hyperkalaemia was significantly related with creatinine levels ≥1·25 mg/dl (P = 0·002) and eGFR values ≤60 ml/min/1·73 m(2) (P = 0·005). Seventy-five per cent of patients (n = 105) were taking PIDs. Potassium levels were significantly related with PIDs (P<0·001), in particularly spironolactone (P = 0·001) and angiotensin-converting enzyme inhibitors (P = 0·008). The category 'others' included 7% of patients (n = 10). RF (83%) and PIDs (75%) remain common causes of hyperkalaemia. Hyperkalaemia is significantly related with four variables: creatinine levels, spironolactone, ACEIs and beta-blocker intake. The causes of hyperkalaemia have not changed in recent years.

Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population.

PubMed

Søeby, Karen; Jensen, Peter Bjødstrup; Werge, Thomas; Sørensen, Steen

2015-09-01

The knowledge of physiological fluctuation and variation of even commonly used biochemical quantities in extreme age groups and during development is sparse. This challenges the clinical interpretation and utility of laboratory tests in these age groups. To explore the utility of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing creatinine levels. Creatinine shows great age dependence from birth throughout childhood. We computed and replicated 95% reference intervals in narrow gender and age bins and showed them to be comparable to those determined in healthy population studies. We identified pronounced transitions in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals.

[New topics regarding equations for GFR estimation based on serum creatinine and cystatin C].

PubMed

Horio, Masaru

2014-02-01

Japanese GFR equations and CKD-EPI equations based on standardized serum creatinine and standardized cystatin C are recommended in recent Japanese CKD guides and KDIGO guidelines for CKD management, respectively. CKD-EPIcreat overestimates GFR in Japanese subjects, probably due to the difference in muscle mass between Japanese and Caucasians. Unlike CKD-EPIcreat, CKD-EPIcys performs well in Japanese subjects, indicating the advantages of using cystatin C as a GFR marker. KDIGO guidelines suggest measuring eGFRcys in adults with eGFRcreat of 45-59 ml/min/1.73 m2 who do not have markers of kidney damage if confirmation of CKD is required. Creatinine is excreted by glomerular filtration, but also secreted by the tubules. Alteration of the tubular secretion of creatinine may influence the performance of GFR equations based on serum creatinine. Multivariate analysis showed that GFR and serum albumin levels were independent parameters affecting the fractional excretion of creatinine (FE-Cr). Alteration of FE-Cr according to the serum albumin levels may be one of the reasons for the bias of GFR equations based on serum creatinine. Low GFR is a risk factor for all-cause and cardiovascular mortality in a general population. However, the relationship between eGFR and the hazard risk of events is different depending on whether cystatin C or creatinine is used to calculate eGFR. The association between eGFRcys and the hazard risk is much stronger compared with eGFRcreat. Cystatin C may be a useful alternative to creatinine for detecting a high risk of complications in a general population and subjects with CKD.

Results of kidney transplantation from high-terminal creatinine donors and the role of time-zero biopsy.

PubMed

Lin, N C; Yang, A H; King, K L; Wu, T H; Yang, W C; Loong, C C

2010-11-01

Deceased-donor kidney transplantation (DDKT) from high-terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times (P = .011) but a higher incidence of delayed graft function after transplantation (P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. With a time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of urinary S100B protein level and lactate/creatinine ratio for early diagnosis and prognostic prediction of neonatal hypoxic-ischemic encephalopathy.

PubMed

Liu, Li; Zheng, Chong-Xun; Peng, Shu-Feng; Zhou, Hong-Yan; Su, Zu-You; He, Li; Ai, Ting

2010-01-01

Early identification and prevention of hypoxic-ischemic encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological dysfunction. To analyze the diagnostic and prognostic values of urinary S100B level and lactate/creatinine ratio in newborns with HIE. Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled. The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental Screening Test were scored. The concentration of urinary S100B protein was determined using the S100B enzyme-linked immunosorbent assay and the levels of urinary lactate and creatinine were measured with the enzyme colorimetric method. Urinary S100B level on days 1-3 after birth and lactate/creatinine ratio on day 1 were significantly higher in newborns with HIE than those in the control group. Both indexes were positively correlated with the clinical grading of HIE. A cutoff value for the S100B level of 0.47 microg/l on day 3 after birth had a sensitivity of 90% and specificity of 92% for prediction of HIE. A lactate/creatinine ratio of more than 0.55 on day 1 showed the highest sensitivity (92%) and specificity (90%). A combination of both indexes improved the sensitivity and specificity to 99 and 97%, respectively. A negative correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1-3 after birth with the NBNA score was identified on days 3, 7 and 14 after birth. The Developmental Screening Test score of 36 newborns with HIE within 6 months after birth showed that 65% of infants with moderate and high HIE had an abnormal developmental quotient. These data suggest that early measurement of both S100B level and lactate/creatinine ratio in the urine of newborns with HIE is a practical convenient and sensitive way to improve diagnosis on the third day of life and prognostic prediction of HIE. Copyright 2009 S. Karger AG, Basel.

Renal function in urinary schistosomiasis in the Natal Province of South Africa.

PubMed

Coopan, R M; Naidoo, K; Jialal, I

1987-11-01

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.

The relationship between transient and persistent worsening renal function and mortality in patients with acute decompensated heart failure.

PubMed

Aronson, Doron; Burger, Andrew J

2010-07-01

Worsening renal function (WRF) is an ominous complication in patients with acute heart failure syndrome (AHFS). Few data are available with regard to the clinical implications of transient versus persistent WRF in this setting. We studied 467 patients with AHFS and creatinine measurements at baseline and on days 2, 5, 14, and 30. WRF (>/= 0.5 mg/dL increase in serum creatinine above baseline at any time point) was defined as persistent when serum creatinine remained >/= 0.5 mg/dL above baseline throughout day 30, and transient when creatinine levels subsequently decreased to < 0.5 mg/dL above baseline. WRF occurred in 115 patients, and was transient in 39 patients (33.9%). The 6-month mortality rates were 17.3%, 20.5%, and 46.1% in patients without WRF, transient WRF, and persistent WRF, respectively. In a multivariable Cox model, compared with patients with stable renal function, the adjusted hazard ratio for mortality was 0.8 (95% CI 0.4-1.7; P = .58) in patients with transient WRF and 3.2 (95% CI 2.1-5.0; P < .0001) in patients with persistent WRF. Transient WRF is frequent among patients with AHFS. Whereas persistent WRF portends increased mortality, transient WRF appears to be associated with a better outcome as compared with persistent renal failure. Copyright 2010 Elsevier Inc. All rights reserved.

Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer.

PubMed

Arikan, Ozgur; Yýldýrým, Asýf; Ýsbilen, Banu; Canakci, Cengiz; Atýs, Gokhan; Gurbuz, Cenk; Erol, Bulent; Ýsman, Ferruh Kemal; Ozkanli, Seyma; Caskurlu, Turhan

2015-01-01

We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine.

PubMed

Cappuccio, Francesco P; Buchanan, Laura A; Ji, Chen; Siani, Alfonso; Miller, Michelle A

2016-08-26

High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. Oral potassium supplementation. Serum or plasma potassium and serum or plasma creatinine. A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10(-5)), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10(-5). Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI -1.19 to 1.78, p=0.70). In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chlorpyrifos exposure in farmers and urban adults: Metabolic characteristic, exposure estimation, and potential effect of oxidative damage.

PubMed

Wang, Lei; Liu, Zhen; Zhang, Junjie; Wu, Yinghong; Sun, Hongwen

2016-08-01

Chlorpyrifos is a widely used organophosphorus pesticide that efficiently protects crops against pests. However, recent studies suggest that severe exposure to chlorpyrifos may present adverse health effects in human. To analyze the exposure level and metabolic characteristics of chlorpyrifos pesticide in urban adults and farmers with/without occupation pesticide contact, the occurrence of urinary chlorpyrifos and methyl chlorpyrifos (CP-me), as well as their metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), was determined in farmers of an agricultural village in China, and in urban adults of a nearby town. The geometric mean (GM) concentrations of TCPy, which is the major marker of chlorpyrifos exposure, were 4.29 and 7.57μg/g-creatinine in urban adults and farmers before pesticide application, respectively. Chlorpyrifos spraying significantly increased the concentrations of urinary TCPy. In the first day after spraying, a GM concentration of 43.7μg/g-creatinine was detected in the urine specimens from farmers, which decreased to 38.1 and 22.8μg/g-creatinine in the second and third day after chlorpyrifos spraying. The ratio of TCPy and its parent compounds, i.e. chlorpyrifos and CP-me, was positively associated with the sum concentration of urinary chlorpyrifos, CP-me, and TCPy, suggesting the increasing metabolic efficiency of chlorpyrifos to TCPy at higher chlorpyrifos exposure levels. To estimate the farmers' occupational exposure to chlorpyrifos pesticide, a new model based on the fitted first-order elimination kinetics of TCPy was established. Occupational chlorpyrifos exposure in a farmer was estimated to be 3.70μg/kg-bw/day (GM), which is an exposure level that is higher than the recommended guideline levels. Significant increase of urinary 8-hydroxydeoxyguanosine (8-OHdG) was observed on the first day after chlorpyrifos spraying, which indicates a potential oxidative damage in farmers. However, urinary 8-OHdG returned to its baseline level within two days. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Effects of Low-Flow Sevoflurane and Low-Flow Desflurane Anaesthesia on Renal Functions Using Cystatin C

PubMed Central

Duymaz, Gökçen; Yağar, Seyhan; Özgök, Ayşegül

2017-01-01

Objective Numerous studies have indicated nephrotoxic effects of sevoflurane because of its two bioproducts compound A and fluoride. Cystatin C (CyC) is a more sensitive biomarker than creatinine to show early and mild changes in kidney function. We designed this prospective randomised study to compare the effects of low-flow sevoflurane anaesthesia and low-flow desflurane anaesthesia on renal functions based on CyC levels. No studies have evaluated the effects of low-flow sevoflurane anaesthesia on renal functions based on CyC levels to date. Methods Thirty American Society of Anesthesiologists (ASA) physical status I–II patients who were scheduled for urological procedures were enrolled in this study. The patients were randomly assigned to 2 groups: low-flow sevoflurane anaesthesia or low-flow desflurane anaesthesia. Serum urea, creatinine and CyC levels were measured before the operation, just before extubation and 24 h after the operation. Creatinine clearance was calculated in the first 24-h urine sample. Results There were no significant differences in serum urea, creatinine and CyC levels or 24 h creatinine clearance between the groups. Conclusion Our study demonstrates with a more sensitive biomarker, CyC, that low-flow sevoflurane anaesthesia is safe in terms of the effects on renal function. PMID:28439441

Serum creatinine role in predicting outcome after cardiac surgery beyond acute kidney injury

PubMed Central

Najafi, Mahdi

2014-01-01

Serum creatinine is still the most important determinant in the assessment of perioperative renal function and in the prediction of adverse outcome in cardiac surgery. Many biomarkers have been studied to date; still, there is no surrogate for serum creatinine measurement in clinical practice because it is feasible and inexpensive. High levels of serum creatinine and its equivalents have been the most important preoperative risk factor for postoperative renal injury. Moreover, creatinine is the mainstay in predicting risk models and risk factor reduction has enhanced its importance in outcome prediction. The future perspective is the development of new definitions and novel tools for the early diagnosis of acute kidney injury largely based on serum creatinine and a panel of novel biomarkers. PMID:25276301

Effect of Inhaling Cymbopogon martinii Essential Oil and Geraniol on Serum Biochemistry Parameters and Oxidative Stress in Rats.

PubMed

Andrade, Bruna Fernanda Murbach Teles; Braga, Camila Pereira; Dos Santos, Klinsmann Carolo; Barbosa, Lidiane Nunes; Rall, Vera Lúcia Mores; Sforcin, José Maurício; Fernandes, Ana Angélica Henrique; Fernandes Júnior, Ary

2014-01-01

The effects of the inhalation of Cymbopogon martinii essential oil (EO) and geraniol on Wistar rats were evaluated for biochemical parameters and hepatic oxidative stress. Wistar rats were divided into three groups (n = 8): G1 was control group, treated with saline solution; G2 received geraniol; and G3 received C. martinii EO by inhalation during 30 days. No significant differences were observed in glycemia and triacylglycerol levels; G2 and G3 decreased (P < 0.05) total cholesterol level. There were no differences in serum protein, urea, aspartate aminotransferase activity, and total hepatic protein. Creatinine levels increased in G2 but decreased in G3. Alanine aminotransferase activity and lipid hydroperoxide were higher in G2 than in G3. Catalase and superoxide dismutase activities were higher in G3. C. martinii EO and geraniol increased glutathione peroxidase. Oxidative stress caused by geraniol may have triggered some degree of hepatic toxicity, as verified by the increase in serum creatinine and alanine aminotransferase. Therefore, the beneficial effects of EO on oxidative stress can prevent the toxicity in the liver. This proves possible interactions between geraniol and numerous chemical compounds present in C. martinii EO.

Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin.

PubMed

Vaishnavi, Kalthi; Bansal, Deepak; Trehan, Amita; Jain, Richa; Attri, Savita Verma

2018-05-16

A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m 2 of MTX (24 hr infusion), respectively. Six doses of leucovorin (15 mg/m 2 /dose), instead of recommended three (for optimally reduced levels) at standard timing (42 hr from start of HD-MTX) were administered. Hydration (125 ml/m 2 /hr) was continued for 72 hr, instead of the recommended 30 hr. Hydration fluid consisted of 0.45% sodium chloride, 5% dextrose, 7.5% sodium bicarbonate (50 mmol/l) and potassium chloride (20 mmol/l). Serum creatinine and urine pH were measured at baseline, 24 and 48 hr. The volume of hydration was increased (200 ml/m 2 /hr) for a serum creatinine > 1.25 times the baseline. The study included 100 cycles of HD-MTX in 53 patients: B-ALL 25 patients (51 cycles), T-ALL 16 patients (28 cycles), T-NHL 10 patients (18 cycles), and relapsed ALL 2 patients (3 cycles). The mean age was 6.8 ± 3.2 years. Patients were underweight in 15 (15%) cycles. Patients in 23% of cycles had a rise in creatinine to >1.25 times the baseline. Toxicities (NCI CTCAE v4.0) included mucositis (32%), diarrhoea (10%), and febrile neutropenia (9%). One patient died from dengue shock syndrome. It is safe to administer 3 or 5 gm/m 2 of MTX (24 hr infusion) without measuring MTX levels, with extended hydration, additional doses of leucovorin, and monitoring of serum creatinine and urine pH. © 2018 Wiley Periodicals, Inc.

Effect of drug-induced hyperuricaemia on renal function in Nigerians with pulmonary tuberculosis.

PubMed

Adebisi, S A; Oluboyo, P O; Okesina, A B

2000-01-01

Some anti-tuberculosis chemotherapeutic agents have been established as causing hyperuricaemia. Hyperuricaemia in turn causes renal damage. This study therefore aims at establishing the effect of anti-tuberculosis drugs-induced hyperuricaemia on renal function of the patients. Fifty patients with newly diagnosed pulmonary tuberculosis with mean age of 36.8 years (SD 13.69) consisting of 14 females and 17 males were longitudinally studied each for 6 months to determine the effect of drug-induced hyperuricaemia on their renal function. The Biochemical indices determined included serum urate level, serum creatinine level, and creatinine clearance of newly diagnosed patient with tuberculosis, before and during treatment with anti-tuberculosis therapy. Serum urate level revealed that 16 (51.6%) and 15 (48.4%) of the patients were hyperuricaemic at the end of the first and second months of anti-tuberculosis therapy. There was no significant difference in the mean serum creatinine level of the control group 96 micromol/L when compared with both the pre-treat value 89 micromol/L (P > 0.25) as well as the value at the end of the sixth month of treatment 91 micromol/L (P > 0.40). However, there was a statistically significant difference in the mean creatinine clearance of the control group 102 ml/min/1.73 m2 when compared with the patient's mean pre-treatment value (89 ml/min/1.73 m2) P < 0.05. Also the mean creatinine clearance increased to (103 ml/min/1.73 m2) by the end of the 6th month of treatment, a value that is statistically significant when compared with the pretreatment value of (89 ml/min/1.73 m2) P < 0.05. We submit as follows: that pulmonary tuberculosis as a disease with significant impairment of renal function; despite the associated drug-induced hyperuricaemia recorded during the treatment, renal function steadily improved with the treatment of pulmonary tuberculosis to the extent that comparable values with control was obtained at the end of treatment. We conclude therefore that drug-induced hyperuricaemia associated with treatment of pulmonary tuberculosis has no detectable negative effect on renal function of the patient.

Correlation of cystatin C and creatinine based estimates of renal function in children with hydronephrosis.

PubMed

Momtaz, Hossein-Emad; Dehghan, Arash; Karimian, Mohammad

2016-01-01

The use of a simple and accurate glomerular filtration rate (GFR) estimating method aiming minute assessment of renal function can be of great clinical importance. This study aimed to determine the association of a GFR estimating by equation that includes only cystatin C (Gentian equation) to equation that include only creatinine (Schwartz equation) among children. A total of 31 children aged from 1 day to 5 years with the final diagnosis of unilateral or bilateral hydronephrosis referred to Besat hospital in Hamadan, between March 2010 and February 2011 were consecutively enrolled. Schwartz and Gentian equations were employed to determine GFR based on plasma creatinine and cystatin C levels, respectively. The proportion of GFR based on Schwartz equation was 70.19± 24.86 ml/min/1.73 m(2), while the level of this parameter based on Gentian method and using cystatin C was 86.97 ± 21.57 ml/min/1.73 m(2). The Pearson correlation coefficient analysis showed a strong direct association between the two levels of GFR measured by Schwartz equation based on serum creatinine level and Gentian method and using cystatin C (r = 0.594, P < 0.001). The linear association between GFR values measured with the two methods included cystatin C based GFR = 50.8+ 0.515 × Schwartz GFR. The correlation between GFR values measured by using serum creatinine and serum cystatin C measurements remained meaningful even after adjustment for patients' gender and age (r = 0.724, P < 0.001). The equation developed based on cystatin C level is comparable with another equation, based on serum creatinine (Schwartz formula) to estimate GFR in children.

Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity.

PubMed

Schroeder, Mariana; Shbiro, Liat; Gelber, Vered; Weller, Aron

2010-04-01

Given the alarming increase in childhood, adolescent and adult obesity there is an imperative need for understanding the early factors affecting obesity and for treatments that may help prevent or at least moderate it. Exercise is frequently considered as an effective treatment for obesity however the empirical literature includes many conflicting findings. In the present study, we used the OLETF rat model of early-onset hyperphagia-induced obesity to examine the influence of early exercise on peripheral adiposity-related parameters in both males and females. Rats were provided voluntary access to running wheels from postnatal day (PND) 22 until PND45. We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and leptin, adiponectin, corticosterone and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake. Early voluntary exercise reduced intake, adiposity and leptin in the OLETF males following a sharp reduction in adipocyte size despite a significant increase in fat cell number. Exercising males from the lean LETO control strain presented stable intake, but reduced body fat, feeding efficiency and increased plasma creatinine, suggesting an increment in muscle mass. OLETF females showed reduced feeding efficiency and liver fat, and a significant increase in brown fat. Exercising LETO control females increased intake, body weight and creatinine, but no changes in body fat. Overall, OLETF rats presented higher adiponectin levels than controls in both basal and post-exercise conditions. The results suggest an effective early time frame, when OLETF males can be successfully "re-programmed" through voluntary exercise; in OLETF females the effect is much more moderate. Findings expose sex-dependent peripheral mechanisms in coping with energy challenges. Copyright 2010 Elsevier Inc. All rights reserved.

Creatinine plasma at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at primary health care in Binjai city, Indonesia

NASA Astrophysics Data System (ADS)

Rusdiana; Savira, M.; Syahputra, M.; Santoso, A.

2018-03-01

The aim of the study knowing the comparison creatinine plasma levels at uncontrolled type 2 diabetes mellitus and controlled type 2 diabetes mellitus patients at Primary Health Care in Binjai city of North Sumatera in Indonesia. This cross-sectional study was conductedon 40 type 2 Diabetes Mellitus patients who attended Primary Health Care in Binjai. Patients with age > 40 years old, (both sexes) were included in the study. We recorded different demographic parameter as age, Body Mass Index, Blood Pressure, and personal history status. And we examined the biochemicalparameters including Hba1c, Fasting Blood Sugar Levels (FBL) and creatinine serum. We separated into two groups base on HbA1c test, controlled type 2 diabetes mellitus and uncontrolled type 2 diabetes mellitus. We measured FBL by using the portable measuring instrument, and Thamrin clinical laboratory measured Hba1c, andwe measured creatinine plasmaby spectrophotometry in Biochemistry laboratory. With statistical analysis using T-test found that there was asignificant differencein creatinine plasma levels between uncontrolled type 2 diabetes mellitus with controlled type 2 diabetes mellitus (p<0.005).

Elevated serum creatinine and low albumin are associated with poor outcomes in patients with liposarcoma.

PubMed

Panotopoulos, Joannis; Posch, Florian; Funovics, Philipp T; Willegger, Madeleine; Scharrer, Anke; Lamm, Wolfgang; Brodowicz, Thomas; Windhager, Reinhard; Ay, Cihan

2016-03-01

Low serum albumin levels and impaired kidney function have been associated with decreased survival in patients with a variety of cancer types. In a retrospective cohort study, we analyzed 84 patients with liposarcoma treated at from May 1994 to October 2011. Uni- and multivariable Cox proportional hazard models and competing risk analyses were performed to evaluate the association between putative biomarkers with disease-specific and overall survival. The median age of the study population was 51.7 (range 19.6-83.8) years. In multivariable analysis adjusted for AJCC tumor stage, serum creatinine was highly associated with disease-specific survival (Subdistribution Hazard ratio (SHR) per 1 mg/dl increase = 2.94; 95%CI 1.39-6.23; p = 0.005). High albumin was associated with improved overall and disease-specific survival (Hazard Ratio (HR) per 10 units increase = 0.50; 95%CI 0.26-0.95; p = 0.033 and SHR = 0.64; 95%CI 0.42-1.00; p = 0.049). The serum albumin-creatinine-ratio emerged to be associated with both overall and disease-specific survival after adjusting for AJCC tumor stage (HR = 0.95; 95%CI 0.92-0.99; p = 0.011 and SHR = 0.96; 95%CI 0.93-0.99; p = 0.08). Our study provides evidence for a tumor-stage-independent association between higher creatinine and lower albumin with worse disease-specific survival. Low albumin and a high albumin-creatinine-ratio independently predict poor overall survival. Our work identified novel prognostic biomarkers for prognosis of patients with liposarcoma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial

PubMed Central

BRISCO, MEREDITH A.; ZILE, MICHAEL R.; HANBERG, JENNIFER S.; WILSON, F. PERRY; PARIKH, CHIRAG R.; COCA, STEVEN G.; TANG, W.H. WILSON; TESTANI, JEFFREY M.

2017-01-01

Background Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. Methods and Results We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67–0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77–1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57–4.03, P <.001). Conclusion The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. PMID:27374839

Long-term patterns of urinary pyroglutamic acid in healthy humans.

PubMed

Lord, Richard S

2016-02-01

An investigation of human biological variation in urinary organic acids, including pyroglutamic acid along with 39 other compounds, was previously reported in which levels were determined for 8 weeks in healthy adult subjects. Here, unique, 4-week-long physiological trends for one of those compounds, pyroglutamic acid (PGA), are reported. When PGA levels for an individual rose above 40 μg/mg creatinine, 4-week downward progressions occurred until levels reached values near 15 μg/mg creatinine and the pattern was reversed when levels for an individual were below that level in the early weeks of the study. The pattern was especially prominent among 8 of the 13 menstruating female subjects suggesting a possible association with metabolic stress of the menstrual cycle. However, it also appeared in 3 of the 8 male subjects where other sources of metabolic stress may be present. The menstrual association is consistent with estrogen-mediated increase in oxidative stress. Since PGA is linked to glutathione turnover, the consistency of extreme values across all individuals displaying the pattern indicates that 15 and 40 μg/mg creatinine may represent limits that trigger shifts in sulfur amino acid metabolism. This is the first observation of approximate month-long cyclic responses in a glutathione-related urinary marker in humans. © 2016 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

[Adsorbent effect of activated carbon on small molecular uremic toxin and its influence factors].

PubMed

Yang, Bo; Jiang, Yun-sheng; Li, Jun

2003-06-01

To analyze the adsorbent effect of activated carbon on uremic toxin and its influence factors. Uremic toxins (urea, creatinine and uric acid) were dissolved in the distilled water to obtain uremic toxic solution. Activated carbon was added to the solution, and the concentrations of uremic toxins were measured at different time spots. To determine the influence factors, some possible related materials, such as bile, amino acid, Ringer's, solution of glucose, HCl or NaOH respectively were added simultaneously. The concentrations of toxins in uremic toxic solution decreased 5 min after adding the activated carbon. The concentration of urea was the lowest at 30 min, but it increased after 50 min; while the concentrations of creatinine and uric acid reached the lowest level from 10 to 30 min after adding the activated carbon, and maintained at the same level after that. The bile, amino acid, electrolyte, glucose and pH value did not influence the adsorption of uric acid significantly, but they influenced the adsorption of urea and creatinine. Bile and amino acid influenced the concentration of urea remarkably, following glucose, NaOH and HCl. The effect of pH 2.0 solution on the creatinine concentration was the most significant, following glucose. Activated carbon has adsorptive effect on uremic toxins, but its adsorptive effect decreases as time goes on. Bile, glucose, amino acid, NaOH and HCl can affect the adsorptive effect of activated carbon on uremic toxins to some extent.

The Effect of Gestational and Lactational Age on the Human Milk Metabolome

PubMed Central

Sundekilde, Ulrik K.; Downey, Eimear; O’Mahony, James A.; O’Shea, Carol-Anne; Ryan, C. Anthony; Kelly, Alan L.; Bertram, Hanne C.

2016-01-01

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by nuclear magnetic resonance (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5–7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery. PMID:27213440

The Effect of Gestational and Lactational Age on the Human Milk Metabolome.

PubMed

Sundekilde, Ulrik K; Downey, Eimear; O'Mahony, James A; O'Shea, Carol-Anne; Ryan, C Anthony; Kelly, Alan L; Bertram, Hanne C

2016-05-19

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by nuclear magnetic resonance (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5-7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery.

Effect of chronic glomerulonephritis on the semen quality and cytokines in the semen of infertile males.

PubMed

Zhang, Huina; Ying, Yingfen; Chen, Yilu; Lu, Xiaosheng; Huang, Yonggang

2017-01-01

The effects of chronic glomerulonephritis (CGN) on semen quality and cytokine levels in the semen of infertile males remain undetermined. Fifty-eight semen samples from normal males and CGN males with and without infertility, respectively, were analyzed. Semen volume, semen pH, sperm density, percentage of forward movement of sperm, sperm activate rate, sperm survival rate, and rate of normal sperm morphology of infertility males with CGN were significantly lower than those of CGN males without infertility and normal males (P<.05). In addition, the blood urea nitrogen and serum creatinine levels and interleukin (IL)-17 and IL-18 levels in infertility males with CGN were significantly higher than those of CGN males without infertility and normal males (P<.05). CGN increased the blood urea nitrogen and serum creatinine levels, which induced abnormal expression of IL-17 and IL-18, and negatively affected male semen quality and might result in male infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rasburicase improves hyperuricemia in patients with acute kidney injury secondary to rhabdomyolysis caused by ecstasy intoxication and exertional heat stroke.

PubMed

Lin, Pei-Yi; Lin, Chun-Chen; Liu, Hsi-Che; Lee, Ming-Dar; Lee, Hung-Chang; Ho, Che-Sheng; Chiu, Nan-Chang; Peng, Chun-Chih; Huang, Fu-Yuan; Tsai, Jeng-Daw

2011-11-01

To report the successful use of rasburicase in two children with hyperuricemia secondary to severe rhabdomyolysis. : Case report. Pediatric intensive care unit in a freestanding quaternary hospital. Two pediatric patients with severe rhabdomyolysis and hyperuricemia caused by ecstasy intoxication and exertional heat stroke. Use of a single low dose (6 mg) of rasburicase, a urate oxidase enzyme. Rasburicase was administered on the first and second hospital days with a single low dose of 6 mg (0.086 mg/kg in patient A and 0.092 mg/kg in patient B). Within 24 hrs, the levels of serum uric acid in both patients decreased dramatically, and their creatinine levels decreased and urine output increased concurrently. Continuous improvements in the uric acid levels, creatinine levels, and urine output were noted during hospitalization. Rasburicase seems to be a safe and effective drug for improving hyperuricemia in patients with rhabdomyolysis and renal failure.

Prevalence and risk factors for diabetic retinopathy in 17 152 patients from the island of Funen, Denmark.

PubMed

Larsen, Morten B; Henriksen, Jan Erik; Grauslund, Jakob; Peto, Tunde

2017-12-01

This study aims to estimate the prevalence and risk factors of diabetic retinopathy (DR) in patients enrolled in a large Danish quality-assuring database for diabetes: the Funen Diabetes Database (FDDB). All patients with type 1 (T1DM) and type 2 DM (T2DM) diabetes mellitus (DM) were included in a cross-sectional study. The level of DR per patient was determined based on the eye with highest level of DR. All ocular and non-ocular data were extracted at the latest examination that corresponded to the most recent DR-grading data. Data from 17 152 patients were analysed; 83.1% had T2DM. Prevalence of DR was 23.8% (T1DM: 54.3%, T2DM: 21.2%). T1/T2DM patients were statistically significantly different regarding age, duration of diabetes, BMI, systolic blood pressure (BP), cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, s-creatinine and u-albumin (p < 0.001 for all). Increasing level of DR showed statistically significant association with age, duration of diabetes, systolic BP, HbA1c, s-creatinine and u-albumine with increasing level of DR (all are p < 0.001) both T1DM/T2DM patients. The patients in FDDB had good systemic control with median values of BP, serum lipids, cholesterol and HbA1c all close to or below national guidelines at the time of data extraction, but still a high level of DR was found in this cohort. DR was more common in patients with T1DM than T2DM, but as T2DM patients are more numerous, their level of DR despite acceptable control is still concerning. Most important associated factors for higher levels of DR were age, duration of diabetes, HbA1c, s-creatinine and u-albumine. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Energetics demands and physiological responses to boxing match and subsequent recovery.

PubMed

Nassib, Sabri; Hammoudi-Nassib, Sarra; Chtara, Mokhtar; Mkaouer, Bessem; Maaouia, Ghazwa; Bezrati-Benayed, Ikram; Chamari, Karim

2017-01-01

Determining the physiological profile of athletes in boxing match is important for defining aspects of physical performance that are important to competitive performance. Therefore, examination of the energy pathway of high-level boxers' athletes can be very helpful for optimizing training and then improving boxing physical fitness and performance. The aim of the present study was to assess the physiological and cardiovascular responses during boxing matches and subsequent recovery. Fifteen male international level boxers (mean age 19.56±3.6 years; mean body mass 72.46±11.86 kg; mean height 176.50±7.22 cm) participated in this study. Blood samples were drawn from the antecubital vein before and after the boxing matches (T1: pre-match rest measure around 11:00 a.m., T2: measure at 3 minutes of post-match recovery; T3: measure at 60 minutes of recovery; T4: measure at 24 hours post-match - the match started around 11:30 a.m.). An analysis of glucose, triglycerides, lactate, cholesterol, creatinine, uric-acid, high density lipoprotein, and low density lipoprotein concentrations was performed for each sample. Participants did perform a maximal incremental test to measure maximal heart rate (HRmax). Heart rate responses to the matches were measured and expressed in percentage of HRmax. The average HR recorded during the match corresponded to 93±3.26% of HRmax. The levels of glucose, lactate, and cholesterol increased significantly from T1 to T2. Likewise, creatinine levels increased significantly from T1 to T2 and T3. However, the cholesterol level decreased significantly at T3 in comparison with T1. Moreover, 24-hour post-match creatinine levels were significantly lower and triglyceride levels were significantly higher compared with T1. The main results of this study revealed that the boxing matches stress the lipid metabolism system during boxing and post-match (for at least 24 hours) even if it is widely recognized boxing being mainly composed of repeated short-duration anaerobic efforts.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

Biochemical monitoring after initiation of aldosterone antagonist therapy in users of renin-angiotensin system blockers: a UK primary care cohort study.

PubMed

Sinnott, Sarah-Jo; Mansfield, Kathryn E; Schmidt, Morten; Bhaskaran, Krishnan; Smeeth, Liam; Nitsch, Dorothea; Tomlinson, Laurie A

2017-11-16

To determine the frequency of biochemical monitoring after initiation of aldosterone antagonists(AA) in patients also using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB). UK primary care. ACEI/ARB users who initiated AA between 2004 and 2014. We calculated the proportions with: (1) biochemical monitoring ≤2 weeks post initiation of AA, (2) adverse biochemical values ≤2 months (potassium ≥6 mmol/L, creatinine ≥220 µmol/L and ≥30% increase in creatinine from baseline) and (3) discontinuers of AA in those with an adverse biochemical value. We used logistic regression to study patient characteristics associated with monitoring and adverse biochemical values. In 10 546 initiators of AA, 3291 (31.2%) had a record of biochemical monitoring ≤2 weeks post initiation. A total of 2.0% and 2.7% of those with follow-up monitoring within 2 months of initiation experienced potassium ≥6 mmol/L and creatinine ≥220 µmol/L, respectively, whereas 13.5% had a ≥30% increase in creatinine. Baseline potassium (OR 3.59, 95% CI 2.43 to 5.32 for 5.0-5.5 mmol/L compared with <5.0 mmol/L) and estimated glomerular filtration rate 45-59 ml/min/1.73 m 2 (OR 2.06, 95% CI 1.26 to 3.35 compared with ≥60 ml/min/1.73 m 2 ) were independently predictive of potassium ≥6 mmol/L. Women and people with diabetes had higher odds of ≥30% increase in creatinine. Less than one-third of patients taking ACEI/ARB had biochemical monitoring within 2 weeks of initiating AAs. Higher levels of monitoring may reduce adverse biochemical events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats.

PubMed

Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

2016-08-04

Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p < 0.05). Moreover, N-carbamylglutamate significantly increased the urine levels of creatinine, ethanol, indoxyl sulfate, lactate, methymalonate, acetoacetate, m-hydroxyphenylacetate, and sarcosine, and decreased the urine levels of acetamide, acetate, citrulline, creatine, glycine, hippurate, homogentisate, N-acetylglutamate, phenylacetyglycine, acetone, and p-hydroxyphenylacetate (p < 0.05). Results suggested that glutamine and N-carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats.

Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats

PubMed Central

Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

2016-01-01

Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution 1H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p < 0.05). Moreover, N-carbamylglutamate significantly increased the urine levels of creatinine, ethanol, indoxyl sulfate, lactate, methymalonate, acetoacetate, m-hydroxyphenylacetate, and sarcosine, and decreased the urine levels of acetamide, acetate, citrulline, creatine, glycine, hippurate, homogentisate, N-acetylglutamate, phenylacetyglycine, acetone, and p-hydroxyphenylacetate (p < 0.05). Results suggested that glutamine and N-carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats. PMID:27527211

Proximal tubular secretion of creatinine by organic cation transporter OCT2 in cancer patients.

PubMed

Ciarimboli, Giuliano; Lancaster, Cynthia S; Schlatter, Eberhard; Franke, Ryan M; Sprowl, Jason A; Pavenstädt, Hermann; Massmann, Vivian; Guckel, Denise; Mathijssen, Ron H J; Yang, Wenjian; Pui, Ching-Hon; Relling, Mary V; Herrmann, Edwin; Sparreboom, Alex

2012-02-15

Knowledge of transporters responsible for the renal secretion of creatinine is key to a proper interpretation of serum creatinine and/or creatinine clearance as markers of renal function in cancer patients receiving chemotherapeutic agents. Creatinine transport was studied in transfected HEK293 cells in vitro and in wild-type mice and age-matched organic cation transporter 1 and 2-deficient [Oct1/2(-/-)] mice ex vivo and in vivo. Clinical pharmacogenetic and transport inhibition studies were done in two separate cohorts of cancer patients. Compared with wild-type mice, creatinine clearance was significantly impaired in Oct1/2(-/-) mice. Furthermore, creatinine inhibited organic cation transport in freshly isolated proximal tubules from wild-type mice and humans, but not in those from Oct1/2(-/-) mice. In a genetic association analysis (n = 590), several polymorphisms around the OCT2/SLC22A2 gene locus, including rs2504954 (P = 0.000873), were significantly associated with age-adjusted creatinine levels. Furthermore, in cancer patients (n = 68), the OCT2 substrate cisplatin caused an acute elevation of serum creatinine (P = 0.0083), consistent with inhibition of an elimination pathway. Collectively, this study shows that OCT2 plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates, which impair the usefulness of creatinine as a marker of renal function. ©2012 AACR.

[Relationship between hyperuricemia and primary nephrotic syndrome in children].

PubMed

Xiao, Huijie; Li, Qian; Wang, Fang; Yao, Yong; Zhong, Xuhui

2014-11-01

To analyze the relationship between hyperuricemia and primary nephrotic syndrome in childhood. A retrospective study was carried out in 107 children with primary nephrotic syndrome. The clinical data were analyzed with statistical methods to identify the related factors with hyperuricemia. The morbidity of hyperuricemia in children with primary nephrotic syndrome was 45% (48/107). Compared to those in normal serum uric acid group, the incidence of hypertension (33%, 16/48), serum triglyceride [2.59(1.62-3.87) mmol/L], creatinine [43.85(33.38-56.38)mmol/L], urea [6.11(3.77-8.40)mmol/L] and blood uric acid/creatinine ratio [9.30(7.03-12.72)] increased while creatinine clearance rate [141.74(103.57-160.97)ml/(min·1.73 (2))] decreased in hyperuricemia group. Hyperuricemia in children with primary nephrotic syndrome correlated with the increase of serum creatinine, urea and blood uric acid/creatinine ratio, the decrease of creatinine clearance rate and the occurance of hypertension.

Feet swelling in a multistage ultraendurance triathlete: a case study

PubMed Central

Knechtle, Beat; Zingg, Matthias Alexander; Knechtle, Patrizia; Rosemann, Thomas; Rüst, Christoph Alexander

2015-01-01

Recent studies investigating ultraendurance athletes showed an association between excessive fluid intake and swelling of the lower limbs such as the feet. To date, this association has been investigated in single-stage ultraendurance races, but not in multistage ultraendurance races. In this case study, we investigated a potential association between fluid intake and feet swelling in a multistage ultraendurance race such as a Deca Iron ultratriathlon with ten Ironman triathlons within 10 consecutive days. A 49-year-old well-experienced ultratriathlete competed in autumn 2013 in the Deca Iron ultratriathlon held in Lonata del Garda, Italy, and finished the race as winner within 129:33 hours:minutes. Changes in body mass (including body fat and lean body mass), foot volume, total body water, and laboratory measurements were assessed. Food and fluid intake during rest and competing were recorded, and energy and fluid turnovers were estimated. During the ten stages, the volume of the feet increased, percentage body fat decreased, creatinine and urea levels increased, hematocrit and hemoglobin values decreased, and plasma [Na+] remained unchanged. The increase in foot volume was significantly and positively related to fluid intake during the stages. The poststage volume of the foot was related to poststage total body water, poststage creatinine, and poststage urea. This case report shows that the volume of the foot increased during the ten stages, and the increase in volume was significantly and positively related to fluid intake during the stages. Furthermore, the poststage volume of the foot was related to poststage total body water, poststage creatinine, and poststage urea. The continuous feet swelling during the race was most probably due to a combination of a high fluid intake and a progressive decline in renal function (ie, continuous increase in creatinine and urea), leading to body fluid retention (ie, increase in total body water). PMID:26508884

Effect of endovascular treatment on nitric oxide and renal function in Takayasu's arteritis with renovascular hypertension.

PubMed

Parildar, Zuhal; Gulter, Ceyda; Parildar, Mustafa; Oran, Ismail; Erdener, Dilek; Memis, Ahmet

2002-01-01

Renal involvement in Takayasu's arteritis (TA) effects the disease outcome and endovascular treatment is an effective treatment of choice. We investigated nitric oxide (NO) levels and the effect of endovascular treatment in renovascular hypertensive TA patients. In five hypertensive patients with renal artery stenosis due to TA, serum creatinine, nitrite, nitrate; urinary microalbumin, nitrite, nitrate measurements and blood pressures were recorded at entry and after 24 h and 6 weeks of endovascular treatment. Serum NO levels were higher in patients than controls (p = 0.008). Serum and urine NO levels increased 24 h after the treatment and decreased after 6 weeks (p = 0.015; p = 0.01, respectively). After the treatment blood pressures decreased. Urinary microalbumin excretions increased after the intervention (p = 0.02) and returned to normal in patients 1 and 4, and decreased in the others. There were no significant differences in estimated glomerular filtration rate (EGFR), serum creatinine, urinary sodium and potassium levels. Increased NO secretion in these patients may contribute to improve the prognosis of renal function through its vasodilator and antiproliferative activities possibly by counterbalancing the excessive vasoconstrictor actions. Endovascular treatment causes a dilatation-induced shear stress that may be responsible for the increased NO release, which in turn leads to the rapid hypotensive response. Copyright 2002 S. Karger AG, Basel

Clinical and prognostic value of spot urinary creatinine in chronic heart failure-An analysis from GISSI-HF.

