Kidney function endpoints in kidney transplant trials: a struggle for power.

PubMed

Ibrahim, A; Garg, A X; Knoll, G A; Akbari, A; White, C A

2013-03-01

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

PubMed

Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

PubMed

Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A

2013-09-01

African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

PubMed

Sevinc, M; Stamp, S; Ling, J; Carter, N; Talbot, D; Sheerin, N

2016-12-01

Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

PubMed Central

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-01-01

Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

PubMed

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-04-01

Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

2015-06-01

This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

PubMed

Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier; Bochud, Murielle

2015-06-01

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. Copyright © 2015 by the American Society of Nephrology.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

PubMed Central

Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier

2015-01-01

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=−2.1; 95% confidence interval [95% CI], −3.3 to −0.8; P=0.002) and kidney length (β=−1.2; 95% CI, −1.9 to −0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. PMID:25270071

The effects of hard water consumption on kidney function: Insights from mathematical modelling

NASA Astrophysics Data System (ADS)

Tambaru, David; Djahi, Bertha S.; Ndii, Meksianis Z.

2018-03-01

Most water sources in Nusa Tenggara Timur contain higher concentration of calcium and magnesium ions, which is known as hard water. Long-term consumption of hard water can cause kidney dysfunction, which may lead to the other diseases such as cerebrovascular disease, diabetes and others. Therefore, understanding the effects of hard water consumption on kidney function is of importance. This paper studies the transmission dynamics of kidney dysfunction due to the consumption of hard water using a mathematical model. We propose a new deterministic mathematical model comprising human and water compartments and conduct a global sensitivity analysis to determine the most influential parameters of the model. The Routh-Hurwitz criterion is used to examine the stability of the steady states. The results shows that the model has two steady states, which are locally stable. Moreover, we found that the most influential parameters are the maximum concentration of magnesium and calcium in the water, the increase rate of calcium and magnesium concentration in the water and the rate of effectiveness of water treatment. The results suggest that better water treatments are required to reduce the concentration of magnesium and calcium in the water. This aid in minimizing the probability of humans to attract kidney dysfunction. Furthermore, water-related data need to be collected for further investigation.

Exposure to waterpipe smoke induces renal functional and oxidative biomarkers variations in mice.

PubMed

Rababa'h, Abeer M; Sultan, Bilal B; Alzoubi, Karem H; Khabour, Omar F; Ababneh, Mera A

2016-09-01

Waterpipe smoking (WPS) has been known for over 400 years. It has been spread widely especially between youth because of the addition of pleasant flavor and because it was misconsidered to be less harmful than cigarette. In this study, we investigated the effect of waterpipe smoking on renal oxidative and functional parameters and compared that at acute and chronic exposure time in mice. Mice were divided into three groups, namely acute, chronic and fresh air control. Acute group was exposed to waterpipe smoke for one hour daily for six days using whole-body exposure system, while chronic group was exposed to waterpipe smoke for one hour daily for 30 days using whole-body exposure system. Exposure to waterpipe smoke has shown significant changes on the mice kidney functional parameters such as creatinine and blood urea nitrogen. Both exposures (acute and chronic) has shown a significant reduction in superoxide dismutase (SOD) activity (p < 0.05), whereas the activity of other antioxidant enzymes (catalase and GPx) reduced only with chronic exposure to waterpipe smoke (p < 0.05). Additionally, the level of thiobarbituric acid reactive substances (TBARS) in mice kidney homogenates has shown a significant elevation following chronic exposure to waterpipe smoke (p < 0.05). In conclusion, chronic waterpipe smoke affects the kidney parameter and antioxidant markers, therefore affecting its functionality of detoxifying and removal of poisonous material from the body.

Older kidneys donor transplantation: five years' experience without biopsy and using clinical laboratory and macroscopic anatomy evaluation.

PubMed

Santangelo, M; Zuccaro, M; De Rosa, P; Tammaro, V; Grassia, S; Federico, S; Ciotola, A L; Spinosa, G; Renda, A

2007-01-01

The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy. Between 2000 and 2005, 58 older kidneys were harvested: 27 were transplanted in our center; 13 were discarded; and 18 were transplanted in other centers. We considered 3 factors to define kidney quality: macroscopic anatomy, multiple factors linked to the donor, and clinical-laboratory data. After transplantation, we observed the patients for at least 1 year and up to 6 years. At 1 year, 24/27 (89%) patients had a functional kidney, 2 patients showed an initial renal failure and 1 patient lost the kidney. At maximum follow-up, 19 patients (70%) had functional kidneys, 4 with initial renal failure. These results compared with the kidneys harvested using Standard Donor Kidney Criteria are acceptable. Obviously we need long-term follow-up to increase, the amount of data and obtain a definitive outcome. Biopsy is the gold standard for the definition of an older kidney's quality. When a biopsy is not feasible, the study of the macroscopic anatomy the kidney's donor and of some donor's parameters represent an acceptable biopsy alternative, being able to rescue some organs that would be otherwise lost.

Biochemical studies on the effect of different water resources in Hail region on liver and kidney functions of rats.

PubMed

Talkhan, Ola F A; Abd Elwahab, Safaa A E; Shalapy, Ebtessam M

2016-08-01

Low concentration of a heavy metal is toxic and can be classified as one of the pollution sources. Industrial and human waste can pollute water with heavy metals and soils breaking down under the effect of acidic rain, which release heavy metals into river, streams, lakes, and ground water. Bioaccumulation of heavy metals in vital organs of the human body damages these organs, including the liver and kidney, which are the main organs for metabolism, detoxification, and excretion. The present study aims to investigate into concentrations of such heavy metals (Fe, Cu, Zn, and Pb) in both ground and tap water samples collected from different areas in Hail region, KSA. Then, this study moves forward to examine the effects of such concentrations on the biochemistry of serum in rats. In this regard, the results demonstrate the presence of significant differences (p < 0.05) in the liver function parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total proteins, albumin, and globulin between all the studied groups that were exposed to heavy-metals-polluted water, when compared with the control group. In addition, there were significant differences (p < 0.05) in the kidney function parameters, uric acid, urea, and creatinine, when compared with the control group. Thence, and as this study indicates, heavy-metals-polluted water can cause disturbance in the liver and kidney function parameters, which highlights health risks of the water polluted with heavy metals. In this sense, the concerned authorities should regularly carry out survey and should monitor underground water, and people have to be aware of such risks.

The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

PubMed

Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

2016-01-01

Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

Practical application of stereological methods in experimental kidney animal models.

PubMed

Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Incremental short daily home hemodialysis: a case series.

PubMed

Toth-Manikowski, Stephanie M; Mullangi, Surekha; Hwang, Seungyoung; Shafi, Tariq

2017-07-05

Patients starting dialysis often have substantial residual kidney function. Incremental hemodialysis provides a hemodialysis prescription that supplements patients' residual kidney function while maintaining total (residual + dialysis) urea clearance (standard Kt/Vurea) targets. We describe our experience with incremental hemodialysis in patients using NxStage System One for home hemodialysis. From 2011 to 2015, we initiated 5 incident hemodialysis patients on an incremental home hemodialysis regimen. The biochemical parameters of all patients remained stable on the incremental hemodialysis regimen and they consistently achieved standard Kt/Vurea targets. Of the two patients with follow-up >6 months, residual kidney function was preserved for ≥2 years. Importantly, the patients were able to transition to home hemodialysis without automatically requiring 5 sessions per week at the outset and gradually increased the number of treatments and/or dialysate volume as the residual kidney function declined. An incremental home hemodialysis regimen can be safely prescribed and may improve acceptability of home hemodialysis. Reducing hemodialysis frequency by even one treatment per week can reduce the number of fistula or graft cannulations or catheter connections by >100 per year, an important consideration for patient well-being, access longevity, and access-related infections. The incremental hemodialysis approach, supported by national guidelines, can be considered for all home hemodialysis patients with residual kidney function.

Sildenafil improves renal function in patients with pulmonary arterial hypertension

PubMed Central

Webb, David J; Vachiery, Jean-Luc; Hwang, Lie-Ju; Maurey, Julie O

2015-01-01

Aim Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival. Methods Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (as tolerated) in the extension study. Results Baseline characteristics were similar among groups (n = 277). PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased sCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios 1.17 [95% CI 1.01, 1.36] and 1.21 [95% CI 1.03, 1.41], respectively, for sCr and 0.97 [95% CI 0.94, 0.99] and 0.97 [95% CI 0.94, 0.99] for eGFR, all P < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min–1 1.73 m–2 appeared to have worse survival. Conclusions Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality. PMID:25727860

Prevalence of cysts in seminal tract and abnormal semen parameters in patients with autosomal dominant polycystic kidney disease.

PubMed

Torra, Roser; Sarquella, Joaquim; Calabia, Jordi; Martí, Jordi; Ars, Elisabet; Fernández-Llama, Patricia; Ballarin, Jose

2008-05-01

Autosomal dominant polycystic kidney disease is a systemic disorder with a wide range of extrarenal involvement. The scope of this study was to analyze the prevalence of seminal cysts and to correlate these findings with the sperm parameters in patients with autosomal dominant polycystic kidney disease. A prospective study enrolled 30 adult men with autosomal dominant polycystic kidney disease. Of these 30 patients, 22 agreed to provide a semen sample for analysis, and 28 of 30 agreed to undergo an ultrasound rectal examination. Data obtained from the semen tests and from the ultrasound study were compared. Cysts in the seminal tract were present in 10 (43.47%) of 28 individuals. Twenty of 22 patients showed abnormal semen parameters, with asthenozoospermia as the most common finding. No correlation between ultrasound findings and sperm abnormalities was observed. The presence of cysts in the seminal tract is remarkably high (43.47%); however, this finding does not correlate with sperm abnormalities, which are also a frequent finding, especially asthenozoospermia. This semen abnormality is probably related to the abnormal function of polycystins. More attention should be paid to reproductive aspects in the initial evaluation of patients with autosomal dominant polycystic kidney disease before their ability to conceive is further impaired by uremia.

Renal functional reserve and renal hemodynamics in hypertensive patients.

PubMed

Gaipov, Abduzhappar; Solak, Yalcin; Zhampeissov, Nurlan; Dzholdasbekova, Aliya; Popova, Nadezhda; Molnar, Miklos Z; Tuganbekova, Saltanat; Iskandirova, Elmira

2016-10-01

The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n = 10) and hypertension without nephropathy (HTN, n = 14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1 mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1 × 100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p < 0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r = -0.435, p = 0.009; dBP, r = -0.504, p = 0.002), RRI (r = -0.456, p = 0.008), micro albuminuria (MAU, r = -0.366, p = 0.031) and positive correlation with Vmax and Vmin (r = 0.556, p = 0.001 and r = 0.643, respectively, p < 0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.

The relationship between renal volume and histology in obese and nonobese kidney donors.

PubMed

Tatar, Erhan; Sen, Sait; Harman, Mustafa; Kircelli, Fatih; Gungor, Ozkan; Sarsik, Banu; Asci, Gulay; Hoscoskun, Cuneyt; Basci, Ali; Toz, Huseyin

2015-06-01

Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Quality of chronic kidney disease management in primary care: a retrospective study.

PubMed

Van Gelder, Vincent A; Scherpbier-De Haan, Nynke D; De Grauw, Wim J C; Vervoort, Gerald M M; Van Weel, Chris; Biermans, Marion C J; Braspenning, Jozé C C; Wetzels, Jack F M

2016-01-01

Early detection and appropriate management of chronic kidney disease (CKD) in primary care are essential to reduce morbidity and mortality. To assess the quality of care (QoC) of CKD in primary healthcare in relation to patient and practice characteristics in order to tailor improvement strategies. Retrospective study using data between 2008 and 2011 from 47 general practices (207 469 patients of whom 162 562 were adults). CKD management of patients under the care of their general practitioner (GP) was qualified using indicators derived from the Dutch interdisciplinary CKD guideline for primary care and nephrology and included (1) monitoring of renal function, albuminuria, blood pressure, and glucose, (2) monitoring of metabolic parameters, and alongside the guideline: (3) recognition of CKD. The outcome indicator was (4) achieving blood pressure targets. Multilevel logistic regression analysis was applied to identify associated patient and practice characteristics. Kidney function or albuminuria data were available for 59 728 adult patients; 9288 patients had CKD, of whom 8794 were under GP care. Monitoring of disease progression was complete in 42% of CKD patients, monitoring of metabolic parameters in 2%, and blood pressure target was reached in 43.1%. GPs documented CKD in 31.4% of CKD patients. High QoC was strongly associated with diabetes, and to a lesser extent with hypertension and male sex. Room for improvement was found in all aspects of CKD management. As QoC was higher in patients who received structured diabetes care, future CKD care may profit from more structured primary care management, e.g. according to the chronic care model. Quality of care for chronic kidney disease patients in primary care can be improved. In comparison with guideline advice, adequate monitoring of disease progression was observed in 42%, of metabolic parameters in 2%, correct recognition of impaired renal function in 31%, and reaching blood pressure targets in 43% of chronic kidney disease patients. Quality of care was higher in patients with diabetes. Chronic kidney disease management may be improved by developing strategies similar to diabetes care.

Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

PubMed Central

Connors, Bret A.; Evan, Andrew P.; Blomgren, Philip M.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Wang, Yak-Nam; Simon, Julianna C.; Paun, Marla; Starr, Frank; Cunitz, Bryan W.; Bailey, Michael R.; Lingeman, James E.

2013-01-01

Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters. PMID:23917165

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other.

PubMed

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients' medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD.

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other

PubMed Central

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients’ medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD. PMID:28497080

Multi-color autofluorescence and scattering spectroscopy provides rapid assessment of kidney function following ischemic injury

NASA Astrophysics Data System (ADS)

Raman, Rajesh N.; Pivetti, Chris D.; Ramsamooj, Rajendra; Troppmann, Christoph; Demos, Stavros G.

2018-02-01

A major source of kidneys for transplant comes from deceased donors whose tissues have suffered an unknown amount of warm ischemia prior to retrieval, with no quantitative means to assess function before transplant. Toward addressing this need, non-contact monitoring of optical signatures in rat kidneys was performed in vivo during ischemia and reperfusion. Kidney autofluorescence images were captured under ultraviolet illumination (355 nm, 325 nm, and 266 nm) in order to provide information on related metabolic and non-metabolic response. In addition, light scattering images under 355 nm, 325 nm, and 266 nm, 500 nm illumination were monitored to report on changes in kidney optical properties giving rise to the observed autofluorescence signals during these processes. During reperfusion, various signal ratios were generated from the recorded signals and then parametrized. Time-dependent parameters derived from the ratio of autofluorescence under 355 nm excitation to that under 266 nm excitation, as well as from 500 nm scattered signal, were found capable of discriminating dysfunctional kidneys from those that were functional (p < 0.01) within hours of reperfusion. Kidney dysfunction was confirmed by subsequent survival study and histology following autopsy up to a week later. Physiologic changes potentially giving rise to the observed signals, including those in cellular metabolism, vascular response, tissue microstructure, and microenvironment chemistry, are discussed.

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

PubMed Central

2014-01-01

Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of 177Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT. PMID:25977880

Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

2013-10-01

Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

Differential associations between glomerular filtration rate and duration of obesity depending on the presence or absence of left ventricular diastolic dysfunction.

PubMed

Ybarra, Juan; Sánchez-Hernández, Joan; Vilallonga, Ramon; Romeo, June H

2016-07-01

A robust and consistent association between increasing body mass index (BMI) and chronic kidney disease (CKD) has been reported in several observational studies. Obesity remains the main preventable risk factor for CKD because it largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease (ESKD). Obesity is associated weakly with early stages of kidney disease but strongly with kidney progression to ESKD, even after adjustment for hypertension and diabetes. To assess the relationship between estimated glomerular filtration rate (eGFR) and trans-thoracic echocardiography left ventricular function parameters in a cohort of patients with obesity. Cross-sectional study involving 324 obese (BMI=44.0±2.2Kg/m(2)) apparently healthy asymptomatic patients with an eGFR >60ml/min/1.73m(2). Each patient underwent transthoracic echocardiography and a blood testing. The eGFR was addressed by the CKD-EPI formula. All patients had a normal systolic function whereas 24.5% disclosed diastolic dysfunction (DD). Hypertension and type 2 diabetes mellitus prevalence were 34.5% and 4.5% (respectively). All patients disclosed an eGFR >60ml/min while none of them disclosed hyperfiltration (eGFR >120ml/min). eGFR correlated inversely with BMI and the duration of obesity and positively with diastolic function parameters (P<0.001 for all, respectively). Patients with diastolic dysfunction displayed lower eGFR (P<0.0005) and longer duration of obesity (P<0.0005). Obesity and its duration are likely to impose hemodynamic changes affecting simultaneously both heart (diastolic dysfunction) and kidney (decreased glomerular filtration rate). Larger prospective studies are warranted. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Uromodulin: a new biomarker of fetal renal function?

PubMed

Botelho, Thais Emanuelle Faria; Pereira, Alamanda Kfoury; Teixeira, Patrícia Gonçalves; Lage, Eura Martins; Osanan, Gabriel Costa; Silva, Ana Cristina Simões E

2016-12-01

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model.

PubMed

Lee, Seung-Jun; Ryu, Min-Ok; Seo, Min-Soo; Park, Sang-Bum; Ahn, Jin-Ok; Han, Sei-Myoung; Kang, Kyung-Sun; Bhang, Dong-Ha; Youn, Hwa-Young

2017-01-01

The kidney excretes waste materials and regulates important metabolic functions, and renal disorders constitute a significant medical problem and can result in fatalities. In the present study, mesenchymal stem cells derived from canine umbilical cord blood (cUCB-MSCs) were isolated and evaluated for their ability to improve renal function in a canine model of acute kidney injury (AKI). The canine AKI model was developed by i.v. injection of cisplatin and gentamycin into 14 male beagle dogs. cUCB-MSCs were administered into the renal corticomedullary junction following AKI induction. Survival time, clinical signs, blood analysis and histological parameters were analyzed. The group treated with AKI plus cUCB-MSCs had decreased blood urea nitrogen and creatinine levels, and showed an extended life-span and improved histological manifestations. MSCs were detected around the tubules of these kidneys at the histological level. Taken together, our findings suggest that cUCB-MSCs could be an alternative therapeutic agent for canine AKI. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Protective effect of grape seed and skin extract against diabetes-induced oxidative stress and renal dysfunction in virgin and pregnant rat.

PubMed

Oueslati, Nourhene; Charradi, Kamel; Bedhiafi, Takwa; Limam, Ferid; Aouani, Ezzedine

2016-10-01

The present work deal with the effect of alloxan-induced diabetes on kidney oxidative stress and dysfunction of virgin and pregnant rat as well as the protection that may be afforded by high dosage GSSE (4g/kg) treatment. Diabetes affected negatively several kidney function parameters as creatinemia, uremia, uricemia and proteinuria without affecting kidney index. Diabetes also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in antioxidant enzyme defenses as catalase, superoxide-dismutase, glutathione-peroxidase, an alteration in transition metals as free iron, copper, selenium and associated enzymes and an increase in calpain and acetyl-cholinesterase activities. Tremendously, GSSE treatment protected efficiently against all the deleterious effects of diabetes-induced kidney dysfunction in both virgin and pregnant animals. High dosage GSSE is a safe and potent anti-oxidant that may be further tested in clinical trials for the long-term preservation of kidney function especially in multiple pregnancies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction.

PubMed

Guerrero Orriach, Jose L; Galán Ortega, M; Ramírez Fernandez, A; Ariza Villanueva, D; Florez Vela, A; Moreno Cortés, I; Rubio Navarro, M; Cruz Mañas, J

2017-02-01

The Acute Kidney Injury Network (AKIN) classification considers SCr values, urea and urine output in order to improve timely diagnose ARF and improve patient prognosis by early treatment. Preoperative levosimendan is a new way for cardiac and kidney protection, we try to evaluate this drug in fifteen patients comparing values of AKIN scale parameters pre and post cardiac surgery in patients with right ventricle dysfunction.

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

PubMed

Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

2016-01-01

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

Grape seed and skin extract alleviates high-fat diet-induced renal lipotoxicity and prevents copper depletion in rat.

PubMed

Charradi, Kamel; Elkahoui, Salem; Karkouch, Ines; Limam, Ferid; Hamdaoui, Ghaith; Ben Hassine, Fethy; El May, Michèle Veronique; El May, Ahmed; Aouani, Ezzedine

2013-03-01

Obesity is a public health problem that contributes to morbidity and mortality from diabetes, heart disease, stroke, and cancers. The purpose of this investigation was to analyse the link between obesity-induced oxidative stress, renal steatosis, and kidney dysfunction, as well as the protective effect of grape seed and skin extract. Rats were fed a standard diet or a high-fat diet for 6 weeks and were either treated or not treated with grape seed and skin extract. Fat-induced oxidative stress was evaluated in the kidney with a special emphasis on transition metals. High-fat diet induced triglyceride deposition and disturbances in kidney function parameters, which are linked to an oxidative stress status and depletion of copper from the kidney. Grape seed and skin extract abrogated almost all fat-induced kidney disturbances. Grape seed and skin extract exerted potential protection against fat-induced kidney lipotoxicity and should find potential application in other kidney-related diseases.

[Quality assurance of the renal applications software].

PubMed

del Real Núñez, R; Contreras Puertas, P I; Moreno Ortega, E; Mena Bares, L M; Maza Muret, F R; Latre Romero, J M

2007-01-01

The need for quality assurance of all technical aspects of nuclear medicine studies is widely recognised. However, little attention has been paid to the quality assurance of the applications software. Our work reported here aims at verifying the analysis software for processing of renal nuclear medicine studies (renograms). The software tools were used to build a synthetic dynamic model of renal system. The model consists of two phases: perfusion and function. The organs of interest (kidneys, bladder and aortic artery) were simple geometric forms. The uptake of the renal structures was described by mathematic functions. Curves corresponding to normal or pathological conditions were simulated for kidneys, bladder and aortic artery by appropriate selection of parameters. There was no difference between the parameters of the mathematic curves and the quantitative data produced by the renal analysis program. Our test procedure is simple to apply, reliable, reproducible and rapid to verify the renal applications software.

High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

PubMed Central

Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

2011-01-01

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

[Contribution of X-ray computed tomography in the evaluation of kidney performance].

PubMed

Lemoine, Sandrine; Rognant, Nicolas; Collet-Benzaquen, Diane; Juillard, Laurent

2012-07-01

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

PubMed

Wang, Mengjing; Obi, Yoshitsugu; Streja, Elani; Rhee, Connie M; Lau, Wei Ling; Chen, Jing; Hao, Chuanming; Hamano, Takayuki; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-07-07

The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m 2 ) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance ( P interaction =0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance ( i.e. , <1.5 ml/min per 1.73 m 2 ), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance ( i.e. , ≥1.5 ml/min per 1.73 m 2 ; P interaction <0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk ( P trend <0.001 for both) irrespective of residual renal urea clearance strata ( P interaction =0.34 and P interaction =0.53, respectively). Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population. Copyright © 2017 by the American Society of Nephrology.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

PubMed

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols limit DNA damage, but only SUL-109 also prevented protein nitrosylation in tubular cells. Therefore SUL-109 offers a promising therapeutic strategy to preserve kidney mitochondrial function.

Renal Safety Pharmacology in Drug Discovery and Development.

PubMed

Benjamin, Amanda; Nogueira da Costa, Andre; Delaunois, Annie; Rosseels, Marie-Luce; Valentin, Jean-Pierre

2015-01-01

The kidney is a complex excretory organ playing a crucial role in various physiological processes such as fluid and electrolyte balance, control of blood pressure, removal of waste products, and drug disposition. Drug-induced kidney injury (DIKI) remains a significant cause of candidate drug attrition during drug development. However, the incidence of renal toxicities in preclinical studies is low, and the mechanisms by which drugs induce kidney injury are still poorly understood. Although some in vitro investigational tools have been developed, the in vivo assessment of renal function remains the most widely used methodology to identify DIKI. Stand-alone safety pharmacology studies usually include assessment of glomerular and hemodynamic function, coupled with urine and plasma analyses. However, as renal function is not part of the ICH S7A core battery, such studies are not routinely conducted by pharmaceutical companies. The most common approach consists in integrating renal/urinary measurements in repeat-dose toxicity studies. In addition to the standard analyses and histopathological examination of kidneys, novel promising urinary biomarkers have emerged over the last decade, offering greater sensitivity and specificity than traditional renal parameters. Seven of these biomarkers have been qualified by regulatory agencies for use in rat toxicity studies.

Improvement in Nutritional Status in Patients With Chronic Kidney Disease-4 by a Nutrition Education Program With No Impact on Renal Function and Determined by Male Sex.

PubMed

Pérez-Torres, Almudena; González Garcia, Elena; Garcia-Llana, Helena; Del Peso, Gloria; López-Sobaler, Ana María; Selgas, Rafael

2017-09-01

Protein-energy wasting (PEW) is associated with increased morbidity and mortality and a rapid deterioration of kidney function in patients with chronic kidney disease (CKD). However, there is little information regarding the effect of nutrition intervention. The aims of this study were to evaluate the efficacy and safety of a nutrition education program (NEP) in patients with nondialysis dependent CKD (NDD-CKD), based on the diagnostic criteria for PEW proposed by the International Society of Renal Nutrition and Metabolism. The design of the study was a 6-month longitudinal, prospective, and interventional study. The study was conducted from March 2008 to September 2011 in the Nephrology Department of La Paz University Hospital in Madrid, Spain. A total of 160 patients with NDD-CKD started the NEP, and 128 finished it. The 6-month NEP consisted of designing an individualized diet plan based on the patient's initial nutritional status, and 4 nutrition education sessions. Changes in nutritional status (PEW) and biochemical, anthropometric and body composition parameters. After 6 months of intervention, potassium and inflammation levels decreased, and an improved lipid profile was found. Body mass index lowered, with increased muscle mass and a stable fat mass. Men showed increased levels of albumin and prealbumin, and women showed decreased proteinuria levels. The prevalence of PEW decreased globally (27.3%-10.9%; P = .000), but differently in men (29.5%-6.5%; P = .000) and in women (25.4%-14.9%; P = .070), 3 of the women having worsened. Kidney function was preserved, despite increased protein intake. The NEP in NDD-CKD generally improved nutritional status as measured by PEW parameters, but individual poorer results indicated the need to pay special attention to female sex and low body mass index at the start of the program. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation.

PubMed

De Deken, J; Rex, S; Lerut, E; Martinet, W; Monbaliu, D; Pirenne, J; Jochmans, I

2018-07-01

Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Preconditioning, reconditioning and postconditioning with argon and xenon protects against renal ischaemia-reperfusion injury in rodent models. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function in a porcine renal autotransplant model was tested. Pigs (n = 6 per group) underwent left nephrectomy after 60 min of warm ischaemia (renal artery and vein clamping). The procured kidney was autotransplanted in a separate procedure after 18 h of cold storage, immediately after a right nephrectomy. Upon reperfusion, pigs were randomized to inhalation of control gas (70 per cent nitrogen and 30 per cent oxygen), argon (70 per cent and 30 per cent oxygen) or xenon (70 per cent and 30 per cent oxygen) for 2 h. The primary outcome parameter was peak plasma creatinine; secondary outcome parameters included further markers of graft function (creatinine course, urine output), graft injury (aspartate aminotransferase, heart-type fatty acid-binding protein, histology), apoptosis and autophagy (western blot, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining), inflammatory mediators and markers of cell survival/growth (mRNA and tissue protein quantification), and animal survival. Results are presented as median (i.q.r.). ANOVA and Kruskal-Wallis tests were used where indicated. Peak plasma creatinine levels were similar between the groups: control 20·8 (16·4-23·1) mg/dl, argon 21·4 (17·1-24·9) mg/dl and xenon 19·4 (17·5-21·0) mg/dl (P = 0·607). Xenon was associated with an increase in autophagy and proapoptotic markers. Creatinine course, urine output, injury markers, histology, survival and inflammatory mediators were not affected by the intervention. Postconditioning with argon or xenon did not improve kidney graft function in this experimental model. Surgical relevance Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Based on mainly small animal experiments, noble gases (argon and xenon) have been proposed to minimize this ischaemia-reperfusion injury and improve outcomes after transplantation. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function was tested in a porcine kidney autotransplantation model. The peak plasma creatinine concentration was similar in the control, argon and xenon groups. No other secondary outcome parameters, including animal survival, were affected by the intervention. Xenon was associated with an increase in autophagy and proapoptotic markers. Despite promising results in small animal models, postconditioning with argon or xenon in a translational model of kidney autotransplantation was not beneficial. Clinical trials would require better results. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

PubMed

Malakasioti, Georgia; Marks, Stephen D; Watson, Tom; Williams, Fariba; Taylor-Allkins, Mariesa; Mamode, Nizam; Morgan, Justin; Hayes, Wesley N

2018-05-11

Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

Preoperative dipstick albuminuria and other urine abnormalities predict acute kidney injury and patient outcomes.

PubMed

Park, Sehoon; Lee, Soojin; Lee, Anna; Paek, Jin Hyuk; Chin, Ho Jun; Na, Ki Young; Chae, Dong-Wan; Kim, Sejoong

2018-05-01

It is unclear whether pathologic findings on preoperative urinalysis are associated with the risk of postoperative acute kidney injury (AKI). Therefore, we performed a retrospective review to investigate this association. We assessed the clinical significance of preoperative dipstick urinalysis in a 10-year surgery cohort from a tertiary hospital in Korea. Patients without available information on perioperative serum creatinine levels or kidney injury prior to surgery were excluded. Preoperative dipstick urinalysis parameters, including albuminuria, hematuria, pyuria, and others were studied. The primary outcome was postoperative acute kidney injury. Secondary outcomes were postoperative 1-year mortality and progression of poor kidney function parameters. We enrolled 40,090 patients. The presence of dipstick albuminuria was associated with an increased risk of postoperative AKI (adjusted odds ratio 1.47 [1.29-1.66], P < .001), and the association showed a dose-response relationship. High specific gravity was significantly associated with increased risk of AKI (adjusted odds ratio 1.30 [1.04-1.63], P = .02). Furthermore, in patients with postoperative AKI, those with baseline albuminuria had a worse prognosis with regard to 1-year mortality (adjusted hazard ratio 2.81 [1.56-5.09], P < .001) and persistent renal function impairment (adjusted odds ratio 2.07 [1.21-3.46], P = .007), independent of estimated glomerular filtration rate values. Patients with baseline hematuria and pyuria also had an inferior postoperative AKI prognosis when compared to those without the urinalysis abnormalities. Baseline dipstick urinalysis may predict postoperative AKI and may be significantly associated with prognosis after surgery. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and hematological data to group different chronic kidney disease patients: A practical approach to establish different groups of patients.

PubMed

Péterle, Vinícius B; Souza, Jéssica de O; Busato, Fernanda de O; Eutrópio, Frederico J; da Costa, Gisele de A P; Olivieri, David N; Tadokoro, Carlos E

2018-06-01

Chronic kidney disease (CKD) is the convergent point of several pathological processes, and its evolution is insidious and characterized by a progressive and irreversible loss of kidney function. This impaired function induces the accumulation of uremic toxins and individuals with terminal CKD often have altered physiological responses, including a persistent state of immuno-suppression and development of diseases. A better characterization and stratification of these patients with CKD in different immuno-compromised groups would contribute to more effective and personalized treatments. The focus of this study was to use two parameters to stratify patients with CKD into four separate groups that are representative of different immunological status. Patients with CKD were chosen randomly and stratified into four separate groups according to the period of time receiving dialysis treatment and leukocyte blood counts. The amount of apoptotic CD4 T cells were measured in each group of patients, and clinical/hematological parameters were correlated by multivariate analysis with each group. Observations reveal that one of the four groups of patients with CKD (group 3) had more apoptotic CD4 T cells than the other group; this group also had an increased malnutrition inflammation score (MIS), an elevated Kt/V, and a higher incidence of smoking. A simple two-parameter-based stratification strategy could be used to design effective immunological therapies that differentiate the degrees of immuno-suppression across groups of patients with CKD. © 2018 Wiley Periodicals, Inc.

Comparative analysis of two porcine kidney decellularization methods for maintenance of functional vascular architectures.