PubMed

Ter Maaten, Jozine M; Maggioni, Aldo Pietro; Latini, Roberto; Masson, Serge; Tognoni, Gianni; Tavazzi, Luigi; Signorini, Stefano; Voors, Adriaan A; Damman, Kevin

2017-06-01

This study aimed to identify patient characteristics associated with low urinary creatinine in morning spot urine and investigate its association with clinical outcome. Twenty-four-hour creatinine excretion is an established marker of muscle mass in heart failure and other populations. Spot urine creatinine might be an easy obtainable, cheap marker of muscle wasting and prognosis in heart failure (HF) patients. Spot urine creatinine concentration was measured in 2130 patients included in the GISSI-HF trial. We evaluated the prognostic value of urinary creatinine and its relation with clinical variables. Median spot urinary creatinine was 0.80 (IQR 0.50-1.10) g/L. Lower spot urinary creatinine was associated with older age, smaller height and weight, higher NYHA class, worse renal function and more frequent spironolactone and diuretic use (all P<.02). During a median follow-up of 2.8 years, 655 patients (31%) experienced the combined endpoint of all-cause mortality or HF hospitalization. Lower urinary creatinine was independently associated with an increased risk of all-cause mortality or HF hospitalization (HR, 1.59 [1.21-2.08] per log decrease, P=.001), and all-cause mortality (HR, 1.75 [1.25-2.45] per log decrease, P=.001). Lower urinary creatinine, measured in morning spot urine in patients with chronic HF, is associated with worse renal function, smaller body size, more severe HF and is independently associated with an increased risk of all-cause death and HF hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreasing influenza impact in lodges: 1997-2000 Calgary Regional Health Authority.

PubMed

McLeod, L; Lau, W W

2001-01-01

Influenza causes high morbidity and hospitalization rates in residents of seniors lodges, I causing increased pressure on emergency departments and hospital beds every winter. This quasi-experimental study assessed the prevention of influenza outbreaks and their consequences in Calgary lodges. A multidisciplinary team worked to improve communication between health professionals, increase resident and staff immunization coverage, obtain weights and creatinines prior to influenza season, and facilitate amantadine prophylaxis during influenza A outbreaks. We had an increase in standing orders for amantadine and up to 56% of residents from one lodge had documented creatinine levels. Amantadine was administered to residents within two days of outbreak notification. Influenza morbidity in lodge outbreaks decreased from a rate of 37% to 9% over the three years and hospitalization rates decreased from 9% to 1%. We recommend that other regions consider a similar approach to decreasing influenza morbidity and hospitalization in lodge residents.

Increased levels of oxidative DNA damage attributable to cooking-oil fumes exposure among cooks.

PubMed

Ke, Yuebin; Cheng, Jinquan; Zhang, Zhicheng; Zhang, Renli; Zhang, Zhunzhen; Shuai, Zhihong; Wu, Tangchun

2009-07-01

Previous investigations have indicated that cooks are exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking-oil fumes. However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks. To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene(1-OHP), a biological marker for PAH exposure. Urine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36); all were male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 h prior to sampling was estimated from questionnaires. The urine samples were frozen for later analyses of 8-OHdG and 1-OHP levels by high-performance liquid chromatography. Excretion in urine of 8-OHdG was similar for controls (mean 1.2micromol/mol creatinine, n = 36), and for those who had been in the kitchen with an exhaust-hood operating (mean 1.5micromol/mol creatinine, n = 45). Cooks exposed to cooking-oil fumes without exhaust-hood operation had significantly increased excretion of 8-OHdG (mean 2.3micromol/mol creatinine, n = 18), compared with controls. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis. The results indicate that exposure to PAH or possibly other compounds in cooking-oil fumes may cause oxidative DNA damage.

Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation.

PubMed

Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

2017-01-01

Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days). Five days after the CP injection, rats were euthanized; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly increased serum levels of creatinine and urea. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CP treatment. Vit E successfully lowered serum levels of urea and creatinine, enhanced creatinine clearance and diuresis, and normalized relative kidney/body weight. Furthermore, Vit E successfully normalized renal MDA and nitrite concentrations, elevated GSH level, and restored CAT and SOD activities in renal tissues. Histopathological examination of rat kidney revealed that Vit E significantly mitigated CP-induced renal damage. Importantly, administration of Vit E reduced kidney total platinum concentration indicating a role of platinum renal accumulation on the ability of Vit E to protect against CP nephrotoxicity. © 2016 Wiley Periodicals, Inc.

New liquid chromatography-tandem mass spectrometry method for routine TDM of vancomycin in patients with both normal and impaired renal functions and comparison with results of polarization fluoroimmunoassay in light of varying creatinine concentrations.

PubMed

Brozmanová, Hana; Kacířová, Ivana; Uřinovská, Romana; Šištík, Pavel; Grundmann, Milan

2017-06-01

A new LC-MS/MS method with simple sample extraction and a relatively short period of vancomycin analysis for routine therapeutic drug monitoring was developed and validated. 50μL serum was precipitated using 20μL 33% trichloroacetic acid and 0.5mol/L NH 4 OH was added to increase pH before analysis. A RP BEH C18, 1.7μm, 2.1×50mm column maintained at 30°C and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results obtained with LC-MS/MS method were correlated with an FPIA assay (Abbott AxSYM) using mouse monoclonal antibody. Subjects were divided into three groups according to creatinine levels (53.5±19.1, 150.2±48.4, 471.7±124.7μmol/L) and Passing-Bablok regression analysis and Bland-Altman analysis were used to compare vancomycin concentrations. The results of subjects with both normal and higher creatinine levels correlated very well and the linear regression model equations were near ideal (LC-MS VAN =0.947×Abbott VAN +0.192 and LC-MS VAN =0.973×Abbott VAN -0.411 respectively). Dialyzed patients with the highest creatinine levels showed about 14% greater vancomycin concentration with the FPIA assay (LC-MS VAN =0.866×Abbott VAN +2.127). This overestimation probably due to the presence of the metabolite CDP ought not to be of clinical relevance owing to the wide range of recommended vancomycin concentration. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

PubMed

Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

2011-05-01

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood. Copyright © 2011 Elsevier Inc. All rights reserved.

Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

PubMed Central

2013-01-01

Introduction Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). Methods Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. Results The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. Conclusions Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least one hour following a large fluid bolus to avoid dilution. Unchanged plasma creatinine post cardiac arrest signifies renal injury and loss of function. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12610001012066. PMID:23327106

Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

PubMed

Karimzadeh, Iman; Khalili, Hossein

2016-06-06

Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

Methods for Quantitative Creatinine Determination.

PubMed

Moore, John F; Sharer, J Daniel

2017-04-06

Reliable measurement of creatinine is necessary to assess kidney function, and also to quantitate drug levels and diagnostic compounds in urine samples. The most commonly used methods are based on the Jaffe principal of alkaline creatinine-picric acid complex color formation. However, other compounds commonly found in serum and urine may interfere with Jaffe creatinine measurements. Therefore, many laboratories have made modifications to the basic method to remove or account for these interfering substances. This appendix will summarize the basic Jaffe method, as well as a modified, automated version. Also described is a high performance liquid chromatography (HPLC) method that separates creatinine from contaminants prior to direct quantification by UV absorption. Lastly, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described that uses stable isotope dilution to reliably quantify creatinine in any sample. This last approach has been recommended by experts in the field as a means to standardize all quantitative creatinine methods against an accepted reference. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Monodisperse, molecularly imprinted polymers for creatinine by modified precipitation polymerization and their applications to creatinine assays for human serum and urine.

PubMed

Miura, Chitose; Funaya, Noriko; Matsunaga, Hisami; Haginaka, Jun

2013-11-01

Molecularly imprinted polymers (MIPs) for creatinine were prepared by modified precipitation polymerization using methacrylic acid as a functional monomer and divinylbenzene as a crosslinker. The prepared MIPs were monodispersed with a narrow particle size distribution. Binding experiments and Scatchard analyses revealed that two classes of binding sites, high- and low-affinity sites, were formed on the MIPs. The retention and molecular-recognition properties of the MIPs were evaluated by hydrophilic interaction chromatography using a mixture of ammonium acetate buffer and acetonitrile as a mobile phase. With an increase of acetonitrile content, the retention factor of creatinine was increased on the MIP. In addition to shape recognition, hydrophilic interactions seemed to enhance the recognition of creatinine on the MIP. The MIPs' molecular-recognition ability was specific for creatinine; the structurally related compounds such as hydantoin, 1-methylhydantoin, 2-pyrrolidone, N-hydroxysuccinimide and creatine were not recognized. Furthermore, the creatinine concentrations in human serum and urine were successfully determined by direct injection of the deproteinized serum and diluted urine samples onto the MIP. Copyright © 2013 Elsevier B.V. All rights reserved.

How we estimate GFR--a pitfall of using a serum creatinine-based formula.

PubMed

Refaie, R; Moochhala, S H; Kanagasundaram, N S

2007-10-01

Chronic kidney disease (CKD) is defined using the estimated glomerular filtration rate (eGFR). This has led to a large increase in the diagnosis of CKD in the United Kingdom, the majority of which is in its earlier stages and is detected in non-hospital settings. It is important to be aware that eGFR calculations will reflect inaccuracies in the measured serum creatinine, as the latter is an important component of the calculation. We report a case in which a patient with high muscle-mass who had consumed large quantities of a creatine-containing nutritional supplement presented with apparently reduced renal function on the basis of the serum creatinine and therefore also the eGFR calculation (MDRD equation). Creatine is an amino acid which is a precursor of creatinine, and is known to transiently increase serum creatinine. 6 weeks after discontinuing creatine ingestion, serum creatinine had fallen but still gave rise to an apparently abnormal calculated eGFR. In fact, renal function was shown to be normal when estimated using 24-hour urinary creatinine clearance. This case demonstrates that the upper extreme of muscle mass and ingestion of creatine can affect not only serum creatinine but also the calculated eGFR. Knowledge of common confounding factors and their effects on serum creatinine and eGFR will allow appreciation of the limitations of these measures of renal function, and can prevent unnecessary over-investigation of such patients.

Fractional excretion of sodium

MedlinePlus

FE sodium; FENa ... a lab. There, they are examined for salt (sodium) and creatinine levels. Creatinine is a chemical waste ... Chernecky CC, Berger BJ. Excretion fraction of filtered sodium-blood and urine. In: Chernecky CC, Berger BJ, ...

Increasing the sensitivity of the Jaffe reaction for creatinine

NASA Technical Reports Server (NTRS)

Tom, H. Y.

1973-01-01

Study of analytical procedure has revealed that linearity of creatinine calibration curve can be extended by using 0.03 molar picric acid solution made up in 70 percent ethanol instead of water. Three to five times more creatinine concentration can be encompassed within linear portion of calibration curve.

A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.

PubMed

Duttaroy, Smita; Thorell, Daniel; Karlsson, Lena; Börjesson, Mats

2012-02-01

While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.

Association of urinary sodium/creatinine ratio with bone mineral density in postmenopausal women: KNHANES 2008-2011.

PubMed

Kim, Sung-Woo; Jeon, Jae-Han; Choi, Yeon-Kyung; Lee, Won-Kee; Hwang, In-Ryang; Kim, Jung-Guk; Lee, In-Kyu; Park, Keun-Gyu

2015-08-01

Accumulating evidence shows that high sodium chloride intake increases urinary calcium excretion and may be a risk factor for osteoporosis. However, the effect of oral sodium chloride intake on bone mineral density (BMD) and risk of osteoporosis has been inadequately researched. The aim of the present study was to determine whether urinary sodium excretion (reflecting oral sodium chloride intake) associates with BMD and prevalence of osteoporosis in postmenopausal women. This cross-sectional study involved a nationally representative sample consisting of 2,779 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys in 2008-2011. The association of urinary sodium/creatinine ratio with BMD and other osteoporosis risk factors was assessed. In addition, the prevalence of osteoporosis was assessed in four groups with different urinary sodium/creatinine ratios. Participants with osteoporosis had significantly higher urinary sodium/creatinine ratios than the participants without osteoporosis. After adjusting for multiple confounding factors, urinary sodium/creatinine ratio correlated inversely with lumbar spine BMD (P = 0.001). Similarly, when participants were divided into quartile groups according to urinary sodium/creatinine ratio, the average BMD dropped as the urinary sodium/creatinine ratio increased. Multiple logistic regression analysis revealed that compared to quartile 1, quartile 4 had a significantly increased prevalence of lumbar spine osteoporosis (odds ratios 1.346, P for trend = 0.044). High urinary sodium excretion was significantly associated with low BMD and high prevalence of osteoporosis in lumbar spine. These results suggest that high sodium chloride intake decreases lumbar spine BMD and increases the risk of osteoporosis in postmenopausal women.

Apparent renal disease due to elevated creatinine levels associated with the use of boldenone.

PubMed

Winnett, Georgia; Cranfield, Lesley; Almond, Michael

2011-02-01

The widespread use of reporting estimated glomerular filtration rate (eGFR) alongside serum creatinine has led to a heightened appreciation of renal disease. However, creatinine is recognized as an insensitive marker of true GFR and therefore can lead to misdiagnosis of renal dysfunction in the absence of true pathology. We report the case of a 37-year-old male referred due to abnormal eGFR and creatinine in the absence of clinical signs, symptoms or other biochemical abnormalities of renal disease. Subsequent investigations based on a high index of suspicion for exogenous substance abuse led to a novel observation of significantly raised creatinine due to the presence of boldenone, an equine anabolic steroid commonly abused in body building.

A role for the organic anion transporter OAT3 in renal creatinine secretion in mice

PubMed Central

Eraly, Satish A.; Rao, Satish Ramachandra; Gerasimova, Maria; Rose, Michael; Nagle, Megha; Anzai, Naohiko; Smith, Travis; Sharma, Kumar; Nigam, Sanjay K.; Rieg, Timo

2012-01-01

Tubular secretion of the organic cation, creatinine, limits its value as a marker of glomerular filtration rate (GFR) but the molecular determinants of this pathway are unclear. The organic anion transporters, OAT1 and OAT3, are expressed on the basolateral membrane of the proximal tubule and transport organic anions but also neutral compounds and cations. Here, we demonstrate specific uptake of creatinine into mouse mOat1- and mOat3-microinjected Xenopus laevis oocytes at a concentration of 10 μM (i.e., similar to physiological plasma levels), which was inhibited by both probenecid and cimetidine, prototypical competitive inhibitors of organic anion and cation transporters, respectively. Renal creatinine clearance was consistently greater than inulin clearance (as a measure of GFR) in wild-type (WT) mice but not in mice lacking OAT1 (Oat1−/−) and OAT3 (Oat3−/−). WT mice presented renal creatinine net secretion (0.23 ± 0.03 μg/min) which represented 45 ± 6% of total renal creatinine excretion. Mean values for renal creatinine net secretion and renal creatinine secretion fraction were not different from zero in Oat1−/− (−0.03 ± 0.10 μg/min; −3 ± 18%) and Oat3−/− (0.01 ± 0.06 μg/min; −6 ± 19%), with greater variability in Oat1−/−. Expression of OAT3 protein in the renal membranes of Oat1−/− mice was reduced to ∼6% of WT levels, and that of OAT1 in Oat3−/− mice to ∼60%, possibly as a consequence of the genes for Oat1 and Oat3 having adjacent chromosomal locations. Plasma creatinine concentrations of Oat3−/− were elevated in clearance studies under anesthesia but not following brief isoflurane anesthesia, indicating that the former condition enhanced the quantitative contribution of OAT3 for renal creatinine secretion. The results are consistent with a contribution of OAT3 and possibly OAT1 to renal creatinine secretion in mice. PMID:22338083

Severe hyperkalemia following adrenalectomy for aldosteronoma: prediction, pathogenesis and approach to clinical management- a case series.

PubMed

Tahir, A; McLaughlin, K; Kline, G

2016-07-27

As the field of Primary Aldosteronism (PA) becomes ever expanded, diagnosis of PA is increasingly diagnosed by endocrinologists. With increased PA screening, many of the cases are now found in patients with complex co-morbidities in addition to their hypertension. Post adrenalectomy renal impairment with hyperkalemia is now increasingly seen in these complex patients, as evidenced by the numerous reports on this issue that have appeared within the past 3 years. We present a small case series to illustrate the breadth of the problem, along with a discussion about how such CKD/hyperkalemic events may be predicted. We present three cases of primary aldosteronism with long standing hypertension (more than 10 years) hypokalemia (2.0-3.0 mmol/l). Serum aldosterone was high with low renin activity leading to high aldosterone to renin ratio (ARR). They underwent abdominal CT scan revealing adrenal mass and adrenal vein sample confirmed lateralization. None of the patients had evidence of renal disease before surgery (as evident by normal eGFR and serum creatinine). Post adrenalectomy they had reduction in the blood pressure and became eukalemic. Serum aldosterone and renin activity were low leading to a low ARR. Case 1 developed hyperkalemia and increased serum creatinine 6 weeks post operatively which resolved with initiation of fludrocortisone and every attempt to discontinue fludrocortisone resulted in hyperkalemia and rising creatinine. Her hyperkalemia is under control with oral sodium bicarbonate. Case 2 developed hyperkalemia and increasing creatinine 2 months post operatively transiently requiring fludrocortisone and later on managed with furosemide for hyperkalemia. Case 3 developed renal impairment and hyperkalemia 2 weeks post operatively requiring fludrocortisone. Post APA resection severe hyperkalemia may be a common entity and screening should be actively considered in high risk patients. Older age, longer duration of hypertension, impaired pre-op and post-op GFR and higher levels of pre-op aldosterone and are all risk factors which predict the likelihood of developing post-operative hyperkalemia. Fludrocortisone, sodium bicarbonate, loop diuretics and potassium binders can be used for treatment. Treatment choice should be tailored to patient characteristics including fluid status, blood pressure and serum creatinine. Potassium binders should be avoided in patients with history of recent abdominal surgery, opioid use and constipation. Serum electrolytes and creatinine should be monitored every 1-2 weeks after starting treatment to ensure an adequate response. Prolonged management may be necessary in some cases and at-risk patients should be counselled as to the meaning and importance of post-operative changes in measured renal function and potassium.

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes).

PubMed

Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Dusse, Luci Maria S; Reis, Janice Sepúlveda; Carvalho, Maria das Graças; Gomes, Karina Braga; Fernandes, Ana Paula

2018-02-01

Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

PubMed

Han, Juyoung; Kim, So Hun; Suh, Young Ju; Lim, Hyun Ae; Shin, Heekyoung; Cho, Soon Gu; Kim, Chei Won; Lee, Seung Youn; Lee, Dae Hyung; Hong, Seongbin; Kim, Yong Seong; Nam, Moon-Suk

2016-06-01

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

Distribution of creatinine following intravenous and oral administration to rats.

PubMed

Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

1981-05-01

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Proximal Tubular Secretion of Creatinine by Organic Cation Transporter OCT2 in Cancer Patients

PubMed Central

Ciarimboli, Giuliano; Lancaster, Cynthia S.; Schlatter, Eberhard; Franke, Ryan M.; Sprowl, Jason A.; Pavenstädt, Hermann; Massmann, Vivian; Guckel, Denise; Mathijssen, Ron H. J.; Yang, Wenjian; Pui, Ching-Hon; Relling, Mary V.; Herrmann, Edwin; Sparreboom, Alex

2012-01-01

Purpose Knowledge of transporters responsible for the renal secretion of creatinine is key to a proper interpretation of serum creatinine and/or creatinine clearance as markers of renal function in cancer patients receiving chemotherapeutic agents. Experimental Design Creatinine transport was studied in transfected HEK293 cells in vitro and in wildtype mice and age-matched organic cation transporter 1 and 2-deficient [Oct1/2(−/−)] mice ex vivo and in vivo. Clinical pharmacogenetic and transport inhibition studies were done in two separate cohorts of cancer patients. Results Compared to wildtype mice, creatinine clearance was significantly impaired in Oct1/2(−/−) mice. Furthermore, creatinine inhibited organic cation transport in freshly-isolated proximal tubules from wild-type mice and humans, but not in those from Oct1/2(−/−) mice. In a genetic-association analysis (n=590), several polymorphisms around the OCT2/SLC22A2 gene locus, including rs2504954 (P=0.000873), were significantly associated with age-adjusted creatinine levels. Furthermore, in cancer patients (n=68), the OCT2 substrate cisplatin caused an acute elevation of serum creatinine (P=0.0083), consistent with inhibition of an elimination pathway. Conclusions Collectively, this study shows that OCT2 plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates, which impair the usefulness of creatinine as a marker of renal function. PMID:22223530

Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent.

PubMed

Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

2017-08-15

For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.

Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent -

PubMed Central

Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

2017-01-01

For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers. PMID:28781321

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics.

PubMed

Quintero-Platt, Geraldine; González-Reimers, Emilio; Rodríguez-Gaspar, Melchor; Martín-González, Candelaria; Pérez-Hernández, Onán; Romero-Acevedo, Lucía; Espelosín-Ortega, Elisa; Vega-Prieto, María José de la; Santolaria-Fernández, Francisco

2017-09-01

Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Urinary excretion values in 2-day food-deprived, unrestrained chimpanzees.

NASA Technical Reports Server (NTRS)

Mcnew, J. J.; Sabbot, I. M.; Hoshizaki, T.; Mandell, A. J.; Spooner, C. E.; Marcus, I.; Adey, W. R.

1972-01-01

A study was conducted to determine the baseline 24-hr urinary excretion values in the young, unrestrained chimpanzee, and also changes in urinary values, if any, induced by the two-day food deprivation stress. Urine was analyzed for volume, osmolarity, creatinine, creatine, urea nitrogen, 17-hydroxycorticosteroids (17-OHCS), 3-methoxy-4-hydroxymandelic acid (VMA), calcium, and inorganic phosphorus. Significant increases due to food deprivation stress were observed for volume, creatine, urea nitrogen, 17-OHCS, VMA, and phosphorus values, with significant decreases in osmolarity and calcium. All values approached normal levels by the second poststress day. No significant changes were observed in creatinine. A comparison is drawn between human and chimpanzee adaptation to stress.

Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat

PubMed Central

Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

2014-01-01

Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition. PMID:24646860

Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.

PubMed

Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

2014-08-01

Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.

Association of high post-transplant soluble CD30 serum levels with chronic allograft nephropathy.

PubMed

Grenzi, Patricia C; Campos, Érika F; Tedesco-Silva, Hélio; Felipe, Claudia R; Franco, Marcello F; Soares, Maria Fernanda; Medina-Pestana, José Osmar; Gerbase-Delima, Maria

2013-12-01

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ≥ 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ≥ 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients. © 2013.

Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity.

PubMed

Bretagne, M; Jouinot, A; Durand, J P; Huillard, O; Boudou Rouquette, P; Tlemsani, C; Arrondeau, J; Sarfati, G; Goldwasser, F; Alexandre, J

2017-07-01

Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFR cysC-creat ) in cancer patients. Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFR cysC-creat (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed. In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but not with cystatin C (r = -0.07, p = 0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFR cysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFR cysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFR cysC-creat ratio threshold predicting severe thrombocytopenia was 1.23. A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFR cysC-creat ratio allows the identification of these patients.

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

PubMed

Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

2017-12-01

Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

Early renal dysfunction after contrast media administration despite prophylactic hydration.

PubMed

Burchardt, Pawel; Guzik, Przemyslaw; Tabaczewski, Piotr; Synowiec, Tomasz; Bogdan, Monika; Faner, Paula; Chmielarz-Sobocińska, Anna; Palasz, Anna

2013-06-01

The actual incidence of renal dysfunction after contrast media administration seems to be underestimated, especially in the context of epidemiological data. There are only few data concerning the monitoring of impaired kidney function within a few hours after iodine contrast medium application. Hence, the purpose of this study is to observe the incidence of early renal function deterioration within 12-18 h after administration of iodine contrast media in patients scheduled for elective coronary angiography, who were intravenously and orally hydrated. In addition, the project aims to reclassify the contrast induced nephropathy phenomenon, by identification of early markers of renal dysfunction. Morphology, electrolytes, blood urea nitrogen (BUN), creatinine, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein, and total cholesterol levels were assessed with the use of typical laboratory techniques in 319 patients referred for coronary angiography. We demonstrated that early deterioration of renal function in patients 12-18 h after administration of contrast during imaging tests (even when appropriate prophylactic hydration was used), may occurred just as an increase (or no change) of serum creatinine level and BUN level and a decrease of creatinine clearance and glomerular filtration rate. Depending on the parameter, the phenomenon can be found in 13-28 % of all respondents. Early renal function impairment defined as above was almost 2 and 2.22 × 10(3) times (respectively) more frequently observed in our study than contrast induced nephropathy defined by current definitions.

Thyroid hormone levels and incident chronic kidney disease in euthyroid individuals: the Kangbuk Samsung Health Study.

PubMed

Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo

2014-10-01

Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored. We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD. In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.

Urinary levels of novel kidney biomarkers and risk of true worsening renal function and mortality in patients with acute heart failure.

PubMed

Sokolski, Mateusz; Zymliński, Robert; Biegus, Jan; Siwołowski, Paweł; Nawrocka-Millward, Sylwia; Todd, John; Yerramilli, Malli Rama; Estis, Joel; Jankowska, Ewa Anita; Banasiak, Waldemar; Ponikowski, Piotr

2017-06-01

Recent studies indicate the need to redefine worsening renal function (WRF) in acute heart failure (AHF), linking a rise in creatinine with clinical status to identify patients who develop 'true WRF'. We evaluated the usefulness of serial assessment of urinary levels of neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), and cystatin C (uCysC) for prediction of 'true WRF'. In 132 patients with AHF, uNGAL, uKIM-1, and uCysC were measured using a highly sensitive immunoassay based on a single-molecule counting technology (Singulex, Alameda, CA, USA) at baseline, day 2, and day 3. Patients who developed WRF (a ≥0.3 mg/dL increase in serum creatinine or a >25% decrease in the estimated glomerular filtration rate from the baseline value) were differentiated into those 'true WRF' (presence of deterioration/no improvement in clinical status during hospitalization) vs. 'pseudo-WRF' (uneventful clinical course). 'True WRF' occurred in 13 (10%), 'pseudo-WRF' in 15 (11%), whereas the remaining 104 (79%) patients did not develop WRF. Patients with 'true WRF' were more often females, had higher levels of NT-proBNP, creatinine, and urea on admission, higher urine albumin to creatinine ratio at day 2, higher uNGAL at baseline, day 2, and day 3, and higher KIM-1 at day 2 (vs. pseudo-WRF vs. without WRF, all P < 0.05). Patients with pseudo-WRF did not differ from those without WRF. In the multivariable model, elevated uNGAL at all time points and uKIM-1 at day 2 remained independent predictors of 'true WRF'. Elevated levels of uNGAL and uKIM-1 may predict development of 'true WRF' in AHF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Overcoming resistance to bisphosphonates through the administration of alfacalcidol: results of a 1-year, open follow-up study.

PubMed

Gaál, János; Bender, Tamás; Varga, József; Horváth, Irén; Kiss, Judit; Somogyi, Péter; Surányi, Péter

2009-11-01

This study intended to determine whether the replacement of vitamin D3 with alfacalcidol results in any bone mineral density (BMD) increase in 76 patients unresponsive to the combination of alendronate and conventional vitamin D3 treatment. In these patients the conventional vitamin D3 had been replaced with alfacalcidol (0.5 μg/day), and then the patients were followed up for a year. After treatment for 1 year, Wilcoxon test revealed a small but statistically significant (P < 0.001) increase in the BMD values of the forearm and lumbar vertebrae, in the serum calcium and urinary calcium/creatinine ratio in first-voided morning urine. However, the serum alkaline phosphatase activity, phosphorus, parathormone, osteocalcin levels and the urinary d-pyr/creatinine ratio decreased significantly (P < 0.001). As suggested by our results, combination therapy with alendronate and alfacalcidol increases bone density and improves the biochemical markers of bone turnover, without any substantial increase in the incidence of adverse effects.

Therapeutic effect of captopril, pentoxifylline, and cordyceps sinensis in pre-hepatic portal hypertensive rats.

PubMed

Ahmed, Ahmed F; El-Maraghy, Nabila N; Abdel Ghaney, Rasha H; Elshazly, Shimaa M

2012-01-01

Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats. Wistar male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days. Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state. Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes. captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level.

Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies.

PubMed

Reischies, Frederike M J; Raggam, Reinhard B; Prattes, Juergen; Krause, Robert; Eigl, Susanne; List, Agnes; Quehenberger, Franz; Strenger, Volker; Wölfler, Albert; Hoenigl, Martin

2016-03-01

Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Probability of reduced renal function after contrast-enhanced CT: a model based on serum creatinine level, patient age, and estimated glomerular filtration rate.

PubMed

Herts, Brian R; Schneider, Erika; Obuchowski, Nancy; Poggio, Emilio; Jain, Anil; Baker, Mark E

2009-08-01

The objectives of our study were to develop a model to predict the probability of reduced renal function after outpatient contrast-enhanced CT (CECT)--based on patient age, sex, and race and on serum creatinine level before CT or directly based on estimated glomerular filtration rate (GFR) before CT--and to determine the relationship between patients with changes in creatinine level that characterize contrast-induced nephropathy and patients with reduced GFR after CECT. Of 5,187 outpatients who underwent CECT, 963 (18.6%) had serum creatinine levels obtained within 6 months before and 4 days after CECT. The estimated GFR was calculated before and after CT using the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. Pre-CT serum creatinine level, age, race, sex, and pre-CT estimated GFR were tested using multiple-variable logistic regression models to determine the probability of having an estimated GFR of < 60 and < 45 mL/min/1.73 m(2) after CECT. Two thirds of the patients were used to create and one third to test the models. We also determined discordance between patients who met standard definitions of contrast-induced nephropathy and those with a reduced estimated GFR after CECT. Significant (p < 0.002) predictors for a post-CT estimated GFR of < 60 mL/min/1.73 m(2) were age, race, sex, pre-CT serum creatinine level, and pre-CT estimated GFR. Sex, serum creatinine level, and pre-CT estimated GFR were significant factors (p < 0.001) for predicting a post-CT estimated GFR of < 45 mL/min/1.73 m(2). The probability is [exp(y) / (1 + exp(y))], where y = 6.21 - (0.10 x pre-CT estimated GFR) for an estimated GFR of < 60 mL/min/1.73 m(2), and y = 3.66 - (0.087 x pre-CT estimated GFR) for an estimated GFR of < 45 mL/min/1.73 m(2). A discrepancy between those who met contrast-induced nephropathy criteria by creatinine changes and those with a post-CT estimated GFR of < 60 mL/min/1.73 m(2) was detected in 208 of the 963 patients (21.6%). The probability of a reduced estimated GFR after CECT can be predicted by the pre-CT estimated GFR using the four-variable MDRD equation. Furthermore, standard criteria for contrast-induced nephropathy are poor predictors of poor renal function after CECT. Criteria need to be established for what is an acceptable risk to manage patients undergoing CECT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruchirawat, Mathuros; Navasumrit, Panida; Settachan, Daam

The effects of air pollution on human health are a great concern, particularly in big cities with severe traffic problems such as Bangkok, Thailand. In this study, exposure to genotoxic compounds in ambient air was studied by analysis of particle-associated polycyclic aromatic hydrocarbons (PAHs) and benzene through direct measurement of concentrations in air as well as through the use of different biomarkers of exposure: urinary 1-hydroxypyrene (1-OHP) for PAHs and urinary t,t-muconic acid (t,t-MA) for benzene. The study was conducted in various susceptible groups of the population with different occupations in 5 traffic-congested areas of Bangkok, as well as inmore » primary school children. The level of total PAHs on the main roads at various sites ranged from 7.10 to 83.04 ng/m{sup 3}, while benzene levels ranged from 16.35 to 49.25 ppb. In contrast, ambient levels in nearby temples, the control sites, ranged from 1.67 to 3.04 ng/m{sup 3} total PAHs and 10.16 to 16.25 ppb benzene. Street vendors selling clothes were exposed to 16.07 {+-} 1.64 ng/m{sup 3} total PAHs and 21.97 {+-} 1.50 ppb benzene, levels higher than in monks and nuns residing in nearby temples (5.34 {+-} 0.65 ng/m{sup 3} total PAHs and 13.69 {+-} 0.77 ppb benzene). Grilled-meat vendors in the same area were exposed to both total PAHs and benzene at even higher levels, possibly due to additional formation of PAHs during the grilling of meat (34.27 {+-} 7.02 ng/m{sup 3} total PAHs; 27.49 {+-} 2.72 ppb benzene). At the end of the workday, urinary 1-OHP levels in street vendors (0.12 and 0.15 {mu}mol/mol creatinine in clothes and grilled-meat vendors, respectively) were significantly higher than in controls (0.04 {mu}mol/mol creatinine; P < 0.01). Afternoon urinary t,t-MA levels in both groups of street vendors (0.12 mg/g creatinine) were also significantly higher than in controls (0.08 mg/g creatinine; P < 0.05). School children from two schools in Bangkok were exposed to total PAHs and benzene at levels of 6.70 {+-} 0.47 ng/m{sup 3} and 4.71 {+-} 0.25 ppb, respectively, higher than those to which children living outside the city were exposed (1.25 {+-} 0.24 ng/m{sup 3} total PAHs; 2.10 {+-} 0.16 ppb benzene). At the end of the school day, levels of urinary 1-OHP and t,t-MA were significantly higher (P < 0.001 and P < 0.01, respectively) in Bangkok school children (0.23 {mu}mol/mol creatinine and 0.27 mg/g creatinine, respectively) than in school children from outside Bangkok (0.10 {mu}mol/mol creatinine and 0.08 mg/g creatinine, respectively)« less

Serum creatinine and cystatin C provide conflicting evidence of acute kidney injury following acute ingestion of potassium permanganate and oxalic acid.

PubMed

Wijerathna, Thilini Madushanka; Gawarammana, Indika Bandara; Dissanayaka, Dhammika Menike; Palanagasinghe, Chathura; Shihana, Fathima; Dassanayaka, Gihani; Shahmy, Seyed; Endre, Zoltan Huba; Mohamed, Fahim; Buckley, Nicholas Alan

2017-11-01

Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H 2 C 2 O 4 ) and potassium permanganate (KMnO 4 ). Early and rapid increases in serum creatinine (sCr) follow severe poisoning. We investigated the relationship of these increases with direct nephrotoxicity in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h. In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H 2 C 2 O 4 and KMnO 4 . Increased early creatinine excretion supports the latter explanation, since creatinine excretion usually decreases transiently in AKIN2/3 from other causes.

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial.

PubMed

Brisco, Meredith A; Zile, Michael R; Hanberg, Jennifer S; Wilson, F Perry; Parikh, Chirag R; Coca, Steven G; Tang, W H Wilson; Testani, Jeffrey M

2016-10-01

Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67-0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77-1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57-4.03, P < .001). The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

PubMed Central

Kolic, Ivana; Purdell-Lewis, Jeremy; Taylor, Rachelle; Pearse, Rupert M.; Kirwan, Christopher J.

2014-01-01

Background and objectives AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness. Design, setting, participants, & measurements A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed. Results In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P<0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR<60 ml/min per 1.73 m2 at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P<0.001). Conclusion Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings. PMID:24742481

Total arsenic concentrations in Chinese children's urine by different geographic locations, ages, and genders.

PubMed

Zhang, Xuan; Wang, Beibei; Cui, Xiaoyong; Lin, Chunye; Liu, Xitao; Ma, Jin

2018-06-01

Little is known about the variation of Chinese children's exposure to arsenic by geography, age, gender, and other potential factors. The main objective of this study was to investigate the total arsenic concentration in Chinese children's urine by geographic locations, ages, and genders. In total, 259 24-h urine samples were collected from 210 2- to 12-year-old children in China and analyzed for total arsenic and creatinine concentrations. The results showed that the upper limit (upper limit of the 90% confidence interval for the 97.5 fractile) was 27.51 µg/L or 55.88 µg/g creatinine for Chinese children. The total urinary arsenic levels were significantly different for children in Guangdong, Hubei, and Gansu provinces (P < 0.05), where the upper limits were 24.29, 58.70, and 44.29 µg/g creatinine, respectively. In addition, the total urinary arsenic levels were higher for 2- to 7-year-old children than for 7- to 12-year-old children (P < 0.05; the upper limits were 59.06 and 44.29 µg/g creatinine, respectively) and higher for rural children than for urban children (P < 0.05; the upper limits were 59.06 and 50.44 µg/g creatinine, respectively). The total urinary arsenic levels for boys were not significantly different from those for girls (P > 0.05), although the level for boys (the upper limit was 59.30 µg/g) was slightly higher than that for girls (the upper limit was 58.64 µg/g creatinine). Because the total urinary arsenic concentrations are significantly different for general populations of children in different locations and age groups, the reference level of total urinary arsenic might be dependent on the geographic site and the child's age.

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology

PubMed Central

Williamson, Lydia; New, David

2014-01-01

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. PMID:25239988

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology.

PubMed

Williamson, Lydia; New, David

2014-09-19

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. 2014 BMJ Publishing Group Ltd.

Factors associated with postoperative requirement of renal replacement therapy following off-pump coronary bypass surgery.

PubMed

Kato, Tomoko S; Machida, Yoichiro; Kuwaki, Kenji; Yamamoto, Taira; Amano, Atsushi

2017-02-01

Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p < 0.05] in the total population, whereas low albumin concentration was the only independent predictor for RRT in patients with preserved renal function (OR 0.062, p < 0.0001). When creatinine levels were below 1.5 mg/dL, the predictive power of hypoalbuminemia for RRT requirement overwhelmed that of creatinine or BNP levels. Older age, preoperative elevated creatinine and BNP levels were associated with a requirement for RRT following off-pump CABG. In patients with preserved renal function, hypoalbuminemia was most significantly related to the RRT requirement.

Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

PubMed Central

2009-01-01

Background Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. Results TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment. PMID:19943946

Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

PubMed

Gharib, Ola Ali

2009-11-27

Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage.

PubMed

Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori

2011-12-01

We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

Effect of Hydroxyethyl Starch Solution on Incidence of Acute Kidney Injury in Patients Suffering from Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kieninger, Martin; Unbekannt, Daniel; Schneiker, André; Sinner, Barbara; Bele, Sylvia; Prasser, Christopher

2017-02-01

The application of third-generation hydroxyethyl starch (HES) solutions in critically ill patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) was often part of the treatment of delayed cerebral ischemia (DCI). However, there is increasing evidence showing a correlation between the application of HES and the incidence of acute kidney injury (AKI). In a single-center retrospective analysis including 81 patients without a preexisting renal disorder suffering from aSAH who had received higher volumes of 6 % HES 130/0.4 due to standard treatment of DCI, the incidence of AKI during intensive care unit (ICU) stay was recorded using AKIN criteria. Furthermore, the course of serum creatinine after discharge from ICU was observed. 6 % HES 130/0.4 was given over a period of 12.9 ± 7.1 days resulting in a cumulative dose of 12543.2 ± 7743.6 mL. Four patients (4.9 %) fulfilled AKIN criteria stage 1 during ICU stay. In two of these patients, serum creatinine was within normal range again on day of discharge. Five patients showed elevated levels of serum creatinine within 1 to 22 months after hospitalization. A correlation between the amount of HES given and the incidence of AKI could not be found. The application of 6 % HES 130/0.4 did not lead to an elevated incidence of AKI in patients without an elevated baseline serum creatinine. However, there is still a lack of high-level evidence as prospective randomized trials are missing yet.

Back-calculating baseline creatinine overestimates prevalence of acute kidney injury with poor sensitivity.

PubMed

Kork, F; Balzer, F; Krannich, A; Bernardi, M H; Eltzschig, H K; Jankowski, J; Spies, C

2017-03-01

Acute kidney injury (AKI) is diagnosed by a 50% increase in creatinine. For patients without a baseline creatinine measurement, guidelines suggest estimating baseline creatinine by back-calculation. The aim of this study was to evaluate different glomerular filtration rate (GFR) equations and different GFR assumptions for back-calculating baseline creatinine as well as the effect on the diagnosis of AKI. The Modification of Diet in Renal Disease, the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Mayo quadratic (MQ) equation were evaluated to estimate baseline creatinine, each under the assumption of either a fixed GFR of 75 mL min -1  1.73 m -2 or an age-adjusted GFR. Estimated baseline creatinine, diagnoses and severity stages of AKI based on estimated baseline creatinine were compared to measured baseline creatinine and corresponding diagnoses and severity stages of AKI. The data of 34 690 surgical patients were analysed. Estimating baseline creatinine overestimated baseline creatinine. Diagnosing AKI based on estimated baseline creatinine had only substantial agreement with AKI diagnoses based on measured baseline creatinine [Cohen's κ ranging from 0.66 (95% CI 0.65-0.68) to 0.77 (95% CI 0.76-0.79)] and overestimated AKI prevalence with fair sensitivity [ranging from 74.3% (95% CI 72.3-76.2) to 90.1% (95% CI 88.6-92.1)]. Staging AKI severity based on estimated baseline creatinine had moderate agreement with AKI severity based on measured baseline creatinine [Cohen's κ ranging from 0.43 (95% CI 0.42-0.44) to 0.53 (95% CI 0.51-0.55)]. Diagnosing AKI and staging AKI severity on the basis of estimated baseline creatinine in surgical patients is not feasible. Patients at risk for post-operative AKI should have a pre-operative creatinine measurement to adequately assess post-operative AKI. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Renal cytokines improve early after bariatric surgery.