PubMed

Zambon, Joao Paulo; Ko, In Kap; Abolbashari, Mehran; Huling, Jennifer; Clouse, Cara; Kim, Tae Hyoung; Smith, Charesa; Atala, Anthony; Yoo, James J

2018-06-05

Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys. While functional re-endothelialization on the porcine whole kidney scaffold was able to improve vascular patency, as compared to the kidney scaffold only, the duration of patency lasted only a few hours. In this study, we hypothesized that significant damage in the microvasculatures within the kidney scaffold resulted in the cessation of blood flow, and that thorough investigation is necessary to accurately evaluate the vascular integrity of the kidney scaffolds. Two decellularization protocols [sodium dodecyl sulfate (SDS) with DNase (SDS + DNase) or Triton X-100 with SDS (TRX + SDS)] were used to evaluate and optimize the levels of vascular integrity within the kidney scaffold. Results from vascular analysis studies using vascular corrosion casting and angiograms demonstrated that the TRX + SDS method was able to better maintain intact and functional microvascular architectures such as glomeruli within the acellular matrices than that by the SDS + DNase treatment. Importantly, in vitro blood perfusion of the re-endothelialized kidney construct revealed improved vascular function of the scaffold by TRX + SDS treatment compared with the SDS + DNase. Our results suggest that the optimized TRX + SDS decellularization method preserves kidney-specific microvasculatures and may contribute to long-term vascular patency following implantation. Kidney transplantation is the only curative therapy for patients with end-stage renal disease (ESRD). However, in the United States, the supply of donor kidneys meets less than one-fifth of the demand; and those patients that receive a donor kidney need life-long immunosuppressive therapy to avoid organ rejection. In the last two decades, regenerative medicine and tissue engineering have emerged as an attractive alternative to overcome these limitations. In 2013, Song et al. published the first experimental orthotopic transplantation of a bioengineering kidney in rodents. In this study, they demonstrated evidences of kidney tissue regeneration and partial function restoration. Despite these initial promising results, there are still many challenges to achieve long-term blood perfusion without graft thrombosis. In this paper, we demonstrated that perfusion of detergents through the renal artery of porcine kidneys damages the glomeruli microarchitecture as well as peritubular capillaries. Modifying dynamic parameters such as flow rate, detergent concentration, and decellularization time, we were able to establish an optimized decellularization protocol with no evidences of disruption of glomeruli microarchitecture. As a proof of concept, we recellularized the kidney scaffolds with endothelial cells and in vitro perfused whole porcine blood successfully for 24 h with no evidences of thrombosis. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Measuring dynamic kidney function in an undergraduate physiology laboratory.

PubMed

Medler, Scott; Harrington, Frederick

2013-12-01

Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on a "dipstick" approach of urinalysis. Although this technique can provide some basic insights into the functioning of the kidneys, it overlooks the dynamic processes of filtration, reabsorption, and secretion. In the present article, we provide a straightforward approach of using renal clearance measurements to estimate glomerular filtration rate, fractional water reabsorption, glucose clearance, and other physiologically relevant parameters. The estimated values from our measurements in laboratory are in close agreement with those anticipated based on textbook parameters. For example, we found glomerular filtration rate to average 124 ± 45 ml/min, serum creatinine to be 1.23 ± 0.4 mg/dl, and fractional water reabsorption to be ∼96.8%. Furthermore, analyses for the class data revealed significant correlations between parameters like fractional water reabsorption and urine concentration, providing opportunities to discuss urine concentrating mechanisms and other physiological processes. The procedures outlined here are general enough that most undergraduate physiology laboratory courses should be able to implement them without difficulty.

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

PubMed

Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

2017-06-01

Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen ( r = -0.23, p < 0.05) and eGFR ( r = -0.36, p < 0.05). FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

Renal and metabolic effects of three months of decarbonated cola beverages in rats.

PubMed

Celec, Peter; Pálffy, Roland; Gardlík, Roman; Behuliak, Michal; Hodosy, Július; Jáni, Peter; Bozek, Peter; Sebeková, Katarína

2010-11-01

Epidemiological studies have shown an association between the intake of cola beverages and chronic kidney diseases. Experimental evidence for the negative effects of cola intake on kidneys is lacking. Male Wistar rats had ad libitum access to water (control group) or three different sugar-sweetened cola beverages for three months. Despite very high cola intake (daily cca 140 mL), no differences were found in body weight, kidney weight, glomerular morphology, oxidative and carbonyl stress or expression of selected marker genes in the renal cortex. Interestingly, all groups consuming cola beverages had lower blood glucose levels during an oral glucose tolerance test, suggesting improved insulin sensitivity. Despite hyperfiltration (5-6-fold increase in diuresis), cola beverages had no effect on assessed parameters of renal function, histology, gene expression or oxidative stress. Moreover, cola intake seems to increase creatinine clearance and to decrease plasma levels of urea. In our study increased insulin sensitivity and altered renal functional parameters were observed in rats receiving cola beverages for three months. Whether the findings are due to the short duration of the study or interspecies metabolic differences should be uncovered in further studies. Even more interesting might be the analysis of effects of cola intake in animal models of diabetes.

Flow cytometry of human embryonic kidney cells: A light scattering approach

NASA Technical Reports Server (NTRS)

Kunze, M. E.; Goolsby, C. L.; Todd, P. W.; Morrison, D. R.; Lewis, M. L.

1985-01-01

The mammalian kidney contains cells that transport water, convert vitamin D to active forms, synthesize hormones such a renin and erythropoietin, and produce enzymes such as urokinase, a plasminogen activator. Several of these functions are maintained by human embryonic kidney cells (HEK) cultivated in vitro. Biochemical study of these functions in their individual cell types in vitro requires purified populations of cells. Light-scattering activated cell sorting (LACS) was explored as a means of achieving such purifications. It was found that HEK cells at the first 1 to 5 passages in culture were heterogeneous with respect to 2-parameter light scattering intensity distribution, in which combined measurements included forward angle scattering (2.5 to 19 deg), 90 deg scattering, and time-of-flight size measurements. Size was measured at a resolution of 0.15 microns/channel in 256 channels using pulse-height independent pulse-width measurements. Two-parameter distributions combining these measurements were obtained for HEK cell subpopulations that had been purified by microgravity electrophoresis and subsequently propagated in culture. These distributions contained at least 3 subpopulations in all purified fractions, and results of experiments with prepurified cultured HEK cells indicated that subpopulations of living cells that were high in plasminogen-activator activity also contained the highest per cent of cells with high 90 deg light scatter intensity.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

PubMed Central

Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

2016-01-01

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

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.

Nutritional factors in the biochemical pathology of Corynebacterial kidney disease in the coho salmon (Oncorhynchus kisutch)

USGS Publications Warehouse

Wedemeyer, Gary A.; Ross, A.J.

1973-01-01

The influence of diet ingredient on the morbidity and biochemical pathogenesis of corynebacterial kidney disease was investigated using juvenile coho salmon (Oncorhynchus kisutch) fed the Abernathy dry ration made up with either corn gluten or cottonseed meal (isoprotein, isocaloric substitution). Evaluation of incidence of infection, pituitary activation and aspects of carbohydrate metabolism, acid-base balance, renal function, and hematopoietic activity showed that the actual disease incidence was about the same for both diets but the nonspecific stress of infection was more severe in fish fed the corn gluten.Discriminant function calculations combining four physiological parameters gave a probability of 0.86 for successfully diagnosing infected fish on the basis of these blood chemistry tests.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The impact of preserved Klotho gene expression on anti-oxidative stress activity in healthy kidney.

PubMed

Kimura, Takaaki; Shiizaki, Kazuhiro; Kurosu, Hiroshi; Akimoto, Tetsu; Shinzato, Takahiro; Shimizu, Toshihiro; Kurosawa, Akira; Kubo, Taro; Nanmoku, Koji; Kuro-O, Makoto; Yagisawa, Takashi

2018-04-25

Klotho, which was originally identified as an anti-aging gene, forms a complex with fibroblast growth factor 23 (FGF23) receptor in kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho including anti-aging effects such as protection from various cellular stress have been shown, however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and anti-oxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with p53 gene, and antioxidant enzyme genes such as Catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function, and pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for PRDX3 and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the anti-oxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition including age, renal function, and histological findings.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

PubMed

Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

2000-08-01

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

[Impact of end-stage renal disease and kidney transplantation on the reproductive system].

PubMed

Delesalle, A-S; Robin, G; Provôt, F; Dewailly, D; Leroy-Billiard, M; Peigné, M

2015-01-01

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Testing the ability of non-methylamine osmolytes present in kidney cells to counteract the deleterious effects of urea on structure, stability and function of proteins.

PubMed

Khan, Sheeza; Bano, Zehra; Singh, Laishram R; Hassan, Md Imtaiyaz; Islam, Asimul; Ahmad, Faizan

2013-01-01

Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o)) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

Testing the Ability of Non-Methylamine Osmolytes Present in Kidney Cells to Counteract the Deleterious Effects of Urea on Structure, Stability and Function of Proteins

PubMed Central

Khan, Sheeza; Bano, Zehra; Singh, Laishram R.; Hassan, Md. Imtaiyaz; Islam, Asimul; Ahmad, Faizan

2013-01-01

Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D o) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively. PMID:24039776

[An experience of the use of angiotensin II receptor blocker losartan in patients with metabolic syndrome and chronic kidney disease].

PubMed

Beloborodova, A V; Morozova, T E; Shilov, E M

2010-01-01

Aim of the study--to assess efficacy and safety of one of angiotensin II receptor blockers in patients with metabolic syndrome (MS) and I-V stage chronic kidney disease. We studied cardiodynamic and renal effects of losartan in average daily dose 50 +/- 13.06 mg in 20 patients (9 men and 11 women aged 32-79 years) with MS and I-V stage chronic kidney disease. Cardiodynamic effects of losartan were assessed by office blood pressure (BP) measurements, 24-hour BP monitoring (24-HBPM), echocardiography. Laboratory investigations included biochemical analysis of the blood with measurement of creatinine levels, lipid blood composition, fasting glucose, and glucose under conditions of oral glucose tolerance test. Renal function was assessed by glomerular filtration rate and microalbuminuria (MAU). Parameters of quality of life were analyzed with the use of questionnaires "Quality of life of patients with hypertensive disease" and EuroQol EQ-5D VAS thermometer. Duration of follow up was 12 weeks. 24-HBPM revealed significant lowering of systolic and diastolic BP in all temporal intervals, significant decrease of elevated diurnal systolic and diastolic BP burden, tendency to lowering of variability and normalization of 24-hour BP profile. We also noted tendency to lowering of MAU from 5.60 mg/dl (median) (3.50; 9.20 [25th and 75th percentile]) to 3.25 mg/dl (0.40; 7.83); significant lowering of levels of triglycerides and glucose under conditions of glucose tolerance test; improvement of parameters characterizing quality of life namely reduction of integral assessment by the "Quality of life of patients with hypertensive disease" questionnaire and improvement of EQ-5D VAS (thermometer) score related to arterial hypertension. We conclude that losartan in patients with MS and early signs of impairment of kidney function in addition to antihypertensive action exerts favorable effect on parameters of 24-hour BP profile, has good safety profile, causes favorable metabolic effects, lowers level of MAU and improves parameters of quality of life.

Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys.

PubMed

He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M

2017-08-01

Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

PubMed

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

NephroCheck data compared to serum creatinine in various clinical settings.

PubMed

Pajenda, Sahra; Ilhan-Mutlu, Aysegül; Preusser, Matthias; Roka, Sebastian; Druml, Wilfred; Wagner, Ludwig

2015-12-09

Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury. A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result. This report revealed that [IGFBP7] · [TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test. This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

Effects of Khaya senegalensis leaves on performance, carcass traits, hemtological and biochemical parameters in rabbits

PubMed Central

Abdel-Wareth, A. A. A.; Hammad, Seddik; Ahmed, Hassan

2014-01-01

One of the challenges facing farmers today is to ensure adequate integration of natural resources into animal feeds. The aim of the present study is to evaluate the effects of Khaya senegalensis (KS) leaves on the performance of growing male rabbits, carcass traits and biochemical as well as hematological parameters. Thirty New Zealand White male growing rabbits were randomly divided into 3 groups (10 rabbits per group). Group I (control) received standard rabbit diet. Rabbits in group II and group III were fed standard rabbit diet supplemented with 35 % and 65 % KS leaves, respectively. All rabbits were fed daily for 25 days. The performance parameters and carcass criteria, including daily body weight gain, final body weight, and the percentage of dressing, were increased in rabbits fed 35 % KS when compared to the control group. Kidney and liver weight ratios increased significantly in group II but dropped in group III. Furthermore, liver enzymes - alanine aminotransferase and aspartate transaminase and kidney function parameters - urea, and creatinine - increased in both group II (significant P<0.05) and in group III (significant P<0.01) when compared to the control group. Moreover, KS leaves induced a significant increase (P<0.05) in the total white blood cell count, the percentage of granulocytes and the platelet count; whereas, the percentage of lymphocytes, red blood cell count, hemoglobin content, mean corpuscular hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration were not statistically significantly changed. This study demonstrates that the performance parameters and carcass traits are improved by the replacement of rabbit's diet with KS leaves. However, KS leaves may adversely affect liver and kidney function in a dose-dependent manner. Therefore, further studies are required to elucidate the maximum tolerable and toxic, as well as lethal doses, and to isolate the pharmacologically active components from KS leaves. PMID:26417277

Nigella sativa oil protects against tartrazine toxicity in male rats.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Hamed, Amani Mohammed; Zamazami, Mazin A

2018-01-01

This study aimed to evaluate the protective role of Nigella sativa oil against the adverse effects of tartrazine on male rats. 18 albino rats were divided randomly into four groups (n = 6). The first (G1) is the negative control, the second group (G2) is the positive control received 10 mg/kg b.w. tartrazine in the diet and the third (G3) received the same dose of tartrazine as in G2 and co-treated with Nigella sativa oil for 8 weeks. Tartrazine decreased total protein, antioxidants and high density lipoproteins, whereas increased liver enzyme, kidney function parameters, total cholesterol, triglycerides, low density lipoproteins and lipid peroxidation in the positive control group. In addition, it caused pathological changes in the tissues of liver, kidney, testes and stomach. Treating tartrazine supplemented rats of G3 with Nigella sativa oil for 8 weeks significantly improved all biochemical parameters and restored the tissues of kidney, stomach, testes and liver to normal. It could be concluded that N. sativa oil succeeded in protecting male rats against the adverse conditions resulted from tartrazine administration.

Characterization of a Cardiorenal-like Syndrome in Aged Chimpanzees (Pan troglodytes).

PubMed

Chilton, J; Wilcox, A; Lammey, M; Meyer, D

2016-03-01

Cardiorenal syndrome involves disease and dysfunction of the heart that leads to progressive renal dysfunction. This study investigated the relationship between cardiac and renal disease in 91 aged chimpanzees at the Alamogordo Primate Facility by evaluation of the medical histories, metabolic parameters, functional measurements of the cardiovascular system, clinical pathology, and histopathology focused on the heart and kidney. Cardiac fibrosis was the most frequent microscopic finding in 82 of 91 animals (90%), followed by glomerulosclerosis with tubulointerstitial fibrosis in 63 of 91 (69%). Cardiac fibrosis with attendant glomerulosclerosis and tubulointerstitial fibrosis was observed in 58 of 91 animals (63%); there was a statistically significant association between the 2 conditions. As the severity of cardiac fibrosis increased, there was corresponding increase in severity of glomerulosclerosis with tubulointerstitial fibrosis. Altered metabolic, cardiovascular, and clinical pathology parameters indicative of heart and kidney failure were commonly associated with the moderate to severe microscopic changes, and concurrent heart and kidney failure were considered the cause of death. The constellation of findings in the chimpanzees were similar to cardiorenal syndrome in humans. © The Author(s) 2016.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Relationships between appetite and quality of life in hemodialysis patients.