PubMed

Bueter, M; Dubb, S S; Gill, A; Joannou, L; Ahmed, A; Frankel, A H; Tam, F W K; le Roux, C W

2010-12-01

Bariatric surgery has been suggested to improve arterial hypertension and renal function. This prospective controlled observational study aimed to investigate changes in renal inflammation, renal function and arterial blood pressure before and after bariatric surgery. Blood pressure was measured, and urine and blood samples were collected from 34 morbidly obese patients before and 4 weeks after bariatric surgery. Serum levels of cystatin C, creatinine, albumin, cholesterol and C-reactive protein (CRP) were measured, along with urinary cytokine/creatinine ratios for macrophage migration inhibitory factor (MIF), monocyte chemotactic protein (MCP) 1, chemokine ligand (CCL) 18 and CCL-15. Mean(s.e.m.) bodyweight dropped from 124·1(2·6) to 114·8(2·4) kg (P < 0·001) and mean arterial blood pressure decreased from 105·7(1·8) to 95·5(1·2) mmHg (P < 0·001) in 4 weeks. Systemic and urinary inflammatory markers improved, with a reduction in serum CRP level (P < 0·001), and decreased urinary MIF/creatinine (P < 0·001), MCP-1/creatinine (P < 0·001) and CCL-18/creatinine (P = 0·003) ratios. In contrast, urinary CCL-15/creatinine ratios did not change and the glomerular filtration rate, measured by serum cystatin C, was unchanged (P = 0·615). Surgically induced weight loss contributed to a decrease in blood pressure and markers of renal inflammation. The reduced levels of CRP and urinary cytokines suggest that bariatric surgery attenuates systemic and renal inflammatory status. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

The Maillard protein cross-link pentosidine in urine from diabetic patients.

PubMed

Takahashi, M; Ohishi, T; Aoshima, H; Kawana, K; Kushida, K; Inoue, T; Horiuchi, K

1993-07-01

The Maillard protein cross-link pentosidine is a fluorescent condensation product of lysine, arginine and ribose. It accumulates in human tissues with age, and the accumulation process is accelerated in the tissues of diabetic patients. Using SP-Sephadex C-25 in the pretreatment for HPLC, we examined levels of pentosidine in urine without hydrolysis (free form) and levels of pentosidine in urine after hydrolysis (total forms), from 23 diabetic patients and 21 control subjects. The mean percentages of the values of free form per total forms (+/- SD) were 89 +/- 15% in diabetic patients, 88 +/- 16% in control subjects and 89 +/- 15% in total populations of diabetic patients and control subjects. There was a significant correlation between the values of free form and total forms in diabetic patients (r = 0.983, p = 0.0001), in control subjects (r = 0.820, p < 0.02) and in total populations of diabetic patients and control subjects (r = 0.951, p = 0.0001). The mean level of pentosidine per mol creatinine (+/- SD) was significantly elevated in urine from diabetic patients as compared to the level in control subjects (8.8 +/- 4.3 mumol/mol creatinine vs 4.2 +/- 1.4 mumol/mol creatinine, p = 0.0001 in free form; 10.1 +/- 5.3 mumol/mol creatinine vs 4.7 +/- 1.4 mumol/mol creatinine, p = 0.0001 in total forms). These results demonstrate that urinary pentosidine, especially in free form, could be a useful marker for the assessment of diabetes and diabetic complications.

The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials.

PubMed

Rovin, B H; Dooley, M A; Radhakrishnan, J; Ginzler, E M; Forrester, T D; Anderson, P W

2016-12-01

Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus. Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio). The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses. Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601. © The Author(s) 2016.

Stability of BUN and creatinine determinations on the Siemens Advia 1800 analyzer.

PubMed

Qin, Jia; Wang, Huiying; Rets, Anton; Harari, Saul; Alexis, Herol; Eid, Ikram; Pincus, Matthew R

2013-11-01

Serum creatinine values of patients tend to change as a result of the use of different blanks used for creatinine determinations on the Advia 1650. After upgrading the analyzer to the Advia 1800, creatinine values tended to be more reproducible. As part of a quality assurance investigation to test the reproducibilities of creatinine values, we determined serial creatinine values in the sera of 13 patients whose initial values were either in the reference range or elevated (range 0.58-7.8 mg/dl). These values were determined concurrently with serum blood urea nitrogen (BUN) determinations (range 6.0-84.4 mg/dl) as these two analytes are used together in evaluation of renal function. We determined BUN and creatinine values, using the glutamate dehydrogenase lined enzyme assay system and the Jaffe method, respectively. We find that all values for creatinine on samples stored at 4 °C were reproducible as were the corresponding BUN values, which is revealed by low values for the coefficients of variation (CVs), that is, mean CV of 4.55% for creatinine and 2.52% for BUN. One sample with relatively high CV (10.6%) for creatinine was found to have an initial value of 1.1 mg/dl, in the reference range; but, on repeat determinations, the obtained levels were as high as 1.5 mg/dl, above the reference range. BUN values for this sample remained in the reference range, suggesting that no renal disease was present. We conclude that creatinine and BUN determinations are stable, but occasional spurious creatinine values can occur on the Advia 1800 analyzer. © 2013 Wiley Periodicals, Inc.

Therapeutic effects of marshmallow (Althaea officinalis L.) extract on plasma biochemical parameters of common carp infected with Aeromonas hydrophila

PubMed Central

Banaee, Mahdi; Soleimany, Vahid; Nematdoost Haghi, Behzad

2017-01-01

This study evaluated preclinical and clinical safety of marshmallow (Althaea officinalis L.) extract as a naturopathic medicine in common carp deliberately infected with Aeromonas hydrophila. The fish were fed 0 (control), 2.50, 5.00 and 10.00 g of marshmallow extract for 60 days in a preclinical experiment and then, challenged with A. hydrophila for a 10-day experiment. Significant increases were observed in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK) activities and plasma creatinine levels in fish fed 10 g marshmallow extract per kg feed. However, alanine aminotransferase (ALT) significantly decreased on day 60. The fish fed 2.50 g marshmallow extract per kg feed indicated increased levels of total protein and globulin. There were no significant changes in albumin levels (p > 0.05). 2.50 and 5.00 g marshmallow significantly decreased triglyceride and cholesterol levels and increased glucose levels (p < 0.05). A. hydrophila significantly increased AST, ALT, LDH, ALP and CPK activities and plasma glucose, cholesterol, triglycerides and creatinine levels after 10 days (p < 0.05). Total plasma protein, albumin and globulin levels in fish challenged with A. hydrophila were significantly lower than the control group (p < 0.05). Marshmallow extract at 5.00 and 10.00 g can adjust plasma biochemical parameters in fish challenged with A. hydrophila. The results of preclinical studies and pharmaceutical toxicity of marshmallow extract revealed that dietary levels lower than 5.00 g were safe and effective. The results of this clinical study demonstrated that marshmallow extract (5.00 g kg-1 feed) can protect fish against A. hydrophila. PMID:28785391

Therapeutic effects of marshmallow (Althaea officinalis L.) extract on plasma biochemical parameters of common carp infected with Aeromonas hydrophila.

PubMed

Banaee, Mahdi; Soleimany, Vahid; Nematdoost Haghi, Behzad

2017-01-01

This study evaluated preclinical and clinical safety of marshmallow ( Althaea officinalis L.) extract as a naturopathic medicine in common carp deliberately infected with Aeromonas hydrophila . The fish were fed 0 (control), 2.50, 5.00 and 10.00 g of marshmallow extract for 60 days in a preclinical experiment and then, challenged with A. hydrophila for a 10-day experiment. Significant increases were observed in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK) activities and plasma creatinine levels in fish fed 10 g marshmallow extract per kg feed. However, alanine aminotransferase (ALT) significantly decreased on day 60. The fish fed 2.50 g marshmallow extract per kg feed indicated increased levels of total protein and globulin. There were no significant changes in albumin levels ( p > 0.05). 2.50 and 5.00 g marshmallow significantly decreased triglyceride and cholesterol levels and increased glucose levels ( p < 0.05). A. hydrophila significantly increased AST, ALT, LDH, ALP and CPK activities and plasma glucose, cholesterol, triglycerides and creatinine levels after 10 days ( p < 0.05). Total plasma protein, albumin and globulin levels in fish challenged with A. hydrophila were significantly lower than the control group ( p < 0.05). Marshmallow extract at 5.00 and 10.00 g can adjust plasma biochemical parameters in fish challenged with A. hydrophila . The results of preclinical studies and pharmaceutical toxicity of marshmallow extract revealed that dietary levels lower than 5.00 g were safe and effective. The results of this clinical study demonstrated that marshmallow extract (5.00 g kg -1 feed) can protect fish against A. hydrophila .

The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

PubMed

Koksal, Guniz Meyancı; Erbabacan, Emre; Tunali, Yusuf; Karaoren, Gulsah; Vehid, Suphi; Oz, Huseyin

2014-01-01

Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition.

Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate.

PubMed

Hannemann, Anke; Friedrich, Nele; Dittmann, Kathleen; Spielhagen, Christin; Wallaschofski, Henri; Völzke, Henry; Rettig, Rainer; Endlich, Karlhans; Lendeckel, Uwe; Stracke, Sylvia; Nauck, Matthias

2011-11-14

Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5-62.2 mL/min/1.73 m², women 75.0-58.2 mL/min/1.73 m²; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.

Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis.

PubMed

Koster, Remco A; Greijdanus, Ben; Alffenaar, Jan-Willem C; Touw, Daan J

2015-02-01

In order to monitor creatinine levels or to adjust the dosage of renally excreted or nephrotoxic drugs, the analysis of creatinine in dried blood spots (DBS) could be a useful addition to DBS analysis. We developed a LC-MS/MS method for the analysis of creatinine in the same DBS extract that was used for the analysis of tacrolimus, sirolimus, everolimus, and cyclosporine A in transplant patients with the use of Whatman FTA DMPK-C cards. The method was validated using three different strategies: a seven-point calibration curve using the intercept of the calibration to correct for the natural presence of creatinine in reference samples, a one-point calibration curve at an extremely high concentration in order to diminish the contribution of the natural presence of creatinine, and the use of creatinine-[(2)H3] with an eight-point calibration curve. The validated range for creatinine was 120 to 480 μmol/L (seven-point calibration curve), 116 to 7000 μmol/L (1-point calibration curve), and 1.00 to 400.0 μmol/L for creatinine-[(2)H3] (eight-point calibration curve). The precision and accuracy results for all three validations showed a maximum CV of 14.0% and a maximum bias of -5.9%. Creatinine in DBS was found stable at ambient temperature and 32 °C for 1 week and at -20 °C for 29 weeks. Good correlations were observed between patient DBS samples and routine enzymatic plasma analysis and showed the capability of the DBS method to be used as an alternative for creatinine plasma measurement.

Got Milk? Breastfeeding and Milk Analysis of a Mother on Chronic Hemodialysis

PubMed Central

Balzer, Michael S.; Gross, Mechthild M.; Lichtinghagen, Ralf; Haller, Hermann; Schmitt, Roland

2015-01-01

Purpose Women on dialysis rarely become pregnant. However, the overall rate of successful pregnancies is increasing in this patient population and breastfeeding becomes an option for mothers on dialysis. In this study we performed a systematic breast milk composition analysis of a mother on chronic hemodialysis (HD). Methods Specimens of breast milk and blood were collected in regular intervals before and after HD from a 39-year old woman starting on day 10 postpartum. Samples were analyzed for electrolytes, retention solutes, nutrients and other laboratory measurements. Breast milk samples from low-risk mothers matched for postpartum age were used as controls. Results Significantly higher levels of creatinine and urea were found in pre-HD breast milk when compared to post-HD. A similar post-dialytic decrease was only found for uric acid but not for any other investigated parameter. Conversely, sodium and chloride were significantly increased in post-HD samples. Compared to controls creatinine and urea were significantly higher in pre-HD samples while the difference remained only significant for post-HD creatinine. Phosphate was significantly lower in pre- and post-HD breast milk when compared to controls, whereas calcium showed no significant differences. In terms of nutrient components glucose levels showed a strong trend for a decrease, whereas protein, triglycerides and cholesterol did not differ. Similarly, no significant differences were found in iron, potassium and magnesium content. Conclusion To the best of our knowledge this is the first report on a breastfeeding mother on chronic dialysis. Although we found differences in creatinine, urea, sodium, chloride and phosphate, our general analysis showed high similarity of our patient’s breast milk to samples from low-risk control mothers. Significant variations in breast milk composition between pre- and post-HD samples suggest that breastfeeding might be preferably performed after dialysis treatment. In summary, our findings indicate that breastfeeding can be considered a viable option for newborns of mothers on dialysis. PMID:26571490

Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

PubMed

Huang, Zhongdi; He, Liqun; Huang, Di; Lei, Shi; Gao, Jiandong

2015-10-21

Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)

PubMed Central

Forman, J; Moline, J; Cernichiari, E; Sayegh, S; Torres, J C; Landrigan, M M; Hudson, J; Adel, H N; Landrigan, P J

2000-01-01

Nine children and their mother were exposed to vapors of metallic mercury. The source of the exposure appears to have been a 6-oz vial of mercury taken from a neighbor's home. The neighbor reportedly operated a business preparing mercury-filled amulets for practitioners of the Afro-Caribbean religion Santeria. At diagnosis, urinary mercury levels in the children ranged from 61 to 1,213 microg/g creatinine, with a geometric mean of 214.3 microg/m creatinine. All of the children were asymptomatic. To prevent development of neurotoxicity, we treated the children with oral meso-2,3-dimercaptosuccinic acid (DMSA). During chelation, the geometric mean urine level rose initially by 268% to 573.2 microg mercury/g creatinine (p<0.0005). At the 6-week follow-up examination after treatment, the geometric mean urine mercury level had fallen to 102.1 microg/g creatinine, which was 17.8% of the geometric mean level observed during treatment (p<0.0005) and 47.6% of the original baseline level (p<0.001). Thus, oral chelation with DMSA produced a significant mercury diuresis in these children. We observed no adverse side effects of treatment. DMSA appears to be an effective and safe chelating agent for treatment of pediatric overexposure to metallic mercury. Images Figure 1 PMID:10856034

Deoxynivalenol Biomarkers in the Urine of UK Vegetarians.

PubMed

Wells, Liz; Hardie, Laura; Williams, Courtney; White, Kay; Liu, Yunru; De Santis, Barbara; Debegnach, Francesca; Moretti, Georgio; Greetham, Stephanie; Brera, Carlo; Papageorgiou, Maria; Thatcher, Natalie J; Rigby, Alan; Atkin, Stephen L; Sathyapalan, Thozhukat

2017-06-22

Deoxynivalenol (DON) is produced by Fusarium graminearum and is one of the most commonly occurring trichothecenes. Vegetarians are alleged to be a high-risk group for DON exposure due to high intakes of cereals susceptible to the growth of the mycotoxin. This study provides the levels of DON and de-epoxi Deoxynivalenol (DOM-1) in urine analysed by liquid chromatography-mass spectrometry (LC-MS) in UK vegetarians. Over two consecutive days, morning urine samples were collected from 32 vegetarians and 31 UK adult volunteers, and associated food consumption 24 h prior to the sample was recorded. Statistically significant differences between the weight of the UK adults and vegetarians ( t = 3.15. df = 61, p ≤ 0.005 two-tailed) were observed. The mean levels of DON in urine for adults on day 1 was 3.05 ng free DON/mg creatinine, and on day 2 was 2.98 ng free DON/mg creatinine. Even though high mean levels were observed, most adults were within the tolerable daily intake. However, for vegetarians, the mean level of urinary DON on day 1 was 6.69 ng free DON/mg creatinine, and on day 2 was 3.42 ng free DON/mg creatinine. These levels equate to up to 32% of vegetarians exceeding recommended tolerable daily intakes (TDI) of exposure (1 µg/kg b.w./day).

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

PubMed

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-11-01

Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

PubMed Central

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-01-01

Background Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Objective Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Results Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). Conclusion We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers. PMID:17107847

Energy demands during a judo match and recovery.

PubMed

Degoutte, F; Jouanel, P; Filaire, E

2003-06-01

To assess energy demand during a judo match and the kinetics of recovery by measuring the metabolites of the oxypurine cascade, lipolytic activity, and glycolytic pathway. Venous blood samples were taken from 16 national judoists (mean (SEM) age 18.4 (1.6) years), before (T(1)) and three minutes (T(2)), one hour (T(3)), and 24 hours (T(4)) after a match. A seven day diet record was used to evaluate nutrient intake. Nutrient analysis indicated that these athletes followed a low carbohydrate diet. Plasma lactate concentration had increased to 12.3 (1.8) mmol/l at the end of the match. An increase in the levels of extracellular markers of muscle adenine nucleotide catabolism, urea, and creatinine was observed at T(2), while uric acid levels remained unchanged. High concentrations of urea persisted for 24 hours during the recovery period. Ammonia, hypoxanthine, xanthine, and creatinine returned to control levels within the 24 hour recovery period. Uric acid concentrations rose from T(3) and had not returned to baseline 24 hours after the match. The levels of triglycerides, glycerol, and free fatty acids had increased significantly (p<0.05) after the match (T(2)) but returned to baseline values within 24 hours. Concentrations of high density lipoprotein cholesterol and total cholesterol were significantly increased after the match. These results show that a judo match induces both protein and lipid metabolism. Carbohydrate availability, training adaptation, and metabolic stress may explain the requirement for these types of metabolism.

Analysis of creatine, creatinine, creatine-d3 and creatinine-d3 in urine, plasma, and red blood cells by HPLC and GC-MS to follow the fate of ingested creatine-d3.

PubMed

MacNeil, Lauren; Hill, Lisa; MacDonald, Daniel; Keefe, Lori; Cormier, James F; Burke, Darren G; Smith-Palmer, Truis

2005-12-05

Creatine, which is increasingly being used as an oral supplement, is naturally present in the body. Studies on the fate of a particular dose of creatine require that the creatine be labeled, and for studies in humans the use of a stable isotopic label is desirable. The concentrations of total creatine and total creatinine were determined using HPLC. Creatine and creatinine were then separated using cation exchange chromatography and each fraction was derivatized with trifluoroacetic anhydride and the ratio of the deuterated:undeuterated species determined using GC-MS. Ratios of creatine:creatine-d(3), and creatinine:creatinine-d(3), and the concentrations of each of these species, were able to be determined in urine, plasma and red blood cells. Thus, the uptake of labeled creatine into plasma and red blood cells and its excretion in urine could be followed for a subject who ingested creatine-d(3). Creatine-d(3) was found in the plasma and red blood cells 10 min after ingestion, while creatine-d(3) and creatinine-d(3) were found in the urine collected after the first hour.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

PubMed

Hirsch, Sheldon; Hirsch, Jackie; Bhatt, Udayan; Rovin, Brad H

2012-01-01

Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use. This study is a retrospective review of 48 mostly African-American patients with CKD treated with multiple and/or high-dose renin-angiotensin system (RAS) inhibition and diuretics, targeting both low BP and reduction of urine protein. RASI was not reduced in response to initial increases in serum creatinine greater than 30%. A clinically well-tolerated increase in serum creatinine over 30% during the first year occurred in 41% of the patients. Treatment was unaltered, and target goals for BP and urine protein were typically achieved. After the point of maximal serum creatinine in the first year, these patients had minimal progression of disease over the next 6 years, with a long-term estimated glomerular filtration rate slope of only -0.52 ml/min/year/1.73 m(2). Only 25% progressed to end-stage renal disease or death. The 30% limitation to initial increases in the serum creatinine still pertains for single RASI at usual doses. However, favorable long-term outcomes suggest that initial increases over 30% should be tolerated in the context of dual goal-directed, more aggressive RASI and diuretic use. Copyright © 2012 S. Karger AG, Basel.

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

PubMed Central

Bottomley, Christian; Loyse, Angela; Brouwer, Annemarie E.; Muzoora, Conrad; Taseera, Kabanda; Jackson, Arthur; Phulusa, Jacob; Hosseinipour, Mina C.; van der Horst, Charles; Limmathurotsakul, Direk; White, Nicholas J.; Wilson, Douglas; Wood, Robin; Meintjes, Graeme; Harrison, Thomas S.; Jarvis, Joseph N.

2015-01-01

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility. PMID:26349818

"Normal" Creatinine Levels Predict Persistent Kidney Injury and Waitlist Mortality in Outpatients with Cirrhosis.

PubMed

Cullaro, Giuseppe; Park, Meyeon; Lai, Jennifer C

2018-04-26

Acute kidney injury (AKI) is a critical determinant of outcomes in hospitalized patients with cirrhosis, but little is known of the impact of AKI in the outpatient setting. We analyzed 385 adult outpatients with cirrhosis listed for liver transplant at a single center; excluded were those with severe hepatic encephalopathy, hepatocellular carcinoma or on hemodialysis. Baseline serum creatinine (bCr) was defined as the lowest value recorded; peak creatinine (pCr) as the highest value; delta creatinine (ΔCr) as pCr minus bCr; AKI as a rise in sCR by ≥0.3 mg/dl from bCr; persistent kidney injury as elevation of sCR by ≥0.3 mg/dl from bCr on each subsequent clinical assessment. Among 385 outpatients with cirrhosis, bCr was ≤0.70, 0.70 - 0.97, and ≥0.97 mg/dL in 28%, 38%, and 34%, respectively. At a median follow-up of 16 (8 - 28) months, 143 (37%) had ≥1 AKI episode, which increased significantly by bCr group (24v.37v.48%, p=0.001). Of these 143 with AKI, 13% developed persistent kidney injury. A multivariable cox-regression analysis highlighted that bCr (HR 2.96) and ΔCr (HR 2.05) were the only factors independently associated with the development of persistent kidney injury [p<0.001]. The likelihood of death/delisting increased by bCr group (14v.19v.28%, p=0.03). A competing risk analysis demonstrated that each 1 mg/dL increase in bCr was independently associated with a 62% higher risk of death/delisting when accounting for transplantation and adjusting for confounders. In conclusion, not only is AKI common in outpatients with cirrhosis, but even "clinically normal" bCr levels significantly impact the risk of persistent kidney injury and waitlist mortality, supporting the need for a lower clinical threshold to initiate monitoring of renal function and implementation of renal-protective strategies. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Kidney stones and kidney function loss: a cohort study.

PubMed

Alexander, R Todd; Hemmelgarn, Brenda R; Wiebe, Natasha; Bello, Aminu; Morgan, Catherine; Samuel, Susan; Klarenbach, Scott W; Curhan, Gary C; Tonelli, Marcello

2012-08-29

To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. Alberta, Canada, between 1997 and 2009. 3,089,194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1,954,836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. One or more kidney stones during follow-up. Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m(2)), and sustained doubling of serum creatinine concentration from baseline. 23,706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68,525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥ 50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms.

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

PubMed

Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

2010-10-01

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Enzymatic cycling method using creatine kinase to measure creatine by real-time detection.

PubMed

Ueda, Shigeru; Sakasegawa, Shin-Ichi

2016-08-01

We have developed a novel enzymatic cycling method that uses creatine kinase (CK) to measure creatine. The method takes advantage of the reversibility of the CK reaction in which the forward (creatine phosphate forming) and reverse reactions are catalyzed in the presence of an excess amount of ATP and IDP, respectively. Real-time detection was accomplished using ADP-dependent glucokinase (ADP-GK) together with glucose-6-phosphate dehydrogenase. ADP, one of the cycling reaction products, was distinguished from IDP by using the nucleotide selectivity of the ADP-GK. The increasing level of ADP was measured from the level of reduced NADP at 340 nm. The method is appropriate for an assay that requires high sensitivity because the rate of increase in absorbance at 340 nm is proportional to the amount of CK present in the reaction mix. We reasoned that the method with CK in combination with creatinine amidohydrolase could be used to assay creatinine, an important marker of kidney function. Our results confirmed the quantitative capability of the assay. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum accumulation of a creatinine oxidative metabolite (NZ-419: 5-hydroxy-1- methylhydatoin) as an intrinsic antioxidant in diabetic patients with or without chronic kidney disease.

PubMed

Hasegawa, G; Nakano, K; Ienaga, K

2011-10-01

In mammals, creatinine (Cr) is catabolized by a dual oxidative pathway via 5-hydroxy-1-methylhydantoin or 5-hydroxycreatinine. The former, an intrinsic antioxidant, termed NZ-419, has been reported to prevent the progression of chronic renal failure in animal models. However, its clinical intrinsic serum level has not yet been reported. We analyzed serum NZ-419 levels in diabetic and nondiabetic patients with or without Stage 3 - 5 chronic kidney disease (CKD). The levels of NZ-419 in diabetic patients with (88.1 ± 17.2 µg/dl, p < 0.001) or without (31.5 ± 2.4 µg/dl, p < 0.05) Stage 3 - 5 CKD were significantly higher than in nondiabetic normal controls (9.0 ± 5.6 µg/dl). The molar ratio data showed NZ-419/Cr was significantly higher in both diabetic patients with (p < 0.01) or without Stage 3 - 5 CKD (p < 0.001) compared to nondiabetic normal controls. No further increase occurred with increasing severity of renal failure. Furthermore, nondiabetic patients with or without Stage 3 - 5 CKD did not show significantly different molar ratio values than controls but had significantly higher values of NZ-419 levels (p < 0.001). Overproduction and decreased clearance played a major role in the increased NZ-419 levels we observed in the patients with diabetes and Stage 3 - 5 CKD, respectively. The existence of chronic renal failure did not further enhance this overproduction.

Development of paper-based sensor coupled with smartphone detector for simple creatinine determination

NASA Astrophysics Data System (ADS)

Tambaru, David; Rupilu, Reski Helena; Nitti, Fidelis; Gauru, Imanuel; Suwari

2017-03-01

Creatinine level in urine is one of the most important indicators for kidney diseases. A routine assay for this compound is vital especially for those who suffer from kidney malfunction. However, the existing methods are mostly expensive, impractical and time consuming. Here in, we report a research on the development of sensor for creatinine analysis by using cheap materials such as paper and coupled with a smartphone as the detector leading to an inexpensive and free-instrument method. This research was done based on the Jaffe reaction in which the creatinine was reacted with picric acid in basic solution to form an orange-red creatinine-picric complex. The red-green-blue intensity of the complex, captured with a smartphone, was measured and then digitized with free-download Microsoft Visual c# 2010I Express applications, as the analytical response. This proposed method was evaluated based on its precision, accuracy, percent of recovery and limit of detection. It was found that the precision, accuracy, percent of recovery and limit of detection of this method were 5.55%, 0.74 %, 96.73 ± 6.12 % and 8.02 ppm, respectively. It can be concluded that the paper based sensors with digital imaging approach using Microsoft Visual c# 2010I Express,with its simplicity and affordabilitycan be applied for on-site determination of creatinine level.

Supplemented creatine induces changes in human metabolism of thiocompounds and one- and two-carbon units.

PubMed

Navrátil, T; Kohlíková, E; Petr, M; Pelclová, D; Heyrovský, M; Pristoupilová, K

2010-01-01

The administration of creatine (5 g/day for one month) to 11 young active sportsmen affected their urinary excretion of creatine, creatinine, and thiodiglycolic acid (TDGA) as well as blood levels of homocysteine, vitamin B12 and folates. The probands were divided into four groups, according to the amount of creatine found in urine, and of folates and vitamin B12 determined in blood. The changes of folates and vitamin B12 were mutually reciprocal. Each group utilized CR as donor of one- and two-carbon (1C and 2C) units by means of homocysteine (HoCySH), folates, and vitamin B12, in different metabolic pathways. In 10 men the creatine administration was accompanied by an increase of HoCySH level in blood, while in the last man, with accidentally discovered hyperhomocysteinemia, the HoCySH level dropped by 50%. Differences between initial and terminal TDGA levels indicate that creatine affects equilibria of redox processes. Creatinine excretion into urine changed in the dependence on the extent of metabolic disturbances.

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study.

PubMed

Khan, Irfanullah; Khan, Amer Hayat; Adnan, Azreen Syazril; Sulaiman, Syed Azhar Syed; Hamzah, Azhar Bin Amir; Ahmed, Nafees; Khan, Amjad

2018-06-01

Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country. The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥ 65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value < 0.05 in serum creatinine level for the three age groups [F (2, 297) = 1.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p value < 0.05 in the mean serum creatinine level for the four groups [F (3, 396) = 2.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient's age and BMI. Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

Intraosseous samples can be used for creatinine measurements--an experimental study in the anaesthetised pig.

PubMed

Strandberg, Gunnar; Lipcsey, Miklós; Eriksson, Mats; Larsson, Anders

2014-01-01

Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements. Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae. There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times. Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.

Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador--A cross-shift study of workers at risk of Mesoamerican nephropathy.

PubMed

García-Trabanino, Ramón; Jarquín, Emmanuel; Wesseling, Catharina; Johnson, Richard J; González-Quiroz, Marvin; Weiss, Ilana; Glaser, Jason; José Vindell, Juan; Stockfelt, Leo; Roncal, Carlos; Harra, Tamara; Barregard, Lars

2015-10-01

An epidemic of progressive kidney failure afflicts sugarcane workers in Central America. Repeated high-intensity work in hot environments is a possible cause. To assess heat stress, dehydration, biomarkers of renal function and their possible associations. A secondary aim was to evaluate the prevalence of pre-shift renal damage and possible causal factors. Sugarcane cutters (N=189, aged 18-49 years, 168 of them male) from three regions in El Salvador were examined before and after shift. Cross-shift changes in markers of dehydration and renal function were examined and associations with temperature, work time, region, and fluid intake were assessed. Pre-shift glomerular filtration rate was estimated (eGFR) from serum creatinine. The mean work-time was 4 (1.4-11) hours. Mean workday temperature was 34-36 °C before noon, and 39-42 °C at noon. The mean liquid intake during work was 0.8L per hour. There were statistically significant changes across shift. The mean urine specific gravity, urine osmolality and creatinine increased, and urinary pH decreased. Serum creatinine, uric acid and urea nitrogen increased, while chloride and potassium decreased. Pre-shift serum uric acid levels were remarkably high and pre-shift eGFR was reduced (<60 mL/min) in 23 male workers (14%). The high prevalence of reduced eGFR, and the cross-shift changes are consistent with recurrent dehydration from strenuous work in a hot and humid environment as an important causal factor. The pathophysiology may include decreased renal blood flow, high demands on tubular reabsorption, and increased levels of uric acid. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

PubMed

Apaydin Yildirim, Betul; Kordali, Saban; Terim Kapakin, Kubra Asena; Yildirim, Fatih; Aktas Senocak, Esra; Altun, Serdar

2017-06-01

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells.

PubMed

Ienaga, Kazuharu; Sohn, Mimi; Naiki, Mitsuru; Jaffa, Ayad A

2014-06-01

A creatinine metabolite, 5-hydroxy-1-methylhydantoin (HMH: NZ-419), a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. In the current study, we demonstrate that HMH modulates the effects of glucose and bradykinin (BK) in vascular smooth muscle cell (VSMC). HMH a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. HMH inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that HMH may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.

An unusual case of crescentic lupus nephritis presenting with normal renal function.

PubMed

Manohar, Sandhya; Subramanian, Chamundeswari; Lakshmi, Kameswari

2015-11-01

Lupus nephritis is a life-threatening manifestation of systemic lupus erythematosus (SLE). This is commonly suspected when lupus patients present with elevated serum creatinine levels. But it is important to be aware that even patients with advanced disease in the kidney from SLE can have normal renal function, thus requiring a high index of suspicion. We present the case of a patient who presented with nonspecific musculoskeletal symptoms and was diagnosed with SLE. He also had nephrotic range proteinuria but his serum creatinine was normal. A renal biopsy revealed diffuse proliferative crescentic lupus nephritis. We have reviewed the literature for correlation between crescents; a sign of severe glomerular damage and creatinine levels.

Comparison of absolute serum creatinine changes versus Kidney Disease: Improving Global Outcomes consensus definitions for characterizing stages of acute kidney injury

PubMed Central

Wang, Henry E.; Jain, Gaurav; Glassock, Richard J.; Warnock, David G.

2013-01-01

Background The Kidney Disease: Improving Global Outcomes (KDIGO) system for classification of acute kidney injury (AKI) severity utilizes a staging schema based on relative changes in serum creatinine (sCr) concentration and urine output. This study compares the in-hospital mortality associated with KDIGO-defined AKI stages and AKI stages defined by absolute sCr increases (‘Delta-Creatinine’). Methods The study included an analysis of hospital discharge and laboratory data from an urban academic medical center over a 1-year period. Including adult in-patients undergoing two or more sCr measurements, the study classified AKI stages using the KDIGO consensus standards as well as absolute increases in sCr (‘Delta-Creatinine’); Stage 0, sCr increase <0.3 mg/dL, Stage 1, sCr increase 0.3–0.69 mg/dL, Stage 2, sCr increase 0.7–1.19 mg/dL and Stage 3, sCr increase ≥1.2 mg/dL or initiation of renal replacement therapy. The Delta-Creatinine cut-points were defined to optimize discrimination of in-patient mortality between AKI stages. The associations between KDIGO and Delta-Creatinine AKI stages and in-hospital mortality were compared using the time-dependent hazard ratios (HRs) and the net reclassification improvement (NRI). Results Of the 19 878 hospitalizations included in the analysis, the prevalence of AKI was 23.4% as defined by the KDIGO criteria. The Delta-Creatinine system discriminated the differences between adjacent AKI stages (i.e. 1 versus 0, 2 versus 1, 3 versus 3) earlier than the KDIGO system. The NRI between Delta-Creatinine and KDIGO for the prediction of mortality was 9.7% [95% confidence interval (CI) 6.2–13.2%]. Stratification by age, sex, race and history of chronic kidney disease (CKD) resulted in similar NRI values. Conclusion The Delta-Creatinine system, based on the absolute increases in sCr, provides a promising alternative to the KDIGO system for characterizing the severity of AKI and its associations with in-patient mortality. PMID:23355628

Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

PubMed

Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

2017-02-01

Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4^th hour of PET as slow transporter (< 0.47), slow-average transporter (0.47 - 0.56), fast-average transporter (0.57 - 0.67), and fast transporter (> 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p < 0.001) and therefore higher peritoneal phosphorus clearance (61.7 ± 15.1 L/week/1.73 m² vs. 48.4 ± 14.0 L/week/1.73 m², p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
.

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

PubMed

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

2018-02-01

Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction. Here, we compared relationships of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) with various measures of kidney function in euthyroid subjects. Relationships of eGFR, based on creatinine (eGFRcrea), cystatin C (eGFRcysC), creatinine+cystatin C combined (eGFRcrea-cysC) and creatinine clearance (CrCl) with TSH, FT4 and FT3 were determined in 2180 euthyroid subjects (TSH, FT4 and FT3 all within the reference range; anti-thyroid peroxidase autoantibodies negative) who did not use thyroid hormones, anti-thyroid drugs, amiodarone or lithium carbonate. In multivariable models including TSH, FT3 and FT4 together, eGFRcrea, eGFRcysC and eGFRcrea-cysC and CrCl were all positively related to FT3 (P≤0.001), translating into a 2.61 to 2.83mL/min/1.73m 2 increase in eGFR measures and a 3.92mL/min increase in CrCl per 1pmol/L increment in FT3. These relationships with FT3 remained taking account of relevant covariates. In euthyroid subjects renal function is associated with thyroid function status, especially by serum FT3, irrespective of the eGFR equation applied. In the euthyroid state, cystatin C-based eGFR equations are appropriate to assess the relationship of renal function with variation in thyroid function status. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Back to Basics: Is There a Good Reason to Not Systematically Measure Urine Creatinine in Acute Kidney Injury Monitoring?

PubMed

Maciel, Alexandre Toledo

2016-01-01

Regardless of the recent advancements in the understanding of the pathophysiology of acute kidney injury (AKI), its diagnosis remains fundamentally dependent on the serum creatinine (sCr) level and urine output (UO), both of which are considered late markers of AKI, offering only a vague idea of the actual creatinine clearance (CrCl). Although not ideal, CrCl is still the most common alternative of the glomerular filtration rate (GFR) in clinical practice. It is generally accepted that early diagnosis of AKI must reveal kidney impairment before sCr increases. Much effort has been made to find tubular and glomerular markers of injury which increase (in blood and/or in urine) before the 'official' diagnosis of AKI. Most of these markers are expensive and not widely available, especially in developing countries. Urine creatinine (CrU), the major link between sCr and UO, has been systematically ignored and clinicians are usually unaware of its value. The reasons for this are unclear, but it may be related to the lack of a reference range, dependence of its concentration value on the urine flow (which in turn is only adequately assessed with an indwelling urinary catheter) and the clinical unavailability of its counterbalance part - creatinine production. Changes in urine tend to precede changes in blood in the course of AKI development and recovery. Hence, it is important to bear in mind that changes in sCr signal renal dysfunction with a significant delay. The search for a more dynamic, 'real-time' but pragmatic assessment of renal function, especially in patients at risk of abrupt decrease in GFR is certainly one of the most relevant focus of research in the field of AKI monitoring. Systematic CrU assessment may be highly relevant in this case. © 2016 S. Karger AG, Basel.

Urinary levels of eight phthalate metabolites and bisphenol A in mother-child pairs from two Spanish locations.

PubMed

Cutanda, Francisco; Koch, Holger M; Esteban, Marta; Sánchez, Jinny; Angerer, Jürgen; Castaño, Argelia

2015-01-01

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother-child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3μg/g creatinine (95% CI 30.2-36.6) for mothers and 63.0μg/g creatinine (95% CI 56.8-69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8μg/g creatinine (95% CI 124.0-183.5) for mothers and 198.9μg/g creatinine (95% CI 165.2-239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0μg/g (95% CI 1.6-2.4) for mothers and 2.01μg/g (95% CI 1.7-2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place. Copyright © 2014 Elsevier GmbH. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, Virginia M., E-mail: vweaver@jhsph.edu; Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, bloodmore » lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 μg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (β coefficient=3.1 mL/min/1.73 m{sup 2}; 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary. - Highlights: • Positive associations between urine metals and creatinine-based eGFR are unexpected. • Optimal approach to urine concentration adjustment for urine biomarkers uncertain. • We compared urine concentration adjustment methods. • Positive associations observed only with urine creatinine adjustment. • Additional research using non-creatinine-based methods of adjustment needed.« less

Citrate-capped silver nanoparticles as a probe for sensitive and selective colorimetric and spectrophotometric sensing of creatinine in human urine.

PubMed

Alula, Melisew Tadele; Karamchand, Leshern; Hendricks, Nicolette R; Blackburn, Jonathan M

2018-05-12

Urinary creatinine concentration is a critical physiological parameter that enables reliable assessment of patient renal function and diagnosis of a broad spectrum of diseases. In this study, a simple and inexpensive sensor comprising monodisperse, citrate-capped silver nanoparticles (cc-AgNPs) was developed, which enabled rapid, sensitive and selective quantitation of creatinine directly in unprocessed urine. The mechanism of this sensor entails the creatinine-mediated aggregation of the cc-AgNPs (within 1 min) under alkaline conditions (pH 12). This is attributed to the tautomerization of creatinine to its amino anionic species at alkaline pH, which cross-link the cc-AgNPs via hydrogen bond networks with the negatively charged citrate caps. Creatinine elicited visibly-discernable color changes of the cc-AgNPs colloids in a concentration-dependent manner up to 10 μM. UV-visible spectroscopic analyses of the cc-AgNPs revealed that creatinine elicited a concentration-dependent decrease in intensity of the localized surface plasmon resonance (LSPR) band centered around 403 nm, with a concomitant increase in intensity of the red-shifted LSPR band at 670 nm. This observation denotes a creatinine-mediated increase in cc-AgNP particle size via aggregation, as confirmed by transmission electron microscopy analysis. The cc-AgNP sensor exhibited a linear correlation between the A 670 /A 403 extinction ratio and creatinine concentration range of 0-4.2 μM in aqueous solutions (R 2  = 0.996), and a low detection limit of 53.4 nM. Hence, the simplicity, short assay time, and high sensitivity and selectivity of our cc-AgNP sensor affirms its utility as a creatinine monitoring assay for low-resource, point-of-care settings. Copyright © 2018 Elsevier B.V. All rights reserved.

False-Positive Rate of AKI Using Consensus Creatinine-Based Criteria.

PubMed

Lin, Jennie; Fernandez, Hilda; Shashaty, Michael G S; Negoianu, Dan; Testani, Jeffrey M; Berns, Jeffrey S; Parikh, Chirag R; Wilson, F Perry

2015-10-07

Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false-positive rates because of inherent laboratory and biologic variabilities of creatinine. We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false-positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient's true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false-positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%-8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false-positive AKI diagnosis rate of 30.5% (interquartile range =30.1%-30.9%) versus 2.0% (interquartile range =1.9%-2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). Use of small serum creatinine changes to diagnose AKI is limited by high false-positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies. Copyright © 2015 by the American Society of Nephrology.

Nadir creatinine in posterior urethral valves: How high is low enough?

PubMed

Coleman, R; King, T; Nicoara, C-D; Bader, M; McCarthy, L; Chandran, H; Parashar, K

2015-12-01

Large retrospective studies of people with posterior urethral valves (PUV) have reported chronic renal insufficiency (CRI) in up to one third of the participants and end-stage renal failure in up to one quarter of them. Nadir creatinine (lowest creatinine during the first year following diagnosis) is the recognised prognostic indicator for renal outcome in PUV, the most commonly used cut-off being 1 mg/dl (88.4 umol/l). To conduct a statistical analysis of nadir creatinine in PUV patients in order to identify the optimal cut-off level as a prognostic indicator for CRI. Patients treated by endoscopic valve ablation at the present institution between 1993 and 2004 were reviewed. Chronic renal insufficiency was defined as CKD2 or higher. Statistical methods included receiver operating characteristic (ROC) curve analysis, Fisher exact test and diagnostic utility tests. Statistical significance was defined as P < 0.05. Nadir creatinine was identified in 96 patients. The median follow-up was 9.4 (IQR 7.0, 13.4) years. A total of 29 (30.2%) patients developed CRI, with nine (9.4%) reaching end-stage renal failure. On ROC analysis, Nadir creatinine was highly prognostic for future CRI, with an Area Under the Curve of 0.887 (P < 0.001). Renal insufficiency occurred in all 10 (100%) patients with nadir creatinine >88.4 umol/l compared with 19 of 86 (22.2%) patients with lower nadir creatinine (P < 0.001). As a test for future CRI, a nadir creatinine cut-off of 88.4 umol/l gave a specificity of 100%, but poor sensitivity of 34.5%. Lowering the cut-off to 75 umol/l resulted in improvement in all diagnostic utility tests (Table). All 14 (100%) patients with nadir creatinine >75 umol/l developed CRI, compared with 15 of 82 (18.3%) patients with lower nadir creatinine (P < 0.001). Sensitivity only approached 95% at 35 umol/l, at which level specificity was low (Table). Two out of 36 (5.6%) patients with nadir creatinine <35 umol/l developed CRI. Multivariate analysis found recurrent UTI (OR 4.733; CI 1.297-17.280) and nadir creatinine >75 umol/l (OR 48.988; CI 4.9-490.11) to be independent risk factors for progression to CRI. Using cut-off values of 35 umol/l and 75 umol/l, patients can be stratified into low-, intermediate- and high-risk groups, with development of CRI in 5.3%, 28.3% and 100%, respectively (P <0.001). The stage of CKD was higher in higher risk groups. Patients with nadir creatinine >75 umol/l (0.85 mg/dl) should be considered at high risk for CRI, while patients with nadir creatinine ≤35 umol/l (0.4 mg/dl) should be considered low risk. Patients with nadir creatinine between these two values have an intermediate risk of CRI. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Diffuse Interstitial Brain Edema in Patients With End-Stage Renal Disease Undergoing Hemodialysis: A Tract-Based Spatial Statistics Study

PubMed Central

Kong, Xiang; Wen, Ji-qiu; Qi, Rong-feng; Luo, Song; Zhong, Jian-hui; Chen, Hui-juan; Ji, Gong-jun; Lu, Guang Ming; Zhang, Long Jiang

2014-01-01

Abstract To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P < 0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P < 0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P > 0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes. PMID:25526483

Urinary 1-hydroxypyrene concentrations in Chinese coke oven workers relative to job category, respirator usage, and cigarette smoking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bo Chen; Yunping Hu; Lixing Zheng

1-Hydroxypyrene (1-OHP) is a biomarker of recent exposure to polycyclic aromatic hydrocarbons (PAHs). We investigated whether urinary 1-OHP concentrations in Chinese coke oven workers (COWs) are modulated by job category, respirator usage, and cigarette smoking. The present cross-sectional study measured urinary 1-OHP concentrations in 197 COWs from Coking plant I and 250 COWs from Coking plant II, as well as 220 unexposed referents from Control plant I and 56 referents from Control plant II. Urinary 1-OHP concentrations (geometric mean, {mu}mol/mol creatinine) were 5.18 and 4.21 in workers from Coking plants I and II, respectively. The highest 1-OHP levels in urinemore » were found among topside workers including lidmen, tar chasers, and whistlers. Benchmen had higher 1-OHP levels than other workers at the sideoven. Above 75% of the COWs exceeded the recommended occupational exposure limit of 2.3 {mu}mol/mol creatinine. Respirator usage and increased body mass index (BMI) slightly reduced 1-OHP levels in COWs. Cigarette smoking significantly increased urinary 1-OHP levels in unexposed referents but had no effect in COWs. Chinese COWs, especially topside workers and benchmen, are exposed to high levels of PAHs. Urinary 1-OHP concentrations appear to be modulated by respirator usage and BMI in COWs, as well as by smoking in unexposed referents.« less

Health status of copper refinery workers with specific reference to selenium exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holness, D.L.; Taraschuk, I.G.; Nethercott, J.R.

1989-09-01

Copper refinery workers exposed to selenium were studied before, during, and after a shutdown period. Urine selenium levels were 83 {plus minus} 30 mumol/mol creatinine and 69 {plus minus} 27 mumol/mol creatinine when measured on two occasions during exposure compared with 56 {plus minus} 17 mumol/mol creatinine when the workers had been free of exposure for 10 wk during a shutdown. The refinery workers reported more nose and eye irritation, indigestion, stomach pain, and fatigue than controls. Garlic-like breath odor was reported to be personally and socially offensive by many of the workers. Reporting of symptoms, pulmonary function indices, andmore » laboratory test results did not change with exposure except for hemoglobin level, which rose during the shutdown. Hemoglobin levels were found to be inversely correlated with the urine selenium level, and there was a positive correlation noted for the interactive effect of urine selenium and urine arsenic levels on hemoglobin.49 references.« less

Toxicologic Characterization of a Novel Explosive, Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT), in Female Rats and in vitro Assays

DTIC Science & Technology

2011-03-01

inflammation, hepatocyte degeneration, centrilobular hepatocyte hyper- trophy, increased mitoses, megakaryocytic hepatocytes, and bile duct ...of 2 g/L. However, TAG-MNT was cytotoxic to bacteria and a human liver cell line at 250 mg/L and greater. Unlike RDX, TAG-MNT did not have an...food intake, weight loss, increased kidney weight, leucopenia, and elevated blood urea nitrogen and creatinine levels. Leucopenia, increased liver mass

Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders.

PubMed

Bull, Gillian; Shattock, Paul; Whiteley, Paul; Anderson, Roz; Groundwater, Paul W; Lough, John W; Lees, George

2003-10-01

Autism is a heterogeneous pervasive developmental disorder with a poorly defined aetiology and pathophysiology. There are indications that the incidence of the disease is rising but still no definitive diagnostic biochemical markers have been isolated. Here we have addressed the hypothesis that urinary levels of trans -indolyl-3-acryloylglycine (IAG) are abnormal in patients diagnosed with autism spectrum disorders (ASD) compared to age-matched controls. Urine samples were collected on an opportunistic basis and analysed for IAG concentration (normalised against creatinine content to account for changes in urinary volume) using reversed phase HPLC with UV detection. Statistical analysis (Mann-Whitney tests) showed highly significant increases (p=0.0002) in the levels of urinary IAG in the ASD group (median 942 microV per mmol/L of creatinine [interquartile range 521-1729], n=22) compared to asymptomatic controls (331 [163-456], n=18). Detailed retrospective analysis showed that gender (boys 625 microV per mmol/L of creatinine [294-1133], n=29; girls 460 [282-1193], n=11: P=0.79) and age (control donor median 10 years [8-14], n=15; ASD median 9 years [7-11] n=22: P=0.54) were not significantly correlated with IAG levels in this non-blinded volunteer study. Our results strongly suggest that urinary titres of IAG may constitute an objective diagnostic indicator for ASD. Mechanisms for the involvement of IAG in ASD are discussed together with future strategies to address its specificity.

Changes in serum biochemical factors associated with opium addiction after addiction desertion.

PubMed

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients.

Effect of sodium chloride intake on urine volume, urinary urea excretion, and milk urea concentration in lactating dairy cattle.

PubMed

Spek, J W; Bannink, A; Gort, G; Hendriks, W H; Dijkstra, J

2012-12-01

Milk urea nitrogen (MUN; mg of N/dL) has been shown to be related to excretion of urinary urea N (UUN; g of N/d) and total excretion of urinary N (UN; g of N/d) in dairy cows. In the present experiment, it was hypothesized that MUN and the relationship between MUN and UUN or UN is affected by urine volume as a result of dietary sodium chloride intake. Twelve lactating Holstein-Friesian dairy cows (mean ± SD: milk production 28.1±3.23 kg/d and 190±41 d in milk), of which 4 were fitted with catheters in the urine bladder and jugular vein, were randomly assigned to 4 dietary levels of sodium chloride (3, 9, 14, and 19 g of Na/kg of DM) according to a triple 4×4 Latin square design. Cows were fed at 95% of ad libitum intake, excluding salt addition. Milk was analyzed for MUN and protein content; urine was analyzed for total N, urea, and creatinine content; feces were analyzed for total N and DM content; and blood plasma was analyzed for urea and creatinine content. Creatinine clearance rate (CCR; L/min) and renal urea reabsorption ratio were estimated based on plasma concentrations of urea and creatinine, and total excretion of urea and creatinine in urine. Intake of DM and N, milk production, and milk protein content were (mean ± SD), on average, 21.4±1.24 kg/d, 522±32.0 g/d, 25.4±2.53 kg/d, and 3.64±0.186%, respectively. A linear relationship was found between Na intake and urine production [urine (kg/d; mean ± SE)=7.5±4.33+0.136±0.0143 × Na intake (g/d)] and between Na intake and MUN [MUN (mg/dL; mean ± SE)=13.5±0.35-0.0068±0.00104 × Na intake (g/d)]. Despite the decrease in MUN with increased Na intake, UN excretion increased linearly with Na intake. Excretion of UUN was not affected by dietary Na content. A linear plateau relationship was observed between CCR and renal urea reabsorption. An increase in CCR coincided with an increase in calculated renal urea reabsorption until a CCR breakpoint value (mean ± SD) of 1.56±0.063 L/min was reached. We conclude that Na intake is negatively related to MUN, whereas UUN is not affected. Variation in mineral intake levels that affect urine volume should, therefore, be taken into account when using MUN as an indicator of UUN in dairy cattle. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Creatinine and calcium in urine and blood after brief exposure to magnetic fields].

PubMed

Schmidt, F; Mannsåker, T; Løvlie, R

1999-02-10

In this experimental study, 35 males were exposed to artificial magnetic fields. The fields were produced by a set of Helmholz coils internally isolated by a Faraday cage which effectively eliminated electrical fields. Each participant stayed inside the coils for 40 minutes on two occasions with an interval of seven days, but was actually only once exposed to a static magnetic field (9.6 mT) and oscillating magnetic fields of variable frequency and strength. Urine and blood samples were taken before and after exposure, and before and after non-exposure. Analysis detected significant changes in serum creatinine level after exposure (p < 0.0001). The changes in serum creatinine level in the nonexposed situation were significantly smaller than the changes found in the exposed situation (p < 0.0001). The changes i urine creatinine after 40 minutes of exposure was also found to be significant (p < 0.01). Exposure to magnetic fields may induce biological reactions.

Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients.

PubMed

Boxma, Paul Y; van den Berg, Else; Geleijnse, Johanna M; Laverman, Gozewijn D; Schurgers, Leon J; Vermeer, Cees; Kema, Ido P; Muskiet, Frits A; Navis, Gerjan; Bakker, Stephan J L; de Borst, Martin H

2012-01-01

Vitamin K is essential for activation of γ-carboxyglutamate (Gla)-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP). Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60) with stable renal function (creatinine clearance 61 [42-77] (median [interquartile range]) ml/min), who were 75 [35-188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP levels (621 vs 852 pmol/L, p<0.05). Accordingly, dp-ucMGP levels were elevated (>500 pmol/L) in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

NASA Astrophysics Data System (ADS)

Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

2018-03-01

Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

Therapeutic Effect of Captopril, Pentoxifylline, and Cordyceps Sinensis in Pre-Hepatic Portal Hypertensive Rats

PubMed Central

Ahmed, Ahmed F.; El-Maraghy, Nabila N.; Ghaney, Rasha H. Abdel; Elshazly, Shimaa M.

2012-01-01

Background/Aim: Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats. Settings and Design: Wister male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days. Patients and Methods: Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state. Results: Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes. Conclusions: captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level. PMID:22626797

Degradation of creatinine using boron-doped diamond electrode: Statistical modeling and degradation mechanism.

PubMed

Zhang, Zhefeng; Xian, Jiahui; Zhang, Chunyong; Fu, Degang

2017-09-01

This study investigated the degradation performance and mechanism of creatinine (a urine metabolite) with boron-doped diamond (BDD) anodes. Experiments were performed using a synthetic creatinine solution containing two supporting electrolytes (NaCl and Na 2 SO 4 ). A three-level central composite design was adopted to optimize the degradation process, a mathematical model was thus constructed and used to explore the optimum operating conditions. A maximum mineralization percentage of 80% following with full creatinine removal had been achieved within 120 min of electrolysis, confirming the strong oxidation capability of BDD anodes. Moreover, the results obtained suggested that supporting electrolyte concentration should be listed as one of the most important parameters in BDD technology. Lastly, based on the results from quantum chemistry calculations and LC/MS analyses, two different reaction pathways which governed the electrocatalytic oxidation of creatinine irrespective of the supporting electrolytes were identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Assessment of exposure to polycyclic aromatic hydrocarbons in asphalt workers by measurement of urinary 1-hydroxypyrene].

PubMed

Campo, Laura; Calisti, R; Polledri, Elisa; Barretta, F; Stopponi, Roberta; Massacesi, Stefania; Bertazzi, P A; Fustinoni, Silvia

2011-01-01

Asphalt workers are potentially exposed to polycyclic aromatic hydrocarbons (PAHs). As some PAHs are classified as carcinogenic, the assessment of occupational exposure to these agents is of the utmost importance in preventing toxic effects. To assess exposure to PAHs by urinary 1-hydroxypyrene (1-OHPyr). We studied 22 asphalt workers (14 smokers) and 5 control subjects (1 smoker). Multiple samples of urine (up to 4per subject) were collected at the end of the shift for the measurement of 1-OHPyr by LCMS/MS. Univariate and multivariate linear models for repeated measurements were used to evaluate the differences between groups and to identify the variables influencing of exposure. The median urinary excretion of 1-OHPyr in asphalt workers was low, but higher than that of control subjects (184 vs. <20 ng/L, or 106 vs. <20 ng/g creatinine, p < 0.001); cigarette smoking marginally increased 1-OHPyr in smoking asphalt workers in comparison to non-smokers (129 vs. 208 ng/L p= 0.09 or 94 vs. 121 ng/g creatinine, p = 0.06). The number of consecutive days at work significantly influenced the urinary excretion of l-OHPyr [+59% every day, CI: (2, 147), p = 0.04]. Subjects using paving machines had the highest exposure. A strong association between 1-OHPyr and urinary creatinine was observed. urinary 1-OHPyr is a useful indicator of occupational exposure to low levels of PAHs, such as those found in the subjects studied; in using this biomarker it is recommended to collect urine samples at the end of the working week and to express levels of the biomarker corrected for urinary creatinine.

Determination of Deoxynivalenol in the Urine of Pregnant Women in the UK

PubMed Central

Wells, Liz; Hardie, Laura; Williams, Courtney; White, Kay; Liu, Yunru; De Santis, Barbara; Debegnach, Francesca; Moretti, Georgio; Greetham, Stephanie; Brera, Carlo; Rigby, Alan; Atkin, Stephen; Sathyapalan, Thozhukat

2016-01-01

Deoxynivalenol (DON) is one of the most commonly occurring trichothecenes, produced mainly by Fusarium graminearum. Little is known about the effect of DON exposure or the levels of DON exposure that occur during pregnancy. The project aimed to provide data on levels of total DON and de-epoxi Deoxynivalenol (DOM-1) in pregnant human urine samples analysed by liquid chromatography-mass spectrometry (LC-MS). Morning urine samples were collected over two consecutive days from 42 volunteers and associated food consumption was recorded for the 24 h prior to the sample. Spearman’s rho non-parametric test for correlation was used to assess the data. Levels of DON did not differ significantly between day 1 (mean 29.7 ng/mL urine or 40.1 ng DON/mg creatinine) and day 2 (mean 28.7 ng/mL urine or 38.8 ng DON/mg creatinine ng/mL/day) urine samples. The only significant positive correlation was found between total ng DON/mg creatinine and parity (rho = 0.307, n = 42, p < 0.005 two-tailed) and total ng DON/mg creatinine with baked goods on day 1 (rho = 0.532, n = 42, p < 0.0005 two-tailed). This study provides data on the DON levels in pregnancy in this suburban population and reassurance that those levels are within acceptable limits. PMID:27792137

Deoxynivalenol Biomarkers in the Urine of UK Vegetarians

PubMed Central

Wells, Liz; Hardie, Laura; Williams, Courtney; White, Kay; Liu, Yunru; De Santis, Barbara; Debegnach, Francesca; Moretti, Georgio; Greetham, Stephanie; Brera, Carlo; Papageorgiou, Maria; Thatcher, Natalie J.; Rigby, Alan; Atkin, Stephen L.; Sathyapalan, Thozhukat

2017-01-01

Deoxynivalenol (DON) is produced by Fusarium graminearum and is one of the most commonly occurring trichothecenes. Vegetarians are alleged to be a high-risk group for DON exposure due to high intakes of cereals susceptible to the growth of the mycotoxin. This study provides the levels of DON and de-epoxi Deoxynivalenol (DOM-1) in urine analysed by liquid chromatography-mass spectrometry (LC-MS) in UK vegetarians. Over two consecutive days, morning urine samples were collected from 32 vegetarians and 31 UK adult volunteers, and associated food consumption 24 h prior to the sample was recorded. Statistically significant differences between the weight of the UK adults and vegetarians (t = 3.15. df = 61, p ≤ 0.005 two-tailed) were observed. The mean levels of DON in urine for adults on day 1 was 3.05 ng free DON/mg creatinine, and on day 2 was 2.98 ng free DON/mg creatinine. Even though high mean levels were observed, most adults were within the tolerable daily intake. However, for vegetarians, the mean level of urinary DON on day 1 was 6.69 ng free DON/mg creatinine, and on day 2 was 3.42 ng free DON/mg creatinine. These levels equate to up to 32% of vegetarians exceeding recommended tolerable daily intakes (TDI) of exposure (1 µg/kg b.w./day). PMID:28640201

Plasma pentosidine levels measured by a newly developed method using ELISA in patients with chronic renal failure.

PubMed

Sanaka, Tsutomu; Funaki, Takenori; Tanaka, Toshihisa; Hoshi, Sayako; Niwayama, Jyun; Taitoh, Takashi; Nishimura, Hideki; Higuchi, Chieko

2002-05-01

The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, beta2-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may be useful for the early diagnosis of mild renal failure and to estimate the degree of the severity of renal diseases. Copyright 2002 S. Karger AG, Basel

The physiological determinants of low-level urine cadmium: an assessment in a cross-sectional study among schoolchildren.

PubMed

Wang, Hongyu; Dumont, Xavier; Haufroid, Vincent; Bernard, Alfred

2017-09-12

Recent studies in children have reported associations of urinary cadmium (U-Cd), used as biomarker of Cd body burden, with renal dysfunction, retarded growth and impaired cognitive development in children. Little is known, however, about factors influencing U-Cd in children and likely to act as confounders. In a cross-sectional study involving 249 schoolchildren (mean age, 5.72 years; 138 boys), we measured the urine concentrations of cadmium, zinc, lead, albumin, alpha 1 -microglobulin (A1M), retinol-binding protein, β 2 -microglobulin and club cell protein (CC16). Determinants of U-Cd expressed per creatinine or adjusted to specific gravity were identified by multiple regression analyses. Girls and boys had similar median concentrations of U-Cd (0.22 and 0.24 μg/L, 0.33 and 0.35 μg/g creatinine, respectively). When models were run without including creatinine or specific gravity among independent variables, urinary zinc, urinary A1M and age emerged as the strongest predictors of U-Cd expressed per g creatinine or adjusted to SG. When adding creatinine among predictors, urinary creatinine emerged as an additional strong predictor correlating negatively with U-Cd per g creatinine. This strong residual influence of diuresis, not seen when adding specific gravity among predictors, linked U-Cd to U-A1M or U-CC16 through secondary associations mimicking those induced by Cd nephrotoxity. In young children U-Cd largely varies with diuresis, zinc metabolism and urinary A1M. These physiological determinants, unrelated to Cd body burden, may confound the child renal and developmental outcomes associated with low-level U-Cd.

Clinical Relevance of Differences in Glomerular Filtration Rate Estimations in Frail Older People by Creatinine- vs. Cystatin C-Based Formulae.

PubMed

Jacobs, Anne; Benraad, Carolien; Wetzels, Jack; Rikkert, Marcel Olde; Kramers, Cornelis

2017-06-01

The risk of incorrect medication dosing is high in frail older people. Therefore, accurate assessment of the glomerular filtration rate is important. The objective of this study was to compare the estimated glomerular filtration rate using creatinine- and cystatin C-based formulae, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in frail older people. We hypothesized that frailty determines the difference between the creatinine- and cystatin C-based formulae. The mean difference between CKD-EPI creatinine and cystatin C was determined using (cross-sectional) data of 55 patients (mean age 73 years) admitted to a psychiatric ward for older adults. The level of agreement of these estimations was assessed by a Bland-Altman analysis. In all patients, the Rockwood's Frailty Index was derived and correlated with the mean difference between CKD-EPI creatinine and cystatin C. The mean difference between CKD-EPI creatinine (mean 71.2 mL/min/1.73 m 2 ) and CKD-EPI cystatin C (mean 57.6 mL/min/1.73 m 2 ) was 13.6 mL/min/1.73 m 2 (p < 0.0001). The two standard deviation limit in the Bland-Altman plot was large (43.2 mL/min/1.73 m 2 ), which represents a low level of agreement. The Frailty Index did not correlate with the mean difference between the creatinine- and cystatin C-based glomerular filtration rate (Pearson correlation coefficient 0.182, p = 0.184). There was a significant gap between a creatinine- and cystatin C-based estimation of glomerular filtration rate, irrespective of frailty. The range of differences between the commonly used estimated glomerular filtration rate formulae might result in clinically relevant differences in drug prescription and differences in chronic kidney disease staging.

[Effectiveness of nephroprotection by the selection of contrast media used during vascular interventions in patients with chronic renal failure?].

PubMed

Schönefeld, E; Höwler, S; Osada, N; Torsello, G

2011-10-01

The increasing number of endovascular procedures made aware of a kidney disease induced by contrast media (CM). Contrast-induced nephropathy (= CIN) can develop in 0.6-44 % of the treated patients by angiography and / or endovascular intervention. The incidence in high-risk patients ranges from 50 to 70 %. In most cases CIN is inconspicuous and reversible. But pre-existing chronic kidney disease, diabetes mellitus, age and variable different risk factors (e. g., PAOD) can induce irreversible renal impairment. The purpose of the presented trial is to investigate incidence, predictors, and out-come of CIN in chronic renal failure patients using two different CM; one non-ionic isoosmolar -iodixanol and the other non-ionic low-osmolar iopromide. To evaluate the incidence of CIN after endovascular diagnostics and intervention two collectives of 100  patients with chronic renal insufficiency were treated with different contrast media (CM). Inclusion followed prospectively in two collectives. One collective received iopromide (Ultravist™, Bayer Health Care, Lever-kusen, Germany), and the second hundred patients received iodixanol (Visipaque™, Nycomed Amersham, Princeton, New Jersey). Demographics, comorbidities, procedure-related data were completed by serum creatinine levels and GFR (= glomerular filtration rate). Inclusion criteria were a serum creatinine level ≥ 1.5 mg% and a GFR ≤ 60 mL / min. Those parameters were measured twice pre-interventionally, and one time 48-72  hours after the endovascular procedure. Collectives were homogenous and comparable concerning pre-existing risk factors, age and gender. Renal function stayed at a constant level and was independent of contrast medium selection, repectively. Average creatinine levels ranged around 1.77 mg% ± 0.75  standard deviation (SD) pre-interventionally; postinterventional measurement exposed a creatinine level of 1.74 mg% ± 0.74 SD as mean of both collectives. GFR (preinterventional 39.64 mL / min ± 12.48 SD) increased non-significantly to 45.48 mL / min ± 16.82 SD. Pre-existing chronic kidney disease had no effect on renal function parameters; no other risk factors could be evaluated. According to cost-effectiveness a low-osmolar monomeric contrast medium (LOCM) is a sufficient selection, under careful renal function control. © Georg Thieme Verlag KG Stuttgart ˙ New York.

M-type phospholipase A2 receptor autoantibodies and renal function in patients with primary membranous nephropathy.

PubMed

Hoxha, Elion; Harendza, Sigrid; Pinnschmidt, Hans; Panzer, Ulf; Stahl, Rolf A K

2014-11-07

Loss of renal function in patients with primary membranous nephropathy cannot be reliably predicted by laboratory or clinical markers at the time of diagnosis. M-type phospholipase A2 receptor autoantibodies have been shown to be associated with changes in proteinuria. Their eventual effect on renal function, however, is unclear. In this prospective, open, multicenter study, the potential role of M-type phospholipase A2 receptor autoantibodies levels on the increase of serum creatinine in 118 consecutive patients with membranous nephropathy and positivity for serum M-type phospholipase A2 receptor autoantibodies was analyzed. Patients were included in the study between April of 2010 and December of 2012 and observed until December of 2013. The clinical end point was defined as an increase of serum creatinine by ≥ 25% and serum creatinine reaching ≥ 1.3 mg/dl. Patients were divided into tertiles according to their M-type phospholipase A2 receptor autoantibody levels at the time of inclusion in the study: tertile 1 levels=20-86 units/ml (low), tertile 2 levels=87-201 units/ml (medium), and tertile 3 levels ≥ 202 units/ml (high). The median follow-up time of all patients in the study was 27 months (interquartile range=18-33 months). The clinical end point was reached in 69% of patients with high M-type phospholipase A2 receptor autoantibodies levels (tertile 3) but only 25% of patients with low M-type phospholipase A2 receptor autoantibodies levels. The average time to reach the study end point was 17.7 months in patients with high M-type phospholipase A2 receptor autoantibodies levels and 30.9 months in patients with low M-type phospholipase A2 receptor autoantibodies levels. A multivariate Cox regression analysis showed that high M-type phospholipase A2 receptor autoantibodies levels-in addition to men and older age-are an independent predictor for progressive loss of renal function. High M-type phospholipase A2 receptor autoantibodies levels were associated with more rapid loss of renal function in this cohort of patients with primary membranous nephropathy and therefore, could be helpful for treatment decisions. Copyright © 2014 by the American Society of Nephrology.

False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

PubMed Central

Lin, Jennie; Fernandez, Hilda; Shashaty, Michael G.S.; Negoianu, Dan; Testani, Jeffrey M.; Berns, Jeffrey S.; Parikh, Chirag R.

2015-01-01

Background and objectives Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false–positive rates because of inherent laboratory and biologic variabilities of creatinine. Design, setting, participants, & measurements We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false–positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient’s true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. Results Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false–positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%–8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false–positive AKI diagnosis rate of 30.5% (interquartile range =30.1%–30.9%) versus 2.0% (interquartile range =1.9%–2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). Conclusions Use of small serum creatinine changes to diagnose AKI is limited by high false–positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies. PMID:26336912

Exposure of the German general population to platinum and rhodium - Urinary levels and determining factors.

PubMed

Munker, Sven; Kilo, Sonja; Röß, Christoph; Jeitner, Peter; Schierl, Rudolf; Göen, Thomas; Drexler, Hans

2016-11-01

In this study the exposure of the general population in Germany to platinum and rhodium and its determinants was investigated in 259 participants (subdivided in three groups) by urine analyses and assessment of the dental status. Complementary, an interview including questions characterising possible exposure to traffic exhaust was conducted. The median excretion was 2.42ng platinum/g creatinine and 7.27ng rhodium/g creatinine. The detailed analysis of the collected data showed significant higher platinum excretion values with increasing number of surfaces covered with restorations containing precious metals (R=0.389; p<0.001), but also higher values for habitants of urban areas (median=3.43ng/g creatinine; 95th percentile=25.2ng/g) compared with those of rural areas (median=2.06ng/g creatinine; 95th percentile=20.0ng/g). Also, participants working in urban areas showed higher platinum excretion values (median=3.27ng/g; 95th percentile=19.6ng/g). Male participants living and working next to highly frequented roads showed higher rhodium excretion values (median=7.27ng/g; 95th percentile=13.5 ng/g). In summary, the study showed that exhaust emissions have an influence on platinum and rhodium excretion, but for platinum this influence is rather low compared to the influence of precious metals containing restorations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Assessment of exposure to mixture pollutants in Mexican indigenous children.

PubMed

Flores-Ramírez, R; Pérez-Vázquez, F J; Cilia-López, V G; Zuki-Orozco, B A; Carrizales, L; Batres-Esquivel, L E; Palacios-Ramírez, A; Díaz-Barriga, F

2016-05-01

The aim of the present work was to complete an exposure assessment in three Mexican indigenous communities using the community-based health risk assessment, which is the first step in the CHILD framework. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to polycyclic aromatic hydrocarbons (PAHs) and trans, trans-muconic acid (t,t-MA) as an exposure biomarker to benzene, persistent organic pollutants (POPs), lead, manganese, arsenic, and fluoride. Anthropometric measurements were also taken. In these communities, high percentages of children with chronic malnutrition were found (28 to 49 %) based on their weight and age. All communities showed a high percentage of children with detectable levels of four or more compounds (70 to 82 %). Additionally, our results showed that in indigenous communities, children are exposed to elevated levels of certain environmental pollutants, including manganese with 17.6, 16.8, and 7.3 μg/L from SMP, TOC, and CUA, respectively. Lead and HCB levels were similar in the indigenous communities (2.5, 3.1, and 4.2 μg/dL and 2.5, 3.1, and 3.7 ng/mL, respectively). 1-OHP and t,t-MA levels were higher in TOC (0.8 μmol/mol of creatinine, 476 μg/g of creatinine, respectively) when compared with SMP (0.1 μmol/mol of creatinine, 215.5 μg/g of creatinine, respectively) and CUA (0.1 μmol/mol of creatinine, 185.2 μg/g of creatinine, respectively). DDE levels were 30.7, 26.9, and 9.6 ng/mL in CUA, SMP, and TOC, respectively. The strength of this study is that it assesses exposure to pollutants with indications for the resultant risk before an intervention is made by the CHILD program to manage this risk in the indigenous communities. Considering the large number of people, especially children, exposed to multiple pollutants, it is important to design effective intervention programs that reduce exposure and the resultant risk in the numerous indigenous communities in Mexico.

A single measurement of biochemical markers of bone turnover has limited utility in the individual person.

PubMed

Beck-Jensen, J E; Kollerup, G; Sørensen, H A; Pors Nielsen, S; Sørensen, O H

1997-07-01

Biochemical markers of bone turnover are used to estimate the rate of bone loss in the individual osteoporotic patient. During recent years it has become increasingly clear that the biological variability of biochemical bone markers has to be taken into consideration in the evaluation of their usefulness in the clinical setting. Eleven premenopausal, 8 perimenopausal and 11 postmenopausal healthy women were included. We assessed the analytical and the biological components of variation for a number of resorptive and formative bone markers: u-hydroxyproline, u-pyridinoline, and u-deoxypyridinoline together with u-calcium and u-creatinine, s-total alkaline phosphatases and s-osteocalcin. Blood and urine samples were collected five times with 7-day intervals. Urinary parameters were expressed as outputs and corrected for creatinine in fasting night urines and second void fasting morning urines. The absolute values differed with a tendency towards increasing values in the postmenopausal women, but the biological variations in relation to menopausal status were not different. The biological variability was much higher for the urinary resorptive markers than for the formative markers in the blood. The critical difference expressing the difference needed between two serial results from the same person to be significant at a 5% level was 15% for s-alkaline phosphatases, 18% for s-osteocalcin, and lowest in the second void fasting morning urines with values of 28% and 34% for u-pyridinoline/creatinine and u-deoxypyridinoline/creatinine, and 50% and 112% for u-hydroxyproline/creatinine and u-calcium/creatinine, respectively. The index of individuality, denoting the individual variation divided by the variation between subjects, was in the range from 0.19 for s-alkaline phosphatases to 1.23 for u-hydroxyproline/minute in second void fasting morning urine making the use of conventional reference intervals difficult. Low indices, however, indicate high test performance and offer the possibility of stratification of persons within a range. The number of samples required to determine the true individual mean value +/- 5% for the single person, ranged from 5 for s-total alkaline phosphatases, 6 for s-osteocalcin, 23 for u-deoxypyridinoline/creatinine in the fasting morning urine to over two hundred for u-calcium analytes. It is concluded that, due to high biological variation, a single measurement of biochemical markers of bone turnover is of limited utility in the individual person. We recommend that routine clinical use of biochemical markers should be restricted until further evidence justifies it.

First indications demonstrating the preventive effects of NZ-419, a novel intrinsic antioxidant, on the initiation and/or progression of chronic renal failure in rats.

PubMed

Ienaga, Kazuharu; Mikami, Hiroki; Yokozawa, Takako

2009-07-01

The concentration of NZ-419 (5-hydroxy-1-methylimidazolidine-2,4-dione), an intrinsic antioxidant, has been shown to increase in the sera of animals and patients with chronic renal failure (CRF). This is the first report that orally administered exogenous NZ-419 prevents the initiation and/or progression of CRF in rats using an adenine-loaded model. After 24 d of adenine loading, there was a ca. 90% decrease in creatinine clearance (C(Cr)) in the control rats. Treatment with NZ-419 from the beginning significantly inhibited the decrease in C(Cr) and also the increase in serum creatinine (sCr). Bio-markers for in vivo hydroxyl radicals, the serum methylguanidine (sMG) level, and sMG/sCr molar ratio, not only in serum but also in the urine, kidney, liver, and muscle indicated that NZ-419 inhibited the increase in oxidative stress induced by CRF in rats. An increase of guanidinosuccinic acid, an another bio-marker of oxidative stress, was also inhibited with NZ-419.

Carnitine status in Thai adults.

PubMed

Tanphaichitr, V; Lerdvuthisopon, N; Dhanamitta, S; Broquist, H P

1980-04-01

Plasma carnitine and urinary carnitine levels were measured in Thai adults living in Bangkok city and Ubol villages. The mean plasma carnitine and urinary carnitine levels expressed in micromoles per liter in Bangkok adults were higher than those in Ubol adults. Their mean plasma carnitine levels were 56.6 +/- 1.8 and 50.3 +/- 1.7 whereas urinary carnitine levels were 161 +/- 19 and 127 +/- 18 micromole/liter, respectively. The nutritional status in Ubol adults was inadequate. This was evidenced by the significant decrease in urinary creatinine excretion, serum albumin, and hematocrit levels. The dietary assessment agreed with the biochemical findings. Since rice, limiting in carnitine, was the main protein and energy source consumed by Ubol adults their inadequate carnitine status could be due to the low carnitine intake. Sex affects plasma carnitine levels in Bangkok adults and urinary carnitine excretion in both groups. This could be related to the lean body mass in which most of the body carnitine resides. This is supported by the higher urinary creatinine excretion in males and the significant positive correlation between carnitine excretion and creatinine-height index.

Phosphate, urea and creatinine clearances: haemodialysis adequacy assessed by weekly monitoring.

PubMed

Debowska, Malgorzata; Wojcik-Zaluska, Alicja; Ksiazek, Andrzej; Zaluska, Wojciech; Waniewski, Jacek

2015-01-01

The specific distribution of phosphate and the control mechanisms for its plasma level makes phosphate kinetics during haemodialysis (HD) considerably different from those of urea and creatinine and makes the quantitative evaluation of adequacy of phosphate removal difficult. We propose the application of equivalent continuous clearance (ECC) as a phosphate adequacy parameter and compare it with ECC for creatinine and urea. Three consecutive dialysis sessions were evaluated for 25 patients on maintenance HD. Concentrations of phosphate, urea and creatinine in plasma were measured every 1h during the treatment and 45 min after, and every 30 min in dialysate. ECC was calculated using the removed solute mass assessed in dialysate and weekly solute profile in plasma. Similar calculations were performed also for the midweek dialysis session only. Different versions of the reference concentration for ECC were applied. ECC with peak average reference concentration was 5.4 ± 1.0 for phosphate, 7.0 ± 1.0 for urea and 4.7 ± 1.0 mL/min for creatinine. ECC for urea and creatinine were well correlated in contrast to the correlations of ECC for phosphate versus urea and creatinine. Midweek ECC were higher than weekly ECC, but they were well correlated for urea and creatinine, but only weakly for phosphate. HD adequacy monitoring for phosphate may be performed using ECC, but it is less predictable than similar indices for urea and creatinine. The values of ECC for phosphate are within the range expected for its molecular size compared with those for urea and creatinine. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Serum Vascular Endothelial Growth Factor (VEGF) as a Biomarker for Disease Activity in Lupus Nephritis.

PubMed

Ghazali, Wan Syamimee Wan; Iberahim, Rahimah; Ashari, Noor Suryani Mohd

2017-10-01

Previous studies have shown that serum VEGF levels were elevated in patients with active systemic lupus erythematosus (SLE), especially in those with lupus nephritis (LN). In this case control study, we aimed to compare serum levels of VEGF in SLE patients between LN, non-LN and healthy participants to determine the association between serum VEGF levels and the activity and histological classes of lupus nephritis. Blood samples were obtained from 92 SLE patients (46 LN and 46 non-LN) and 26 controls. Data were collected from medical records. Serum VEGF assays were performed by specific, enzyme-linked immunosorbent assay kits (ELISA). Laboratory investigations included urinalysis, urine protein-creatinine ratio, serum creatinine, albumin and VEGF levels. Blood pressure, renal biopsy result and treatment were recorded. LN activity was evaluated using the renal subscale of the British Isles Lupus Assessment Group (rBILAG, 2004). The rBILAG measures blood pressure (diastolic and systolic), urine protein, serum creatinine, calculated glomerular filtration rate (GFR), presence of active urinary sediments and histological evidence of active nephritis. Serum VEGF was elevated in SLE patients with LN compared with the non-LN group and healthy controls. The levels found were significantly higher in the sera of patients with active nephritis compared to those with quiescent nephritis ( P = 0.024). The study did not find a statistically significant relationship between serum VEGF levels and histological classes of LN. There was no significant difference of serum VEGF level between LN and non-LN SLE groups and between the non-LN group and healthy controls. However, there were increased levels of serum VEGF in the LN group, especially in patients with active nephritis as compared to quiescent nephritis group. This reflects the role of VEGF in the pathogenesis of lupus nephritis, however the clinical potential of this biomarker needs further study.

A Simple Method to Detect Recovery of Glomerular Filtration Rate following Acute Kidney Injury

PubMed Central

Pickering, John W.