PubMed

Zabel, Rachel; Ash, Susan; King, Neil; Juffs, Philip; Bauer, Judith

2012-08-01

The aim of this paper was to investigate the association between appetite and kidney-disease specific quality of life in maintenance hemodialysis patients. Quality of life (QoL) was measured using the kidney disease quality of life survey. Appetite was measured using self-reported categories and a visual analog scale. Other nutritional parameters included Patient-Generated Subjective Global Assessment (PGSGA), dietary intake, body mass index and biochemical markers C-reactive protein and albumin. Even in this well nourished sample (n=62) of hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations (r=0.420) and body mass index (r=-0.409) were all significantly associated with the physical health domain of QoL. As self-reported appetite declined, QoL was significantly lower in nine domains which were mostly in the SF36 component and covered social functioning and physical domains. Appetite and other nutritional parameters were not as strongly associated with the Mental Health domain and Kidney Disease Component Summary Domains. Nutritional parameters, especially PGSGA score and appetite, appear to be important components of the physical health domain of QoL. As even small reductions in nutritional status were associated with significantly lower QoL scores, monitoring appetite and nutritional status is an important component of care for hemodialysis patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of behavioral parameters, hematological markers, liver and kidney functions in rodents exposed to Deepwater Horizon crude oil and Corexit.

PubMed

Ramesh, Sindhu; Bhattacharya, Dwipayan; Majrashi, Mohammed; Morgan, Marlee; Prabhakar Clement, T; Dhanasekaran, Muralikrishnan

2018-04-15

The 2010 Deepwater Horizon (DWH) oil spill is the largest marine oil spill in US history. In the aftermath of the spill, the response efforts used a chemical dispersant, Corexit, to disperse the oil spill. The health impacts of crude oil and Corexit mixture to humans, mammals, fishes, and birds are mostly unknown. The purpose of this study is to investigate the in vivo effects of DWH oil, Corexit, and oil-Corexit mixture on the general behavior, hematological markers, and liver and kidney functions of rodents. C57 Bl6 mice were treated with DWH oil (80 mg/kg) and/or Corexit (95 mg/kg), and several hematological markers, lipid profile, liver and kidney functions were monitored. The results show that both DWH oil and Corexit altered the white blood cells and platelet counts. Moreover, they also impacted the lipid profile and induced toxic effects on the liver and kidney functions. The impacts were more pronounced when the mice were treated with a mixture of DWH-oil and Corexit. This study provides preliminary data to elucidate the potential toxicological effects of DWH oil, Corexit, and their mixtures on mammalian health. Residues from the DWH spill continue to remain trapped along various Gulf Coast beaches and therefore further studies are needed to fully understand their long-term impacts on coastal ecosystems. Copyright © 2018. Published by Elsevier Inc.

Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

PubMed Central

Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

2015-01-01

Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

Prevalence of Hypertension in Children with Early-Stage ADPKD.

PubMed

Massella, Laura; Mekahli, Djalila; Paripović, Dušan; Prikhodina, Larisa; Godefroid, Nathalie; Niemirska, Anna; Ağbaş, Ayşe; Kalicka, Karolina; Jankauskiene, Augustina; Mizerska-Wasiak, Malgorzata; Afonso, Alberto Caldas; Salomon, Rémi; Deschênes, Georges; Ariceta, Gema; Özçakar, Z Birsin; Teixeira, Ana; Duzova, Ali; Harambat, Jérôme; Seeman, Tomáš; Hrčková, Gabriela; Lungu, Adrian Catalin; Papizh, Svetlana; Peco-Antic, Amira; De Rechter, Stéphanie; Giordano, Ugo; Kirchner, Marietta; Lutz, Teresa; Schaefer, Franz; Devuyst, Olivier; Wühl, Elke; Emma, Francesco

2018-04-19

Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P =0.10). These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages. Copyright © 2018 by the American Society of Nephrology.

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial.

PubMed

Ederoth, Per; Dardashti, Alain; Grins, Edgars; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

2018-04-01

Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.

Monosodium glutamate (MSG) consumption is associated with urolithiasis and urinary tract obstruction in rats.

PubMed

Sharma, Amod; Prasongwattana, Vitoon; Cha'on, Ubon; Selmi, Carlo; Hipkaeo, Wiphawi; Boonnate, Piyanard; Pethlert, Supattra; Titipungul, Tanin; Intarawichian, Piyapharom; Waraasawapati, Sakda; Puapiroj, Anucha; Sitprija, Visith; Reungjui, Sirirat

2013-01-01

The peritoneal injection of monosodium glutamate (MSG) can induce kidney injury in adult rats but the effects of long-term oral intake have not been determined. We investigated the kidney histology and function in adult male Wistar rats that were fed ad libitum with a standard rat chow pellet and water with or without the addition of 2 mg/g body weight MSG/day in drinking water (n=10 per group). Both MSG-treated and control animals were sacrificed after 9 months when renal function parameters, blood and urine electrolytes, and tissue histopathology were determined. MSG-treated rats were more prone to kidney stone formation, as represented by the alkaline urine and significantly higher activity product of calcium phosphate. Accordingly, 3/10 MSG-treated rats developed kidney stones over 9 months versus none of the control animals. Further, 2/10 MSG-treated rats but none (0/10) of the controls manifested hydronephrosis. MSG-treated rats had significantly higher levels of serum creatinine and potassium including urine output volume, urinary excretion sodium and citrate compared to controls. In contrast, MSG-treated rats had significantly lower ammonium and magnesium urinary excretion. Oral MSG consumption appears to cause alkaline urine and may increase the risks of kidney stones with hydronephrosis in rats. Similar effects in humans must be verified by dedicated studies.

Monosodium Glutamate (MSG) Consumption Is Associated with Urolithiasis and Urinary Tract Obstruction in Rats

PubMed Central

Sharma, Amod; Prasongwattana, Vitoon; Cha’on, Ubon; Selmi, Carlo; Hipkaeo, Wiphawi; Boonnate, Piyanard; Pethlert, Supattra; Titipungul, Tanin; Intarawichian, Piyapharom; Waraasawapati, Sakda; Puapiroj, Anucha; Sitprija, Visith; Reungjui, Sirirat

2013-01-01

Background The peritoneal injection of monosodium glutamate (MSG) can induce kidney injury in adult rats but the effects of long-term oral intake have not been determined. Methods We investigated the kidney histology and function in adult male Wistar rats that were fed ad libitum with a standard rat chow pellet and water with or without the addition of 2 mg/g body weight MSG/day in drinking water (n=10 per group). Both MSG-treated and control animals were sacrificed after 9 months when renal function parameters, blood and urine electrolytes, and tissue histopathology were determined. Results MSG-treated rats were more prone to kidney stone formation, as represented by the alkaline urine and significantly higher activity product of calcium phosphate. Accordingly, 3/10 MSG-treated rats developed kidney stones over 9 months versus none of the control animals. Further, 2/10 MSG-treated rats but none (0/10) of the controls manifested hydronephrosis. MSG-treated rats had significantly higher levels of serum creatinine and potassium including urine output volume, urinary excretion sodium and citrate compared to controls. In contrast, MSG-treated rats had significantly lower ammonium and magnesium urinary excretion. Conclusion Oral MSG consumption appears to cause alkaline urine and may increase the risks of kidney stones with hydronephrosis in rats. Similar effects in humans must be verified by dedicated studies. PMID:24086562

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Fetal kidney length as a useful adjunct parameter for better determination of gestational age.

PubMed

Ugur, Mete G; Mustafa, Aynur; Ozcan, Huseyin C; Tepe, Neslihan B; Kurt, Huseyin; Akcil, Emre; Gunduz, Reyhan

2016-05-01

To determine the validity of fetal kidney length and amniotic fluid index (AFI) in labor dating.  This prospective study included 180 pregnant women followed up in the outpatient clinic at the Department of Obstetrics and Gynecology, Gaziantep University, Turkey, between January 2014 and January 2015. The gestational age (GA) was estimated by early fetal ultrasound measures and last menstrual period. Routine fetal biometric parameters, fetal kidney length, and amniotic fluid index were measured. We studied the correlation between fetal kidney length, amniotic fluid index, and gestational age.  The mean gestational age depending on last menstrual period and early ultrasound was 31.98±4.29 (24-39 weeks). The mean kidney length was 35.66±6.61 (19-49 mm). There was a significant correlation between gestational age and fetal kidney length (r=0.947, p=0.001). However, there was a moderate negative correlation between GA and AFI. Adding fetal kidney length to the routine biometrics improved the effectiveness of the model used to estimate GA (R2=0.965 to R2=0.987).  Gestational age can be better predicted by adding fetal kidney length to other routine parameters.

Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens.

PubMed

Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

2018-01-01

Renal prognostic factors of chronic kidney disease are important concerns for patients. Kidney biopsy can be used to evaluate not only the activity of the original disease but also various risk factors related to the lifestyle of patients. Considering that lifestyle-related factors, including obesity and metabolic syndrome, are crucial prognostic risk factors of kidney disease progression and all-cause mortality, evaluation of lifestyle-related prognostic factors in kidney biopsy of all kidney diseases is important. Renal corpuscle size (glomerular size) is an easily measured parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscle found on kidney biopsy is a classic and simple indicator, and has merit owing to its quantitative nature, but it has yet to be used to its full potential in clinical settings. Large renal corpuscle is an index that includes not only the activity of the original disease but also the damage of various metabolic risk states as represented by obesity, diabetes, and metabolic syndrome. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that measurement of the maximum renal corpuscle profile (glomerular profile) in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases. © 2018 S. Karger AG, Basel.

Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthus occitanus) in gentamicin treated rats.

PubMed

Bekheet, Souad H M; Awadalla, Eatemaad A; Salman, Muhammad M; Hassan, Mohamed K

2013-04-01

The present investigation report the effect of a bradykinin-potentiating factor (BPF) on gentamicin-induced oxidative stress in rat liver and kidney. BPF is a peptide fraction isolated from the venom of the Egyptian scorpion (Buthus occitanus) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Thirty male Rattus norvegicus (130-150 g) were included and divided into three equal groups as follows: Group I (control), group II was (ip) injected with gentamicin alone (80 mg/kg/day) for 15 days, group III was given (ip) injection of BPF (1mg/kg/day) one hour prior to gentamicin treatment for 15 days with the same dose of gentamicin as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Gentamicin caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, ALT, AST, ALP, as well as creatinine, uric acid and urea concentrations in versus to control groups in both liver and kidney. Co-administration of gentamicin and BPF significantly increased the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA and maintained serum (ALT); (AST); (ALP), creatinine, uric acid and urea concentrations as the same level as control group. Moreover, administration of gentamicin resulted in damage to liver and kidney structures. Administration of BPF before gentamicin exposure prevented severe alterations of biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with BPF significantly attenuated the physiological and histopathological alterations induced by gentamicin. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs dysfunctions and diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values.

PubMed

Tofts, Paul S; Cutajar, Marica; Mendichovszky, Iosif A; Peters, A Michael; Gordon, Isky

2012-06-01

To model the uptake phase of T(1)-weighted DCE-MRI data in normal kidneys and to demonstrate that the fitted physiological parameters correlate with published normal values. The model incorporates delay and broadening of the arterial vascular peak as it appears in the capillary bed, two distinct compartments for renal intravascular and extravascular Gd tracer, and uses a small-vessel haematocrit value of 24%. Four physiological parameters can be estimated: regional filtration K ( trans ) (ml min(-1) [ml tissue](-1)), perfusion F (ml min(-1) [100 ml tissue](-1)), blood volume v ( b ) (%) and mean residence time MRT (s). From these are found the filtration fraction (FF; %) and total GFR (ml min(-1)). Fifteen healthy volunteers were imaged twice using oblique coronal slices every 2.5 s to determine the reproducibility. Using parenchymal ROIs, group mean values for renal biomarkers all agreed with published values: K ( trans ): 0.25; F: 219; v ( b ): 34; MRT: 5.5; FF: 15; GFR: 115. Nominally cortical ROIs consistently underestimated total filtration (by ~50%). Reproducibility was 7-18%. Sensitivity analysis showed that these fitted parameters are most vulnerable to errors in the fixed parameters kidney T(1), flip angle, haematocrit and relaxivity. These renal biomarkers can potentially measure renal physiology in diagnosis and treatment. • Dynamic contrast-enhanced magnetic resonance imaging can measure renal function. • Filtration and perfusion values in healthy volunteers agree with published normal values. • Precision measured in healthy volunteers is between 7 and 15%.

Impact of the Di(2-Ethylhexyl) Phthalate Administration on Trace Element and Mineral Levels in Relation of Kidney and Liver Damage in Rats.

PubMed

Aydemir, Duygu; Karabulut, Gözde; Şimşek, Gülsu; Gok, Muslum; Barlas, Nurhayat; Ulusu, Nuriye Nuray

2018-04-13

Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of mineral and bone disorders in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus of long duration.

PubMed

Biragova, Margarita S; Gracheva, Svetlana A; Glazunova, Alexandra M; Martynov, Sergey A; Ulaynova, Irina N; Ilyin, Alexandr V; Philippov, Yury I; Musaeva, Guliya M; Shamkhalova, Minara S; Shestakova, Marina V

2016-08-01

The objective of our study was to evaluate the role of mineral and bone metabolism disorders associated with chronic kidney disease (MBD-CKD) in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus (T1DM) of long duration. We investigated 96 patients with T1DM of long duration, with CKD at different stages (0-5), including patients on hemodialysis (HD) and with kidney transplantation (KT). Along with overall clinical examination, we assessed markers of MBD (calcium, phosphorus, parathormone, vitamin D, fibroblast growth factor (FGF) 23) and levels of cardiac injury marker (atrial natriuretic peptide, NT-proBNP). Multispiral computer tomography with Agatston index calculation was also included. Decreased kidney function was associated with increased of levels phosphorus, parathormone, FGF 23, and vitamin D deficiency, with the highest deviation from the reference ranges seen in patients on HD with a very high risk of cardiovascular events. In KT patients with satisfactory graft function, these parameters were at the same levels as in patients with CKD stages 0-4. Progression of cardiovascular pathology was accompanied by elevation of NT-proBNP levels as CKD duration increased, decreased glomerular filtration rate, and were correlated with the main parameters of mineral homeostasis. The severity of coronary arteries calcification was associated with patient age and duration of T1DM and arterial hypertension. Development and progression of kidney dysfunction is accompanied by MBD, a significant factor in progression of cardiac pathology, which remains a major cause of mortality in this patient population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Home-based versus center-based aerobic exercise on cardiopulmonary performance, physical function, quality of life and quality of sleep of overweight patients with chronic kidney disease.

PubMed

Aoike, Danilo Takashi; Baria, Flavia; Kamimura, Maria Ayako; Ammirati, Adriano; Cuppari, Lilian

2018-02-01

The association between chronic kidney disease (CKD) and obesity can decrease the patients' cardiopulmonary capacity, physical functioning and quality of life. The search for effective and practical alternative methods of exercise to engage patients in training programs is of great importance. Therefore, we aimed to compare the effects of home-based versus center-based aerobic exercise on the cardiopulmonary and functional capacities, quality of life and quality of sleep of overweight non-dialysis-dependent patients with CKD (NDD-CKD). Forty sedentary overweight patients CKD stages 3 and 4 were randomly assigned to an exercise group [home-based group (n = 12) or center-based exercise group (n = 13)] or to a control group (n = 15) that did not perform any exercise. Cardiopulmonary exercise test, functional capacity tests, quality of life, quality of sleep and clinical parameters were assessed at baseline, 12 and 24 weeks. The VO 2peak and all cardiopulmonary parameters evaluated were similarly improved (p < 0.05) after 12 and 24 weeks in both exercise groups. The functional capacity tests improved during the follow-up in the home-based group (p < 0.05) and reached values similar to those obtained in the center-based group. The benefits achieved in both exercise groups were also reflected in improvement of quality of life and sleep (p < 0.05). No differences were observed between the exercise groups, and no changes in any of the parameters investigated were found in the control group. Home-based aerobic training was as effective as center-based training in improving the physical and functional capabilities, quality of life and sleep in overweight NDD-CKD patients.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney

PubMed Central

Engbersen, Richard; Moons, Miek M; Wouterse, Alfons C; Dijkman, Henry B; Kramers, Cees; Smits, Paul; Russel, Frans G M

2000-01-01

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 μM) and glibenclamide (10 μM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3±1.5 for hypoxic perfusions vs 4.9±1.6 for normoxic perfusions, mean±s.e.mean, P<0.05), which could be completely restored by 200 μM tolbutamide (5.7±0.4 for tolbutamide vs 14.3±1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220±100 mU for tolbutamide vs 1220±160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 μM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations. PMID:10928974

[The phylogenetic theory of pathology. The arterial hypertension--a test of metabolic disorder. The biological basis of damage of target organs (a lecture)].