2014-01-01

In acute kidney injury (AKI), elevated plasma creatinine is diagnostic of an earlier loss of glomerular filtration rate (GFR) but not of the concomitant GFR. Only subsequent creatinine changes will inform if GFR had already recovered or not. We hypothesized that the creatinine excretion rate to production rate ratio would provide this information. A retrospective analysis of 482 critically ill patients from two intensive care units (ICU) is shown. Plasma creatinine was measured on ICU entry and 12 hours later. Four-hour creatinine excretion rates (E) were measured on entry. Creatinine production rates were estimated (eG). The ability of the ratio E/eG to predict a decrease in plasma creatinine concentration, identify recovered AKI (≥0.3 mg/dL decrease), and predict AKI (≥0.3 mg/dL increase) was assessed by the area under the receiver operator characteristic curves (AUC). There was a linear relationship between reduced creatinine concentration and E/eG (r 2 = 0.15; P < 0.0001). E/eG predicted a decrease in creatinine (AUC 0.70 (0.65 to 0.74)), identified recovered AKI (0.75 (0.67 to 0.84)), and predicted AKI (0.80 (0.73 to 0.86)). A ratio of the rates of creatinine excretion to estimated production much less than 1 indicated a concomitant GFR below baseline, whereas a ratio much more than 1 indicated a recovering or recovered GFR. PMID:24982893

Effectiveness of Essence of Chicken in Improving Cognitive Function in Young People Under Work-Related Stress

PubMed Central

Chan, Lung; Wang, Hsuan-Min; Chen, Kuan-Yu; Lin, Ying-Chin; Wu, Pei-Jung; Hsieh, Wan-Lin; Chen, Ying-Ru; Liu, Cheung-Pin; Tsai, Han-Yin; Chen, Yun-Ru; Chang, Hsiu-Hui; Hsieh, Yi-Chen; Hu, Chaur-Jong

2016-01-01

Abstract Work-related stress (WS) can result in considerable and extensive changes in physiological and psychological performance. WS beyond the optimal levels induces anxiety, confusion, exhaustion, and burnout. Chronic WS affects neurocognitive performance, particularly attention and visuospatial memory. Essence of chicken (EC) has been reported to improve neurocognitive function after mental stress. To investigate the beneficial effects of EC in improving neurocognitive performance under WS, we conducted a randomized, double blind trial. Total 102 young workers in New Taipei City with high WS, evaluated using the Individual Subjective Perception Job Stress Scale scores (>36 for job leaders and 33 for nonleaders) were recruited. Fifty-one participants received 70 mL of EC and 51 received a placebo daily for 2 weeks. Blood tests and neurocognitive assessment were performed before treatment, at the end of treatment, and 2 weeks after treatment. EC improved the performance of participants with high depression scores in the form-color associative memory test, used for assessing short-term memory. Although creatinine and glutamic-pyruvic transaminase (GPT) levels increased in week 2, but the levels returned to the baseline in week 4. Blood urea nitrogen (BUN) levels decreased in week 4. EC significantly improved short-term memory in participants with high WS and concomitant depressive mood, although it slightly increased GPT and creatinine levels and reduced BUN levels. The long-term treatment effects of EC warrant further investigation. PMID:27175681

Effectiveness of Essence of Chicken in Improving Cognitive Function in Young People Under Work-Related Stress: A Randomized Double-Blind Trial.

PubMed

Chan, Lung; Wang, Hsuan-Min; Chen, Kuan-Yu; Lin, Ying-Chin; Wu, Pei-Jung; Hsieh, Wan-Lin; Chen, Ying-Ru; Liu, Cheung-Pin; Tsai, Han-Yin; Chen, Yun-Ru; Chang, Hsiu-Hui; Hsieh, Yi-Chen; Hu, Chaur-Jong

2016-05-01

Work-related stress (WS) can result in considerable and extensive changes in physiological and psychological performance. WS beyond the optimal levels induces anxiety, confusion, exhaustion, and burnout. Chronic WS affects neurocognitive performance, particularly attention and visuospatial memory. Essence of chicken (EC) has been reported to improve neurocognitive function after mental stress.To investigate the beneficial effects of EC in improving neurocognitive performance under WS, we conducted a randomized, double blind trial. Total 102 young workers in New Taipei City with high WS, evaluated using the Individual Subjective Perception Job Stress Scale scores (>36 for job leaders and 33 for nonleaders) were recruited. Fifty-one participants received 70 mL of EC and 51 received a placebo daily for 2 weeks. Blood tests and neurocognitive assessment were performed before treatment, at the end of treatment, and 2 weeks after treatment.EC improved the performance of participants with high depression scores in the form-color associative memory test, used for assessing short-term memory. Although creatinine and glutamic-pyruvic transaminase (GPT) levels increased in week 2, but the levels returned to the baseline in week 4. Blood urea nitrogen (BUN) levels decreased in week 4.EC significantly improved short-term memory in participants with high WS and concomitant depressive mood, although it slightly increased GPT and creatinine levels and reduced BUN levels. The long-term treatment effects of EC warrant further investigation.

Recognition and Sensing of Creatinine.

PubMed

Guinovart, Tomàs; Hernández-Alonso, Daniel; Adriaenssens, Louis; Blondeau, Pascal; Martínez-Belmonte, Marta; Rius, F Xavier; Andrade, Francisco J; Ballester, Pablo

2016-02-12

Current methods for creatinine quantification suffer from significant drawbacks when aiming to combine accuracy, simplicity, and affordability. Here, an unprecedented synthetic receptor, an aryl-substituted calix[4]pyrrole with a monophosphonate bridge, is reported that displays remarkable affinity for creatinine and the creatininium cation. The receptor works by including the guest in its deep and polar aromatic cavity and establishing directional interactions in three dimensions. When incorporated into a suitable polymeric membrane, this molecule acts as an ionophore. A highly sensitive and selective potentiometric sensor suitable for the determination of creatinine levels in biological fluids, such as urine or plasma, in an accurate, fast, simple, and cost-effective way has thus been developed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

PubMed

Wang, Yang; Hu, Jia-Wen; Qu, Peng-Fei; Wang, Ke-Ke; Yan, Yu; Chu, Chao; Zheng, Wen-Ling; Xu, Xian-Jing; Lv, Yong-Bo; Ma, Qiong; Gao, Ke; Yuan, Yue; Li, Hao; Yuan, Zu-Yi; Mu, Jian-Jun

2018-05-17

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Morphine Glucuronidation and Elimination in Intensive Care Patients: A Comparison with Healthy Volunteers.

PubMed

Ahlers, Sabine J G M; Välitalo, Pyry A J; Peeters, Mariska Y M; Gulik, Laura van; van Dongen, Eric P A; Dahan, Albert; Tibboel, Dick; Knibbe, Catherijne A J

2015-11-01

Although morphine is used frequently to treat pain in the intensive care unit, its pharmacokinetics has not been adequately quantified in critically ill patients. We evaluated the glucuronidation and elimination clearance of morphine in intensive care patients compared with healthy volunteers based on the morphine and morphine-3-glucuronide (M3G) concentrations. A population pharmacokinetic model with covariate analysis was developed with the nonlinear mixed-effects modeling software (NONMEM 7.3). The analysis included 3012 morphine and M3G concentrations from 135 intensive care patients (117 cardiothoracic surgery patients and 18 critically ill patients), who received continuous morphine infusions adapted to individual pain levels, and 622 morphine and M3G concentrations from a previously published study of 20 healthy volunteers, who received an IV bolus of morphine followed by a 1-hour infusion. For morphine, a 3-compartment model best described the data, whereas for M3G, a 1-compartment model fits best. In intensive care patients with a normal creatinine concentration, a decrease of 76% was estimated in M3G clearance compared with healthy subjects, conditional on the M3G volume of distribution being the same in intensive care patients and healthy volunteers. Furthermore, serum creatinine concentration was identified as a covariate for both elimination clearance of M3G in intensive care patients and unchanged morphine clearance in all patients and healthy volunteers. Under the assumptions in the model, M3G elimination was significantly decreased in intensive care patients when compared with healthy volunteers, which resulted in substantially increased M3G concentrations. Increased M3G levels were even more pronounced in patients with increased serum creatinine levels. Model-based simulations show that, because of the reduction in morphine clearance in intensive care patients with renal failure, a 33% reduction in the maintenance dose would result in morphine serum concentrations equal to those in healthy volunteers and intensive care patients with normal renal function, although M3G concentrations remain increased. Future pharmacodynamic investigations are needed to identify target concentrations in this population, after which final dosing recommendations can be made.

Evaluation of the performance of urine albumin, creatinine and albumin-creatinine ratio assay on two POCT analyzers relative to a central laboratory method.

PubMed

Omoruyi, Felix O; Mustafa, Gul M; Okorodudu, Anthony O; Petersen, John R

2012-03-22

The evaluation of microalbumin, creatinine and albumin-creatinine ratio is very important in patients with diabetes for the early detection of kidney disease and the identification of patients at risk for complications from diabetes or hypertension. A total of 88 spot urine samples previously analyzed using the Vitros 5,1 FS (creatinine) and Beckman Coulter Immage (microalbumin) located in the central laboratory and having microalbumin and creatinine values within the Afinion and DCA Vantage reportable ranges were run on 2 point of care (POC) instruments (Siemens DCA Vantage and Axis-Shield Afinion). The mean values for the DCA Vantage were: 42.6 mg/l for albumin, 10.3 mol/l for creatinine, and 5.4 mg/mol for ACR. For the Afinion AS100, the mean values were: 48.5mg/l for albumin, 9.5 mol/l for creatinine, and 6.7 mg/mol for ACR. The mean values obtained for CL were: 40.8 mg/l for albumin, 10.0 mol/l for creatinine, and 5.4 mg/mol for ACR. All POC analyzers showed good correlation to the central laboratory tests for microalbumin, creatinine and albumin creatinine ratio (ACR) for Afinion (R(2)=0.954, 0.974, and 0.964, respectively) and DCA Vantage (R(2)=0.989, 0.987, and 0.991, respectively). With the exception of the DCA Vantage ACR (p=0.53), the levels of microalbumin, creatinine and ACR obtained for the Afinion and DCA Vantage instruments as compared to the CL were statistically different (p<0.05). The inter and intraday imprecision for both POC instruments was <2.9% and total imprecision <8.7%. The 2 instruments evaluated in this study were in good agreement with the quantitative laboratory results and thus can be used for microalbumin, creatinine and ACR assays at the POC. However, facilities using Afinion will have to use different normal range for ACR. Copyright © 2011 Elsevier B.V. All rights reserved.

Performance of Chronic Kidney Disease Epidemiology Collaboration Creatinine-Cystatin C Equation for Estimating Kidney Function in Cirrhosis

PubMed Central

Mindikoglu, Ayse L.; Dowling, Thomas C.; Weir, Matthew R.; Seliger, Stephen L.; Christenson, Robert H.; Magder, Laurence S.

2013-01-01

Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by non-radiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the “bias”, “precision” and “accuracy” of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG) and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores [differences between mGFR and estimated GFR (eGFR) or between mGFR and CrCl, or between mGFR and CG equation for each subject] (RMSE=23.56) was significantly better than that of CrCl (37.69, P=0.001), CG (RMSE=36.12, P=0.002) and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P=0.024), CG (P=0.0001), 4-variable MDRD (P=0.027) and CKD-EPI creatinine 2009 (P=0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%. CONCLUSIONS The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than reported in subjects without cirrhosis. PMID:23744636

Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

PubMed

Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

2015-11-01

The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

[Effects of a structured exercise programme on cardiovascular risk programmes in post-menopausal women. CLIDERICA study].

PubMed

Saucedo Rodrigo, Pedro; Abellán Alemán, José; Gómez Jara, Purificación; Leal Hernández, Mariano; Ortega Toro, Enrique; Colado, Juan Carlos; Colado Sánchez, Juan Carlos; Sáinz de Baranda Andújar, Pilar

2008-07-01

To analyse the influence of a physical exercise programme of strength/stamina on cardiovascular risk factors in low-risk post-menopausal women. Six-month randomised clinical trial with post-menopausal women. Three health centres in the autonomous community of Murcia, Spain. Sixty-three post-menopausal women aged 45 to 59 at low cardiovascular risk. INTERVENTIONS AND MAIN MEASUREMENTS: They were split into 2 groups: a) control: 23 people with no specific intervention, and b) 40 people with an intervention of strength/stamina exercise with protocol for in water and on land. At their initial and final visits, everyone in the 2 groups had anamnesis, physical examination, and general analyses, including Apo A, Apo B, insulin, serum creatinine, creatinine clearance, creatinine in urine, albuminuria, ultrasensitive PCR, and HOMA index. The insulin levels increased in the control group by 2.02 mU/L and dropped in the experimental group by 0.13 mU/L (P=.021). At the start of the study, creatinine in the control group was 0.83+/-0.12 mg/dL; and at the end, 0.91+/-0.02 mg/dL. In the intervention group it was 0.84+/-0.12 mg/dL at the start and 0.90+/-0.13 mg/dL at the end (NS). Systolic blood pressure dropped in both groups, with a bigger drop in the exercise group (11.81 vs 0.17 mm Hg) (P=.0001). HDL-C values increased in the control group by 4.97 mg/dL; and in the experimental group, by 3.46 mg/dL (NS). A controlled programme of strength/stamina physical exercise reduces the cardiovascular risk of post-menopausal women.

Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion.

PubMed

Lai, Chang-Chi; Huang, Po-Hsung; Yang, An-Han; Chiang, Shu-Chiung; Tang, Chia-Yu; Tseng, Kuo-Wei; Huang, Cheng-Hsiung

2016-02-01

Acute kidney injury is a common and severe complication of acute myocardial infarction and cardiac surgery. It results in increased mortality, morbidity, and duration of hospitalization. Baicalein is a component of the root of Scutellaria baicalensis, which has traditionally been used to treat cardiovascular and liver diseases in Asia. In this study, we investigated whether baicalein can attenuate kidney injury induced by myocardial ischemia and reperfusion in rats. Myocardial ischemia and reperfusion, induced by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery, significantly increased blood urea nitrogen and creatinine levels in addition to causing histological changes in the kidneys. Kidney apoptosis was also significantly increased. Furthermore, myocardial ischemia and reperfusion significantly increased the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6 as well as the tumor necrosis factor-α levels in the kidneys. Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion. In addition, the increases in the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6, and of tumor necrosis factor-α in the kidneys were significantly reduced. Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys. The phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was also significantly increased. In conclusion, baicalein significantly attenuates kidney injury induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to the inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-α production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2. Georg Thieme Verlag KG Stuttgart · New York.

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

PubMed Central

Sakr, Saber; Rashed, Laila; Zarouk, Waheba; El-Shamy, Rania

2013-01-01

Objective To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s). PMID:23620833

Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder.

PubMed

Kurahashi, Hiroaki; Watanabe, Masami; Sugimoto, Morito; Ariyoshi, Yuichi; Mahmood, Sabina; Araki, Motoo; Ishii, Kazushi; Nasu, Yasutomo; Nagai, Atsushi; Kumon, Hiromi

2013-01-01

Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

Influence of hypernatremia and polyuria of brain-dead donors before organ procurement on kidney allograft function.

PubMed

Kazemeyni, Seyed Mohammad; Esfahani, Fatemah

2008-01-01

Polyuria and hypernatremia are common problems during the pretransplant care of brain-dead donors. They have not only important role in hemodynamic stability, but also may influence organ transplantation outcomes. The influence of donor hypernatremia in liver transplantation was reported. This study aimed to determine these effects on kidney allograft. We retrospectively studied on 57 transplanted kidney allografts from cadaveric donors. The effects of the urine output volume and serum level of sodium of the donors were on the recipients' serum creatinine levels 1 week after transplantation and at the last follow-up visit were assessed. Of the donors, 58% had polyuria and 45% had hypernatremia. The median pretransplant urine output of the donors was 130 mL/h (range, 35 mL/h to 450 mL/h), and their mean serum sodium level was 152.0 +/- 13.0 mEq/L. Serum creatinine concentrations in the recipients at the 1st posttransplant week correlated significantly with the recipients' age (r = 0.355, P = .02) and the donors' urine output volume (r = 0.329, P = .04). The serum creatinine measured in the last follow-up visit significantly correlated only with the donors' serum sodium levels (r = 0.316, P = .02) and the donors' age (r = 0.306, P = .02). Multivariate regression analysis showed that the donors' serum levels of sodium and potassium were the predictors of the last measured serum creatinine level. Polyuria and hypernatremia in brain-dead donors are frequent. Elevated serum level of sodium and polyuria in the donor can have adverse effects on kidney allograft function.

LC-QTOF-MS-based targeted metabolomics of arginine-creatine metabolic pathway-related compounds in plasma: application to identify potential biomarkers in pediatric chronic kidney disease.

PubMed

Benito, Sandra; Sánchez, Alicia; Unceta, Nora; Andrade, Fernando; Aldámiz-Echevarria, Luis; Goicolea, M Aránzazu; Barrio, Ramón J

2016-01-01

Chronic kidney disease (CKD) is a major epidemiologic problem which causes several disturbances in adults and in pediatrics. Despite being a worldwide public health problem, information available for CKD in the pediatric population is scarce. For that reason, an ion-pair reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method has been developed and validated in order to analyze 16 amino acids, amino acid derivatives, and analogous compounds related to the arginine-creatine metabolic pathway that are suspicious of being increased or decreased in plasma from patients with CKD. The analytical method involved the addition of dithiothreitol, a reducing agent which reduces disulfide and thus giving total aminothiol concentration, as well as a simple precipitation of plasma proteins. Moreover, despite amino acids being usually derivatized to improve their retention time and to enhance their signal, for this method, an ion-pairing reagent was used, thus avoiding the need for derivatization. Subsequently, analysis of plasma from pediatric patients suffering from CKD and control pediatrics was carried out. As a result, glycine, citrulline, creatinine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were significantly increased in patients with CKD, regardless of their creatinine level, whereas in addition to these compounds dimethylglycine was also increased when CKD patients had plasma creatinine concentrations above 12 μg mL(-1), thus all are suggested as potential biomarkers for renal impairment.

Plasma volume and renal function during and after ultramarathon running.

PubMed

Irving, R A; Noakes, T D; Burger, S C; Myburgh, K H; Querido, D; van Zyl Smit, R

1990-10-01

Plasma volume (PV) and renal function were studied in eight subjects for 3 d prior to and 6 d after a 56 km footrace. Immediately following the race, PV, creatinine clearance, and urine flow were unchanged from pre-race values. Over the subsequent 3 d, PV increased due initially to a 17 g influx of serum albumin and an associated increase in plasma sodium content, which persisted throughout the study period. A reduction in urine sodium secretion occurred during the race day. Creatinine clearance increased after the race and remained elevated for 48 h. Increases serum enzyme activities, C-reactive protein concentration, serum uric acid content, and plasma creatinine concentration and production suggest muscle damage. We suggested the following. First, the persistent post-exercise plasma volume expansion is initiated by an influx of albumin into the intravascular space with an associated increase in plasma sodium content. A decrease in urine sodium excretion during the race day would contribute to the latter. Second, the interpretation of post-race changes in serum constituents must take account of changes in plasma volume. Third, there is an increase in creatinine clearance, indicating an increase in glomerular filtration rate, after both standard and ultramarathon running. This may be caused by the products of muscle cell damage although the physiologic mechanism for this is unclear.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

PubMed

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

Protective effect of Cassia fistula fruit extract on bromobenzene-induced nephrotoxicity in mice.

PubMed

Kalantari, Heibatullah; Jalali, Mohammadtaha; Jalali, Amir; Salimi, Abobakr; Alhalvachi, Foad; Varga, Balazs; Juhasz, Bela; Jakab, Anita; Kemeny-Beke, Adam; Gesztelyi, Rudolf; Tosaki, Arpad; Zsuga, Judit

2011-10-01

The efficacy of a crude hydro-alcoholic extract of Cassia fistula (golden shower tree) fruit to protect the kidney against bromobenzene-induced toxicity was studied. Negative control mice received normal saline; positive control mice were given 460 mg/kg of bromobenzene; Cassia fistula treated mice received 200, 400, 600 and 800 mg/kg of Cassia fistula fruit extract followed by 460 mg/kg bromobenzene (daily by oral gavage for 10 days). On the 11th day, the mice were sacrificed, blood samples were obtained to assess blood urea nitrogen (BUN) and creatinine levels, and kidneys were removed for histological examination. We found that bromobenzene induced significant nephrotoxicity reflected by an increase in levels of BUN and creatinine that was dose dependently prevented by the Cassia fistula fruit extract. The nephroprotective effect of the Cassia fistula fruit extract was confirmed by the histological examination of the kidneys. To the best of our knowledge, this is the first study to demonstrate the protective effect of Cassia fistula in nephrotoxicity.

Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.

PubMed

van Vliet, Esther I; de Herder, Wouter W; de Rijke, Yolanda B; Zillikens, M Carola; Kam, Boen L R; Teunissen, Jaap J M; Peeters, Robin P; Krenning, Eric P; Kwekkeboom, Dik J

2013-12-01

The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

PubMed Central

Glastras, Sarah J.; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T.; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A.; Saad, Sonia

2017-01-01

Aims/Hypothesis Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Methods Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. Results HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Conclusion Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity. PMID:28225809

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

PubMed

Glastras, Sarah J; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A; Saad, Sonia

2017-01-01

Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study.

PubMed

Mazzone, Annette L; Baker, Robert A; McNicholas, Kym; Woodman, Richard J; Michael, Michael Z; Gleadle, Jonathan M

2018-03-01

A pilot study to measure and compare blood and urine microRNAs miR-210 and miR-16 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting surgery. Frequent serial blood and urine samples were taken from patients undergoing cardiac surgery with CPB (n = 10) and undergoing off-pump cardiac surgery (n = 5) before, during, and after surgery. Circulating miR-210 and miR-16 levels were determined by relative quantification real-time polymerase chain reaction. Levels of plasma-free haemoglobin (fHb), troponin-T, creatine kinase, and creatinine were measured. Perioperative serum miR-210 and miR-16 were elevated significantly compared to preoperative levels in patients undergoing cardiac surgery with CPB (CPB vs. Pre Op and Rewarm vs. Pre Op; p < .05 for both). There were increases of greater than 200% in miR-210 levels during rewarming and immediately postoperatively and a 3,000% increase in miR-16 levels immediately postoperatively in urine normalized to urinary creatinine concentration. Serum levels of miR-16 were relatively constant during off-pump surgery. miR-210 levels increased significantly in off-pump patients perioperatively ( p < .05 Octopus on vs. Pre Op); however, the release was less marked when compared to cardiac surgery with CPB. A significant association was observed between both miR-16 and miR-210 and plasma fHb when CPB was used ( r = -.549, p < .0001 and r = -.463, p < .0001 respectively). Serum and urine concentrations of hypoxically regulated miR-210 and hemolysis-associated miR-16 increased in cardiac surgery using CPB compared to off-pump surgery. These molecules may have utility in indicating severity of cardiac, red cell, and renal injury during cardiac surgery.

Reduced serum club cell protein as a pulmonary damage marker for chronic fine particulate matter exposure in Chinese population.

PubMed

Wang, Yanhua; Duan, Huawei; Meng, Tao; Shen, Meili; Ji, Qianpeng; Xing, Jie; Wang, Qingrong; Wang, Ting; Niu, Yong; Yu, Tao; Liu, Zhong; Jia, Hongbing; Zhan, Yuliang; Chen, Wen; Zhang, Zhihu; Su, Wenge; Dai, Yufei; Zhang, Xuchun; Zheng, Yuxin

2018-03-01

Exposure to fine particulate matter (PM 2.5 ) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM 2.5 exposure. We designed a two-stage study. In the first stage (training set), we assessed the associations between PM 2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. Serum CC16 levels decreased in a dose response manner in association with both external and internal PM 2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM 2.5 exposure history. An interquartile range (IQR) (122.0μg/m 3 ) increase in PM 2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM 2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. Serum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM 2.5 exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

11-dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period.

PubMed

Maga, P; Sanak, M; Jawien, J; Rewerska, B; Maga, M; Wachsmann, A; Koziej, M; Gregorczyk-Maga, I; Nizankowski, R

2016-06-01

The aim of our study was to determine if the generation of thromboxane is altered in patients with peripheral arterial occlusive disease following percutaneous transluminal angioplasty (PTA) during a one year follow-up period. In this study, 175 patients diagnosed with peripheral arterial occlusive disease (PAOD) and demonstrating short-distance claudication or ischemic rest pain, requiring PTA in either the iliac, femoral, or popliteal arteries, were enrolled. The excretion of 11-dehydro thromboxane B2 (TXB2) was measured in urine samples by high-performance liquid chromatography-mass spectrometry and recalculated based on the creatinine concentration. The urine samples were collected the morning prior to PTA, immediately following PTA and the day after PTA. All of the study subjects were then observed for a period of 12 months. Urine samples were also collected during the follow-up visits, and the levels of 11-dehydro TXB2 were measured at 1 month (1458.1 pg/mg creatinine ± 1240.8), 3 months (1623.3 pg/mg creatinine ± 1362.2), 6 months (1314.8 pg/mg creatinine ± 1378.7) and 12 months (1473.2 pg/mg creatinine ± 1455.2) after the PTA procedure. All of the patients were taking 75 mg of aspirin per day throughout the course of the study, as well as 75 mg of clopidogrel for six weeks following PTA. Overall, the mean TXB2 values immediately after PTA were significantly higher than either before the procedure (1524.4 pg/mg creatinine ± 1411.1 vs. 2098.1 pg/mg creatinine ± 1661.8; P = 0.00002), the day after PTA, or at any other point during the study. Moreover, preoperative TXB2 levels correlated well with the composite endpoints of death, myocardial infarction and stroke during the follow-up period (OR 7.42 [CI 95% = 1.2-48.8]; P = 0.02). Our findings suggest that clinicians should consider the use of TXA2 synthase inhibitors and receptor antagonists in combination with peripheral percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease.

Point of care testing provides an accurate measurement of creatinine, anion gap, and osmolal gap in ex-vivo whole blood samples with nitromethane.

PubMed

Cao, D; Maynard, S; Mitchell, A M; Kerns, W P; Beuhler, M

2014-07-01

Nitromethane interferes with Jaffé measurements of creatinine, potentially mimicking acute kidney injury. We determined the proportional contribution of nitromethane in blood samples to creatinine measured by the Jaffé colorimetric and the point-of-care (POC) reactions and determined whether the difference can reliably estimate the concentration of nitromethane. Additionally, we determined whether the presence of nitromethane interferes with anion/osmolal gaps and ascertained the stability of nitromethane in serum after 7 days. Nitromethane was added to whole blood from four healthy volunteers to achieve concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. The following tests were performed: creatinine (Jaffé and POC), electrolytes (associated with Jaffé and POC), osmolality and nitromethane concentration (gas chromatography [GC]). Remaining samples were refrigerated and reanalyzed using GC at 7 days. Anion and osmolal gaps were calculated. Proportional recovery and degradation of nitromethane were measured using GC. Data were analyzed for agreement with single-factor ANOVA (p = 0.05). Mean creatinine for POC and Jaff methods were 0.93 vs. 0.76 mg/dL, respectively. Jaff creatinine concentrations increased linearly with increasing nitromethane concentrations (R(2) = 1, p = 0.01): measured creatinine (mg/dL) = 7.1*nitromethane (mmol/L) = 0.79. POC creatinine remained unchanged across the range of nitromethane concentrations (p = 0.99). Anion and osmolal gaps also remained unchanged. Nitromethane was reliably identified in all sample concentrations using GC on Day 0. Detection of 0.25 mmol/L nitromethane was not consistently recovered on Day 7. Nitromethane degradation was most pronounced at 2 mmol/L concentrations (81% recovery). Nitromethane alters apparent concentration of creatinine using the Jaffé reaction in a linear fashion but not when using the POC reaction. Measured difference between Jaffé and POC creatinine may identify the presence and estimate concentration of nitromethane. Presence of nitromethane did not alter the anion or osmolal gap; thus it would not potentially interfere with the diagnosis of co-exposure to a toxic alcohol.

Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study.

PubMed

Chiò, Adriano; Calvo, Andrea; Bovio, Giacomo; Canosa, Antonio; Bertuzzo, Davide; Galmozzi, Francesco; Cugnasco, Paolo; Clerico, Marinella; De Mercanti, Stefania; Bersano, Enrica; Cammarosano, Stefania; Ilardi, Antonio; Manera, Umberto; Moglia, Cristina; Sideri, Riccardo; Marinou, Kalliopi; Bottacchi, Edo; Pisano, Fabrizio; Cantello, Roberto; Mazzini, Letizia; Mora, Gabriele

2014-09-01

There is an urgent need to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS) progression for clinical practice and pharmacological trials. To correlate several hematological markers evaluated at diagnosis with ALS outcome in a population-based series of patients (discovery cohort) and replicate the findings in an independent validation cohort from an ALS tertiary center. The discovery cohort included 712 patients with ALS from the Piemonte and Valle d'Aosta Register for Amyotrophic Lateral Sclerosis from January 1, 2007, to December 31, 2011. The validation cohort comprised 122 patients with ALS at different stages of disease consecutively seen at an ALS tertiary center between January 1, 2007, and January 1, 2009. The following hematological factors were investigated and correlated with survival: total leukocytes, neutrophils, lymphocytes, monocytes, glucose, creatinine, uric acid, albumin, bilirubin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, creatine kinase, thyroid-stimulating hormones, and erythrocyte sedimentation rate; all analyses were performed separately by sex. The patient of the validation cohort also underwent bioelectrical impedance analysis for the calculation of fat-free mass. Of the 712 patients in the examined period in Piemonte and Valle d'Aosta, 638 (89.6%) were included in the study. Only serum albumin (men: ≤ 4.3 vs >4.3 mg/dL, P < .001; women: ≤ 4.3 vs >4.3 mg/dL, P < .001) and creatinine levels (men: ≤ 0.82 vs >0.82 mg/dL, P = .004; women: ≤ 0.65 vs >0.05 mg/dL, P = .004) and lymphocyte count (men: ≤ 1700 vs >1700/μL, P = .04; women: ≤ 1700 vs >1700/μL, P = .02) were significantly associated with ALS outcome in both sexes with a dose-response effect (better survival with increasing levels). These findings were confirmed in the validation cohort. Multivariable analysis showed that serum albumin (men: hazard ratio [HR], 1.39; 95% CI, 1.05-1.90; P = .02; women: HR, 1.73; 95 % CI, 1.35-2.39; P = .001) and creatinine (men: HR, 1.47; 95% CI, 1.11-1.95; P = .007; women: HR, 1.49; 95% CI, 1.07-2.05; P = .02) were independent predictors of survival in both sexes; no other hematological factor was retained in the model. In patients with ALS, serum albumin was correlated with markers of inflammatory state while serum creatinine was correlated with fat-free mass, which is a marker of muscle mass. In ALS, serum albumin and creatinine are independent markers of outcome in both sexes. Creatinine reflects the muscle waste whereas albumin is connected with inflammatory state. Both creatinine and albumin are reliable markers of the severity of clinical status in patients with ALS and can be used in defining prognosis at the time of diagnosis.

Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

PubMed Central

Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

2016-01-01

Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

Choice of Reference Serum Creatinine in Defining AKI

PubMed Central

Siew, Edward D.; Matheny, Michael E.

2015-01-01

Background/Aims The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations. Methods We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating estimation of baseline renal function, using Pubmed and reference back-tracing within known works. Results 1) Prehospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, 2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations 3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, 4) using more specific definitions of AKI (e.g. KIDGO Stage 2 and 3) may help to reduce the effects of misclassification when using surrogate values, and 5) leveraging available clinical data may help refine the estimate of reference creatinine. Conclusions Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine is needed. PMID:26332325

[Considerations when using creatinine as a measure of kidney function].

PubMed

Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

2013-01-01

Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function.

First evidence of subclinical renal tubular injury during sickle-cell crisis.

PubMed

Audard, Vincent; Moutereau, Stéphane; Vandemelebrouck, Gaetana; Habibi, Anoosha; Khellaf, Mehdi; Grimbert, Philippe; Levy, Yves; Loric, Sylvain; Renaud, Bertrand; Lang, Philippe; Godeau, Bertrand; Galactéros, Frédéric; Bartolucci, Pablo

2014-04-29

The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC.

Development of a database and processing method for detecting hematotoxicity adverse drug events.

PubMed

Shimai, Yoshie; Takeda, Toshihiro; Manabe, Shirou; Teramoto, Kei; Mihara, Naoki; Matsumura, Yasushi

2015-01-01

Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.

Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

PubMed

Amirshahrokhi, Keyvan; Khalili, Ali-Reza

2015-04-01

Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

Clinical Efficacy and Safety of Pamidronate Therapy on Bone Mass Density in Early Post-Renal Transplant Period: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Zijie; Han, Zhijian; Tao, Jun; Lu, Pei; Liu, Xuzhong; Wang, Jun; Wu, Bian; Huang, Zhengkai; Yin, Changjun; Tan, Ruoyun; Gu, Min

2014-01-01

Introduction The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. Materials and Methods A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate. Results Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD)  = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD  = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD  = −3.101 [−5.33, −0.89]; serum calcium: SMD  = 2.18 [−0.8, 5.16]; serum iPTH: SMD  = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. Conclusions This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate. PMID:25265508

Association of target organ damage with 24-hour systolic and diastolic blood pressure levels and hypertension subtypes in untreated Chinese.

PubMed

Wei, Fang-Fei; Li, Yan; Zhang, Lu; Xu, Ting-Yan; Ding, Feng-Hua; Staessen, Jan A; Wang, Ji-Guang

2014-02-01

The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure <130/<80 mm Hg. Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P≤0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic blood pressure were +3.31/-0.36 g/m(2) (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/-0.05 m/s (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m(2) (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/-0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study.

PubMed

Barr, Elizabeth Lm; Maple-Brown, Louise J; Barzi, Federica; Hughes, Jaquelyne T; Jerums, George; Ekinci, Elif I; Ellis, Andrew G; Jones, Graham Rd; Lawton, Paul D; Sajiv, Cherian; Majoni, Sandawana W; Brown, Alex Dh; Hoy, Wendy E; O'Dea, Kerin; Cass, Alan; MacIsaac, Richard J

2017-04-01

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m 2 ; 95% CI 13.3-16.4, p<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

[Evaluation of adiponectin level in children and adolescents with diabetes type 1].

PubMed

Peczyńska, Jadwiga; Urban, Mirosława; Głowińska, Barbara; Florys, Bozena

2008-01-01

Adipose tissue is not only an energy storage place, but it also secretes numerous "adipocytokines" - substances that have systemic influence. Adiponectin has an anti-inflammatory, antiatherogenic properties and increases insulin sensitivity. It is emphasized that adiponectin levels are different in type 1 and type 2 diabetes. was to evaluate adiponectin levels in young patients with diabetes type 1, and to analyse of the correlation between adiponectin and: BMI, lipid parameters, glomerular filtration rate and microalbuminuria. The study group was formed by 95 patients from the Outpatient Diabetology Department 2nd Department of Children's Diseases, 45 girls and 50 boys, aged from 7 to 20 years (mean - 14.97 yrs) suffering from diabetes from 1 to 17 years (mean 6.68 yrs). Control group consisted of healthy children, age matched, without family history of cardiovascular diseases. In all patients anthropometric measurements were performed (BMI was calculated), metabolic control was evaluated on the basis of HbA1c level, microalbuminuria was studied in 24 hour urine sample. We assessed glomerular filtration rate (endogenous creatinine clearance), lipid parameters and adiponectin level. In children and adolescents with diabetes type 1 we found significantly higher levels of adiponectin compared to control group: 32.72+/-13.49 vs. 26.53+/-7.63 ug/ml; p=0.024. Adiponectin level was higher in girls than in boys (33.56 vs. 28.75 ug/ml; p=0.036). Adiponectin level did not depend on metabolic control and on diabetes duration. We found a statistically significant negative correlation between adiponectin and creatinine (r=-0.26; p=0.011). In patients with diabetic complications we found insignificantly lower adiponectin level compared to patients without complications (30.99+/-14.29 vs. 33.67+/-11.68 ug/ml; p=0.35). 1. In patients with diabetes type 1 significantly higher level of adiponectin was found compared to healthy control group. 2. Adiponectin level correlated negatively with creatinine level end microalbuminuria. 3. Elevated level of adiponectin in patients without diabetic complications may help to explain the pathogenesis of diabetic angiopathy.

Life-threatening hyperkalemia – an overlooked acute kidney injury with a serum creatinine rise in the ‘normal’ range

PubMed Central

Latus, Joerg; Braun, Niko; Alscher, M Dominik; Kimmel, Martin

2012-01-01

A 76-year-old woman (51 kg, 158 cm, body mass index 20.5) was admitted to the hospital because of an acute kidney injury with hyperkalemia. On admission, she reported progredient muscle weakness of all limbs for several days. Serum potassium level was dramatically elevated and ECG showed QRS with a ‘sine-wave’ pattern and haemodialysis was started. 45 days ago, Hartmann’s operation was done because of stenosing sigmoid diverticulitis. At this time, the serum creatinine was 0.4 mg/dl (‘normal’ 0.5–1.2). Thereafter, she got severe ‘high output-ileostoma’ with severe intestinal fluid losses and treatment with potassium supplementation and spironolactone was started by the surgeons. She was discharged with elevated serum potassium levels and serum creatinine of 1.0 mg/dl (‘normal’ range (0.5–1.2 mg/dl)). This case illustrates impressively the lack of serum creatinine as an ideal kidney function test, because it is depending on muscle mass and there is no interindividual normal range. PMID:22605836

Do Serum Creatinine Levels Show Clinically Significant Fluctuations on Serial Determinations on the Siemens Advia 1800 Analyzer?

PubMed

Levitan, Daniel; Harper, Aaron E; Sun, Yi; Scarpa Carniello, Jose V; Momeni, Amir; Kagan, Joshua; Alexis, Herol; Eid, Ikram; Harris, Loretta; Marshal, Barbara; Tafani, Edlira; Pincus, Matthew

2017-01-01

The goal of this work was to determine whether there are clinically significant fluctuations in the level of serum creatinine on serial determinations, especially in the borderline range (1.1-1.3 mg/dl), after specimen storage. Sixty-one serum samples were analyzed. They were divided into three categories based on the initial serum creatinine measurement: low (≤1.0 mg/dl), borderline (1.1-1.3 mg/dl), and high (≥1.4 mg/dl). The specimens were stored at 4°C and run on the Siemens Advia 1800 chemistry analyzer on days 1, 3, and 11. Statistical comparisons of the three groups were made using the unpaired t-test, yielding a two-tailed P-value for each group comparison. The P-values ranged from 0.0829 to 0.3892, indicating no statistically significant difference between the standard deviations of each group. Mild-to-moderate fluctuations in precision occur in successive serum creatinine determinations. The overwhelming majority of these fluctuations should not affect clinical decision making. © 2016 Wiley Periodicals, Inc.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

PubMed Central

Weaver, Virginia M.; Kim, Nam-Soo; Lee, Byung-Kook; Parsons, Patrick J.; Spector, June; Fadrowski, Jeffrey; Jaar, Bernard G.; Steuerwald, Amy J.; Todd, Andrew C.; Simon, David; Schwartz, Brian S.

2011-01-01

Cadmium is a well known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs = 0.5; p less than 0.001). After adjustment, ln(urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln(urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient = 4.1 ml/min/1.73 m2; 95% confidence interval =1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential. PMID:21871619

Changes in Serum Biochemical Factors Associated with Opium Addiction after Addiction Desertion

PubMed Central

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

Background The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. Methods In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. Findings According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. Conclusion According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients. PMID:25984281

Investigated the safety of intra-renal arterial transfusion of autologous CD34+ cells and time courses of creatinine levels, endothelial dysfunction biomarkers and micro-RNAs in chronic kidney disease patients-phase I clinical trial.

PubMed

Lee, Mel S; Lee, Fan-Yen; Chen, Yung-Lung; Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Kuan-Hung; Huang, Tien-Hung; Chen, Yi-Ling; Chiang, John Y; Yin, Tsung-Cheng; Chang, Hsueh-Wen; Yip, Hon-Kan

2017-03-14

This was a phase I clinical trial to investigate the safety of autologous peripheral-blood-derived CD34+ cell therapy for patients with chronic kidney disease (CKD-treatment) (i.e., at Stages III and IV). Between November 2014 and October 2015, a total of 10 study patients were prospectively enrolled into this phase I trial. Patients who failed to enroll into the trial in the initial state of eligibility assessment were served as CKD-control group (n = 9). The health-control group was composed of 10 volunteers for the purposes of comparing (1) circulation level of endothelial progenitor cells (EPCs), (2) angiogenesis ability, and (3) anti-apoptotic miRNAs between healthy subjects and CKD patients. CD34+ cells (5.0 x 107) were transfused into right-renal artery after subcutaneous G-CSF injection (5μg/kg/twice a day for 4 days). Circulating EPC number, angiogenesis capacity (i.e., Matrigel assay) and anti-apoptotic miRNAs (miR-374a-5p/miR-19a-3p/ miR-106b-5p/miR-26b-5p/ miR-20a-5p) were significantly lower in CKD patients than in healthy subjects (all p < 0.001). Flow-cytometric analysis of renal-vein blood samplings (i.e., at 0/5/10/30 mins after cell transfusion) showed the EPC level was significantly progressively increased (p < 0.001). Procedural safety was 100% with all patients uneventfully discharged and one-year survival rate was 100%. The paired-t test showed serum creatinine maintained the same level between the baseline and at the end of one-year follow-up (all p > 0.4), whereas the net increase between initial and final creatinine level was higher in CKD-control than in CKD-treatment. In conclusion, CD34+ cell therapy was safe and maintained the renal function in stationary state at the end of study period.