PubMed

Titov, V N

2013-05-01

The increase of blood tension is a diagnostic test of disorders of homeostasis, trophology, endoecology and adaptation in paracrine regulated coenosis of cells. This conditions results in disorder of microcirculation in the distal section of arterial race and in compensatory increase of blood tension in its proximal section. The increase of blood tension disturbs the function of paracrine coenosis of cells which have one's own system of hemo- and hydrodynamics such as brain with system of spinal liquor and kidneys with local pool of primary urine. They counteract the rise of blood tension and activate local, humoral system of renin-angiotensin-II increasing peripheral resistance to blood flow. At that, the compensatory blood tension becomes even higher. The aldosterone and natriuretic peptides are functional synergists. So, they preserve and excrete ions of Na+ and support the stability of unified pool of intercellular medium ("Inner Ocean" of organism) where all cells live. The parameters of this pool are limited most strictly in vivo. If at the level of nephron the conditions are formed that can alter the parameters of unified pool of intercellular medium the vasomotor center rises blood tension from the level of organism "forcing" nephrons to re-establish the parameters of this pool and normalize the biological functions and biological reactions. The blood pressure increase under pathology of kidneys is caused because of pathological compensation at the level of organism mediated by vegetal nervous system and dictated by necessity to preserve the parameters of inner medium of organism.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

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

Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

2012-01-15

Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox statusmore » in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter. ►Oxidatively modified proteins in renal mitochondria from diabetic rats.« less

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Cadaveric renal preservation with hyperosmolar, intracellular hypothermic washout solution and cold storage.

PubMed

Diethelm, A G; Blackstone, E H

1978-07-01

All 54 kidneys obtained from heart-beating cadavers functioned when preserved by a brief washout using a hypothermic, hyperosmolar, hyperkalemic perfusate, followed by cold storage. The duration of preservation ranged from two hours and 57 minutes to 39 hours and 47 minutes. Two other kidneys retrieved from a nonheart-beating cadaver and preserved by the same technique failed to function because of irreversible acute tubular necrosis. Fifty-six consecutive transplant patients were divided into four groups according to the period of preservation. There was no correlation between graft rejection, frequency of post-transplant dialysis, long term graft function and survival time, when the duration of preservation was less than 24 hours. The advantages of this technique included technical simplicity, low cost, minimal risk of graft infection and easy transportation. The two primary disadvantages were an apparent 24 to 30 hour limit of organ preservation with prompt function and the inability to determine intrarenal perfusion pressure during preservation, thereby missing an important parameter of graft viability.

Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney oxidative stress in rats: In vivo investigation and LC-MS analysis.

PubMed

Katanić, Jelena; Matić, Sanja; Pferschy-Wenzig, Eva-Maria; Kretschmer, Nadine; Boroja, Tatjana; Mihailović, Vladimir; Stanković, Vesna; Stanković, Nevena; Mladenović, Milan; Stanić, Snežana; Mihailović, Mirjana; Bauer, Rudolf

2017-01-01

Filipendula ulmaria, known as meadowsweet, is a perennial herb found in wild and cultivated habitats in Europe and Asia. Usage of F. ulmaria in traditional medicine is based on diuretic, astringent, antirheumatic, and anti-inflammatory properties of this plant. Exposure to cisplatin at a dose of 7.5 mg/kg caused significant increase in serum parameters of liver and kidneys function and tissue oxidative stress markers along with some histopathological changes in liver and kidney tissues of experimental rats, as well as high level of genotoxicity. Administration of F. ulmaria extracts in three different concentrations (100, 200, and 400 mg/kg/day) for 10 days resulted in a reduction of oxidative stress in tissues and decrease of serum parameters. Moreover, tested extracts attenuated the genotoxicity of cisplatin in reverse dose-dependent manner. F. ulmaria extracts had no in vitro cytotoxic activity at all applied concentrations (IC 50  > 50 μg/mL). Tested extracts, rich in polyphenolic compounds, attenuate cisplatin-induced liver and kidney oxidative stress, reduce tissue damage, and enhance the antioxidative status of experimental animals during cisplatin application. Therefore, F. ulmaria extracts may be used as supportive agent for the prevention and amelioration of cisplatin side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Iron isotopic composition of blood serum in anemia of chronic kidney disease.

PubMed

Anoshkina, Yulia; Costas-Rodríguez, Marta; Speeckaert, Marijn; Van Biesen, Wim; Delanghe, Joris; Vanhaecke, Frank

2017-05-24

Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with CKD and/or iron disorders showed a heavier serum Fe isotopic composition than controls. Many clinical parameters used for the diagnosis and follow-up of anemia correlated significantly with the serum Fe isotopic composition. In contrast, no relation was observed between the serum Fe isotopic composition and the estimated glomerular filtration rate as a measure of kidney function. Among the CKD patients, the serum Fe isotopic composition was substantially heavier in the occurrence of ID anemia, while erythropoietin-related anemia did not exert this effect. The Fe isotopic composition can thus be useful for distinguishing these different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin-related anemia.

Quantitative and semi-quantitative histopathological examination of renal biopsies in healthy individuals, and associations with kidney function.

PubMed

Bar, Yael; Barregard, Lars; Sallsten, Gerd; Wallin, Maria; Mölne, Johan

2016-05-01

This study assesed the prevalence of histopathological changes in renal biopsies from healthy individuals, and the association with age, sex and smoking. Donor biopsies from 109 subjects were obtained from living kidney donors, and blood and urine samples were collected together with medical history. All biopsies were scored according to the Banff '97 classification with some modifications. The parameters included in this study were tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, arteriolohyalinosis and a sclerosis score. An alternative scoring system for tubular atrophy was examined (using ≤5% rather than <1% as a cut-off for grade 0). Glomerular filtration rate was measured in most cases as chromium ethylenediaminetetra-acetic acid (Cr-EDTA) clearance. Age was a significant predictor for tubular atrophy, fibrosis and sclerosis. Pack-years of smoking increased the risk of tubular atrophy, fibrosis and arteriolohyalinosis. The alternative scoring of tubular atrophy showed a stronger association with smoking, but a weaker association with age, compared with the original one. Limited histopathological changes are common in healthy kidney donors around 50 years of age with normal kidney function. We propose that a cut-off of ≤5% yields a better definition of grade 0 tubular atrophy compared with the established cut-off of >0%. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Radionuclides in nephrology

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

Lausanne, A.B.D.

In 47 expert contributions, this volume provides a summary of the latest research on radionuclides in nephro-urology together with current and new clinical applications especially in renovascular hypertension, kidney transplantation, and metabolic and urological diseases. In addition, attention is given to aspects of basic renal physiology and function and possible applications of nuclear magnetic resonance and spectroscopy in nephro-urology. New testing procedures which promise to improve diagnosis, and new radiopharmaceuticals are described. The reports are divided into eight sections, the first of which features studies on the renin-angiotensin system, cisplatin, atrial natriuretic factor and determining plasma oxalate. Four papers describemore » a number of new radiopharmaceuticals which have the potential to replace hippuran. In the third section, radionuclide methods for the measurement of renal function parameters are discussed. The book then focuses on the potential role of captopril in the improved diagnosis of renovascular hypertension. Applications of nuclear magnetic resonance and spectroscopy are demonstrated in the diagnosis of acute pyelonephritis, kidney assessment after lithotripsy, kidney evaluation prior to transplantation, and in monitoring renal ischemia during hypotension.« less

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.

Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats

PubMed Central

Visnagri, Asjad; Adil, Mohammad; Kandhare, Amit D.; Bodhankar, Subhash L.

2015-01-01

Background: Renal artery occlusion (RAO) induced hypertension is a major health problem associated with structural and functional variations of the renal and cardiac vasculature. Naringin a flavanone glycoside derived possesses metal-chelating, antioxidant and free radical scavenging properties. Objective: The objective of this study was to investigate the antihypertensive activity of naringin in RAO induced hypertension in rats. Material and Methods: Male Wistar rats (180-200 g) were divided into five groups Sham, RAO, naringin (20, 40 and 80 mg/kg). Animals were pretreated with naringin (20, 40 and 80 mg/kg p.o) for 4 weeks. On the last day of the experiment, left renal artery was occluded with renal bulldog clamp for 4 h. After assessment of hemodynamic and left ventricular function various biochemical (superoxide dismutase [SOD], glutathione [GSH] and malondialdehyde [MDA]) and histological parameters were determined in the kidney. Results: RAO group significantly (P < 0.001) increased hemodynamic parameters at 15, 30 and 45 min of clamp removal. Naringin (40 and 80 mg/kg) treated groups showed a significant decrease in hemodynamic parameters at 15 min. after clamp removal that remained sustained for 60 min. Naringin (40 and 80 mg/kg) treated groups showed significant improvement in left ventricular function at 15, 30 and 45 min after clamp removal. Alteration in level of SOD, GSH and MDA was significantly restored by naringin (40 and 80 mg/kg) treatment. It also reduced histological aberration induced in kidney by RAO. Conclusion: It is concluded that the antihypertensive activity of naringin may result through inhibition of oxidative stress. PMID:25883516

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of increased pressure during pulsatile pump perfusion of deceased donor kidneys in transplantation.

PubMed

Patel, S K; Pankewycz, O G; Weber-Shrikant, E; Zachariah, M; Kohli, R; Nader, N D; Laftavi, M R

2012-09-01

Pulsatile pump perfusion of potential kidneys for transplantation is known to decrease the rate of delayed graft function (DGF) and improve their 1-year survival. Flow and resistance parameters are often used to determine the suitability of kidneys for transplantation. Kidneys with low flow rates are often subjected to higher pressures to improve flow. This study evaluated the effect of higher pump pressures on posttransplant renal function. We performed a retrospective analysis of 73 deceased donor kidneys preserved using pump perfusion (LifePort) at our center between May 2006 and September 2009. We calculated the mean pump pressure (MP) for the duration of perfusion of each kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with the following formula: (MP = DP + 1/3 (SP - DP). The kidneys were divided into a low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff value of 23 mm Hg. The two groups were then compared for differences in perfusion dynamics and primary endpoints including DGF and 1-year graft survival. Statistical analysis was performed using paired Student t test and chi-square analysis. The two groups were comparable for donor age, extended criteria, sensitization, and cold ischemic times. They differed significantly in higher initial (0.65 ± 0.4 versus 0.4 ± 0.2, P = .01), average (0.25 ± 0.08 versus 0.18 ± 0.06, P = .0006), and terminal resistance (0.21 ± 0.07 versus 0.17 ± 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006) with similar 1-year graft survival (87.5% versus 89%, P = .7). Perfusate flow through a kidney can be improved by increasing pressure settings to overcome elevated resistance. This maneuver was not associated with a lower rate of DGF after transplantation. One-year graft survival remained unaffected. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative effectiveness of liver transplant strategies for end-stage liver disease patients on renal replacement therapy.

PubMed

Chang, Yaojen; Gallon, Lorenzo; Jay, Colleen; Shetty, Kirti; Ho, Bing; Levitsky, Josh; Baker, Talia; Ladner, Daniela; Friedewald, John; Abecassis, Michael; Hazen, Gordon; Skaro, Anton I

2014-09-01

There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy. © 2014 American Association for the Study of Liver Diseases.

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.

PubMed

Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2016-10-01

The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

PubMed

Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; Li, Jian H; Wess, Jürgen; Svelto, Maria

2014-07-01

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice

PubMed Central

Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; H. Li, Jian; Wess, Jürgen; Svelto, Maria

2014-01-01

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI. PMID:24522493

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Effects of combination of aliskiren and pentoxyfylline on renal function in the rat remnant kidney model of chronic renal failure.

PubMed

Soni, Hitesh M; Patel, Praful P; Patel, Savan; Rath, Akshyaya C; Acharya, Aviseka; Trivedi, Harshkant D; Jain, Mukul R

2015-01-01

The aim was to investigate the nephroprotective effect of combination of aliskiren (ASK), a direct renin inhibitor and pentoxifylline (PTX), inhibitor of tumor necrotic factor-alpha (TNF-alpha), in rat remnant kidney model of chronic kidney disease (CKD). Nephrectomized (NPX) rats were treated with ASK (10 mg/kg, p.o.), PTX (100 mg/kg, p.o.), and combination of PTX + ASK once daily for 28 days. We have performed analysis of various renal injury parameters after 4 weeks of treatment. Treatment with PTX, ASK and combination showed significant improvement in urea, creatinine and total protein in plasma when compared with vehicle treated group in NPX rats. ASK and combination of PTX + ASK elicited significant reduction in blood pressure but PTX alone did not produce blood pressure reduction. ASK treatment showed significant elevation in TNF-alpha, whereas PTX and ASK + PTX showed significant reduction in TNF-alpha in plasma. Histopathologically, the extent of the kidney injury was similar in NPX + vehicle and NPX + ASK-treated rats. PTX and ASK + PTX-treated group showed lesser extent of kidney injury. There was good correlation of mRNA expression levels of kidney injury molecule-1 and bradykinin B1 receptor data with histopathological findings in kidney samples and elevated TNF-alpha levels in plasma. We conclude that combination of PTX + ASK may be better therapeutic intervention for nephroprotection in CKD patients.

Vitamin B12 and folate levels in healthy Swiss senior citizens: a prospective study evaluating reference intervals and decision limits.

PubMed

Risch, Martin; Meier, Dominik W; Sakem, Benjamin; Medina Escobar, Pedro; Risch, Corina; Nydegger, Urs; Risch, Lorenz

2015-07-11

The vitamin B12 and folate status in nonanaemic healthy older persons needs attention the more so as decrease in levels may be anticipated from reduced haematinic provision and/or impaired intestinal uptake. A total of 1143 subjectively healthy Swiss midlands participants (637 females and 506 males), ≥60 years of age were included in this study. Levels of vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), homocysteine (Hcy), serum folate, red blood cell (RBC) folate were measured. Further, Fedosov's wellness score was determined. Associations of age, gender, and cystatin C/creatinine-based estimated kidney function, with the investigated parameters were assessed. Reference intervals were calculated. Further, ROC analysis was done to assess accuracy of the individual parameters in recognizing a deficient vitamin B12 status. Finally, decision limits for sensitive, specific and optimal recognition of vitamin B12 status with individual parameters were derived. Three age groups: 60-69, 70-79 and ≥ 80 had median B12 (pmol/L) levels of 237, 228 and 231 respectively (p = 0.22), holoTC (pmol/L) of 52, 546 and 52 (p = 0.60) but Hcy (μmol/L) 12, 15 and 16 (p < 0.001), MMA (nmol/L) 207, 221 and 244 (p < 0.001). Hcy and MMA (both p < 0.001), but not holoTC (p = 0.12) and vitamin B12 (p = 0.44) were found to be affected by kidney function. In a linear regression model Fedosov's wellness score was independently associated with kidney function (p < 0.001) but not with age. Total serum folate and red blood cell (RBC) folate drift apart with increasing age: whereas the former decreases (p = 0.01) RBC folate remains in the same bandwidth across all age groups (p = 0.12) A common reference interval combining age and gender strata can be obtained for vitamin B12 and holoTC, whereas a more differentiated approach seems warranted for serum folate and RBC folate. Whereas the vitamin B12 and holoTC levels remain steady after 60 years of age, we observed a significant increment in MMA levels accompanied by increments in Hcy; this is better explained by age-related reduced kidney function than by vitamin B12 insufficiency. Total serum folate levels but not RBC folate levels decreased with progressing age.

Atherosclerotic renovascular disease among hypertensive adults

PubMed Central

Davis, Ross P.; Pearce, Jeffrey D.; Craven, Timothy E.; Moore, Phillip S.; Edwards, Matthew S.; Godshall, Christopher J.; Hansen, Kimberley J.

2010-01-01

Purpose Ths report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan. Methods From Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change. Results A total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 ± 12.2 years) provided 1351 studies (mean, 3.2 ± 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 ± 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year ± standard error of the mean [SEM]: 0.042 ± 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (−0.152 ± 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression. Conclusion A total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications. PMID:19700093

Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study.

PubMed

Alkhedaide, Adel; Soliman, Mohamed Mohamed; Salah-Eldin, Alaa-Eldin; Ismail, Tamer Ahmed; Alshehiri, Zafer Saad; Attia, Hossam Fouad

2016-06-01

The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca‑Cola, Pepsi and 7‑Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi‑quantitative reverse transcription polymerase chain reaction was used to observe the changes in the expression of genes in the liver and kidney, which are associated with oxidative stress resistance. Histopathological investigations were performed to determine the changes in bone, liver and kidney tissues using hematoxylin and eosin stains. SDC affected liver, kidney and bone function biomarkers. Soft drinks increased oxidative stress, which is represented by an increase in malondialdehyde and a decrease in antioxidant levels. SDC affected serum mineral levels, particularly calcium and phosphorus. Soft drinks downregulated the expression levels of glutathione‑S‑transferase and super oxide dismutase in the liver compared with that of control rats. Rats administered Coca‑Cola exhibited a hepatic decrease in the mRNA expression of α2‑macroglobulin compared with rats administered Pepsi and 7‑Up. On the other hand, SDC increased the mRNA expression of α1‑acid glycoprotein. The present renal studies revealed that Coca‑Cola increased the mRNA expression levels of desmin, angiotensinogen and angiotensinogen receptor compared with the other groups, together with mild congestion in renal histopathology. Deleterious histopathological changes were reported predominantly in the bone and liver of the Coca‑Cola and Pepsi groups. In conclusion, a very strict caution must be considered with SDC due to the increase in oxidative stress biomarkers and disruption in the expression of certain genes associated with the bio‑vital function of both the liver and kidney.

Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study

PubMed Central

ALKHEDAIDE, ADEL; SOLIMAN, MOHAMED MOHAMED; SALAH-ELDIN, ALAA-ELDIN; ISMAIL, TAMER AHMED; ALSHEHIRI, ZAFER SAAD; ATTIA, HOSSAM FOUAD

2016-01-01

The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca-Cola, Pepsi and 7-Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi-quantitative reverse transcription polymerase chain reaction was used to observe the changes in the expression of genes in the liver and kidney, which are associated with oxidative stress resistance. Histopathological investigations were performed to determine the changes in bone, liver and kidney tissues using hematoxylin and eosin stains. SDC affected liver, kidney and bone function biomarkers. Soft drinks increased oxidative stress, which is represented by an increase in malondialdehyde and a decrease in antioxidant levels. SDC affected serum mineral levels, particularly calcium and phosphorus. Soft drinks downregulated the expression levels of glutathione-S-transferase and super oxide dismutase in the liver compared with that of control rats. Rats administered Coca-Cola exhibited a hepatic decrease in the mRNA expression of α2-macroglobulin compared with rats administered Pepsi and 7-Up. On the other hand, SDC increased the mRNA expression of α1-acid glycoprotein. The present renal studies revealed that Coca-Cola increased the mRNA expression levels of desmin, angiotensinogen and angiotensinogen receptor compared with the other groups, together with mild congestion in renal histopathology. Deleterious histopathological changes were reported predominantly in the bone and liver of the Coca-Cola and Pepsi groups. In conclusion, a very strict caution must be considered with SDC due to the increase in oxidative stress biomarkers and disruption in the expression of certain genes associated with the bio-vital function of both the liver and kidney. PMID:27121771

The value of Doppler ultrasound in predicting delayed graft function occurrence after kidney transplantation.

PubMed

Mocny, Grzegorz; Bachul, Piotr; Chang, Ea-Sle; Kulig, Piotr

The aim of this study was to assess the predictive value of blood flow velocity and vascular resistance measured by Doppler ultrasound in terms of pulsatility index (PI) and resistive index (RI) respectively, in the occurrence of delayed graft function (DGF) after kidney transplantation. This prospective study enrolled kidney transplant recipients operated from January 2005 to April 2009 in the 1st Department of General, Oncological and Gastroenterological Surgery, Jagiellonian University Medical College, Kraków, Poland. The medical records of 53 kidney transplant recipients from deceased donors were reviewed. PI and RI values of the graft arcuate artery were calculated immediately after blood flow restoration and on the 1st, 2nd, 4th and 8th post-operative day. DGF was observed in 20 patients (37.7%), while 33 patients (62.3%) had immediate restoration of the kidney function. The mean intraoperative values of RI and PI from patients with DGF were significantly higher in comparison to patients without DGF (0.9 vs. 0.74, p <0.001; 1.76 vs. 1.54, p = 0.019, respectively). Post-operatively, the RI and PI values remained stable and significantly higher in DGF group. The highest sensitivity of RI to predict DGF occurrence was observed intraoperatively and on the first postoperative day, with values of 77.8% and 72.2%, respectively. The risk of DGF occurrence with intraoperative RI value ≥0.9 increased by 13-fold, and with intraoperative PI value ≥1.9 by 12-fold. This increase was even more prominent during the first post-operative day with RI value ≥0.9 or PI value ≥1.9 with 19-fold increase in the risk of DGF occurrence. According to our study, the utilization of Doppler ultrasound with measurement of hemodynamic parameters (PI, RI), play a crucial role in predicting the outcomes of kidney transplantation.

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Health related quality of life in renal transplantation: 2 years of longitudinal follow-up.

PubMed

Costa-Requena, Gema; Cantarell, M Carmen; Moreso, Francesc; Parramon, Gemma; Seron, Daniel

2017-08-10

Health related quality of life (HRQoL) is recognized as an outcome measure in kidney transplantation. In this study was assessed changes on HRQoL and kidney-specific symptoms, also was evaluated the effect of socio-demographic and clinical parameters on patient's perceived HRQoL. A longitudinal study was done, at 5 time-points over 2 years after transplantation. To evaluate HRQoL the Kidney Disease Quality of Life Questionnaire Short Form was administrated, and Hospital Anxiety and Depression Scale was used to assess psychological distress. At 6-months after transplantation, patients had similar HRQoL scores compared to the general population. The improvement on effects of kidney disease domain could be considered as large (η 2 =0.29), and medium on burden of kidney disease domain (η 2 =0.12), work status domain (η 2 =0.12), and sexual function domain (η 2 =0.13). Psychological distress, depressive symptoms, haemoglobin, and serum creatinine had significant influence on patient's perceived HRQoL over 2 years after transplantation. An improvement of HRQoL was observed on general and specific-targeted symptoms over 2 years after renal transplantation. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.

PubMed

Wilcox, Joanne; Waite, Chantelle; Tomlinson, Lyndsey; Driscoll, Joanne; Karim, Asra; Day, Edward; Sharif, Adnan

2016-08-22

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).

A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors

PubMed Central

Corridon, Peter R.; Rhodes, George J.; Leonard, Ellen C.; Basile, David P.; Gattone, Vincent H.; Bacallao, Robert L.

2013-01-01

Gene therapy has been proposed as a novel alternative to treat kidney disease. This goal has been hindered by the inability to reliably deliver transgenes to target cells throughout the kidney, while minimizing injury. Since hydrodynamic forces have previously shown promising results, we optimized this approach and designed a method that utilizes retrograde renal vein injections to facilitate transgene expression in rat kidneys. We show, using intravital fluorescence two-photon microscopy, that fluorescent albumin and dextrans injected into the renal vein under defined conditions of hydrodynamic pressure distribute broadly throughout the kidney in live animals. We found injection parameters that result in no kidney injury as determined by intravital microscopy, histology, and serum creatinine measurements. Plasmids, baculovirus, and adenovirus vectors, designed to express EGFP, EGFP-actin, EGFP-occludin, EGFP-tubulin, tdTomato-H2B, or RFP-actin fusion proteins, were introduced into live kidneys in a similar fashion. Gene expression was then observed in live and ex vivo kidneys using two-photon imaging and confocal laser scanning microscopy. We recorded widespread fluorescent protein expression lasting more than 1 mo after introduction of transgenes. Plasmid and adenovirus vectors provided gene transfer efficiencies ranging from 50 to 90%, compared with 10–50% using baculovirus. Using plasmids and adenovirus, fluorescent protein expression was observed 1) in proximal and distal tubule epithelial cells; 2) within glomeruli; and 3) within the peritubular interstitium. In isolated kidneys, fluorescent protein expression was observed from the cortex to the papilla. These results provide a robust approach for gene delivery and the study of protein function in live mammal kidneys. PMID:23467422

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.

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

Hypothermic machine perfusion in kidney transplantation.

PubMed

De Deken, Julie; Kocabayoglu, Peri; Moers, Cyril

2016-06-01

This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors. HMP has undergone a renaissance in recent years. This renewed interest has arisen parallel to a shift in paradigms; not only optimal preservation of an often marginal quality graft is required, but also improved graft function and tools to predict the latter are expected from HMP. The focus of attention in this field is currently drawn to the protection of endothelial integrity by means of additives to the perfusion solution, improvement of the HMP solution, choice of temperature, duration of perfusion, and machine settings. HMP may offer the opportunity to assess aspects of graft viability before transplantation, which can potentially aid preselection of grafts based on characteristics such as perfusate biomarkers, as well as measurement of machine perfusion dynamics parameters. HMP has proven to be beneficial as a kidney preservation method for all types of renal grafts, most notably those retrieved from extended criteria donors. Large numbers of variables during HMP, such as duration, machine settings and additives to the perfusion solution are currently being investigated to improve renal function and graft survival. In addition, the search for biomarkers has become a focus of attention to predict graft function posttransplant.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.

PubMed

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette; Ezquer, Marcelo

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus

PubMed Central

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected. PMID:26167475

TH-EF-207A-04: A Dynamic Contrast Enhanced Cone Beam CT Technique for Evaluation of Renal Functions

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

Wang, Z; Shi, J; Yang, Y

Purpose: To develop a simple but robust method for the early detection and evaluation of renal functions using dynamic contrast enhanced cone beam CT technique. Methods: Experiments were performed on an integrated imaging and radiation research platform developed by our lab. Animals (n=3) were anesthetized with 20uL Ketamine/Xylazine cocktail, and then received 200uL injection of iodinated contrast agent Iopamidol via tail vein. Cone beam CT was acquired following contrast injection once per minute and up to 25 minutes. The cone beam CT was reconstructed with a dimension of 300×300×800 voxels of 130×130×130um voxel resolution. The middle kidney slices in themore » transvers and coronal planes were selected for image analysis. A double exponential function was used to fit the contrast enhanced signal intensity versus the time after contrast injection. Both pixel-based and region of interest (ROI)-based curve fitting were performed. Four parameters obtained from the curve fitting, namely the amplitude and flow constant for both contrast wash in and wash out phases, were investigated for further analysis. Results: Robust curve fitting was demonstrated for both pixel based (with R{sup 2}>0.8 for >85% pixels within the kidney contour) and ROI based (R{sup 2}>0.9 for all regions) analysis. Three different functional regions: renal pelvis, medulla and cortex, were clearly differentiated in the functional parameter map in the pixel based analysis. ROI based analysis showed the half-life T1/2 for contrast wash in and wash out phases were 0.98±0.15 and 17.04±7.16, 0.63±0.07 and 17.88±4.51, and 1.48±0.40 and 10.79±3.88 minutes for the renal pelvis, medulla and cortex, respectively. Conclusion: A robust method based on dynamic contrast enhanced cone beam CT and double exponential curve fitting has been developed to analyze the renal functions for different functional regions. Future study will be performed to investigate the sensitivity of this technique in the detection of radiation induced kidney dysfunction.« less

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

The Importance of Residual Kidney Function in Haemodialysis Patients.

PubMed

Kong, Jessica; Davies, Matthew; Mount, Peter

2018-06-19

In contrast to peritoneal dialysis, residual kidney function is commonly disregarded for haemodialysis patients, and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of residual kidney function in haemodialysis patients associate with better outcomes including survival, total solute clearance, nutrition, inflammation, and fluid balance. This review aims to summarise the clinical effects of residual kidney function specifically in haemodialysis patients. Some level of residual kidney function is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on haemodialysis for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve residual kidney function in haemodialysis patients, although it has been observed that intensive haemodialysis regimens in incident haemodialysis patients appear to accelerate residual kidney function decline. Residual kidney function is not commonly factored in to haemodialysis prescription and measures of adequacy, despite the fact that some guidelines such as KDOQI and European Best Practice Guidelines suggest that it is reasonable to do. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections, and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of haemodialysis with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of residual kidney function in haemodialysis patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

No effect of mercury exposure on kidney function during ongoing artisanal gold mining activities in Colombia.

PubMed

Rodríguez, Luz Helena Sánchez; Rodríguez-Villamizar, Laura Andrea; Flórez-Vargas, Oscar; Fiallo, Yolanda Vargas; Ordoñez, Álvaro; Gutiérrez, Myriam Del Carmen

2017-01-01

This cross-sectional study examined whether people who are exposed to mercury (Hg) vapours in ongoing artisanal gold mining activities have alteration in kidney function monitoring parameters. The study enrolled 164 miners and 127 participant controls. The Hg concentrations for miners and control participants were measured in blood (B-Hg; median 7.0 vs. 2.5 µg/L), urine (U-Hg; median 3.9 vs. 1.5 µg/g creatinine) and hair (H-Hg; median 0.8 vs. 0.4 µg/g hair). The biomarkers of renal function were creatinine, albumin and excretion of β-2 microglobulin. Glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation. Significant statistical differences were found in Hg concentrations and eGFR levels between the two study groups ( p < 0.01) but not with the other biomarkers of renal function. A multiple regression model was applied to explore the relationship of eGFR levels and Hg concentrations. However, no association was found between the prevalence of reduced eGFR (<71.96 mL/min/1.73 m 2 ) and the B-Hg or U-Hg levels after adjustment for covariates. Nevertheless, it was observed that having B-Hg levels above 10 µg Hg/L decreased the eGFR by 1.7 mL/min/1.73 m 2 (confidence interval 95% -5.1 to 1.7) compared to having levels below 2.0 µg Hg/L. Our results found no support for kidney damage associated with Hg vapour exposure in ongoing artisanal gold mining, whose population has a level of Hg exposure from low to moderate (B-Hg from 3.4 to 11.0 µg/L and U-Hg from 1.3 to 9.6 µg/g creatinine).

Biolasol: novel perfusion and preservation solution for kidneys.

PubMed

Cierpka, L; Ryszka, F; Dolińska, B; Smorąg, Z; Słomski, R; Wiaderkiewicz, R; Caban, A; Budziński, G; Oczkowicz, G; Wieczorek, J

2014-10-01

Biolasol solution (Pharmaceutical Research and Production Plant "Biochefa," Sosnowiec, Poland) is a novel extracellular perfusion and ex vivo hypothermic kidney preservation solution. It ensures maintenance of homeostasis, reduces tissue edema, has low viscosity, and allows the graft to preserve structural and functional integrity. It minimizes ischemia-reperfusion damage. Perfundates from control and transplanted kidneys flushed with Biolasol or ViaSpan solutions (Arkas, Warszawa, Poland) were analyzed. Parameters of serum and urine collected from 12 pigs after auto-transplantation were also analyzed. Renal medulla was investigated for structural alterations by analyzing hematoxylin and eosin-stained slides. The mean survival time of pigs after the auto-transplantation procedure was the measure for the novel Biolasol solution effectiveness. We observed a statistically significant decrease in marker enzyme levels alanine transaminase, aspartate transaminase, lactic dehydrogenase, and ions (Na and K) in pigs with grafts flushed with Biolasol. Histopathologic examination revealed that the renal cortex structure was not damaged after the use of Biolasol solution. Biolasol solution protects kidneys against ischemia damage and does not differ significantly from the "golden standard" ViaSpan solution.

Nephroprotective potential of artichoke leaves extract against gentamicin in rats: Antioxidant mechanisms.

PubMed

Khattab, Hala Ah; Wazzan, Maha Am; Al-Ahdab, Maha A

2016-09-01

Nephrotoxicity represents a major health problem. This study aims to determine nephroprotective of artichoke leaves extract (ALE) against gentamicin (GM) injection in male rats. Rats (n=30) were divided into; negative control, nephrotoxic (GM) injected intraperitoneally (i.p.) with GM (100 mg/kg b.wt/d for 10 days), and groups administered orally with ALE (200, 400 or 600 mg/kg b.wt/d) and injected with GM. The results revealed that, GM injection induced marked nephrotoxicity as evidenced by significant increase in kidney functions, albumin and potassium (K+), with significant decrease in serum levels of total protein and sodium (Na + ) as compared with negative control group. There was significant increase in malondialdehyde (MDA) level in GM group compared with negative control group. Renal examined tissues showed severe changes manifested by atrophy of glomerular tuft, necrosis of epithelial lining renal tubules with apoptosis of tubular epithelium and renal hemorrhage. Simultaneous administration of ALE during GM therapy protected kidney tissues as evidenced by normalization of kidney biochemical parameters and minimized the histopathological changes. Therefore, ALE has nephroprotective and antioxidant effects, thus could be beneficial for kidney patients.

Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups'.

PubMed

Mahmoudi, Asma; Ghorbel, Héla; Bouallegui, Zouhair; Marrekchi, Rim; Isoda, Hiroko; Sayadi, Sami

2015-01-01

Bisphenol A (BPA) is a chemical found in hard plastics and the coatings of food and drinks cans which can behave in a similar way to estrogen and other hormones in the human body. This study aimed to evaluate the significance of the treatment with oleuropein and hydroxytyrosol olive leaves rich extracts in reducing functional perturbations and oxidative stress arising from BPA treatment in livers and kidneys of lactating mother rats and their pups'. For this, four groups of lactating mothers were used: controls (group A), treated with bisphenol A (group B), treated with bisphenol A and oleuropein (group C) and with bisphenol A and hydroxytyrosol (group D). As results, we had found, in BPA treated group, either in mothers or in their pups', a significant decrease in morphological parameters, in catalase activity and in total antioxidant capacity associated to an increase in malondialdehyde levels in livers and kidneys. For these rats, the histological aspect showed, also, deep changes. Indeed, we had observed, in livers, hepatocellular necrosis associated to leucocytes infiltration and in kidneys tubular and glomerular necrosis. The co-treatments with BPA and oleuropein (group C) or with BPA and hydroxytyrosol (group D) ameliorate all morphological, biochemical and histological parameters as compared to BPA treated group B. The analysis of BPA and its derivatives with LC-MS/MS showed changes in their localizations between serum, livers or kidneys in all studied groups. In conclusion, the present study demonstrates the hepato-protective and reno-protective effects of oleuropein and hydroxytyrosol olive leaves extracts from BPA and its derivates toxicity. Copyright © 2015 Elsevier GmbH. All rights reserved.

Clinical Pharmacodynamics: Principles of Drug Response and Alterations in Kidney Disease.

PubMed

Keller, Frieder; Hann, Alexander

2018-05-16

Pharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is found, but pharmacodynamics is as important. Alterations of pharmacodynamic parameters are conceivable but only rarely reported in kidney failure. Sometimes surprising dosing adjustments are needed when pharmacodynamic concepts are brought into the decision process of which dose to choose. Pharmacokinetics and pharmacodynamics should both be considered when any dosing regimen is determined. Copyright © 2018 by the American Society of Nephrology.

Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study.

PubMed

Pietrzak-Nowacka, Maria; Safranow, Krzysztof; Bińczak-Kuleta, Agnieszka; Rózański, Jacek; Ciechanowski, Kazimierz; Ciechanowicz, Andrzej

2012-01-01

The aim of the study was to evaluate an association between the C49620T ABCC8 gene polymorphism and anthropometric, biochemical parameters, pancreatic β-cell function and insulin sensitivity among autosomal dominant polycystic kidney disease (ADPKD) patients. Forty-nine ADPKD patients (M/F: 19/30) and fifty healthy controls (M/F: 22/28) aged above 18 years, with normal kidney function and no diagnosis of diabetes, were enrolled into the study. The ABCC8 (SUR1) C49620T (IVS15-3C/T, rs1799854) genotypes were determined using a PCR-RFLP technique. In the ADPKD group among TT homozygous patients, total body fat content and percentage of fat in body weight were significantly lower than among C allele carriers (16.1 +/- 7.7 vs 22.9 +/- 7.1kg, p=0.04 and 22.8 +/- 6.5 vs 30.0 +/- 6.1%, p=0.001, respectively) while total body water was higher (58.4 +/- 4.3 vs 53.7 +/- 4.0kg, p=0.003). Among TT homozygous controls higher BMI values and LDL-cholesterol levels were observed if compared to C variant carriers (26.3 +/- 3.9 vs 23.8 +/3.4kg/m2 p=0.04 and 133.1 +/- 27.0 vs 114.3 +/- 35.2mg/dL, p=0.05, respectively), as well as higher area under curve of glucose concentrations (115.9 +/- 23.9 vs 102.7 +/- 25.2 mmol*h/L, p=0.046) during an oral glucose tolerance test. In the ADPKD group and among controls no association between the investigated polymorphism and secretory function of the pancreatic β-cells or insulin sensitivity was found. The C49620T ABCC8 polymorphism is associated with anthropometric risk factors for type 2 diabetes among ADPKD patients, with a protective effect of the TT genotype, but without influence on pancreatic β-cell secretory function or insulin sensitivity.

CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney.

PubMed

von Schrenck, T; Ahrens, M; de Weerth, A; Bobrowski, C; Wolf, G; Jonas, L; Jocks, T; Schulz, M; Bläker, M; Neumaier, M; Stahl, R A

2000-09-01

To evaluate the function of cholecystokinin B (CCKB)/gastrin receptors in the rat kidney, we identified the receptors by Northern blot and localized the receptors by immunohistochemistry. The functional effects of gastrin were studied under standardized in vitro conditions using the isolated perfused kidney. Rat kidneys were mounted in an organ bath by attaching the renal artery to a perfusion system. A catheter was inserted into the renal vein and the ureter to collect samples that were analyzed for the concentrations of electrolytes. After a preperfusion period, gastrin-17-I was given via the renal artery (10-8 to 10-6 mol/L). Subsequently, hemodynamic parameters (for example, perfusate flow) and changes in sodium and potassium absorption were determined. All data were subjected to a nonparametric analysis of variance and, in case of significant results, to subsequent paired comparisons by the a posteriori Wilcoxon test. Northern blot analysis detected CCKB receptor transcripts in total RNA isolated from kidneys. Immunohistochemistry localized CCKB receptors on tubules and collecting duct cells. Compared with controls, gastrin (10-6 mol/L) caused a decrease in the fractional sodium reabsorption (basal 80%, 10 minutes after application of gastrin 71%, after 20 minutes 62%, P < 0.05). This effect was inhibited by the CCKB receptor antagonist L-365,260. Gastrin decreased urinary potassium excretion at 10-8 and 10-6 mol/L [maximal decrease at 10-6 mol/L from baseline values (100%) to 49% after 10 minutes and to 69% after 20 minutes, P < 0.05, N = 6]. This effect was also abolished by the CCKB receptor antagonist L-365,260. Gastrin (10-6 mol/L) reduced perfusate flow by 31% (P < 0.05). CCKB receptors are expressed in the rat kidney on tubules and collecting ducts. These receptors mediate changes in renal potassium and sodium absorption. In addition, gastrin causes a decrease in perfusate flow, indicating that CCKB receptors might also modulate vascular resistance in the kidney.

Podocyte Depletion in Thin GBM and Alport Syndrome.

PubMed

Wickman, Larysa; Hodgin, Jeffrey B; Wang, Su Q; Afshinnia, Farsad; Kershaw, David; Wiggins, Roger C

2016-01-01

The proximate genetic cause of both Thin GBM and Alport Syndrome (AS) is abnormal α3, 4 and 5 collagen IV chains resulting in abnormal glomerular basement membrane (GBM) structure/function. We previously reported that podocyte detachment rate measured in urine is increased in AS, suggesting that podocyte depletion could play a role in causing progressive loss of kidney function. To test this hypothesis podometric parameters were measured in 26 kidney biopsies from 21 patients aged 2-17 years with a clinic-pathologic diagnosis including both classic Alport Syndrome with thin and thick GBM segments and lamellated lamina densa [n = 15] and Thin GBM cases [n = 6]. Protocol biopsies from deceased donor kidneys were used as age-matched controls. Podocyte depletion was present in AS biopsies prior to detectable histologic abnormalities. No abnormality was detected by light microscopy at <30% podocyte depletion, minor pathologic changes (mesangial expansion and adhesions to Bowman's capsule) were present at 30-50% podocyte depletion, and FSGS was progressively present above 50% podocyte depletion. eGFR did not change measurably until >70% podocyte depletion. Low level proteinuria was an early event at about 25% podocyte depletion and increased in proportion to podocyte depletion. These quantitative data parallel those from model systems where podocyte depletion is the causative event. This result supports a hypothesis that in AS podocyte adherence to the GBM is defective resulting in accelerated podocyte detachment causing progressive podocyte depletion leading to FSGS-like pathologic changes and eventual End Stage Kidney Disease. Early intervention to reduce podocyte depletion is projected to prolong kidney survival in AS.

Sub-chronic safety evaluation of aqueous extract of Alangium salvifolium (L.f.) Wangerin leaves in rats.

PubMed

Kapoor, Bhupinder; Kaur, Gagandeep; Gupta, Mukta; Gupta, Reena

2017-01-01

Conventionally, the juice and extract of Alangium salvifolium leaves have been used for the treatment of diabetes, wound healing, dog bite, and as a poultice in rheumatism. To carry out the sub-chronic toxicity and thereafter safety evaluation of A. salvifolium leaves. The aqueous extract of A. salvifolium leaves was administered orally at the doses of 200, 400, and 800 mg/kg/day for 90 days. All the animals were observed daily for general behavior, changes in body weight, food, and water consumption. At the end of the treatment period, biochemical and hematological parameters were analyzed; and the animals were sacrificed for histopathological examination of heart, lungs, liver, and kidney. The general behavior and water intake were normal in all the rats. The increase in body weight was observed in female rats of all the groups while body weight was decreased in high dose group animals of both sexes. Hematological parameters were not disturbed by the continuous use of extract. A significant decrease in glucose level was observed in intermediate- and high-dose group animals while urea and creatinine level were significantly high in animals of high-dose group. Although histopathological examination of most of the organs exhibited no structural changes, some tubal damage in kidneys was observed in high-dose group animals. The high dose of extract has shown mild signs of toxicity on kidney function test, but no toxic response was observed on hematological and liver biochemical parameters. The extract also exhibited hypoglycemic potential.

Impact of Momordica charantia extract on kidney function and structure in mice.

PubMed

Mardani, Saeed; Nasri, Hamid; Hajian, Shabnam; Ahmadi, Ali; Kazemi, Reyhane; Rafieian-Kopaei, Mahmoud

2014-01-01

Bitter Melon (BM) is known for its hypoglycemic effect and is commonly used in populations. This study examined the effects and safety of bitter melon fruit in laboratory mice. In this experimental study 70 male mice (25-30 gr) were randomly divided into 7 groups. The mice were injected intraperitoneally with single doses of 0, 100, 500, 1000, 2000 and 4000 mg/kg and multiple doses 500 mg/kg daily for 7 days. The mice were then observed for 72 hours before sacrificing. Immediately kidneys were taken out for histological examinations. Tubular cell vacuolization and flattening as well as hyaline casts, debris and dilatation of tubular lumen were the morphologic lesions which were assessed with scores from 0 to 4, while zero score addressed normal renal tissue. Serum samples were assayed for kidney function (creatinine; Cr and Blood Urea Nitrogen; BUN). Blood and bitter melon antioxidant activities were measured, too. Data were analyzed with Stata software (Stata Corp. 2011. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP)using ANOVA and Bonferroni tests. All single dose groups showed normal behavior after the dosing and no statistical changes were observed in blood parameters (p>0.05). Histological examinations revealed normal organ structures, however, the group treated for 7 days showed statistically a significant change in BUN (p=0.002) and a borderline significance in Cr (p=0.051). Administration of up to 4000 mg/kg did not have any effect on the mice kidney function and histology, however chronic administration were nephrotoxic. More studies with different dosage regimens are suggested.

Nutritional evaluation of raw and extruded kidney bean (Phaseolus vulgaris L. var. pinto) in chicken diets.

PubMed

Arija, I; Centeno, C; Viveros, A; Brenes, A; Marzo, F; Illera, J C; Silvan, G

2006-04-01

An experiment was conducted to study the effect of inclusion of different concentrations (0, 100, 200, and 300 g/kg) of raw kidney bean and extruded kidney bean in broiler chick (0 to 21 d of age) diets on performance, digestive organ sizes, protein and amino acid digestibilities, intestinal viscosity, cecal pH, and blood parameters. Data were analyzed as a 3 x 2 factorial arrangement with 3 levels of kidney bean with and without extrusion. Positive control without kidney bean was used. Increasing the kidney bean content in the diet reduced weight gain and consumption, and increased the feed-to-gain ratio. Relative pancreas, liver, and jejunum weights, and intestinal viscosity were increased in response to increasing kidney bean concentration in the diet. The inclusion of different concentrations of kidney bean did not affect the apparent ileal digestibility of essential and nonessential amino acids, except for Met, Phe, and Cys, which were increased. Increasing kidney bean in the diet did not affect blood parameters, except for total protein, which was increased, and for androstenedione and testosterone, which were reduced. Extrusion significantly improved weight gain, feed consumption, and feed conversion. Relative pancreas, liver, and jejunum weights were reduced and spleen weight, cecal and intestinal viscosity were increased by extrusion. Apparent ileal digestibility of crude protein and all essential and nonessential amino acids were improved by extrusion. Like-wise, extrusion increased significantly the concentrations of cholesterol, triglycerides, glucose, and testosterone. We concluded that the inclusion of kidney bean in chicken diets cause a negative effect on performance and CP and amino acid digestibilities, and modified digestive organ sizes, intestinal viscosity, cecal pH, and some blood parameters. These effects were counteracted by the extrusion of kidney bean. However, the inclusion of extruded kidney bean in a chick diet resulted in poorer performance compared with that obtained with a corn-soybean diet.

Application of the statistical process control method for prospective patient safety monitoring during the learning phase: robotic kidney transplantation with regional hypothermia (IDEAL phase 2a-b).

PubMed

Sood, Akshay; Ghani, Khurshid R; Ahlawat, Rajesh; Modi, Pranjal; Abaza, Ronney; Jeong, Wooju; Sammon, Jesse D; Diaz, Mireya; Kher, Vijay; Menon, Mani; Bhandari, Mahendra

2014-08-01

Traditional evaluation of the learning curve (LC) of an operation has been retrospective. Furthermore, LC analysis does not permit patient safety monitoring. To prospectively monitor patient safety during the learning phase of robotic kidney transplantation (RKT) and determine when it could be considered learned using the techniques of statistical process control (SPC). From January through May 2013, 41 patients with end-stage renal disease underwent RKT with regional hypothermia at one of two tertiary referral centers adopting RKT. Transplant recipients were classified into three groups based on the robotic training and kidney transplant experience of the surgeons: group 1, robot trained with limited kidney transplant experience (n=7); group 2, robot trained and kidney transplant experienced (n=20); and group 3, kidney transplant experienced with limited robot training (n=14). We employed prospective monitoring using SPC techniques, including cumulative summation (CUSUM) and Shewhart control charts, to perform LC analysis and patient safety monitoring, respectively. Outcomes assessed included post-transplant graft function and measures of surgical process (anastomotic and ischemic times). CUSUM and Shewhart control charts are time trend analytic techniques that allow comparative assessment of outcomes following a new intervention (RKT) relative to those achieved with established techniques (open kidney transplant; target value) in a prospective fashion. CUSUM analysis revealed an initial learning phase for group 3, whereas groups 1 and 2 had no to minimal learning time. The learning phase for group 3 varied depending on the parameter assessed. Shewhart control charts demonstrated no compromise in functional outcomes for groups 1 and 2. Graft function was compromised in one patient in group 3 (p<0.05) secondary to reasons unrelated to RKT. In multivariable analysis, robot training was significantly associated with improved task-completion times (p<0.01). Graft function was not adversely affected by either the lack of robotic training (p=0.22) or kidney transplant experience (p=0.72). The LC and patient safety of a new surgical technique can be assessed prospectively using CUSUM and Shewhart control chart analytic techniques. These methods allow determination of the duration of mentorship and identification of adverse events in a timely manner. A new operation can be considered learned when outcomes achieved with the new intervention are at par with outcomes following established techniques. Statistical process control techniques allowed for robust, objective, and prospective monitoring of robotic kidney transplantation and can similarly be applied to other new interventions during the introduction and adoption phase. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Effects of green tea tannin on cisplatin-induced nephropathy in LLC-PK1 cells and rats.