Investigated the safety of intra-renal arterial transfusion of autologous CD34+ cells and time courses of creatinine levels, endothelial dysfunction biomarkers and micro-RNAs in chronic kidney disease patients-phase I clinical trial

PubMed Central

Chen, Yung-Lung; Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Kuan-Hung; Huang, Tien-Hung; Chen, Yi-Ling; Chiang, John Y.; Yin, Tsung-Cheng; Chang, Hsueh-Wen; Yip, Hon-Kan

2017-01-01

This was a phase I clinical trial to investigate the safety of autologous peripheral-blood-derived CD34+ cell therapy for patients with chronic kidney disease (CKD-treatment) (i.e., at Stages III and IV). Between November 2014 and October 2015, a total of 10 study patients were prospectively enrolled into this phase I trial. Patients who failed to enroll into the trial in the initial state of eligibility assessment were served as CKD-control group (n = 9). The health-control group was composed of 10 volunteers for the purposes of comparing (1) circulation level of endothelial progenitor cells (EPCs), (2) angiogenesis ability, and (3) anti-apoptotic miRNAs between healthy subjects and CKD patients. CD34+ cells (5.0 × 107) were transfused into right-renal artery after subcutaneous G-CSF injection (5μg/kg/twice a day for 4 days). Circulating EPC number, angiogenesis capacity (i.e., Matrigel assay) and anti-apoptotic miRNAs (miR-374a-5p/miR-19a-3p/ miR-106b-5p/miR-26b-5p/ miR-20a-5p) were significantly lower in CKD patients than in healthy subjects (all p < 0.001). Flow-cytometric analysis of renal-vein blood samplings (i.e., at 0/5/10/30 mins after cell transfusion) showed the EPC level was significantly progressively increased (p < 0.001). Procedural safety was 100% with all patients uneventfully discharged and one-year survival rate was 100%. The paired-t test showed serum creatinine maintained the same level between the baseline and at the end of one-year follow-up (all p > 0.4), whereas the net increase between initial and final creatinine level was higher in CKD-control than in CKD-treatment. In conclusion, CD34+ cell therapy was safe and maintained the renal function in stationary state at the end of study period. PMID:28148896

Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

PubMed

Kesik, V; Demirkaya, E; Buyukpamukçu, M

2015-12-01

Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary β2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine β2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for β2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease.

PubMed

Ahmed, Heba Mostafa; Ezzat, Dina Ahmed; Doudar, Noha A; Adel, Mai

2018-03-01

Early diagnosis of minimal change disease (MCD) is challenging in nephrotic children. CD80 is a protein expressed on the surface of podocytes associated with nephrotic syndrome and it is implicated in the induction of proteinuria. This study aimed to investigate the use of urinary CD80 for the diagnosis of MCD. Urinary CD80 levels were evaluated in 36 children with nephrotic syndrome and normal glomerular filtration rate. They were divided into three groups of MCD (n = 21), focal segmental glomerulosclerosis (n = 9), and other glomerulopathies (n = 6). The MCD group was subdivided into 2 of those with remission (n = 11) and those in the active stage (n = 10). Forty healthy children were included as controls. The urinary CD80 level was significantly higher in the MCD group (3.5 ± 2.1 ng/mg creatinine) than in the focal segmental glomerulosclerosis group (1.2 ± 0.5 ng/mg creatinine, P < .001), the other glomerulopathies group (1.4 ± 0.7 ng/mg creatinine, P < .001), and the control group (0.7 ± 0.2 ng/mg creatinine, P < .001), while it showed no significant difference among the non-MCD groups. There was no significant difference between MCD in remission and MCD in relapse, either. A urinary CD80 cutoff value of 1.5 ng/gm creatinine showed a sensitivity of 100% and a specificity of 86% for diagnosis of MCD. Urinary CD80 levels were significantly higher in the children with MCD than in the controls and patients with other causes of nephrotic syndrome.

Combined aliskiren and amlodipine reduce albuminuria via reduction in renal inflammation in diabetic rats.

PubMed

Matavelli, Luis C; Huang, Jiqian; Siragy, Helmy M

2012-03-01

We hypothesized that compared with hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of blood pressure (BP) changes. We studied normal and streptozotocin-induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ, or AMLO individually and combined and evaluated the effects of treatments on BP, urine albumin to creatinine ratio, renal interstitial fluid levels of angiotensin II, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) and renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B. There were no differences in BP between treatments. Only ALISK and its combinations reduced renal interstitial fluid angiotensin II. Urine albumin to creatinine ratio increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence urine albumin to creatinine ratio. Renal interstitial fluid TNF-α and IL-6, and the renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes.

Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India.

PubMed

Basu, Arin; Mitra, Soma; Chung, Joyce; Guha Mazumder, D N; Ghosh, Nilima; Kalman, David; von Ehrenstein, Ondine S; Steinmaus, Craig; Liaw, Jane; Smith, Allan H

2011-09-01

Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic. We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data. We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine. Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%. Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

Fibroblast growth factor 23 and renal function among young and healthy individuals.

PubMed

Bernasconi, Raffaele; Aeschbacher, Stefanie; Blum, Steffen; Mongiat, Michel; Girod, Marc; Todd, John; Estis, Joel; Nolan, Niamh; Renz, Harald; Risch, Lorenz; Conen, David; Risch, Martin

2018-05-01

Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. Healthy individuals aged 25-41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion. The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR - CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase -3.81; 95% CI [-5.42; -2.20]; p<0.0001). Furthermore, we found a linear association between FGF-23 and endothelin-1 (β per 1 log-unit increase 0.06; [0.01, 0.11]; p=0.01). In addition, we established a significant relationship of FGF-23 with fractional phosphate excretion (β per 1 log-unit increase 0.62; [0.08, 1.16]; p=0.03). Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.

Mortality predictability of body size and muscle mass surrogates in Asian vs white and African American hemodialysis patients.

PubMed

Park, Jongha; Jin, Dong Chan; Molnar, Miklos Z; Dukkipati, Ramanath; Kim, Yong-Lim; Jing, Jennie; Levin, Nathan W; Nissenson, Allen R; Lee, Jong Soo; Kalantar-Zadeh, Kamyar

2013-05-01

To determine whether the association of body size and muscle mass with survival among patients undergoing long-term hemodialysis (HD) is consistent across race, especially in East Asian vs white and African American patients. Using data from 20,818 patients from South Korea who underwent HD from February 1, 2001, to June 30, 2009, and 20,000 matched patients from the United States (10,000 whites and 10,000 African Americans) who underwent HD from July 1, 2001, to June 30, 2006, we compared mortality associations of baseline body mass index (BMI) and serum creatinine level as likely surrogates of obesity and muscle mass across the 3 races. In Korean HD patients, higher BMI together with higher serum creatinine levels were associated with greater survival, as previously reported from US and European studies. In the matched cohort (10,000 patients from each of the 3 races), mortality risks were lower across higher BMI and serum creatinine levels, and these associations were similar in all 3 races (reference groups: patients with BMI >25.0 kg/m(2) or serum creatinine >12 mg/dL in each race). White, African American, and Korean patients with BMI levels of 18.5 kg/m(2) or less (underweight) had 78%, 79%, and 57% higher mortality risk, respectively, and white, African American, and Korean patients with serum creatinine levels of 6.0 mg/dL or less had 108%, 87%, and 78% higher mortality, respectively. This study shows that race does not modify the association of higher body size and muscle mass with greater survival in HD patients. Given the consistency of the obesity paradox, which may be related to a mitigated effect of protein-energy wasting on mortality irrespective of racial disparities, nutritional support to improve survival should be tested in HD patients of all races. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Validity of the International Classification of Diseases, Tenth Revision code for acute kidney injury in elderly patients at presentation to the emergency department and at hospital admission

PubMed Central

Hwang, Y Joseph; Shariff, Salimah Z; Gandhi, Sonja; Wald, Ron; Clark, Edward; Fleet, Jamie L; Garg, Amit X

2012-01-01

Objective To evaluate the validity of the International Classification of Diseases, Tenth Revision (ICD-10) code N17x for acute kidney injury (AKI) in elderly patients in two settings: at presentation to the emergency department and at hospital admission. Design A population-based retrospective validation study. Setting Southwestern Ontario, Canada, from 2003 to 2010. Participants Elderly patients with serum creatinine measurements at presentation to the emergency department (n=36 049) or hospital admission (n=38 566). The baseline serum creatinine measurement was a median of 102 and 39 days prior to presentation to the emergency department and hospital admission, respectively. Main outcome measures Sensitivity, specificity and positive and negative predictive values of ICD-10 diagnostic coding algorithms for AKI using a reference standard based on changes in serum creatinine from the baseline value. Median changes in serum creatinine of patients who were code positive and code negative for AKI. Results The sensitivity of the best-performing coding algorithm for AKI (defined as a ≥2-fold increase in serum creatinine concentration) was 37.4% (95% CI 32.1% to 43.1%) at presentation to the emergency department and 61.6% (95% CI 57.5% to 65.5%) at hospital admission. The specificity was greater than 95% in both settings. In patients who were code positive for AKI, the median (IQR) increase in serum creatinine from the baseline was 133 (62 to 288) µmol/l at presentation to the emergency department and 98 (43 to 200) µmol/l at hospital admission. In those who were code negative, the increase in serum creatinine was 2 (−8 to 14) and 6 (−4 to 20) µmol/l, respectively. Conclusions The presence or absence of ICD-10 code N17× differentiates two groups of patients with distinct changes in serum creatinine at the time of a hospital encounter. However, the code underestimates the true incidence of AKI due to a limited sensitivity. PMID:23204077

Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery

PubMed Central

Coca, Steven G.; Garg, Amit X.; Swaminathan, Madhav; Garwood, Susan; Hong, Kwangik; Thiessen-Philbrook, Heather; Passik, Cary; Koyner, Jay L.; Parikh, Chirag R.; Jai, Raman; Jeevanandam, Valluvan; Akhter, Shahab; Devarajan, Prasad; Bennett, Michael; Edelsteinm, Charles; Patel, Uptal; Chu, Michael; Goldbach, Martin; Guo, Lin Ruo; McKenzie, Neil; Myers, Mary Lee; Novick, Richard; Quantz, Mac; Zappitelli, Michael; Dewar, Michael; Darr, Umer; Hashim, Sabet; Elefteriades, John; Geirsson, Arnar

2013-01-01

Background Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to ‘functional’ postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for ‘structural’ AKI, measured with new urinary biomarkers, is unknown. Methods The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: ‘none’ (no exposure prior to surgery), ‘held’ (on chronic ACEi/ARB but held on the morning of surgery) or ‘continued’ (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were ‘functional’ AKI based upon changes in pre- to postoperative serum creatinine, and ‘structural AKI’, based upon peak postoperative levels of four urinary biomarkers of kidney injury. Results Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein). Conclusions Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted. PMID:24081864

Two low-cost digital camera-based platforms for quantitative creatinine analysis in urine.

PubMed

Debus, Bruno; Kirsanov, Dmitry; Yaroshenko, Irina; Sidorova, Alla; Piven, Alena; Legin, Andrey

2015-10-01

In clinical analysis creatinine is a routine biomarker for the assessment of renal and muscular dysfunctions. Although several techniques have been proposed for a fast and accurate quantification of creatinine in human serum or urine, most of them require expensive or complex apparatus, advanced sample preparation or skilled operators. To circumvent these issues, we propose two home-made platforms based on a CD Spectroscope (CDS) and Computer Screen Photo-assisted Technique (CSPT) for the rapid assessment of creatinine level in human urine. Both systems display a linear range (r(2) = 0.9967 and 0.9972, respectively) from 160 μmol L(-1) to 1.6 mmol L(-1) for standard creatinine solutions (n = 15) with respective detection limits of 89 μmol L(-1) and 111 μmol L(-1). Good repeatability was observed for intra-day (1.7-2.9%) and inter-day (3.6-6.5%) measurements evaluated on three consecutive days. The performance of CDS and CSPT was also validated in real human urine samples (n = 26) using capillary electrophoresis data as reference. Corresponding Partial Least-Squares (PLS) regression models provided for mean relative errors below 10% in creatinine quantification. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum Symmetric Dimethylarginine as an Early Marker of Excretory Dysfunction in Canine Leishmaniosis (L. infantum) Induced Nephropathy.

PubMed

Torrent, Esther; Planellas, Marta; Ordeix, Laura; Pastor, Josep; Rodon, Jaume; Solano-Gallego, Laia

2018-01-01

The aims of the study were to determine whether symmetric dimethylarginine (SDMA) was increased in dogs with leishmaniosis and to assess its relationship with creatinine concentration and urinary protein : creatinine ratio (UPC) to determine its utility as a marker of early excretory dysfunction. Fifty-three dogs with leishmaniosis classified according to the LeishVet clinical staging (stage I, n = 5, stage II, n = 30; stage III, n = 12; stage IV, n = 6) were selected and compared with 41 clinically healthy dogs. Thirty-nine dogs with leishmaniosis were also followed up for six months. SDMA concentrations on the day of diagnosis were significantly higher in dogs with leishmaniosis with respect to control dogs and in dogs from LeishVet stage IV when compared with the other stages. Increased UPC (>0.5), SDMA (>19  μ g/dL), and creatinine concentrations (≥1.4 mg/dL) were found in 47.1%, 15.1%, and 9.4% of dogs with leishmaniosis, respectively. SDMA concentration was increased in 24% of proteinuric dogs, in 7% of nonproteinuric dogs, and in four of five dogs with increased creatinine. SDMA concentration ≥ 25  μ g/dL was associated with clinical chronic kidney disease (CKD) after six months. Our results did not demonstrate advantages in using SDMA concentration as an early marker of CKD when compared to creatinine and UPC in canine leishmaniosis.

Serum Symmetric Dimethylarginine as an Early Marker of Excretory Dysfunction in Canine Leishmaniosis (L. infantum) Induced Nephropathy

PubMed Central

Torrent, Esther; Planellas, Marta; Ordeix, Laura; Pastor, Josep; Rodon, Jaume

2018-01-01

The aims of the study were to determine whether symmetric dimethylarginine (SDMA) was increased in dogs with leishmaniosis and to assess its relationship with creatinine concentration and urinary protein : creatinine ratio (UPC) to determine its utility as a marker of early excretory dysfunction. Fifty-three dogs with leishmaniosis classified according to the LeishVet clinical staging (stage I, n = 5, stage II, n = 30; stage III, n = 12; stage IV, n = 6) were selected and compared with 41 clinically healthy dogs. Thirty-nine dogs with leishmaniosis were also followed up for six months. SDMA concentrations on the day of diagnosis were significantly higher in dogs with leishmaniosis with respect to control dogs and in dogs from LeishVet stage IV when compared with the other stages. Increased UPC (>0.5), SDMA (>19 μg/dL), and creatinine concentrations (≥1.4 mg/dL) were found in 47.1%, 15.1%, and 9.4% of dogs with leishmaniosis, respectively. SDMA concentration was increased in 24% of proteinuric dogs, in 7% of nonproteinuric dogs, and in four of five dogs with increased creatinine. SDMA concentration ≥ 25 μg/dL was associated with clinical chronic kidney disease (CKD) after six months. Our results did not demonstrate advantages in using SDMA concentration as an early marker of CKD when compared to creatinine and UPC in canine leishmaniosis.

Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

PubMed

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

2015-12-01

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p<0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g(-1), p>0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p<0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p<0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β2-MG (p<0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p<0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers. Copyright © 2015. Published by Elsevier B.V.

Urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene as markers of exposure to diesel exhaust.

PubMed

Kuusimäki, Leea; Peltonen, Yrjö; Mutanen, Pertti; Peltonen, Kimmo; Savela, Kirsti

2004-01-01

The objective of this study was to assess the exposure of bus-garage and waste-collection workers to polycyclic aromatic hydrocarbons (PAHs) derived from diesel exhaust by the measurement of levels of seven urinary PAH metabolites: 2-naphthol, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 1+9-hydroxyphenanthrene, 4-hydroxyphenanthrene and 1-hydroxypyrene. One urine sample from each of 46 control persons, and one pre-shift and two post-shift spot urine samples from 32 exposed workers were obtained in winter and in summer. The metabolites were analysed after enzymatic hydrolysis by high performance liquid chromatography (HPLC) with fluorescence detection. The sum of seven PAH metabolites (mean 3.94 +/- 3.40 and 5.60 +/- 6.37 micromol/mol creatinine in winter and summer, respectively) was higher [P=0.01, degrees of freedom (df) =61.2 and P=0.01, df=67.6 in winter and summer, respectively] in the exposed group than in the control group (mean 3.18 +/- 3.99 and 3.03 +/- 2.01 micromol/mol creatinine in winter and summer, respectively). The mean concentrations of 2-naphthol among exposed and controls ranged between 3.34 and 4.85 micromol/mol creatinine and 2.51 and 2.58 micromol/mol creatinine, respectively (P<0.01 in winter, P<0.03 in summer). The mean level of the hydroxyphenanthrenes in the samples of exposed workers was between 0.40 and 0.70 micromol/mol creatinine and in the control samples 0.40-0.60 micromol/mol creatinine. The concentration of 1-hydroxypyrene was higher among exposed workers in both pre-shift and post-shift samples (mean 0.10-0.15 micromol/mol creatinine) than in control group (mean 0.05-0.06 micromol/mol creatinine) in winter (P=0.002, df=78) and in summer (P<0.001, df=68). The urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene showed low exposure to diesel-derived PAHs; however, it was higher in exposed workers than in control group. Urinary PAH monohydroxy-metabolites measured in this study did not correlate with the PAHs in the air samples, reported earlier, in 2002 and 2003.

Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study

PubMed Central

McGregor, Tracy L.; Jones, Deborah P.; Wang, Li; Danciu, Ioana; Bridges, Brian C.; Fleming, Geoffrey M.; Shirey-Rice, Jana; Chen, Lixin; Byrne, Daniel W.; Van Driest, Sara L.

2015-01-01

Background Acute kidney injury (AKI) has been characterized in young high-risk inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. Study Design Retrospective cohort study Setting & Participants 13,914 noncritical admissions during 2011–2012 at our tertiary referral pediatric hospital were evaluated. Patients <28 days or >21 years of age, or with chronic kidney disease (CKD), were excluded. Admissions with ≥2 serum creatinine measurements were evaluated. Factors Demographic features, laboratory measurements, medication exposures, and length of stay. Outcome AKI defined by increased serum creatinine in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically-obtained data. Results Two or more creatinine measurements (one baseline before or during admission, and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference of ≥0.3 mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. Limitations Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with ≥2 clinically obtained serum creatinine measurements, and baseline creatinine may have been measured after the AKI episode. Conclusions AKI occurs in at least 5% of all non-critically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with serum creatinine measurements in this population so that exacerbating factors such as nephrotoxic medication exposures may be modified as indicated. PMID:26319754

Prevalence of kidney disease in anaemia differs by GFR-estimating method: The Third National Health and Nutrition Examination Survey (1988–94)

PubMed Central

Estrella, Michelle M.; Astor, Brad C.; Köttgen, Anna; Selvin, Elizabeth; Coresh, Josef; Parekh, Rulan S.

2010-01-01

Background. Anaemia worsens as kidney function declines. Both conditions are associated with increased mortality. Serum cystatin C is purportedly a more sensitive marker of kidney disease and a better predictor of mortality than serum creatinine. However, studies suggest that extrarenal factors also influence cystatin C levels. Methods. We determined whether estimates of glomerular filtration rate [estimated glomerular filtration rate (eGFR)] based on serum cystatin C alone or in combination with serum creatinine were superior to those based on serum creatinine in recognizing impaired kidney function in the setting of anaemia in a sub-sample of the Third National Health and Nutrition Examination Survey of the USA consisting of 6734 participants, 20 years or older. Results. The prevalence of moderate to severe kidney disease (eGFR 15–59 mL/min/1.73 m2) among anaemic persons was 15–16% when based on serum creatinine alone (eGFRSCR) or combined with cystatin C (eGFRSCR + CYSC); this estimate increased to nearly 25% when kidney function was estimated by cystatin C (eGFRCYSC). The adjusted odds ratios of kidney disease in anaemic versus non-anaemic persons were slightly higher with eGFRCYSC than eGFRSCR and eGFRSCR + CYSC in younger adults [odds ratio (OR) = 5.22, 95% confidence interval (CI): 2.23, 12.17], women (OR = 5.34, 95% CI: 2.36, 12.06) and those with elevated C-reactive protein (CRP) (OR = 7.36, 95% CI: 1.98–27.36). Conclusions. Impaired kidney function was common in individuals with anaemia. Among anaemic individuals, the prevalence estimate for kidney disease was notably higher when kidney function was estimated by cystatin C alone compared with the estimations by serum creatinine alone or in combination with serum cystatin C. eGFRCYSC may be particularly helpful in identifying kidney disease in the setting of anaemia among younger persons, women and those with elevated CRP. Regardless of which renal biomarker is used, our study suggests that an evaluation for underlying kidney disease should be considered in the standard workup of anaemia. PMID:20176612

Neonatal handling reduces renal function in adult rats.

PubMed

Donadio, Márcio Vinícius Fagundes; Jacobs, Silvana; Corezola, Kizzy Ludnila; Melo, Denizar Alberto da Silva; Dias, Henrique Bregolin; Reichel, Carlos Luiz; Franci, Celso Rodrigues; Jeckel-Neto, Emilio Antonio; Lulhier, Francisco; Lucion, Aldo Bolten; de Oliveira, Jarbas Rodrigues; Sanvitto, Gilberto Luiz

2009-01-01

To evaluate the effects of neonatal handling on hydroelectrolytic balance in adult rats. The litters were divided into two groups: nonhandled and handled. The procedure consisted of handling the pups for 1 min/day in the first 10 days postnatally. When adults, animals had their body weight verified and were housed in individual metabolic cages. After a 24-hour period, urine samples were collected and the urinary and water intake volumes measured. Blood samples to determine osmolality, aldosterone, corticosterone, angiotensin II, creatinine, urea, sodium and potassium levels were collected. The kidneys were removed for histological assessment. Urinary osmolality, sodium, urea and creatinine were also measured and the creatinine clearance (CC) calculated. No difference between groups was found in the body weight. Handled animals showed a reduction in the total kidney wet weight, water intake, urinary volume, CC, plasma angiotensin II, corticosterone and aldosterone when compared to the nonhandled and an increase in the urinary osmolality and sodium excretion fraction. No differences in serum potassium and no evidence of structural changes were demonstrated by histological analysis. Neonatal handling induced long-lasting effects decreasing renal function without evidence of kidney structural changes. (c) 2009 S. Karger AG, Basel.

Assessment of chronic kidney disease using skin texture as a key parameter: for South Indian population.

PubMed

Udhayarasu, Madhanlal; Ramakrishnan, Kalpana; Periasamy, Soundararajan

2017-12-01

Periodical monitoring of renal function, specifically for subjects with history of diabetic or hypertension would prevent them from entering into chronic kidney disease (CKD) condition. The recent increase in numbers may be due to food habits or lack of physical exercise, necessitates a rapid kidney function monitoring system. Presently, it is determined by evaluating glomerular filtration rate (GFR) that is mainly dependent on serum creatinine value and demographic parameters and ethnic value. Attempted here is to develop ethnic parameter based on skin texture for every individual. This value when used in GFR computation, the results are much agreeable with GFR obtained through standard modification of diet in renal disease and CKD epidemiology collaboration equations. Once correlation between CKD and skin texture is established, classification tool using artificial neural network is built to categorise CKD level based on demographic values and parameter obtained through skin texture (without using creatinine). This network when tested gives almost at par results with the network that is trained with demographic and creatinine values. The results of this Letter demonstrate the possibility of non-invasively determining kidney function and hence for making a device that would readily assess the kidney function even at home.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhakhova, Z.N.; Braun, A.D.

Disturbance of the creatine-creatinine balance in radiation sickness is an indication of general dystrophy. The normal excretion of creatine in the urine of healthy rats is 0.7 mg per day and that of creatinine is 4.6 mg per day. A fivefold increase in the amount of creatine excreted was observed on the second day after administration of a dose of 500 r with a return to normal levels on the 5th to 6th day after irradiation. The severity of the creatinuria is significantly higher for pregnant rats irradiated just before childbirth than it is for pregnant rats irradiated on themore » 1lth to 12th day of pregnancy or for nonpregnant irradiated rats. The clinical symptoms of radiation sickness in the group of rats irradiated on the 11th to 12th day of pregnancy were much less pronounced. but the fetus died and was readsorbed. Irradiation of rats on the 19th day of pregnancy results in a prolongation of the gestation period to 24 to 25 days instead of a normal period of 21 to 22 days. The determination of the content of creatine and of creatinine can serve as a diagnostic aid in radiation sickness. (TTT)« less

Molecular phenotyping of clinical AKI with novel urinary biomarkers

PubMed Central

Huen, Sarah C.

2015-01-01

Acute kidney injury (AKI) is a common hospital complication. There are no effective treatments to minimize kidney injury or limit associated morbidity and mortality. Currently, serum creatinine and urine output remain the gold standard used clinically in the diagnosis of AKI. Several novel biomarkers can diagnose AKI earlier than elevations of serum creatinine and changes in urine output. Recent long-term observational studies have elucidated a subgroup of patients who have positive biomarkers of AKI but do not meet criteria for AKI by serum creatinine or urine output, termed subclinical AKI. These patients with subclinical AKI have increased risk of both short- and long-term mortality. In this review, we will highlight the implications of what these patients may represent and the need for better phenotyping of AKI by etiology, severity of injury, and ability to recover. We will discuss two AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and breast regression protein-39 (BRP-39)/YKL-40, that exemplify the need to characterize the complexity of the biological meaning behind the biomarker, beyond elevated levels reporting on tissue injury. Ultimately, careful phenotyping of AKI will lead to identification of therapeutic targets and appropriate patient populations for clinical trials. PMID:26084933

The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

PubMed

Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

2016-01-01

Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

PubMed

Lytvyn, Yuliya; Xiao, Fengxia; Kennedy, Christopher R J; Perkins, Bruce A; Reich, Heather N; Scholey, James W; Cherney, David Z; Burger, Dylan

2017-03-01

Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry. Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/μmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/μmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/μmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/μmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia. Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.

Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury.

PubMed

Mercantepe, Filiz; Mercantepe, Tolga; Topcu, Atilla; Yılmaz, Adnan; Tumkaya, Levent

2018-06-02

Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5). Rats in all groups except the control group were administered a single intraperitoneal dose of 7.5 mg/kg cisplatin. All animals were sacrificed under anesthesia on the sixth day after cisplatin administration. Cisplatin increased serum urea and serum creatinine levels and caused an increase in tubular necrosis scores (TNS), HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). Additionally, we observed basal membrane thickening in glomerules, intense electron deposition in the subendothelial region, and atypical folds in podocyte pedicels. Amifostine, curcumin, and melatonin reduced the increases in serum urea and serum creatinine levels following cisplatin administration and reduced the levels of TNS, HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). ROS-scavenging antioxidants may be a promising means of preventing acute kidney disease in patients using cisplatin in the treatment of malignant tumors.

Changes in biochemical proxy indicators for nutritional stress resilience from Boran and Nguni cows reared in dry arid rangeland.

PubMed

Mapfumo, Lizwell; Muchenje, Voster; Mupangwa, John F; Scholtz, Michiel M

2017-10-01

The objective of this study was to determine the changes in biochemical indicators for nutritional stress from a herd of Boran and Nguni cows. A total of 40 cows (20 from each herd) were randomly selected for the study. The animals were identified according to their parities as follows: parity 1 (n = 8), parity 2 (n = 16), parity 3 (n = 8) and parity 4 (n = 8). Serum chemistry levels of glucose, total cholesterol, urea, creatinine, albumin, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutylaminotransferase (GGT), leukocytes, erythrocytes, haemoglobin, packed cell volume (PCV) and platelet counts were determined for 12 consecutive months spanning across the wet and dry seasons. The Boran cows had different creatinine concentration levels at different parities. The Boran cows in parity 1 had the highest (P < 0.05) concentration of creatinine 87.2 ± 5.17 μmol/L than other cows in different parities within the herd. There were significant differences in enzymes such as AST, ALP and ALT among the herd and parities. Boran cows in parity 3 had the lowest (P < 0.05) AST concentration levels of 52.6 ± 3.48 U/L, Nguni cows in parity 4 had the highest concentration of ALP of 161.3 ± 8.10 U/L while Nguni cows in parity 1 had the highest concentration level of ALT 55.1 ± 1.56 U/L than all the cows within the same herd. The Nguni herd had significantly higher (P < 0.05) levels of creatinine in both the wet (97.8 ± 3.27 μmol/L) and dry seasons (108.7 ± 3.29 μmol/L) compared with the Boran herd. Cows from the Nguni herd maintained significantly higher amount of urea, creatinine, albumin and total protein in both the wet and dry seasons as compared with cows from the Boran herd. Cows from the Nguni herd maintained significantly higher amount of urea, creatinine, albumin and total protein in both the wet and dry seasons as compared with those from the Boran herd.

Renal and blood pressure effects from environmental cadmium exposure in Thai children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Jeekeeree, Wanpen

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming ricemore » grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.« less

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

Influence of Moringa oleifera extract, vitamin C, and sodium bicarbonate on heat stress-induced HSP70 expression and cellular immune response in rabbits.

PubMed

Abdel-Latif, Mahmoud; Sakran, Thabet; Badawi, Yasser K; Abdel-Hady, Doaa S

2018-05-04

The current study aimed to test the effect of Moringa oleifera extract (MOE), vitamin (Vit) C, and sodium bicarbonate (NaHCO 3 ) on heat stress (HS)-induced alterations in rabbits. Five groups of rabbits were designed as control, HS, HS + MOE, HS + Vit C, and HS + NaHCO 3 . HS groups were exposed to high temperatures, while treatments were given in drinking water for 6 weeks. Levels of blood cortisol, leptin, IFN-γ, TNF-α, and IL-10 were assayed using ELISA, while adrenaline was assayed calorimetrically. Expression of HSP70, FOXP3, T cell receptor (TCR) γ, and δ mRNA was tested using real-time (RT)-PCR, while HSP70 protein expression was tested using western blotting in liver and kidney tissues. Infiltration of regulatory T cells (Treg; CD25 + ) and NK (CD56 + ) cells were tested using immunohistochemistry (IHC). The levels of liver enzymes (ALT & AST), urea, and creatinine were assayed calorimetrically, while body weight gain (BWG) and feed conversion ratio (FCR) were calculated. The results showed increased levels of cortisol, adrenaline, leptin, IFN-γ, TNF-α, ALT, AST, urea, and creatinine but decreased IL-10 in the HS group. Increased expression of HSP70 on both mRNA and protein levels was associated with increased NK and γδ T cells versus decreased Treg cell infiltration in liver and kidney tissues of the HS group. In the same group, BWG was decreased, while FCR was increased with respect to the control group. All treatments used in this study reversed the effects of HS significantly. In conclusion, MOE, Vit C, and NaHCO 3 can be added to rabbit diets for the amelioration of HS-induced symptoms.

Comparative effects of vitamin E and kolaviron (a biflavonoid from Garcinia kola) on carbon tetrachloride-induced renal oxidative damage in mice.

PubMed

Adaramoye, O A

2009-08-15

It became evident in this study that carbon tetrachloride (CCl4), can induce renal oxidative damage. The hepatoprotective effects of vitamin E (Vit. E) and kolaviron (KV), a biflavonoid complex from the seeds of Garcinia kola are well documented. The present study was designed to investigate and compare the renal protective effects of Vit. E and KV in mice given CCl4 (1.2 g kg(-1)) intra-peritoneally thrice a week for two weeks. CCl4 caused a marked increase in serum and renal lipid peroxidation (LPO) by 106 and 225%, respectively. Treatment with KV at 100 and 200 mg kg(-1) and Vit. E at 100 mg kg(-1) significantly (p < 0.05) decreased the CCl4-mediated increase in LPO. Furthermore, CCl4-intoxication decreased the levels of renal reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) by 44, 56 and 43%, respectively. Treatment with KV and Vit. E significantly (p < 0.05) ameliorated the GSH and SOD levels. Specifically, KV at 100 and 200 mg kg(-1) increased GSH by 32 and 27% and SOD levels by 50 and 53%, respectively. Likewise, treatment with Vit. E increased GSH and SOD levels by 31 and 53%, respectively. Effects on markers of renal functions showed that CCl4-intoxication significantly (p < 0.05) elevated serum urea and creatinine by 287 and 186%, respectively. While treatment with Vit. E decreased serum urea and creatinine by 60 and 55%, respectively, KV produced insignificant (p > 0.05) effect on these parameters. This study found KV unable to protect against CCl4-induced renal damage but confirmed the potency of Vit. E to enhance recovery from renal oxidative damage.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Sensitive albuminuria analysis using dye-binding based test strips.

PubMed

Delanghe, Joris R; Himpe, Jonas; De Cock, Naomi; Delanghe, Sigurd; De Herde, Kevin; Stove, Veronique; Speeckaert, Marijn M

2017-08-01

Populations at increased risk for chronic kidney disease should be screened for albuminuria. Possibilities of advanced urine strip readers based on complementary metal oxide semiconductor (CMOS) sensor technology were investigated for obtaining quantitative albuminuria results. Reflectance data of test strips (Sysmex UFC 3500 reader+CMOS) were compared with albuminuria (BNII) and with proteinuria (Cobas 8000). Urinary creatinine was assayed using a Jaffe-based creatinine assay (Cobas 8000). Calibration curve was made between 11.5 and 121.5mg/L with detection limit of 5.5mg/L. Within-run CV values of reflectance data were 0.21% (UC-Control L; 10mg/L) and 0.37% (UC-Control H; >150mg/L) for albumin, and 0.71%/3.97% for creatinine. Between-run CV values were 0.24%/0.42% for albumin and 0.93%/5.13% for creatinine. A strong correlation (r=0.92) was obtained between albuminuria (BNII) and protein strip reflectance data. Creatinine reflectance data correlated well with Jaffe-based urinary creatinine data (r=0.90). Albumin:creatinine ratio obtained by test strip and by wet chemistry showed a good correlation (r=0.59). Carbamylated, glycated and partially hydrolyzed isoforms of albumin could be detected by test strip. Dye-binding based albumin test strip assay in combination with a CMOS based reader would potentially allow quantitative analysis of albuminuria and determination of albumin:creatinine ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, Virginia M., E-mail: vweaver@jhsph.edu; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD

Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) {mu}g/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73more » m{sup 2}, respectively. The eGFR measures were moderately correlated (r{sub s}=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m{sup 2}; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.« less

Stability of renal allograft recipients after conversion from cyclosporine to azathioprine.

PubMed

Carpenter, C B; Milford, E L; Kirkman, R L; Strom, T B; Lazarus, J M; Tilney, N L

1985-08-01

Forty-eight patients with stable renal function after allotransplantation have been converted from CsA/prednisone to azathioprine/prednisone to assess the short- and long-term effects upon renal function. Virtually all patients show an initial improvement in serum creatinine levels. Three patients developed chronic renal failure after 12 to 21 months, and three died of pneumonia 7, 12, and 19 months later. The mean serum creatinine level at latest follow-up (seven to 36 months) was 2.5 +/- 1.5 mg/dL for all 48 patients. Of interest, a control group of 21 patients not converted to azathioprine had serum creatinine levels of 2.5 +/- 0.8 mg/dL, over a follow-up period of five to 25 months. It is not immediately apparent that either group will have a superior overall outcome, although patients on azathioprine seem to have more of a risk for graft loss. More data are needed with various dosage schedules, and with randomized controls.

Clinical outcomes and survival in AA amyloidosis patients.

PubMed

Ayar, Yavuz; Ersoy, Alparslan; Oksuz, Mustafa Ferhat; Ocakoglu, Gokhan; Vuruskan, Berna Aytac; Yildiz, Abdülmecit; Isiktas, Emel; Oruc, Aysegül; Celikci, Sedat; Arslan, Ismail; Sahin, Ahmet Bilgehan; Güllülü, Mustafa

Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis. Copyright © 2017. Published by Elsevier Editora Ltda.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats

PubMed Central

Apaydin Yildirim, Betul; Kordali, Saban; Terim Kapakin, Kubra Asena; Yildirim, Fatih; Aktas Senocak, Esra; Altun, Serdar

2017-01-01

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters. PMID:28585426

Risk Factors for Cisplatin-Induced Nephrotoxicity and Potential of Magnesium Supplementation for Renal Protection

PubMed Central

Sakiyama, Tsutomu; Okamoto, Kunio; Tanaka, Kaoru; Takeda, Masayuki; Kaneda, Hiroyasu; Nishina, Shin-ichi; Tsurutani, Junji; Fujiwara, Kimiko; Nomura, Morihiro; Yamazoe, Yuzuru; Chiba, Yasutaka; Nishida, Shozo; Tamura, Takao; Nakagawa, Kazuhiko

2014-01-01

Background Nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. We retrospectively evaluated potential risk factors for cisplatin-induced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. Patients and Methods We reviewed clinical data for 401 patients who underwent chemotherapy including a high dose (≥60 mg/m2) of cisplatin in the first-line setting. Nephrotoxicity was defined as an increase in the serum creatinine concentration of at least grade 2 during the first course of cisplatin chemotherapy, as assessed on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The severity of nephrotoxicity was evaluated on the basis of the mean change in the serum creatinine level. Magnesium was administered intravenously to 67 patients (17%). Results Cisplatin-induced nephrotoxicity was observed in 127 patients (32%). Multivariable analysis revealed that an Eastern Cooperative Oncology Group performance status of 2 (risk ratio, 1.876; P = 0.004) and the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) (risk ratio, 1.357; P = 0.047) were significantly associated with an increased risk for cisplatin nephrotoxicity, whereas intravenous magnesium supplementation was associated with a significantly reduced risk for such toxicity (risk ratio, 0.175; P = 0.0004). The development of hypomagnesemia during cisplatin treatment was significantly associated with a greater increase in serum creatinine level (P = 0.0025). Magnesium supplementation therapy was also associated with a significantly reduced severity of renal toxicity (P = 0.012). Conclusions A relatively poor performance status and the regular use of NSAIDs were significantly associated with cisplatin-induced nephrotoxicity, although the latter association was marginal. Our findings also suggest that the ability of magnesium supplementation to protect against the renal toxicity of cisplatin warrants further investigation in a prospective trial. PMID:25020203

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

[Mercury impregnation in dentists and dental assistants in Monastir city, Tunisia].

PubMed

Chaari, N; Kerkeni, A; Saadeddine, S; Neffati, F; Khalfallah, T; Akrout, M

2009-06-01

The property of mercury to amalgamate with other metals is used to create a material for filling teeth. This material remains the cheapest and most efficient in tooth restoration. Mercurial toxicity has been documented since Antiquity but the metal remains widely used in some countries. This study compared mercury impregnation in dentists and dental assistants in Monastir (Tunisia) to another population not exposed professionally. A cross-sectional study was made on 52 dentists and dental assistants working in private offices and in the stomatology unit of the Monastir teaching hospital, with a control group of 52 physicians and nurses working in the Monastir Fattouma Bourguiba hospital. The groups were paired according to age and gender. The study lasted three months. A questionnaire investigated the socioprofessional features of the study population, non professional mercury exposure, work environment, the various amalgam handling and preparation techniques, and preventive hygiene measures. Urinary and salivary sampling was performed so as to prevent any accidental mercurial contamination. Mercury level was assessed by atomic absorption spectroscopy in an automatic sampler, urine creatinine with Jaffé's colorimetric reaction. The results of mercury level assessment were expressed in microg/g of creatinine, salivary mercury in mug/l. The statistical analysis was made with the Epi.info 6 software. Khi(2) and Fisher tests were used to compare qualitative variables. The ANOVA test was used to compare averages with a statistic significance threshold at 0.05. Sixty-one percent of individuals with risk exposure worked in a dental clinic. Bruxism and onychophagia were more important in the control group with a significant statistical difference (respectively, p=0.01 and p<0.0001). The urinary and salivary mercury levels were significantly increased in the exposed group, with respective values of 20.4+/-42.4microg/g of creatinine and 10.6+/-13.02microg/l versus 0.04+/-0.3microg/g of creatinine and 0microg/l in the control group. Disposing of amalgam waste was inadequate in 94% of the cases. The variation of mercury in urine was significantly influenced by the presence of fabric curtains (p=0.04). Eating lunch at meals at the work place was also linked to a significant increase of mercury levels in urine (p=0.04). The storage mode of mercury in open containers was a significant factor for variation of mercury level (p=0.03). Most dentists' private offices in Monastir do not comply or comply weakly with prevention measures linked to risk of mercury poisoning. Awareness campaigns were launched as well as actions for the improvement of work conditions: efficient aspiration of offices containing fixed sources of mercury, adequate storage of mercury and waste, and compliance to occupational hygiene rules.

Renal damage induced by the pesticide methyl parathion in male Wistar rats.

PubMed

Fuentes-Delgado, Victor Hugo; Martínez-Saldaña, María Consolación; Rodríguez-Vázquez, María Luisa; Reyes-Romero, Miguel Arturo; Reyes-Sánchez, José Luis; Jaramillo-Juárez, Fernando

2018-01-01

Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD 50 ), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.

THE PATTERN OF LONGITUDINAL CHANGE IN SERUM CREATININE AND NINETY-DAY MORTALITY AFTER MAJOR SURGERY

PubMed Central

Hobson, Charles E; Pardalos, Panos

2016-01-01

Objective Calculate mortality risk that accounts for both severity and recovery of postoperative kidney dysfunction using the pattern of longitudinal change in creatinine. Summary Background Data Although the importance of renal recovery after acute kidney injury (AKI) is increasingly recognized, the complex association that accounts for longitudinal creatinine changes and mortality is not fully described. Methods We used routinely collected clinical information for 46,299 adult patients undergoing major surgery to develop a multivariable probabilistic model optimized for non-linearity of serum creatinine time series that calculates the risk function for ninety-day mortality. We performed a 70/30 cross validation analysis to assess the accuracy of the model. Results All creatinine time series exhibited nonlinear risk function in relation to ninety-day mortality and their addition to other clinical factors improved the model discrimination. For any given severity of AKI, patients with complete renal recovery, as manifested by the return of the discharge creatinine to the baseline value, experienced a significant decrease in the odds of dying within ninety days of admission compared to patients with partial recovery. Yet, for any severity of AKI even complete renal recovery did not entirely mitigate the increased odds of dying as patients with mild AKI and complete renal recovery still had significantly increased odds for dying compared to patients without AKI (odds ratio 1,48 (95% confidence interval 1.30-1.68). Conclusions We demonstrate the nonlinear relationship between both severity and recovery of renal dysfunction and ninety-day mortality after major surgery. We have developed an easily applicable computer algorithm that calculates this complex relationship. PMID:26181482

[Selective preimplantation pathological evaluation in renal transplantation: a single center's experience].

PubMed

Peng, F H; Chen, J J; Peng, L K; Xie, X B; Lan, G B; Yu, S J; Wang, Y; Tang, X T; Dai, H L; Gao, C; Fang, C H

2018-01-16

Objective: To summarize the clinical data of pre-implantation biopsy donors in our hospital and explore the clinical characteristics of those donors in pathological high-risk, and to provide references for the selective histological evaluation of extended criteria donor kidneys. Methods: We retrospectively reviewed the clinical data and pre-implantation renal pathologic score of donors from January 1, 2015 to May 1, 2017.During this period, 247 cases of donation after citizen's death (DCD) occurred.After clinical evaluation and selective machine perfusion( Lifeport) evaluation, 30 cases of pre-implantation pathological evaluation were performed.According to Remuzzi scores, donors were divided into low-risk and high-risk group.Nine cases of low-risk group (bilateral kidney's Remuzzi score ≤3) and 16 cases of high-risk group (bilateral or unilateral kidney's Remuzzi score ≥4, severe glomerular micro-thrombi or severe tubular necrosis) were included.Five cases of donors were excluded due to only unilateral renal pathological result available.Both high-risk and low-risk groups' clinical data, including sex, age, height, body weight, body mass index, proteinuria, hematuria, urinary glucose, baseline or admission serum creatinine, serum creatinine before procurement, history of hypertension and/or diabetes mellitus, cardiopulmonary resuscitation or not, with or without the history of shock, urine output prior to acquisition, macroscopical manifestations of donor kidney, cause of death were statistically analyzed. Results: The donors' baseline serum creatinine/upper limit of normal serum creatinine range in high-risk group were significantly higher than that in low-risk group [(129.8±42.2)% vs(92.4±30.5)%, P =0.029]. The poor macroscopical manifestations of donor kidneys were significantly more frequent in high-risk group than that in low-risk group (12/16 vs 0/9, P = 0). No significant differences between two groups were found regarding their age, height, weight, BMI, proteinuria, hematuria, urine glucose, pre-procure creatinine level, history of hypertension and/or diabetes mellitus, cause of death and so on ( P >0.05). Conclusions: After clinical evaluation and selective Lifeport evaluation, donor grafts of whose baseline serum creatinine levels increased beyond normal range and of whose grafts' macroscopical manifestations were poor, should undergo pre-implantation pathological evaluation further.Also, it is reasonable to perform pre-implantation biopsy in cases of equivocal results after Lifeport evaluation.This will be beneficial to identify histological high-risk donors and also be predictive to allocate the grafts.

Can baseline serum creatinine and e-GFR predict renal function outcome after augmentation cystoplasty in children?

PubMed

Singh, Prempal; Bansal, Ankur; Sekhon, Virender; Nunia, Sandeep; Ansari, M S

2018-01-01

To assess cut-off value of creatinine and glomerular filtration rate for augmentation cystoplasty (AC) in paediatric age-group. Data of all paediatric-patients (<18 years) with small capacity bladder, in whom AC was advised between 2005-2015 were reviewed. All patients were divided in two-groups, AC-group and control-group (without AC). Creatinine and e-GFR were assessed at the time of surgery, at 6 months and at last follow-up. Renal function deterioration was defined as increase in creatinine by ≥25% from baseline value or new-onset stage-3 CKD or worsening of CKD stage with pre-operative-CKD stage-3. ROCs were plotted using creatinine and e-GFR for AC. A total of 94 patients with mean-age 8.9 years were included. The mean creatinine and e-GFR were 1.33mg/dL and 57.68mL/min respectively. Out of 94 patients, AC was performed in 45 patients and in the remaining 49 patients AC was not done (control-group), as they were not willing for the same. Baseline patient's characteristics were comparable in both Groups. 22 underwent gastro-cystoplasty (GC) and 25 underwent ileo-cystoplasty (IC). Decline in renal function was observed in 15 (33.3%) patients of AC-group and in 31 (63.3%) patients of control-group. Patients having creatinine ≥1.54mg/dL (P=0.004, sensitivity (S) 63.6% and specificity (s) 90.5%) at baseline and e-GFR ≤46mL/min (P=0.000, S=100% and s=85.7%) at the time of surgery had significantly increased probability of renal function deterioration on follow-up after AC. e-GFR ≤46mL/min and creatinine ≥1.54mg/dL at time of surgery could serve as a predictor of renal function deterioration in AC in paediatric patients. Copyright® by the International Brazilian Journal of Urology.

Trueness verification of actual creatinine assays in the European market demonstrates a disappointing variability that needs substantial improvement. An international study in the framework of the EC4 creatinine standardization working group.

PubMed

Delanghe, Joris R; Cobbaert, Christa; Galteau, Marie-Madeleine; Harmoinen, Aimo; Jansen, Rob; Kruse, Rolf; Laitinen, Päivi; Thienpont, Linda M; Wuyts, Birgitte; Weykamp, Cas; Panteghini, Mauro

2008-01-01

The European In Vitro Diagnostics (IVD) directive requires traceability to reference methods and materials of analytes. It is a task of the profession to verify the trueness of results and IVD compatibility. The results of a trueness verification study by the European Communities Confederation of Clinical Chemistry (EC4) working group on creatinine standardization are described, in which 189 European laboratories analyzed serum creatinine in a commutable serum-based material, using analytical systems from seven companies. Values were targeted using isotope dilution gas chromatography/mass spectrometry. Results were tested on their compliance to a set of three criteria: trueness, i.e., no significant bias relative to the target value, between-laboratory variation and within-laboratory variation relative to the maximum allowable error. For the lower and intermediate level, values differed significantly from the target value in the Jaffe and the dry chemistry methods. At the high level, dry chemistry yielded higher results. Between-laboratory coefficients of variation ranged from 4.37% to 8.74%. Total error budget was mainly consumed by the bias. Non-compensated Jaffe methods largely exceeded the total error budget. Best results were obtained for the enzymatic method. The dry chemistry method consumed a large part of its error budget due to calibration bias. Despite the European IVD directive and the growing needs for creatinine standardization, an unacceptable inter-laboratory variation was observed, which was mainly due to calibration differences. The calibration variation has major clinical consequences, in particular in pediatrics, where reference ranges for serum and plasma creatinine are low, and in the estimation of glomerular filtration rate.

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease.

PubMed

Cavalcante, Antonio George Matos; de Bruin, Pedro Felipe Carvalhedo; de Bruin, Veralice Meireles Sales; Pereira, Eanes Delgado Barros; Cavalcante, Marina Medeiros; Nunes, Deuzilane Muniz; Viana, Cynthia Sampaio

2012-08-01

To investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD). RLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1±8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen. Thirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5=59.6%; p=0.002), worse fatigue (FSS >27=51%; p=0.005), and more depressive symptoms (BDI-II >10=14.4%; p=0.005). Patients with RLS also presented more severe dyspnea (p=0.009) and lower creatinine levels (p=0.005). Overall, fatigue severity was correlated with older age (p=0.001); level of dyspnea was positively correlated with PSQI and FSS (p<0.005) and negatively correlated with ferritin (p=0.03) and creatinine (p=0.005), and PSQI scores correlated positively with FSS (p<0.005) and negatively with ferritin (p=0.005) and creatinine (p=0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression. RLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea. Copyright © 2012 Elsevier B.V. All rights reserved.

Assessment of the RIFLE criteria for the diagnosis of Acute Kidney Injury; a retrospective study in South-Western Ghana.

PubMed

Ephraim, Richard K D; Darkwah, Kwame O; Sakyi, Samuel A; Ephraim, Mabel; Antoh, Enoch O; Adoba, Prince

2016-07-26

Acute kidney injury (AKI) affects 3-7 % of patients admitted to the hospital and approximately 25-30 % of patients in the intensive care unit. RIFLE, a newly developed international consensus classification for AKI, defines three grades of severity-class R (risk), I (injury) and F (failure). The aim of this study was to evaluate whether the RIFLE system of classification can detect the incidence of AKI using retrospective data of in-patients at the Effia-Nkwanta Regional Hospital. A total of 1070 in-patients' records spanning a period of 6 months, from July 2014 to December 2014, was used. Demographic data and hospital admission serum creatinine of each participant were used for the calculation of estimated glomerular filtration rate (eGFR) using the 4-variable modification of diet in renal disease (MDRD) equation. Also, the baseline serum creatinine was estimated assuming a standard GFR of 75 ml/min/1.73 m(2) using the simplified MDRD equation. Males had higher serum creatinine, eGFR, and baseline serum creatinine than females (P < 0.0001). However, the level of increase in baseline serum creatinine was higher in females than males (P = 0.0212). The percentage ratios of the various classes from the SCr/ePCr (hospital admission serum creatinine/estimated plasma creatinine) criteria (R-1.45, I-1.53 and F-3.26) were higher than that of the eGFR criteria (R-0.34, I-0.11, F-0.12). The SCr/ePCr criteria gave more risk (89.7 %) than that of the eGFR criteria (23.1 %). The number of Injury and normal patients from the eGFR criteria was higher than the SCr/ePCr criteria. AKI was common in the ICU population with SCr/ePCr detecting more AKI than the eGFR criteria. Males had more injury and failure than females using the eGFR criteria whereas the SCr/ePCr gave females more risk and injury than males. A prospective cohort study must be employed in subsequent studies using the RIFLE criteria to assess the incidence of AKI in hospitalized patients with known diseases or medical conditions.

Gestational changes in iodine status in a cohort study of pregnant women from the United Kingdom: season as an effect modifier123

PubMed Central

Bath, Sarah C; Furmidge-Owen, Victoria L; Redman, Christopher WG

2015-01-01

Background: Iodine is required throughout pregnancy for thyroid hormone production, which is essential for fetal brain development. Studies of iodine status in pregnant women from the United Kingdom (UK) have focused on early gestation (<16 wk). Data on the effect of advancing gestation on urinary iodine excretion are conflicting, with suggestions of both an increase and a decrease. Objectives: The aims were to evaluate iodine status in a cohort of UK pregnant women and to explore how it changes throughout gestation. Design: We used samples and data from 230 UK pregnant women who were recruited to the Selenium in PRegnancy INTervention study. Iodine concentration was measured in spot-urine samples that were collected at ∼12, 20, and 35 wk of gestation; creatinine concentration was also measured to correct for urine dilution. A linear mixed model was used to explore the effect of gestational week on iodine-to-creatinine ratio, with change in season, body mass index, daily milk intake, and maternal age controlled for. Results: The median urinary iodine concentration from urine samples collected at all time points (n = 662) was 56.8 μg/L, and the iodine-to-creatinine ratio was 116 μg/g, thus classifying this cohort as mildly-to-moderately iodine deficient. The median iodine-to-creatinine ratios at 12, 20, and 35 wk were 102.5, 120.0, and 126.0 μg/g, respectively. Only 3% of women were taking iodine-containing prenatal supplements. The iodine-to-creatinine ratio increased with advancing gestation, and there was a significant interaction between gestational week and season (P = 0.026). For a 1-wk increase in gestation, the iodine-to-creatinine ratio increased by a factor of 1.05 (95% CI: 1.02, 1.08) in winter and by a factor of 1.04 (95% CI: 1.00, 1.08) in summer. Conclusions: This group of UK pregnant women was mildly-to-moderately iodine deficient at all trimesters, which is of public health concern. The finding that the iodine-to-creatinine ratio increased over the course of gestation may not be generalizable to populations with different iodine status from ours and merits further investigation. This trial was registered at www.isrctn.com as ISRCTN37927591. PMID:25948667

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats

PubMed Central

Sathya, S.; Kokilavani, R.; Gurusamy, K.

2008-01-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

PubMed

Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

2014-07-01

This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

Urine protein/creatinine ratio as a mortality risk predictor in non-diabetics with normal renal function.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2012-01-01

Determine the relative mortality in apparently healthy adults with various levels of urinary protein measured by urine protein/creatinine (p/c) ratio. By use of the Social Security Death Master File, mortality in 2010 was determined for 7.5 million life insurance applicants age 20 to 89 providing urine samples between 1992 and 2006. Relative mortality by Cox regression for bands of p/c ratios was determined using age and sex as covariates and with an age split at 60 after excluding those with hematuria (> 3 red cells/hpf), diabetes, evidence of blood sugar elevation, or eGFR < 60 mL/min. After the exclusions noted above, relative mortality increased to 160% beginning at a p/c ratio of 0.11 mg/mg and rose steadily above that value regardless of sex and age. Most of this risk was not explained by a history of hypertension or elevated systolic blood pressure. Albumin testing identified roughly a third of urine samples with elevated p/c ratios as not containing albumin; those cases appeared to be associated with much lower risk as long as the p/c ratio was < or = 1.0 mg/mg. Low levels of proteinuria identified as urine protein/creatinine ratios of 0.11 mg/mg or higher (much lower than the usual lower cut-off value of 0.21) are associated with substantial excess mortality risk, even after excluding diabetics and those with reduced kidney function or hematuria.

Effects of losartan/hydrochlorothiazide treatment, after change from ARB at usual dosage, on blood pressure and various metabolic parameters including high-molecular weight adiponectin in Japanese male hypertensive subjects.

PubMed

Hirose, Hiroshi; Kawabe, Hiroshi; Saito, Ikuo

2011-01-01

Losartan, an angiotensin II receptor blocker (ARB), has been reported to increase serum level of high-molecular weight (HMW) adiponectin, which has beneficial effects on insulin resistance and atherosclerosis. On the other hand, treatment with diuretics was reported to decrease the adiponectin level. In the present study, we investigated the effects of changing the treatment to losartan/hydrochlorothiazide (HCTZ) on blood pressure (BP) and various metabolic parameters in Japanese male hypertensive subjects. This study included 15 subjects whose therapy was changed from a usual dosage of ARB to losartan 50mg/HCTZ 12.5mg daily, and also 14 subjects who continued losartan treatment (50mg/day). Serum HMW-adiponectin concentration was assayed using a commercially available HMW-specific ELISA kit. In the losartan/HCTZ patient group, systolic/diastolic BP decreased from 146/95 to 130/84 mmHg (P = 0.0012 for both). The HbA1c level tended to increase from 5.44 ± 0.39 to 5.55 ± 0.44% (P = 0.0554) and serum creatinine level slightly increased from 0.82 ± 0.12 to 0.87 ± 0.12 mg/dl (P = 0.0015). In contrast, serum TG (125 ± 77 to 149 ± 112 mg/dl), uric acid, and HMW-adiponectin levels (3.24 ± 2.97 to 3.36 ± 2.43 μg/ml) were unchanged. In the 14 patients who continued losartan treatment, systolic/diastolic BP was unchanged from 134/86 to 129/80 mmHg. The HbA1c level tended to increase from 5.26 ± 0.63 to 5.39 ± 0.71% (P = 0.0880), serum creatinine and uric acid levels were unchanged, serum lipids tended to improve, and serum HMW-adiponectin levels increased from 3.03 ± 1.06 to 3.46 ± 1.28 μg/ml (P = 0.0105). In summary, changing treatment to losartan/HCTZ, when changed from a usual dosage of ARB, exerted good BP control, while the HMW-adiponectin level was unchanged in male hypertensive subjects.

Certified reference materials (GBW09170 and 09171) of creatinine in human serum.

PubMed

Dai, Xinhua; Fang, Xiang; Shao, Mingwu; Li, Ming; Huang, Zejian; Li, Hongmei; Jiang, You; Song, Dewei; He, Yajuan

2011-02-15

Creatinine is the most widely used clinical marker for assessing renal function. Concentrations of creatinine in human serum need to be carefully checked in order to ensure accurate diagnosis of renal function. Therefore, development of certified reference materials (CRMs) of creatinine in serum is of increasing importance. In this study, two new CRMs (Nos. GBW09170 and 09171) for creatinine in human serum have been developed. They were prepared with mixtures of several dozens of healthy people's and kidney disease patient's serum, respectively. The certified values of 8.10, 34.1 mg/kg for these two CRMs have been assigned by liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) method which was validated by using standard reference material (SRM) of SRM909b (a reference material obtained from National Institute of Standards and Technology, NIST). The expanded uncertainties of certified values for low and high concentrations were estimated to be 1.2 and 1.1%, respectively. The certified values were further confirmed by an international intercomparison for the determination of creatinine in human serum (Consultative Committee for Amount of Substance, CCQM) of K80 (CCQM-K80). These new CRMs of creatinine in human serum pool are totally native without additional creatinine spiked for enrichment. These new CRMs are capable of validating routine clinical methods for ensuring accuracy, reliability and comparability of analytical results from different clinical laboratories. They can also be used for instrument validation, development of secondary reference materials, and evaluating the accuracy of high order clinical methods for the determination of creatinine in human serum. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagata, Chisato, E-mail: chisato@gifu-u.ac.jp

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinarymore » cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal women.« less

The elevated serum urea:creatinine ratio in canine babesiosis in South Africa is not of renal origin.

PubMed

de Scally, M P; Leisewitz, A L; Lobetti, R G; Thompson, P N

2006-12-01

Pigmented serum, usually due to free haemoglobin and/or bilirubin, is a common finding in dogs with babesiosis, resulting in interference with all biochemical tests that rely on photochemistry. This is particularly true of urea and creatinine determinations, complicating the diagnosis of acute renal failure, which is a serious complication of babesiosis. A disproportionately raised serum urea concentration of unknown origin occurs in severely anaemic canine babesiosis patients and gives rise to an increased serum urea:creatinine ratio. The assay for cystatin-C, an excellent measure of glomerular filtration rate, is unaffected by free serum haemoglobin, and due to its different intrinsic origins, is free of influence by the metabolic derangements and organ pathology, other than renal disease, encountered in canine babesiosis. Serum cystatin-C was used to compare the concentrations of serum urea and serum creatinine in dogs with the severely anaemic form of canine babesiosis as well as a canine babesiosis-free reference group. Mean serum urea and mean serum urea:creatinine ratio were significantly elevated in the babesia-infected group relative to the reference population in this study. Mean serum creatinine and mean serum cystatin-C were within the reference ranges. Therefore an elevated urea:creatinine ratio in canine babesiosis in the presence of a normal serum creatinine concentration is considered to be caused by an elevated serum urea concentration and is most likely of non-renal origin. Serum creatinine was therefore as specific a measure of renal function as serum cystatin-C in canine babesiosis in this study. The sensitivity of serum creatinine as a measure of renal function was not established by this study. Serum urea, however, proved to be of little use compared to serum cystatin-C and serum creatinine. Serum urea should therefore not be used to diagnose renal failure in canine babesiosis.

Choice of Reference Serum Creatinine in Defining Acute Kidney Injury.

PubMed

Siew, Edward D; Matheny, Michael E

2015-01-01

The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations. We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating the estimation of baseline renal function, using PubMed and reference back-tracing within known works. (1) Pre-hospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, (2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations, (3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, (4) using more specific definitions of AKI (e.g., KIDGO stages 2 and 3) may help to reduce the effects of misclassification when using surrogate values and (5) leveraging available clinical data may help refine the estimate of reference creatinine. Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine is needed. © 2015 S. Karger AG, Basel.

Allopurinol Against Progression of Chronic Kidney Disease.

PubMed

Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

2017-07-01

Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P < .001) after administration of allopurinol. These effects were not observed in the control subgroups. Allopurinol may slow down stage 3 chronic kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

PubMed Central

Ndoye Foe, Chantal Florentine; Njankouo Ndam, Youchahou; Njayou, Frédéric Nico; Fonkoua, Marie Christine; Etoa, François-Xavier

2017-01-01

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days' subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p < 0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p < 0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose. PMID:29234391

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribedburn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changes inmore » urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: A pilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2009-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest ServiceFSavannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relating changesmore » in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Biological monitoring of smoke exposure among wildland firefighters: Apilot study comparing urinary methoxyphenols with personal exposures to carbon monoxide, particulate matter, and levoglucosan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neitzel, R.; Naeher, L., P.; Paulsen, M.

2008-04-01

Urinary methoxyphenols (MPs) have been proposed as biomarkers of woodsmoke exposure. However, few field studies have been undertaken to evaluate the relationship between woodsmoke exposure and urinary MP concentrations. We conducted a pilot study at the US Forest Service Savannah River Site, in which carbon monoxide (CO), levoglucosan (LG), and particulate matter (PM2.5) exposures were measured in wildland firefighters on prescribed burn days. Pre- and post-shift urine samples were collected from each subject, and cross-shift changes in creatinine-corrected urinary MP concentrations were calculated. Correlations between exposure measures and creatine-adjusted urinary MP concentrations were explored, and regression models were developed relatingmore » changes in urinary MP concentrations to measured exposure levels. Full-shift measurements were made on 13 firefighters over 20 work shifts in winter 2004 at the US Forest Service Savannah River site, a National Environmental Research Park. The average workshift length across the 20 measured shifts was 701±95 min. LG and CO exposures were significantly correlated for samples where the filter measurement captured at least 60% of the work shift (16 samples), as well as for the smaller set of full-shift exposure samples (n¼9). PM2.5 and CO exposures were not significantly correlated, and LG and PM2.5 exposures were only significantly correlated for samples representing at least 60% of the work shift. Creatinine-corrected urinary concentrations for 20 of the 22 MPs showed cross-shift increases, with 14 of these changes showing statistical significance. Individual and summed creatinine-adjusted guaiacol urinary MPs were highly associated with CO (and, to a lesser degree, LG) exposure levels, and random-effects regression models including CO and LG exposure levels explained up to 80% of the variance in cross-shift changes in summed creatinine-adjusted guaiacol urinary MP concentrations. Although limited by the small sample size, this pilot study demonstrates that urinary MP concentrations may be effective biomarkers of occupational exposure to wood smoke among wildland firefighters.« less

Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats.

PubMed

Sheashaa, Hussein; Lotfy, Ahmed; Elhusseini, Fatma; Aziz, Azza Abdel; Baiomy, Azza; Awad, Samah; Alsayed, Aziza; El-Gilany, Abdel-Hady; Saad, Mohamed-Ahdy A A; Mahmoud, Khaled; Zahran, Faten; Salem, Dalia A; Sarhan, Ahmed; Ghaffar, Hassan Abdel; Sobh, Mohamed

2016-05-01

Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250-300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×10 6 ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.

Urinary 3-methylhistidine and progressive winter undernutrition in white-tailed deer

USGS Publications Warehouse

DelGiudice, G.D.; Kerr, K.D.; Mech, L.D.; Riggs, M.R.; Seal, U.S.

1998-01-01

Physiological indicators of muscle catabolism would aid assessment of winter nutritional restriction of ungulates, and urinary 3-methylhistidine has exhibited potential in this regard in several species. We examined the effect of chronic moderate and severe nutritional restriction during winter on urinary 3-methylhistidine:creatinine ratios in seven adult white-tailed deer (Odocoileus virginianus) and the relationship of these ratios to urinary urea nitrogen:creatinine ratios. Mean base line estimates of urinary 3-methylhistidine:creatinine ratio for the control and severely restricted deer (0.043 and 0.086 ??mol:mg, respectively) were similar (P = 0.280) and remained unchanged in the control deer throughout the study. In contrast, mean 3-methylhistidine:creatinine ratios increased dramatically as nutritional restriction and cumulative mass loss progressed; the quadratic component of the data for the chronically restricted deer was significant (P < 0.001). Likewise, there was a strong curvilinear relationship (R2 = 0.82) between cumulative mass loss (up to 29%) of the pooled deer and urinary 3-methylhistidine:creatinine ratios. Further, urinary urea nitrogen:creatinine ratios were strongly related to 3-methylhistidine:creatinine ratios (r2 = 0.89). Our study indicates that further investigation of 3-methylhistidine as an indicator of physical condition and muscle protein breakdown is warranted.

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis.

PubMed

Nitsch, Dorothea; Grams, Morgan; Sang, Yingying; Black, Corri; Cirillo, Massimo; Djurdjev, Ognjenka; Iseki, Kunitoshi; Jassal, Simerjot K; Kimm, Heejin; Kronenberg, Florian; Oien, Cecilia M; Levey, Andrew S; Levin, Adeera; Woodward, Mark; Hemmelgarn, Brenda R

2013-01-29

To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. Random effects meta-analysis using pooled individual participant data. 46 cohorts from Europe, North and South America, Asia, and Australasia. 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g). Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk. Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

Exposure assessment approach through mycotoxin/creatinine ratio evaluation in urine by GC-MS/MS.

PubMed

Rodríguez-Carrasco, Yelko; Moltó, Juan Carlos; Mañes, Jordi; Berrada, Houda

2014-10-01

In this pilot survey human urine samples were analyzed for presence of 15 mycotoxins and some of their metabolites using a novel urinary multi-mycotoxin GC-MS/MS method following salting-out liquid-liquid extraction. Fifty-four urine samples from children and adults residents in Valencia were analyzed for presence of urinary mycotoxin and expressed in gram of creatinine. Three out of 15 mycotoxins were detected namely, HT-2 toxin, nivalenol and deoxynivalenol (DON). 37 samples showed quantifiable values of mycotoxins. Co-occurrence of these contaminants was also observed in 20.4% of assayed samples. DON was the most frequently detected mycotoxin (68.5%) with mean levels of 23.3 μg/g creatinine (range: 2.8-69.1 μg/g creatinine). The levels of urinary DON were used to carry out an exposure assessment approach. 8.1% of total subjects were estimated to exceed the DON provisional maximum tolerable daily intake (PMTDI) (1 μg/kg b.w.). Two out of 9 exposed children exceeded the DON PMTDI thus, making them the most exposed based on the urinary results. Copyright © 2014 Elsevier Ltd. All rights reserved.

CREATININE DETERMINATION IN URINE BY LIQUID CHROMATOGRAPHY-ELECTROSPRAY IONIZATION-TANDEM MASS SPECTROMETRY METHOD.

PubMed

Dereziński, Paweł; Klupczyńska, Agnieszka; Sawicki, Wojciech; Kokot, Zenon J

2016-01-01

Creatinine determination in urine is used to estimate the completeness of the 24-h urine collection, compensation for variable diuresis and as a preliminary step in protein profiling in urine. Despite the fact that a wide range of methods of measuring creatinine level in biofluids has been developed, many of them are adversely affected by interfering substances. A new liquid chromatography-tandem mass spectrometry method for creatinine determination in urine has been developed. Chromatographic separation was performed by applying C18 column and a gradient elution. Analyses were carried out on a triple quadrupole mass spectrometer equipped with an electrospray ion source. The developed method was fully validated according to the international guidelines. The quantification range of the method was 5-1500 ng/mL, which corresponds to 1-300 mg/dL in urine. Limit of detection and quantitation were 2 and 5 ng/mL, respectively. Additionally, the comparison of creatinine determination by newly developed method to the colorimetric method was performed. The method enables the determination of creatinine in urine samples with a minimal sample preparation, excellent sensitivity and prominent selectivity. Since mass spectrometry allows to measure a number of compounds simultaneously, a future perspective would be to incorporate the determination of other clinically important compounds excreted in urine.

Renal ultrafiltration changes induced by focused US.

PubMed

Fischer, Krisztina; McDannold, Nathan J; Zhang, Yongzhi; Kardos, Magdolna; Szabo, Andras; Szabo, Antal; Reusz, Gyorgy S; Jolesz, Ferenc A

2009-12-01

To determine if focused ultrasonography (US) combined with a diagnostic microbubble-based US contrast agent can be used to modulate glomerular ultrafiltration and size selectivity. The experiments were approved by the animal care committee. The left kidney of 17 healthy rabbits was sonicated by using a 260-kHz focused US transducer in the presence of a microbubble-based US contrast agent. The right kidney served as the control. Three acoustic power levels were applied: 0.4 W (six rabbits), 0.9 W (six rabbits), and 1.7 W (five rabbits). Three rabbits were not treated with focused US and served as control animals. The authors evaluated changes in glomerular size selectivity by measuring the clearance rates of 3000- and 70,000-Da fluorescence-neutral dextrans. The creatinine clearance was calculated for estimation of the glomerular filtration rate. The urinary protein-creatinine ratio was monitored during the experiments. The authors assessed tubular function by evaluating the fractional sodium excretion, tubular reabsorption of phosphate, and gamma-glutamyltransferase-creatinine ratio. Whole-kidney histologic analysis was performed. For each measurement, the values obtained before and after sonication were compared by using the paired t test. Significant (P < .05) increases in the relative (ratio of treated kidney value/nontreated kidney value) clearance of small- and large-molecule agents and the urine flow rates that resulted from the focused US treatments were observed. Overall, 1.23-, 1.23-, 1.61-, and 1.47-fold enhancement of creatinine clearance, 3000-Da dextran clearance, 70 000-Da dextran clearance, and urine flow rate, respectively, were observed. Focal tubular hemorrhage and transient functional tubular alterations were observed at only the highest (1.7-W) acoustic power level tested. Glomerular ultrafiltration and size selectivity can be temporarily modified with simultaneous application of US and microbubbles. This method could offer new opportunities for treatment of renal disease.

An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats.

PubMed

Tripathi, Yamini B; Shukla, Rashmi; Pandey, Nidhi; Pandey, Vivek; Kumar, Mohan

2017-02-01

Currently, no drug is available to directly target the signaling molecules involved in the pathogenesis of diabetic nephropathy (DN); only antihypertensive and antidiabetic drugs are in clinical use. In the present study, the therapeutic effects of a active fraction of tubers from Pueraria tuberosa (hereafter referred to as PTY-2) were investigated in streptozotocin (STZ)-diabetic rats with DN, with particular emphasis on its effects on extracellular matrix (ECM) accumulation and matrix metalloproteinase (Mmp)-9 expression in kidney tissue. Rats were injected with 55 mg/kg, i.p., STZ. After 40 days, rats were divided into groups as follows (n = 6 per group): Group 1, age-matched rats not injected with STZ (non-diabetic control); Group 2, STZ-diabetic DN rats; and Group 3, PTY-2 (30 mg/100 g, p.o.)-treated DN rats. After 20 days treatment, the effects of PTY-2 on serum urea and creatinine concentrations, urinary levels of glucose, creatinine, protein, and ketone bodies, and urine pH were determined. Kidney tissue was evaluated for Mmp-9 expression and histological changes. Blood glucose, serum urea, creatinine, and urine protein levels were significantly higher, and creatinine clearance was significantly lower, in Group 2 versus Group 1 rats. There was a higher degree of glomerulosclerosis, expansion of the mesangial matrix, and excess ECM deposition and eosinophilic casts in kidneys from Group 2 versus Group 1 rats. Furthermore, Mmp-9 activity and expression were significantly reduced in kidney homogenate of Group 2 versus Group 1 rats. Interestingly, PTY-2 treatment significantly reversed all these changes in DN rats. Treatment of DN rats with PTY-2 significantly attenuated the severity of DN by increasing the expression and activity of Mmp-9, consequently degrading the ECM accumulated in kidney tissue. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury.

PubMed

Zulu, Mildred; Kaile, Trevor; Kantenga, Timothy; Chileshe, Chisanga; Nkhoma, Panji; Sinkala, Musalula

2016-01-01

Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury.

Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury

PubMed Central

Zulu, Mildred; Kaile, Trevor; Kantenga, Timothy; Chileshe, Chisanga; Nkhoma, Panji; Sinkala, Musalula

2016-01-01

Introduction Kidney injury affects renal excretion of plasma analytes and metabolic waste products with grave pathologic consequences. Early detection, thus of kidney injury is essential for injury specific intervention that may avert permanent renal damage and delay progression of kidney injury. We aimed to evaluate Kidney Injury Molecule-1 (KIM-1) and Microalbuminuria (MAU), as biomarkers of kidney injury, in comparison with creatinine. Methods We compared the levels of urine MAU, urine KIM-1 and other plasma biochemical tests in specimens from 80 individuals with and without kidney disease. Results We found no difference in KIM-1 levels between the kidney disease group (2.82± 1.36ng/mL) and controls (3.29 ± 1.14ng/mL), p = 0.122. MAU was higher in participants with kidney disease (130.809± 84.744 µg/mL) than the controls (15.983± 20.442µg/mL), p ?0.001. KIM-1 showed a weak negative correlation with creatinine (r = -0.279, p = 0.09), whereas MAU was positively correlated with creatinine in participants with kidney disease with statistical significance (r = 0.556, p = 0.001). Conclusion The study demonstrated that in Zambian setting MAU and creatinine are sensitive biomarkers in the diagnosis of kidney damage. We moreover propose further evaluation of KIM-1 as a biomarker of kidney injury. PMID:27642395

Association of Van Wyk Grumbach and Debre Semelaigne Syndromes with Severe Hypothyroidism.

PubMed

Oden Akman, Alkim; Tayfun, Meltem; Demirel, Fatma; Ucakturk, Seyit Ahmed; Gungor, Ali

2015-12-01

Van Wyk Grumbach syndrome (VWGS) and Kocher-Debre Semelaigne syndrome (KDSS) are rare forms of pseudo-precocious puberty and myopathy in patients with longstanding untreated hypothyroidism. We present the case of an adolescent girl who developed pseudo-precocious puberty and myopathy caused by long-term untreated hypothyroidism. A 17-year-old female patient was referred to our outpatient clinic due to menstrual irregularities. She had muscle pain and multiple cystic ovaries in addition to clinical signs of severe congenital hypothyroidism. High levels of creatinine and creatinine kinase and accompanying muscle hypertrophy were present. After the initiation of L-thyroxine therapy, the symptoms were alleviated in a short time. Congenital and acquired hypothyroidism should be considered in the differential diagnosis of pseudo-precocious puberty and myopathy that presents with muscle pain, muscle hypertrophy, and elevated creatinine kinase levels. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy

PubMed Central

Huh, Ji Hye; Choi, Soo In; Lim, Jung Soo; Chung, Choon Hee; Shin, Jang Yel; Lee, Mi Young

2015-01-01

Background Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function. Methods Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45–95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008–2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia. Results In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ –1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74−0.96] at the total hip, OR = 0.8 [95% CI = 0.68−0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73–0.95] at the total hip, OR=0.81 [95% CI = 0.67–0.99] at the lumbar spine). Conclusions Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function. PMID:26207750

Re-Transplantation, Higher Creatinine Levels in Hepatitis C Virus Patients, and Donor Age Are Predictors of Mortality in Long-Term Analysis of Late Acute Rejection in Liver Transplantation.

PubMed

Nacif, Lucas Souto; Pinheiro, Rafael Soares; de Arruda Pécora, Rafael Antônio; Tanigawa, Ryan Yukimatsu; Rocha-Santos, Vinicius; Andraus, Wellington; Alves, Venancio Avancini Ferreira; D'Albuquerque, Luiz Carneiro

2017-01-10

BACKGROUND Late acute rejection (LAR) differs in its clinical and histological presentation and management from early acute rejection. This clinical entity is not completely understood; thus, we aimed to identify significant prognostic factors that can influence post-transplant survival in LAR patients. The purpose of this study was to evaluate the incidence and post-transplant survival of patients from a single center with a focus on late acute rejection. MATERIAL AND METHODS From January 2002 to June 2013, all liver biopsies from patients with rejection were scored using the Banff criteria. The groups were compared, and simple and multiple logistic regression and survival curves were created. RESULTS A total of 779 liver transplants were performed; 585 patients with no rejections and 194 patients with rejections were analyzed. The overall incidence of LAR was 6.7%, and there was a higher prevalence of early acute cellular rejection than LAR. The mean time to LAR was 564 days (median 214 days, range 91-2642). LAR had a more severe grade (35.3%) than early acute rejection (23.5%). The survival rates were similar between both modalities for the long-term period. Worse mortality rates were observed in liver re-transplantation (HR 4.77; p<0.0001); in hepatitis C virus patients with increased creatinine levels (HR 22.48; p=0.016); and in donors >41 years of age (OR 2.1; p=0.047) in a long-term analysis of LAR. CONCLUSIONS Liver re-transplantation, higher creatinine levels in hepatitis C virus patients, and donor age were predictors of mortality in this long-term analysis of late acute rejection in liver transplantation.

Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach.

PubMed

Abu Bakar Sajak, Azliana; Mediani, Ahmed; Maulidiani; Mohd Dom, Nur Sumirah; Machap, Chandradevan; Hamid, Muhajir; Ismail, Amin; Khatib, Alfi; Abas, Faridah

2017-12-01

Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown. This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract. By using a combination of 1 H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified. The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified. I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism. Copyright © 2017 Elsevier GmbH. All rights reserved.

High serum creatinine in acute pancreatitis: a marker for pancreatic necrosis?

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Maisonneuve, Patrick; Lowenfels, Albert B

2010-05-01

High serum creatinine is a well-known unfavorable prognostic parameter in acute pancreatitis. Elevated creatinine at 48 h after admission was recently described as a marker for pancreatic necrosis. As pancreatic necrosis is a serious complication of acute pancreatitis and its identification by a simple single laboratory test would be very helpful, the aim of this study was to test that statement. In a prospective multicenter study of 462 patients with a first attack of acute pancreatitis, serum creatinine was determined on admission, and at 24 and 48 h thereafter, and compared with the findings of contrast-enhanced computed tomography (CT) performed within 96 h of admission. Pancreatic necrosis was present in 62 (13%) of the patients. Serum creatinine levels (abnormal > or = 2 mg/dl) on admission and after 24 and 48 h were evaluated vs. the presence or absence of pancreatic necrosis. Sensitivity rates varied between 14 and 23%, specificity between 95 and 97%, positive predictive values between 41 and 50%, and negative predictive values between 87 and 89%. Receiver operating characteristic curves revealed an area under the curve of between 0.604 and 0.669. An elevated serum creatinine concentration at any time during the first 48 h of admission is not a marker for pancreatic necrosis in a first attack of acute pancreatitis. If serum creatinine is normal, necrotizing pancreatitis is unlikely, and contrast-enhanced CT need not be performed unless complications occur and/or the patient's condition deteriorates.

Quantitative analysis of elevation of serum creatinine via renal transporter inhibition by trimethoprim in healthy subjects using physiologically-based pharmacokinetic model.

PubMed

Nakada, Tomohisa; Kudo, Toshiyuki; Kume, Toshiyuki; Kusuhara, Hiroyuki; Ito, Kiyomi

2018-02-01

Serum creatinine (SCr) levels rise during trimethoprim therapy for infectious diseases. This study aimed to investigate whether the elevation of SCr can be quantitatively explained using a physiologically-based pharmacokinetic (PBPK) model incorporating inhibition by trimethoprim on tubular secretion of creatinine via renal transporters such as organic cation transporter 2 (OCT2), OCT3, multidrug and toxin extrusion protein 1 (MATE1), and MATE2-K. Firstly, pharmacokinetic parameters in the PBPK model of trimethoprim were determined to reproduce the blood concentration profile after a single intravenous and oral administration of trimethoprim in healthy subjects. The model was verified with datasets of both cumulative urinary excretions after a single administration and the blood concentration profile after repeated oral administration. The pharmacokinetic model of creatinine consisted of the creatinine synthesis rate, distribution volume, and creatinine clearance (CL cre ), including tubular secretion via each transporter. When combining the models for trimethoprim and creatinine, the predicted increments in SCr from baseline were 29.0%, 39.5%, and 25.8% at trimethoprim dosages of 5 mg/kg (b.i.d.), 5 mg/kg (q.i.d.), and 200 mg (b.i.d.), respectively, which were comparable with the observed values. The present model analysis enabled us to quantitatively explain increments in SCr during trimethoprim treatment by its inhibition of renal transporters. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Effect of Pre-Transplant Serum Creatinine on the Survival Benefit of Liver Transplantation

PubMed Central

Sharma, Pratima; Schaubel, Douglas E.; Guidinger, Mary K.; Merion, Robert M.

2010-01-01

More candidates with creatinine ≥2mg/dl have undergone liver transplantation (LT) since implementation of Model for End-stage Liver Disease (MELD)-based allocation. These candidates have higher post-transplant mortality. This study examined the effect of serum creatinine on survival benefit among candidates undergoing LT. Scientific Registry of Transplant Recipients data were analyzed for adult LT candidates listed between September 2001 and December 2006 (n=38,899). The effect of serum creatinine on survival benefit (contrast between waitlist and post-LT mortality rates) was assessed by sequential stratification, an extension of Cox regression. At the same MELD score, serum creatinine at LT was inversely associated with survival benefit within certain defined MELD categories. The survival benefit significantly decreased as creatinine increased for candidates with MELD 15-17 and 24-40 at LT (MELD 15-17, p<0.0001; MELD 24-40, p=0.04). Renal replacement therapy at LT was also associated with significantly decreased LT benefit for patients with MELD scores 21-23 (p=0.04) and 24-26 (p=0.01). In conclusion, serum creatinine at LT significantly affects survival benefit at MELD 15-17 and 24-40. Given the same MELD score, patients with higher creatinine have less benefit on average and the relative ranking of a large number of wait-listed candidates with MELD scores 15-17 and 24-40 would be markedly affected if these findings were incorporated into the allocation policy. PMID:19938142

Diet-induced hyperinsulinemia differentially affects glucose and protein metabolism: a high-throughput metabolomic approach in rats.

PubMed

Etxeberria, U; de la Garza, A L; Martínez, J A; Milagro, F I

2013-09-01

Metabolomics is a high-throughput tool that quantifies and identifies the complete set of biofluid metabolites. This "omics" science is playing an increasing role in understanding the mechanisms involved in disease progression. The aim of this study was to determine whether a nontargeted metabolomic approach could be applied to investigate metabolic differences between obese rats fed a high-fat sucrose (HFS) diet for 9 weeks and control diet-fed rats. Animals fed with the HFS diet became obese, hyperleptinemic, hyperglycemic, hyperinsulinemic, and resistant to insulin. Serum samples of overnight-fasted animals were analyzed by (1)H NMR technique, and 49 metabolites were identified and quantified. The biochemical changes observed suggest that major metabolic processes like carbohydrate metabolism, β-oxidation, tricarboxylic acid cycle, Kennedy pathway, and folate-mediated one-carbon metabolism were altered in obese rats. The circulating levels of most amino acids were lower in obese animals. Serum levels of docosahexaenoic acid, linoleic acid, unsaturated n-6 fatty acids, and total polyunsaturated fatty acids also decreased in HFS-fed rats. The circulating levels of urea, six water-soluble metabolites (creatine, creatinine, choline, acetyl carnitine, formate, and allantoin), and two lipid compounds (phosphatidylcholines and sphingomyelin) were also significantly reduced by the HFS diet intake. This study offers further insight of the possible mechanisms implicated in the development of diet-induced obesity. It suggests that the HFS diet-induced hyperinsulinemia is responsible for the decrease in the circulating levels of urea, creatinine, and many amino acids, despite an increase in serum glucose levels.

Ameliorative effects of Spirulina platensis against lead-induced nephrotoxicity in newborn rats: Modulation of oxidative stress and histopathological changes

PubMed Central

Gargouri, Manel; Soussi, Ahlem; Akrouti, Amel; Magné, Christian; El Feki, Abdelfattah

2018-01-01

Our experimental work was aimed at evaluating the safety and protective effects of dietary spirulina supplementation on the kidney of newborn rats, the offspring of lead contaminated lactating mothers. Female rats were randomly divided into four groups: group I (control) was given a normal diet, group II (positive control, S) received a diet enriched with spirulina, group III received only lead through drinking water (Pb), and group IV received both a diet enriched with spirulina and lead contaminated water (S Pb). The treatment of pregnant rats with lead administrated in drinking water, from the 5th day of pregnancy until day 14 after delivery, induced an increased level of renal lipid peroxidation, protein carbonyl, hydrogen peroxide and advanced oxidation protein product, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in newborns. A statistically significant increase of renal DNA, mRNA, hematological parameters as well as in plasma urea and creatinine serum levels and lactate dehydrogenase was seen in pups, while those of uric acid declined. Interestingly, these biochemical modifications were accompanied by a significant decrease of lactate dehydrogenase in kidney, plasma alkaline phosphatase and gamma glutamyl-transpeptidase levels, urinary levels of creatinine and urea. Conversely, supplementation of lead-treated mother's with spirulina alleviated hematotoxicity induced by lead as evidenced, by restoring the biochemical markers cited above to near normal levels. Nevertheless, the distorted histoarchitecture in rat kidney attenuated following spirulina supplementation. It can be then concluded that spirulina is an important protective source against kidney impairments. PMID:29743860

Worsening renal function defined as an absolute increase in serum creatinine is a biased metric for the study of cardio-renal interactions.

PubMed

Testani, Jeffrey M; McCauley, Brian D; Chen, Jennifer; Shumski, Michael; Shannon, Richard P

2010-01-01

Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was compared to a decrease in GFR >or=20% (WRF(GFR)). Overall, 993 admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%. WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1-4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11). WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions. Copyright 2010 S. Karger AG, Basel.

Evaluation of Aution Max AX-4030 and 9UB Uriflet, 10PA Aution Sticks urine dipsticks in the automated urine test strip analysis.

PubMed

Rota, Cristina; Biondi, Marco; Trenti, Tommaso

2011-09-26

Aution Max AX-4030, a test strip analyzer recently introduced to the market, represents an upgrade of the Aution Max AX-4280 widely employed for urinalysis. This new instrument model can allocate two different test strips at the same time. In the present study the two instruments have been compared together with the usage of Uriflet 9UB and the recently produced Aution Sticks 10PA urine strips, the latter presenting an additional test area for the measurement of urinary creatinine. Imprecision and correlation between instruments and strips have been evaluated for chemical-physical parameters. Accuracy was evaluated for protein, glucose and creatinine by comparing the semi-quantitative results to those obtained by quantitative methods. The well-known interference effect of high ascorbic acid levels on urine glucose test strip determination was evaluated, ascorbic acid influence was also evaluated on protein and creatinine determination. The two instruments have demonstrated comparable performances: precision and correlation between instruments and strips, evaluated for chemical-physical parameters, were always good. Furthermore, accuracy was always very good: results of protein and glucose semi-quantitative measurements resulted to be highly correlated with those obtained by quantitative methods. Moreover, the semi-quantitative measurements of creatinine, employing Aution Sticks 10PA urine strips, were highly comparable with quantitative results. 10PA urine strips are eligible for urine creatinine determination with the possibility of correcting urinalysis results for urinary creatinine concentration, whenever necessary and calculating the protein creatinine ratio. Further studies should be carried out to evaluate effectiveness and appropriateness of the usage of creatinine semi-quantitative analysis.

Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial.

PubMed

Ghorbani, Ali; Omidvar, Bita; Parsi, Abazar

2013-04-01

Renal injury is common following cisplatin infusion. Some agents have been used to attenuate cisplatin nephrotoxicity. However, except hydration, none of them has been proved to be effective. In this study selenium as an antioxidant supplement was tested on cisplatin induced renal injury. 122 cancerous patients (85 male and 37 female; age range of 14 to 82 years old) were enrolled to receive chemotherapy regimens consisting cisplatin. They were allocated into two groups using a random number list . Investigators, patients and analyzers all, were blinded in allocation by using sealed opaque envelopes. Intervention group received a single 400 mcg selenium tablet and patients in control group took a placebo tablet which was similar with selenium preparation in color, weight, shape and taste. Primary end points were an increase in plasma creatinine above 1.5 mg/dl in men and 1.4mg/dl in women, or increase of plasma creatinine more than 50% from baseline or urine flow rate less than 0.5 ml/kg/h. Creatinine level was measured initially and on the 5th day after cisplatin therapy. There was no difference in cumulative dose of cisplatin between the groups (p=0.54). There were not evidences of acute renal failure (ARF) in cases. While, among placebo group, 7 patients had criteria of acute kidney injury. Conclusions :selenium could probably prevent cisplatin-induced acute kidney injury, when it is added to hydration therapy in cancerous patients.

Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Limpatanachote, Pisit

Risk for hypertension and diabetes has not been conclusively found to be a result of cadmium exposure. A population-based study was conducted in 2009 to examine the correlations of urinary cadmium, a good biomarker of long-term cadmium exposure, with hypertension and diabetes in persons aged 35 years and older who lived in the 12 cadmium-contaminated rural villages in northwestern Thailand. A total of 5273 persons were interviewed and screened for urinary cadmium, hypertension, and diabetes. The geometric mean level of urinary cadmium for women (2.4{+-}2.3 {mu}g/g creatinine) was significantly greater than that for men (2.0{+-}2.2 {mu}g/g creatinine). Hypertension was presentedmore » in 29.8% of the study population and diabetes was detected in 6.6%. The prevalence of hypertension significantly increased from 25.0% among persons in the lowest tertile of urinary cadmium to 35.0% in the highest tertile. In women, the rate of hypertension significantly increased with increasing urinary cadmium levels in both ever and never smokers, after adjusting for age, alcohol consumption, body mass index, and diabetes. In men, such association was less significantly found in never smokers. The study revealed no significant association between urinary cadmium and diabetes in either gender. Our study supports the hypothesis that environmental exposure to cadmium may increase the risk of hypertension. Risk for diabetes in relation to cadmium exposure remains uncertain in this exposed population.« less

Expression of renal Oat5 and NaDC1 transporters in rats with acute biliary obstruction

PubMed Central

Brandoni, Anabel; Torres, Adriana Mónica

2015-01-01

AIM: To examine renal expression of organic anion transporter 5 (Oat5) and sodium-dicarboxylate cotransporter 1 (NaDC1), and excretion of citrate in rats with acute extrahepatic cholestasis. METHODS: Obstructive jaundice was induced in rats by double ligation and division of the common bile duct (BDL group). Controls underwent sham operation that consisted of exposure, but not ligation, of the common bile duct (Sham group). Studies were performed 21 h after surgery. During this period, animals were maintained in metabolic cages in order to collect urine. The urinary volume was determined by gravimetry. The day of the experiment, blood samples were withdrawn and used to measure total and direct bilirubin as indicative parameters of hepatic function. Serum and urine samples were used for biochemical determinations. Immunoblotting for Oat5 and NaDC1 were performed in renal homogenates and brush border membranes from Sham and BDL rats. Immunohistochemistry studies were performed in kidneys from both experimental groups. Total RNA was extracted from rat renal tissue in order to perform reverse transcription polymerase chain reaction. Another set of experimental animals were used to evaluate medullar renal blood flow (mRBF) using fluorescent microspheres. RESULTS: Total and direct bilirubin levels were significantly higher in BDL animals, attesting to the adequacy of biliary obstruction. An important increase in mRBF was determined in BDL group (Sham: 0.53 ± 0.12 mL/min per 100 g body weight vs BDL: 1.58 ± 0.24 mL/min per 100 g body weight, P < 0.05). An increase in the urinary volume was observed in BDL animals. An important decrease in urinary levels of citrate was seen in BDL group. Besides, a decrease in urinary citrate excretion (Sham: 0.53 ± 0.11 g/g creatinine vs BDL: 0.07 ± 0.02 g/g creatinine, P < 0.05) and an increase in urinary excretion of H+ (Sham: 0.082 ± 0.03 μmol/g creatinine vs BDL: 0.21 ± 0.04 μmol/g creatinine, P < 0.05) were observed in BDL animals. We found upregulations of both proteins Oat5 and NaDC1 in brush border membranes where they are functional. Immunohistochemistry technique corroborated these results for both proteins. No modifications were observed in Oat5 mRNA and in NaDC1 mRNA levels in kidney from BDL group as compared with Sham ones. CONCLUSION: Citrate excretion is decreased in BDL rats, at least in part, because of the higher NaDC1 expression. Using the outward gradient of citrate generated by NaDC1, Oat5 can reabsorb/eliminate different organic anions of pathophysiological importance. PMID:26269671

Lack of Serum Creatinine Decrease After Coronary Angiography Despite Prophylactic Hydration After Routine Coronary Angiography/Angioplasty in Stable Angina Patients--Pilot Study.

PubMed

Burchardt, Pawel; Rzezniczak, Janusz; Synowiec, Tomasz; Angerer, Dariusz; Palasz, Anna; Zurawski, Jakub

2016-01-01

To prevent contrast induced renal dysfunction a periprocedural prophylactic hydration is applied. Due to dilution it should cause a drop in serum creatinine concentration (SCR). Surprisingly, no reduction in SCR after contrast admission is found in up to 25% of patients as early as 12-18 hours after coronary angiography/angioplasty. This study aims to find a clinical explanation as well as predict circumstances for this phenomenon. Retrospective clinical and laboratory data was used from 341 patients who underwent elective coronary angiography/angioplasty, received a prophylactic hydration, and had serum creatinine concentration measured prior to, and 12-18 hours after invasive procedure with iodine contrast administration. To exclude an improper hydration due to no creatinine decrease, the number of red blood cells was analysed as well as hemoglobin and hematocrit in blood donations collected during the study time points. The resulting lack of serum creatinine reduction could be explained by dehydration (measured by increase in number of RBC, HGB and HCT) only in 13.5% , 10.8%, and 20% of cases, respectively. Any form of abnormal glucose metabolism combined with either baseline serum creatinine concentration <0.87 mg/dL or creatinine clearance >86.77 mL/min, or GFR by CKD EPI >80.08 mL/min/1.73 m2, or GFR by MDRD >74.48 mL/min/1.73 m2 were the predictors for no creatinine decrease at outcome. Additionally, it was demonstrated that the lack of creatinine decrease was more often observed among those patients whose initial renal function was better than in the subjects with reduction of SCR. This observation requires further prospective investigation on extended group of patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.

PubMed

Kemperman, F A; Silberbusch, J; Slaats, E H; van Zanten, A P; Weber, J A; Krediet, R T; Arisz, L

1999-05-01

Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.

PubMed

Sundin, Per-Ola; Sjöström, Per; Jones, Ian; Olsson, Lovisa A; Udumyan, Ruzan; Grubb, Anders; Lindström, Veronica; Montgomery, Scott

2017-04-01

Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model. Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Cause-effect relations between 55 kD soluble TNF receptor concentrations and specific and unspecific symptoms in a patient with mild SLE disease activity: an exploratory time series analysis study.

PubMed

Schubert, Christian; Haberkorn, Julia; Ocaña-Peinado, Francisco M; König, Paul; Sepp, Norbert; Schnapka-Köpf, Mirjam; Fuchs, Dietmar

2015-09-21

This integrative single-case study investigated the 12 h-to-12 h cause-effect relations between 55 kD soluble tumor necrosis factor receptor type 1 (sTNF-R55) and specific and unspecific symptoms in a 52-year-old Caucasian woman with mild systemic lupus erythematosus (SLE) disease activity. The patient collected her entire urine for 56 days in 12 h-intervals to determine sTNF-R55/creatinine and protein/creatinine levels (ELISA, HPLC). Additionally, twice a day, she took notes on oral ulceration and facial rash; answered questionnaires (VAS) on fatigue, weakness, and joint pain; and measured body temperature orally. Time series analysis consisted of ARIMA modeling and cross-correlational analyses (significance level = p < 0.05). Time series analysis revealed both a circadian and a circasemiseptan rhythm in the urinary sTNF-R55 data. Moreover, several significant lagged correlations between urinary sTNF-R55 concentrations and SLE symptoms in both directions of effect were identified. Specifically, increased urinary sTNF-R55 concentrations preceded decreased urinary protein levels by 36-48 h (r = -0.213) and, in the opposite direction of effect, increased protein levels preceded increased sTNF-R55 concentrations by 24-36 h (r = +0.202). In addition, increased urinary sTNF-R55 levels preceded increased oral ulcers by 36-48 h (r = +0.277) and, conversely, increased oral ulceration preceded decreased sTNF-R55 levels by 36-48 h (r = -0.313). Moreover, increased urinary sTNF-R55 levels preceded decreased facial rash by 36-48 h (r = -0.223) and followed increased body temperature after 36-48 h (r = +0.209). Weakness, fatigue and joint pain were not significantly correlated with urinary sTNF-R55 levels. This study gathered first evidence of real-life, long-term feedback loops between cytokines and SLE symptoms in mild SLE disease activity. Such insights into the potential role of sTNF-R55 in SLE would not have been possible had we applied a pre-post design group study. These findings require replication before firm conclusions can be drawn.

Factors influencing brain natriuretic peptide levels in healthy pregnant women.

PubMed

Mayama, Michinori; Yoshihara, Masato; Uno, Kaname; Tano, Sho; Takeda, Takehiko; Ukai, Mayu; Kishigami, Yasuyuki; Oguchi, Hidenori

2017-02-01

The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9, p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre-delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP was positively associated with body weight change during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004). Even normal pregnancy affects plasma BNP, particularly in the early postpartum period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body weight changes, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Can duration of hemodialysis be estimated based on the on-arrival laboratory tests and clinical manifestations in methanol-poisoned patients?

PubMed

Pajoumand, Abdolkarim; Zamani, Nasim; Hassanian-Moghaddam, Hossein; Shadnia, Shahin

2017-06-01

We aimed to evaluate the efficacy of Lachance formula and more readily available clinical or laboratory factors (other than serum methanol level) in prediction of the needed time for hemodialysis in methanol-poisoned patients. In a retrospective study, all methanol-poisoned patients referred to us between March 2008 and March 2016 were enrolled. The patients' demographic characteristics, on-arrival vital signs, signs/symptoms, and laboratory tests were evaluated for factors that could prognosticate the dialysis duration. Of 72 patients enrolled, 54 underwent hemodialysis once (group 1) and 18 needed more than one session of hemodialysis (group 2). All were treated by ethanol, bicarbonate, and leucovorin. Lachance formula overestimated the patients in higher methanol levels and underestimated them in lower methanol levels. It properly predicted the needed time for hemodialysis when the methanol level was between 15 and 25 mg/dL. Groups 1 and 2 were different in terms of their ingested alcohol dose (P = 0.001), creatinine (P = 0.02), dyspnea on presentation (P = 0.002), and the place they had been dialyzed (P = 0.013). Dialysis duration significantly correlated with dyspnea on presentation (P = 0.028) and ingested alcohol dose (P = 0.02). After performance of logistic regression analysis, only creatinine was statistically significantly different between the two groups (P = 0.02). Median creatinine levels were 1.3 [1, 6] (0.8-2.7) and 1.4 [1.35, 2.1] (0.8-6.5) in the patients who were dialyzed once and twice, respectively. As a conclusion, creatinine is possibly a readily available test that can predict the appropriate time needed for hemodialysis in methanol-poisoned patients.

Stratifying the risks of oral anticoagulation in patients with liver disease.

PubMed

Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American Heart Association, Inc.

Concurrence of Serum Creatinine and Albumin with Lower Risk for Death in Twice-Weekly Hemodialysis Patients

PubMed Central

Wang, Jialin; Streja, Elani; Soohoo, Melissa; Chen, Joline L.T.; Rhee, Connie M.; Kim, Taehee; Molnar, Miklos Z.; Kovesdy, Csaba P.; Mehrotra, Rajnish; Kalantar-Zadeh, Kamyar

2016-01-01

Objective Markers of better nutritional status including both higher levels of serum albumin (as a measure of visceral proteins) and creatinine (as a measure of the muscle mass) are associated with lower mortality in conventional (thrice-weekly) hemodialysis patients. However, data for these associations in twice-weekly hemodialysis patients, in whom less frequent hemodialysis may confound nutritional predictors, are lacking. Design, Settings and Subjects We identified 1,113 twice-weekly and matched 4,448 thrice-weekly hemodialysis patients from a large national dialysis cohort of incident hemodialysis patients over 5 years (2007-2011). Mortality risk, adjusted for potential confounders, was examined across two-by-two combinations of serum creatinine (<6 mg/dl vs. ≥6 mg/dl) and albumin (<3.5 g/dl vs. ≥3.5 g/dl) for each treatment frequency yielding a total of eight groups. Results Patients were 70±14 years old and included 48% women, and 55% diabetics. Using the thrice-weekly hemodialysis patients with creatinine≥6mg/dl and albumin≥3.5g/dl as reference, patients with creatinine<6mg/dl and albumin<3.5g/dl had a 1.8-fold higher risk of mortality (HR: 1.75, 95%CI: 1.33-2.30) in twice-weekly and 2.2-fold increased risk of mortality (HR: 2.21, 95%CI: 1.81-2.70) in thrice-weekly hemodialysis patients, respectively in fully adjusted models adjusted for demographics, comorbidities and markers of malnutrition and inflammation. A test for interaction showed there was no significant difference in albumin creatinine mortality associations between twice-weekly and thrice-weekly hemodialysis patients (p-for-interaction 0.7667). Conclusions Surrogate markers of higher visceral protein and muscle mass combined may confer greatest survival in both twice-weekly and thrice-weekly hemodialysis patients. PMID:27528412

Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.

PubMed

James, Stefan; Budaj, Andrzej; Aylward, Philip; Buck, Kristen K; Cannon, Christopher P; Cornel, Jan H; Harrington, Robert A; Horrow, Jay; Katus, Hugo; Keltai, Matyas; Lewis, Basil S; Parikh, Keyur; Storey, Robert F; Szummer, Karolina; Wojdyla, Daniel; Wallentin, Lars

2010-09-14

Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding. URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Long-Term Effects of Pregnancy on Renal Graft Function in Women After Kidney Transplantation Compared With Matched Controls.

PubMed

Svetitsky, S; Baruch, R; Schwartz, I F; Schwartz, D; Nakache, R; Goykhman, Y; Katz, P; Grupper, A

2018-06-01

An important benefit associated with kidney transplantation in women of child-bearing age is increased fertility. We retrospectively evaluated the maternal and fetal complications and evolution of graft function associated with 22 pregnancies post-kidney and kidney-pancreas transplantation, compared with controls without pregnancy post-transplantation, who were matched for gender, year of transplantation, type of donor, age at transplantation, number of transplants, type of transplant (kidney vs kidney-pancreas), and cause of native kidney failure, as well as for renal parameters including serum creatinine and urine protein excretion 1 year before delivery. The mean age at time of transplantation was 22.32 (range, 19.45-33.1) years. The mean interval between transplantation and delivery was 75.7 (range, 34-147.8) months. Main maternal complications were pre-eclampsia in 27.3%. The main fetal complications included delayed intrauterine growth (18.2%), preterm deliveries (89.4%), and one death at 3 days postdelivery. The mean serum creatinine level pre-pregnancy was 1.17 (range, 0.7-3.1) mg/dL. Graft failure was higher in the pregnancy group (6 vs 3) but did not differ statistically from the control group, and was associated with creatinine pre-pregnancy (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.15-3.45; P = .04), age at transplantation (1.13 [1.03-1.21]; P = .032), and time of follow-up (2.14 [1.27-2.98]; P = .026). Delta serum creatinine was not different in both groups: 1.05 ± 0.51 versus 0.99 ± 0.92 mg/dL, study versus control group, respectively (P = .17). Pregnancy after kidney transplantation is associated with serious maternal and fetal complications. We did not observe a significantly increased risk of graft loss or reduced graft function in comparison with recipients with similar clinical characteristics. Copyright © 2018 Elsevier Inc. All rights reserved.

Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats.

PubMed

Rana, Md Azmat; Khan, Rahat Ali; Nasiruddin, Mohammad; Khan, Aijaz Ahmed

2016-01-01

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Differences in levels of albumin, ALT, AST, γ-GT and creatinine in frail, moderately healthy and healthy elderly individuals.

PubMed

Edvardsson, Maria; Sund-Levander, Märtha; Milberg, Anna; Wressle, Ewa; Marcusson, Jan; Grodzinsky, Ewa

2018-02-23

Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and γ-glutamyl transferase (γ-GT) in frail, moderately healthy and healthy elderly indivuduals. Blood samples were collected from individuals >80 years old, nursing home residents, in the Elderly in Linköping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and γ-GT were analyzed using routine methods. Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of γ-GT variation. Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.

Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus.

PubMed

Nie, Fang; Wu, Dongming; Du, Hongfei; Yang, Xianggui; Yang, Min; Pang, Xueli; Xu, Ying

2017-03-01

To investigate the associations of serum α-Klotho and β-Klotho levels with type 2 diabetes mellitus (T2DM) progression. We evaluated 106 healthy controls and 261 cases of T2DM with or without diabetic complications (range: 45-84years). Serum α-Klotho and β-Klotho levels were analyzed using enzyme-linked immunosorbent assays. Compared to the healthy controls, α-Klotho and β-Klotho levels were significantly lower among patients with T2DM and with or without diabetic complications (P<0.05). Furthermore, α-Klotho levels were lower in the microalbuminuric and macroalbuminuric groups, compared to the normoalbuminuric group. However, β-Klotho levels were only lower in the macroalbuminuric group (P<0.05). Multiple linear regression analyses revealed that α-Klotho and β-Klotho levels were positively correlated with the creatinine clearance rate, and negatively correlated with the urinary albumin to creatinine ratio and randomly sampled serum levels of creatinine, blood urea nitrogen, and blood glucose. Moreover, α-Klotho and β-Klotho levels were positively correlated among patients with T2DM (r=0.693, P<0.001). Serum levels of α-Klotho and β-Klotho are down-regulated in patients with T2DM. Thus, these proteins may participate in the pathological mechanism of diabetes, and the positive correlation of α-Klotho and β-Klotho levels indicates that they might have similar mechanisms in T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

PubMed

Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

2015-07-01

The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

The Effect of Concentrate Supplementation on Creatinine Excretion in Thin-Tailed Lambs and Sheep

NASA Astrophysics Data System (ADS)

Purnami, N. A.; Prima, A.

2018-02-01

An experimental study was carried out to examine the effect of concentrates supplementation on creatinine excretion in lambs and sheep. The study used 8 male thin tailed lambs (aged ±3-4 months, weighed ±15.20 kg) and 8 sheep (aged ±1 year and weighed ±22.71kg). The animals were fed the diet contained 100% napier grass (100G) and 50% napier grass 50% concentrate as much as 3.5% of body weight (50G50C). This study used a complete randomized nested design. The parameters observed were dry matter intake (DMI) and creatinine excretion. The results showed that the diet significantly affect (P<0.05) DMI. The consumption of 100G was lower than that of 50G50C both lambs (0.32 vs 0.62 kg/d) and sheep (0.47 vs 0.88 kg/d). On the other hand, the diet did not affect the creatinine excretion (P 0.05) either G100 or G50C50 in lambs or sheep. However, the creatinine excretion in sheep (185.66 mg/d) was higher than that of lambs (299.1 md/d) (P<0.05). It can be concluded that concentrate supplementation of grass diet increased DMI but did not affect creatinine excretion. The creatinine excretion of sheep was higher than that of lambs .

Quercetin, a Flavonoid Antioxidant, Ameliorated Procarbazine-Induced Oxidative Damage to Murine Tissues

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Adeyemo, Oluwatobi Adewumi; Ola, Olaniyi Solomon; Olotu, Olaoluwa Oluwaseun; Echebiri, Roseline Chinonye

2015-01-01

Procarbazine (PCZ) (indicated in Hodgkin’s disease), is an alkylating agent known to generate free radicals in vivo, while Quercetin (QCT) is a flavonoid antioxidant with proven free radical scavenging capacity. This study investigated the protective effects of QCT on PCZ-induced oxidative damage in the rat. Male Wistar rats (160–180 g) were randomized into five groups (n = 5/group): I (control), II PCZ-treated (2 mg/kg body weight (bw) for seven days); III pre-treated with QCT (20 mg/kg bw) for seven days, followed by PCZ for seven days; IV co-treated with PCZ and QCT for seven days and V administered QCT alone for seven days. PCZ caused a significant increase in plasma total bilirubin, urea, and creatinine when compared with control (P < 0.05). Similarly, plasma activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GT) were significantly increased in the PCZ-treated group relative to control. Furthermore, PCZ caused a significant decrease in the activities of hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) as well as levels of ascorbic acid (AA) and glutathione (GSH). This was followed by a significant increase in hepatic malondialdehyde (MDA) content. However, QCT pre-treatment and co-treatment ameliorated the PCZ-induced changes in plasma levels of urea, creatinine, and bilirubin as well as the activities of ALP, AST, ALT, and GGT. QCT also ameliorated hepatic AA and GSH levels and the activities of SOD, CAT, and GST. This all suggests that QCT protected against PCZ-induced oxidative damage in rats. PMID:26783707

Serum cystatin C levels in preterm newborns in our setting: Correlation with serum creatinine and preterm pathologies.

PubMed

Bardallo Cruzado, Leonor; Pérez González, Elena; Martínez Martos, Zoraima; Bermudo Guitarte, Carmen; Granero Asencio, Mercedes; Luna Lagares, Salud; Marín Patón, Mariano; Polo Padilla, Juan

2015-01-01

Cystatin C (CysC) is a renal function marker that is not as influenced as creatinine (Cr) by endogenous or exogenous agents, so it is therefore proposed as a marker in preterm infants. To determine serum CysC values in preterm infants during the first week of life, compared to Cr. To analyze alterations caused by prematurity diseases. The design involved a longitudinal, observational study of prospective cohorts. Groups were based on gestational age (GA): Group A (24-27 weeks), Group B (28-33 weeks), Group C (34-36 weeks). Blood samples were collected at birth, within 48-72hours and after 7 days of life. SPSS v.20 software was used. The statistical methods applied included chi-squared test and ANOVA. A total of 109 preterm infants were included in the study. CysC levels were: 1.54mg/L (±0.28) at birth; 1.38mg/L (±0.36) within 48-72hours of life; 1.50mg/L (±0.31) after 7 days (p<0.05). Cr levels were: 0.64mg/dL (±0.17) at birth; 0.64mg/dL (±0.28) within 48-72hours; 0.56mg/dL (±0.19) after 7 days (P<.05). CysC values were lower in hypotensive patients and those with a respiratory disease (P<.05), and no alterations associated with other diseases were observed. There were no differences in Cr levels associated with any disease. Creatinine levels were higher in patients ≤1.500g (P<.05). Serum CysC decreased within 48-72hours of life, and this decline showed significance (P<.05). The levels increased after 7 days in all 3 GA groups, and there was no difference in CysC levels among the groups. More studies in preterm infants with hypotension and respiratory disease are required. CysC is a better glomerular filtration (GF) marker in ≤1.500g preterm infants. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Active Ghrelin and the Postpartum

PubMed Central

Baker, Jessica H.; Pedersen, Cort; Leserman, Jane; Brownley, Kimberly A.

2015-01-01

Purpose Postpartum depression (PPD) occurs in 10%–15% of women. The appetite hormone ghrelin, which fluctuates during pregnancy, is associated with depression in nonpregnant samples. Here, we examine the association between PPD and active ghrelin from pregnancy to postpartum. We additionally examine whether ghrelin changes from pregnancy to postpartum and differs between breastfeeding and non-breastfeeding women. Methods Sixty women participated in a survey examining PPD and had information in regard to ghrelin concentrations were included in the study. The Edinburgh Postnatal Depression Scale was used to assess symptoms of PPD. Raw ghrelin levels and ghrelin levels adjusted for creatinine were included as outcomes. Results Women screening positive for PPD at 12-weeks postpartum had higher pregnancy ghrelin concentrations. Ghrelin concentrations significantly decreased from pregnancy to 6-weeks postpartum and this change differed based on pregnancy depression status. Finally, ghrelin levels were lower in women who breastfed compared with women who were bottle-feeding. No significant findings remained once ghrelin levels were adjusted for creatinine. Conclusions Although results do not suggest an association between PPD and ghrelin after adjusting for creatinine, future research should continue to explore this possibility extending further across the postpartum period with larger sample sizes. PMID:26424410

Neopterin: A candidate biomarker for the early assessment of toxicity of aluminum among bauxite dust exposed mine workers

PubMed Central

Pingle, Shubhangi K.; Thakkar, Lucky R.; Jawade, Aruna A.; Tumane, Rajani G.; Jain, Ruchika K.; Soni, Pravin N.

2015-01-01

Introduction: Bauxite ore is a major source of aluminum (Al) which contains approximately 35–60% Al by weight. Occupational and environmental bauxite dust exposure may cause toxicity by interaction with human biological systems resulting in oxidative stress (OS) and cell death. A neopterin derivative as an antioxidant is able to modulate cytotoxicity by the induction of OS. Materials and Methods: A total of 273 subjects were selected for blood collection from three different major Al producing bauxite mines and were categorized into three groups as experimental (Exp) (n = 150), experimental controls (ExC) (n = 73) and control (Con) (n = 50). Whole blood and serum samples were used for measurement of Al, neopterin, urea and creatinine values. Statistical analysis was performed using R-2.15.1 programming language. Results and Discussion: The result showed that age, body mass index and the behavioral habits, that is, smoking, tobacco and alcohol consumption have possible effects on neopterin level. Serum neopterin levels were found to be significantly higher (P <0.0001) in the experimental group as compared to other groups. Significantly positive correlation (P < 0.0001) was observed between neopterin and creatinine. It was also observed that neopterin level increases as the duration of exposure increases. Conclusion: On the basis of findings it was concluded that exposure to bauxite dust (even at low levels of Al) changes biochemical profile leading to high levels of serum neopterin. Levels of serum neopterin in workers exposed to bauxite dust were probably examined for the 1st time in India. The outcome of this study suggested that serum neopterin may be used as potential biomarker for early detection of health risks associated with bauxite dust exposed population. PMID:26500413

Occupational exposure of cashiers to Bisphenol A via thermal paper: urinary biomonitoring study.

PubMed

Ndaw, Sophie; Remy, Aurélie; Jargot, Danièle; Robert, Alain

2016-08-01

As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion. We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC-MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire. Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions. A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.

Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study.

PubMed

Kitao, Tetsuya; Kimata, Takahisa; Yamanouchi, Sohsaku; Kato, Shogo; Tsuji, Shoji; Kaneko, Kazunari

2015-09-01

Recurrent febrile urinary tract infections during infancy cause renal scarring, which is characterized by progressive focal interstitial fibrosis and may lead to renal failure. Renal scarring can be diagnosed through scintigraphy, although it seems impractical to perform renal scintigraphy for all infants with febrile urinary tract infections. Therefore, it is important to search for a biomarker to identify the presence of renal scarring. We hypothesized that urinary biomarkers of nephropathy may increase in infants with renal scarring following febrile urinary tract infections. A total of 49 infants who underwent renal scintigraphy for febrile urinary tract infections were enrolled in the study. Several measurements were performed using urine samples, including total proteins, beta2-microglobulins, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase associated lipocalin, liver-type fatty acid binding protein and angiotensinogen. Values were corrected by creatinine and compared between patients with and without renal scarring. Among urinary biomarkers only angiotensinogen in patients with scarring (median 14.6 μg/gm creatinine) demonstrated significantly higher levels than in patients without scarring (3.6 μg/gm creatinine, p <0.001). Urinary angiotensinogen may be useful for diagnosing the presence of renal scarring. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Conversion to everolimus in kidney transplant recipients with decreased renal function.

PubMed

Inza, A; Balda, S; Alvarez, E; Zárraga, S; Gaínza, F J; Lampreabe, I

2009-01-01

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1-3 mg/d that was sufficient to achieve the recommended levels of 3-8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.

Health status of birds fed diets containing three differently processed discarded vegetable-bovine blood-rumen content mixtures.

PubMed

Ekunseitan, D A; Balogun, O O; Sogunle, O M; Yusuf, A O; Ayoola, A A; Egbeyale, L T; Adeyemi, O A; Allison, I B; Iyanda, A I

2013-04-01

This study was conducted to determine the effect of feeding three differently processed mixtures on health status of broilers. A total of 1080 day-old Marshal broilers were fed; discarded vegetable-fresh bovine blood-fresh rumen digesta (P1), discarded vegetable-ensiled bovine blood-fresh rumen digesta (P2) and discarded vegetable-fresh bovine blood-ensiled rumen digesta (P3) at three levels of inclusion (0, 3 and 6%). Data on blood parameters was taken and were subjected to 3 x 3 factorial arrangements in a completely randomized design. Birds fed P1 had least values (p < 0.05) of serum glucose, total protein, globulin, uric acid and creatinine at starter phase. Birds fed diets containing 3 and 6% level of inclusion recorded the highest (p < 0.05) Packed cell volume, Haemoglobin, White blood cell and Red blood cell values. However, those fed at 0% level of inclusion recorded the highest albumin value. At finisher phase, birds fed P2 and P3 had the highest glucose, uric acid and creatinine values. 6% level of inclusion significantly (p < 0.05) increased the total protein and albumin values. Therefore, for enhanced performance and without comprising the health condition of birds; broiler chickens could be fed diets containing discarded vegetable-fresh bovine blood-ensiled rumen digesta (P3) up to 6% level of inclusion.

High levels of PAH-metabolites in urine of e-waste recycling workers from Agbogbloshie, Ghana.

PubMed

Feldt, Torsten; Fobil, Julius N; Wittsiepe, Jürgen; Wilhelm, Michael; Till, Holger; Zoufaly, Alexander; Burchard, Gerd; Göen, Thomas

2014-01-01

The informal recycling of electronic waste (e-waste) is an emerging source of environmental pollution in Africa. Among other toxins, polycyclic aromatic hydrocarbons (PAHs) are a major health concern for exposed individuals. In a cross-sectional study, the levels of PAH metabolites in the urine of individuals working on one of the largest e-waste recycling sites of Africa, and in controls from a suburb of Accra without direct exposure to e-waste recycling activities, were investigated. Socioeconomic data, basic health data and urine samples were collected from 72 exposed individuals and 40 controls. In the urine samples, concentrations of the hydroxylate PAH metabolites (OH-PAH) 1-hydroxyphenanthrene (1-OH-phenanthrene), the sum of 2- and 9-hydroxyphenanthrene (2-/9-OH-phenanthrene), 3-hydroxyphenanthrene (3-OH-phenanthrene), 4-hydroxyphenanthrene (4-OH-phenanthrene) and 1-hydroxypyrene (1-OH-pyrene), as well as cotinine and creatinine, were determined. In the exposed group, median urinary concentrations were 0.85 μg/g creatinine for 1-OH-phenanthrene, 0.54 μg/g creatinine for 2-/9-OH-phenanthrene, 0.99 μg/g creatinine for 3-OH-phenanthrene, 0.22 μg/g creatinine for 4-OH-phenanthrene, and 1.33 μg/g creatinine for 1-OH-pyrene, all being significantly higher compared to the control group (0.55, 0.37, 0.63, 0.11 and 0.54 μg/g creatinine, respectively). Using a multivariate linear regression analysis including sex, cotinine and tobacco smoking as covariates, exposure to e-waste recycling activities was the most important determinant for PAH exposure. On physical examination, pathological findings were rare, but about two thirds of exposed individuals complained about cough, and one quarter about chest pain. In conclusion, we observed significantly higher urinary PAH metabolite concentrations in individuals who were exposed to e-waste recycling compared to controls who were not exposed to e-waste recycling activities. The impact of e-waste recycling on exposure to environmental toxins and health of individuals living in the surroundings of e-waste recycling sites warrant further investigation. © 2013 Elsevier B.V. All rights reserved.

Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry.

PubMed

Sun, Xiaowei; Xu, Wei; Zeng, Yan; Hou, Yurong; Guo, Lin; Zhao, Xiujuan; Sun, Changhao

2014-02-01

The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg⁻¹ body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N⁷G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry. Copyright © 2012 John Wiley & Sons, Ltd.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

PubMed

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Diuretic activity of Maydis stigma extract in rats.

PubMed

Maksimović, Z; Dobrić, S; Kovacević, N; Milovanović, Z

2004-12-01

Maydis stigma (corn silk) is a herbal drug reputed for the treatment of urinary ailments in various traditional medicine systems. To determine its influence on urinary volume and the excretion of sodium, potassium and chloride, 5% and 10% decoctions were administered daily to adult male Wistar rats for eight days. The concentration of electrolytes and urea in plasma, the influence of treatment on urinary pH value as well as creatinine clearance were also investigated. Daily oral administration of 5% decoction at the dose of 10 ml/kg led to a significant and acute diuresis in rats, reaching the peak value in the first 24 h of treatment. Over a similar period, application of 10% decoction did not affect urinary excretion of water, but significantly increased the pH value of excreted urine. A significant decrease in sodium and chloride plasma levels was observed in both treated groups. The creatinine clearance was markedly increased after the treatment with both extracts. Our findings indicate that the diuretic effect of 5% aqueous Maydis stigma extract is in accordance with the increase in glomerular filtration rate and inhibition of sodium and chloride tubular reabsorption, caused a by still unidentified intrinsic factor, but not the salt-loading effect.