PubMed

Yokozawa, T; Nakagawa, T; Lee, K I; Cho, E J; Terasawa, K; Takeuchi, S

1999-11-01

A study was conducted to clarify whether green tea tannin ameliorated cisplatin-induced renal injury in terms of lactate dehydrogenase and malondialdehyde leakage from a renal epithelial cell line, swine-derived LLC-PK1 cells in culture. Green tea tannin was shown to suppress the cytotoxicity of cisplatin, the suppressive effect increasing with the dose of green tea tannin. The effect of cisplatin was then investigated in rats given green tea tannin for 40 days before cisplatin administration and in control rats given no green tea tannin. In control rats, blood, urinary and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, rats given green tea tannin showed decreased blood levels of urea nitrogen and creatinine, and decreased urinary levels of protein and glucose, reflecting less damage to the kidney. In this group, the activity of catalase in the renal tissue was increased, while the level of malondialdehyde was decreased, suggesting the involvement of radicals in the normalizing of kidney function. Based on the evidence available it appeared that green tea tannin eliminated oxidative stress and was beneficial to renal function.

Chemical composition and biological evaluation of Physalis peruviana root as hepato-renal protective agent.

PubMed

El-Gengaihi, Souad E; Hassan, Emad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

2013-03-01

This study was designed to investigate the potential of Physalis peruviana root as a functional food with hepato-renal protective effects against fibrosis. The chemical composition of the plant root suggested the presence of alkaloids, withanolides and flavonoids. Five compounds were isolated and their structures elucidated by different spectral analysis techniques. One compound was isolated from the roots: cuscohygrine. The biological evaluation was conducted on different animal groups; control rats, control treated with ethanolic root extract, CCl(4) group, CCl(4) treated with root extract, and CCl(4) treated with silymarin as a standard herbal drug. The evaluation used the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). The liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea, and serum protein were also evaluated. The results suggested safe administration, and improvement of all the investigated parameters. The liver and kidney histopathological analysis confirmed the results. In conclusion, P. peruviana succeeded in protecting the liver and kidney against fibrosis. Further studies are needed to discern their pharmacological applications and clinical uses.

Comparative toxicity of low dose tributyltin chloride on serum, liver, lung and kidney following subchronic exposure.

PubMed

Mitra, Sumonto; Gera, Ruchi; Singh, Vikas; Khandelwal, Shashi

2014-02-01

Tributyltin (TBT) pollution is rampant worldwide and is a growing threat due to its bio-accumulative property. Isolated studies of TBT toxicity on different organs are available but consolidated information is greatly lacking. We planned this study to delineate the effect of subchronic (1 month) exposure to low dose TBT-chloride (TBTC) (1 and 5 mg/kg) in male Wistar rats. Total tin concentration was found to be significantly increased in liver, kidney and blood, and marginally in lungs. Organo-somatic indices were seen to be altered with little effect on serum biochemical markers (liver and kidney function, and general parameters). Reactive oxygen species but not lipid peroxidation content was observed to be significantly elevated both in the tissues and serum. TBTC was found to act as a hyperlipidemic agent and it also affected heme biosynthetic pathway. Hematological analysis showed that TBTC exposure resulted in minor alterations in RBC parameters. Histological studies demonstrated marked tissue damage in all the 3 organs. Calcium inhibitors (BAPTA-AM, EGTA) and antioxidants (NAC, C-PC) significantly restored TBTC induced loss in cell viability, under ex-vivo conditions. Antioxidants were evidently more efficient in comparison to the calcium inhibitors, implying major role of oxidative stress pathways in TBTC toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Kidney function tests

MedlinePlus

Kidney function tests are common lab tests used to evaluate how well the kidneys are working. Such tests include: ... Oh MS, Briefel G. Evaluation of renal function, water, electrolytes ... and Management by Laboratory Methods . 23rd ed. Philadelphia, ...

Maximum urine concentrating capability in a mathematical model of the inner medulla of the rat kidney.

PubMed

Marcano, Mariano; Layton, Anita T; Layton, Harold E

2010-02-01

In a mathematical model of the urine concentrating mechanism of the inner medulla of the rat kidney, a nonlinear optimization technique was used to estimate parameter sets that maximize the urine-to-plasma osmolality ratio (U/P) while maintaining the urine flow rate within a plausible physiologic range. The model, which used a central core formulation, represented loops of Henle turning at all levels of the inner medulla and a composite collecting duct (CD). The parameters varied were: water flow and urea concentration in tubular fluid entering the descending thin limbs and the composite CD at the outer-inner medullary boundary; scaling factors for the number of loops of Henle and CDs as a function of medullary depth; location and increase rate of the urea permeability profile along the CD; and a scaling factor for the maximum rate of NaCl transport from the CD. The optimization algorithm sought to maximize a quantity E that equaled U/P minus a penalty function for insufficient urine flow. Maxima of E were sought by changing parameter values in the direction in parameter space in which E increased. The algorithm attained a maximum E that increased urine osmolality and inner medullary concentrating capability by 37.5% and 80.2%, respectively, above base-case values; the corresponding urine flow rate and the concentrations of NaCl and urea were all within or near reported experimental ranges. Our results predict that urine osmolality is particularly sensitive to three parameters: the urea concentration in tubular fluid entering the CD at the outer-inner medullary boundary, the location and increase rate of the urea permeability profile along the CD, and the rate of decrease of the CD population (and thus of CD surface area) along the cortico-medullary axis.

The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

PubMed

Li, Rui; Dai, Jinna; Kang, Hui

2018-03-01

Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

PubMed

Tautenhahn, Hans-Michael; Brückner, Sandra; Uder, Christiane; Erler, Silvio; Hempel, Madlen; von Bergen, Martin; Brach, Janine; Winkler, Sandra; Pankow, Franziska; Gittel, Claudia; Baunack, Manja; Lange, Undine; Broschewitz, Johannes; Dollinger, Matthias; Bartels, Michael; Pietsch, Uta; Amann, Kerstin; Christ, Bruno

2017-06-01

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

Central arterial characteristics of gout patients with chronic kidney diseases.

PubMed

Celik, Gulperi; Yilmaz, Sema; Kebapcilar, Levent; Gundogdu, Ali

2017-05-01

The aim of this study was to investigate the relationship between central blood pressure, arterial stiffness parameters and renal function parameters in gout patients with chronic kidney disease (CKD) and without CKD. The study enrolled 48 gout patients and 32 control subjects. Central blood pressure, arterial stiffness parameters and renal function parameters in gout patients were investigated. The vascular measurements were performed with an arteriograph. Of the gout patients, 40.1% had CKD. The 24-h pulse pressure (PP) (P < 0.001), central systolic blood pressure (SBP) (P < 0.001), central diastolic blood pressure (DBP) (P < 0.001), cardiac output (CO) (P < 0.001) and peripheral resistance (P = 0.004) were significantly higher in the all patients with gout compared to healthy control subjects. Moreover, when the gout patients with and without CKD were compared, the gout patients with CKD had higher 24-h PP (P = 0.009), 24-h augmentation index standardized to a heart rate of 75 beats per min (AIx@75) (P < 0.023), daytime PP (P = 0.001), daytime AIx@75 (P = 0.027), and nighttime PP (P = 0.035) than the gout patients without CKD. In our study, gout patients with CKD had worse and more emphasized evidence of arterial stiffness than gout patients without CKD. Further investigations with large sample sizes are needed to evaluate the effect of CKD on the arterial stiffness of gout patients. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Acute effects of alemtuzumab infusion in patients with active relapsing-remitting MS

PubMed Central

Thomas, Katja; Eisele, Judith; Rodriguez-Leal, Francisco Alejandro; Hainke, Undine

2016-01-01

Objective: Alemtuzumab exerts its clinical efficacy by its specific pattern of depletion and repopulation of different immune cells. Beyond long-term immunologic and clinical data, little is known about acute changes in immunologic and routine laboratory parameters and their clinical relevance during the initial alemtuzumab infusion. Methods: Fifteen patients with highly active MS were recruited. In addition to parameters including heart rate, blood pressure, body temperature, and monitoring of adverse events, complete blood cell count, liver enzymes, kidney function, acute-phase proteins, serum cytokine profile, complement activation, peripheral immune cell distribution, and their potential of cytokine release were investigated prior to and after methylprednisolone and after alemtuzumab on each day of alemtuzumab infusion. Results: After the first alemtuzumab infusion, both the total leukocyte and granulocyte counts markedly increased, whereas lymphocyte counts dramatically decreased. In addition to lymphocyte depletion, cell subtypes important for innate immunity also decreased within the first week after alemtuzumab infusion. Although patients reported feeling well, C-reactive protein and procalcitonin peaked at serum levels consistent with septic conditions. Increases in liver enzymes were detected, although kidney function remained stable. Proinflammatory serum cytokine levels clearly rose after the first alemtuzumab infusion. Alemtuzumab led to impaired cytokine release ex vivo in nondepleted cells. Normal clinical parameters and mild adverse events were presented. Conclusions: Dramatic immunologic effects were observed. Standardized infusion procedure and pretreatment management attenuated infusion-related reactions. Alemtuzumab-mediated effects led to artificially altered parameters in standard blood testing. We recommend clinical decision-making based on primarily clinical symptoms within the first alemtuzumab treatment week. PMID:27213173

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Kidney transplantation does not increase the level of basic hope or life satisfaction compared with hemodialysis in patients with chronic kidney disease.

PubMed

Zegarow, P; Jankowska, M; Sańko-Resmer, J; Durlik, M; Grzeszczyk, M; Pączek, L

2014-10-01

Although renal replacement therapy can lead to improved health, it also can cause emotional disturbances in patients. It is believed that the success of renal replacement therapy hinges not only on medical parameters, but also on psychosocial factors, which is why modern medicine provides an ever-increasing role in the improvement of patients' quality of life. The purpose of this study was to compare the level of life satisfaction, purpose in life, and basic hope in patients who had received renal replacement due to chronic kidney disease. We also tested whether the specific type of renal replacement therapy and kidney function parameters were influential factors on the above variables. Sixty-one adult patients treated via renal replacement for chronic kidney disease took part in the study. Patients were divided into two groups: 31 hemodialysis patients (15 women and 16 men, ages 23-77 years, mean 51.19 years, SD 14.53 years) and 30 patients who had undergone kidney transplantation (14 women and 16 men, ages 22-69 years, mean 48.40 years, SD 12.64 years). The following research tools were used for analysis: Satisfaction With Life Scale (SWLS), Purpose in Life Test (PIL), and Basic Hope Inventory (BHI-12). There were no statistical differences in the level of satisfaction with life between hemodialysis patients and postkidney transplant patients. The results for the SWLS obtained from both groups fell within the normal range. The average SWLS for hemodialysis patients remained 20.61, SD = 5.79; for postkidney transplant patients, it was 22.57, SD = 5.16. The PIL level in the group of hemodialysis patients (101.5, SD = 15.64) was significantly lower than in the group of postkidney transplant patients (109.7, SD = 15.54). The average BHI-12 level was similar in both groups. The average BHI-12 result for hemodialysis patients was 29.00 (SD = 5.06), and for postkidney transplant patients 29.93 (SD = 3.55). The correlations between the psychological variables and selected biochemical parameters are worthy of particular attention. Among hemodialysis patients, there was an additional correlation between SWLS and hematocrit; whereas for postkidney transplant patients, there was an additional correlation of PIL and eGFR. Our data show that satisfaction with life and basic hope do not increase in patients after renal replacement therapy. The form of renal replacement therapy (hemodialysis or kidney transplantation) does not change the above variables. Patients treated via renal replacement require specialized psychological support to improve the efficacy of renal replacement therapy.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Effect of an intensive nutrition intervention of a high protein and low glycemic-index diet on weight of kidney transplant recipients: study protocol for a randomized clinical trial.

PubMed

Pedrollo, Elis Forcellini; Nicoletto, Bruna Bellincanta; Carpes, Larissa Salomoni; de Freitas, Júlia de Melo Cardoso; Buboltz, Julia Roberta; Forte, Cristina Carra; Bauer, Andrea Carla; Manfro, Roberto Ceratti; Souza, Gabriela Corrêa; Leitão, Cristiane Bauermann

2017-09-06

Excessive weight gain is commonly observed within the first year after kidney transplantation and is associated with negative outcomes, such as graft loss and cardiovascular events. The purpose of this study is to evaluate the effect of a high protein and low glycemic-index diet on preventing weight gain after kidney transplantation. We designed a prospective, single-center, open-label, randomized controlled study to compare the efficacy of a high protein (1.3-1.4 g/kg/day) and low-glycemic index diet versus a conventional diet (0.8-1.0 g/kg/day of protein) on preventing weight gain after kidney transplantation. A total of 120 eligible patients 2 months after transplantation will be recruited. Patients with an estimated glomerular filtration rate through the modification of diet of renal disease (MDRD) formula < 30 mL/min/1.73 m 2 or urinary albumin excretion > 300 mg/24 h will be excluded. Patients' diets will be allocated through simple sequential randomization. Patients will be followed-up for 12 months with nine clinic appointments with a dietitian and the evaluations will include nutritional assessment (anthropometrics, body composition, and resting metabolic rate) and laboratory tests. The primary outcome is weight maintenance or body weight gain under 5% after 12 months. Secondary outcomes include body composition, resting metabolic rate, satiety sensation, kidney function, and other metabolic parameters. Diets with higher protein content and lower glycemic index may lead to weight loss because of higher satiety sensation. However, there is a concern about the association of high protein intake and kidney damage. Nevertheless, there is little evidence on the impact of high protein intake on long-term kidney function outcome. Therefore, we designed a study to test if a high protein diet with low-glycemic index will be an effective and safe nutritional intervention to prevent weight gain in kidney transplant patients. ClinicalTrials.gov identifier, NCT02883777 . Registered on 3 August 2016.

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

PubMed

Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

PubMed

Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

2017-04-01

At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

PubMed

Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

2017-07-01

Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

MRI tools for assessment of microstructure and nephron function of the kidney.

PubMed

Xie, Luke; Bennett, Kevin M; Liu, Chunlei; Johnson, G Allan; Zhang, Jeff Lei; Lee, Vivian S

2016-12-01

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology. Copyright © 2016 the American Physiological Society.

Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

PubMed

Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

2017-07-27

The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Quercetin-Rich Guava (Psidium guajava) Juice in Combination with Trehalose Reduces Autophagy, Apoptosis and Pyroptosis Formation in the Kidney and Pancreas of Type II Diabetic Rats.

PubMed

Lin, Chia-Fa; Kuo, Yen-Ting; Chen, Tsung-Ying; Chien, Chiang-Ting

2016-03-10

We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-β (β cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H2O2 and HOCl, whereas trehalose selectively reduced H2O2, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-β, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1β/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury.

Periodontitis associated with chronic kidney disease among Mexican Americans.

PubMed

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2013-01-01

In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.

Periodontitis associated with Chronic Kidney Disease among Mexican Americans

PubMed Central

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2012-01-01

Objective In comparison to non-Hispanic whites, a number of healthcare disparities, including poor oral health, have been identified among Hispanics in general and Mexican-Americans in particular. We hypothesized that Mexican-Americans with Chronic Kidney disease (CKD) would have higher prevalence of chronic periodontitis compared to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (p<0.001). Mexican Americans with reduced kidney function were 2-fold more likely to have periodontitis compared to Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes and socioeconomic status. Multivariate adjusted Odds Ratio for periodontitis significantly increased with 1, 5 and 10 mL/minute eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287

Chronic kidney disease: Pathological and functional evaluation with intravoxel incoherent motion diffusion-weighted imaging.

PubMed

Mao, Wei; Zhou, Jianjun; Zeng, Mengsu; Ding, Yuqin; Qu, Lijie; Chen, Caizhong; Ding, Xiaoqiang; Wang, Yaqiong; Fu, Caixia

2018-05-01

Because chronic kidney disease (CKD) is a worldwide problem, accurate pathological and functional evaluation is required for planning treatment and follow-up. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can assess both capillary perfusion and tissue diffusion and may be helpful in evaluating renal function and pathology. To evaluate functional and pathological alterations in CKD by applying IVIM-DWI. Prospective study. In all, 72 CKD patients who required renal biopsy and 20 healthy volunteers. 1.5T. All subjects underwent IVIM-DWI of the kidneys, and image analysis was performed by two radiologists. The mean values of true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were acquired from renal parenchyma. Correlation between IVIM-DWI parameters and estimated glomerular filtration rate (eGFR), as well as pathological damage, were assessed. One-way analysis of variance (ANOVA), paired sample t-test and Spearman correlation analysis. The paired sample t-test revealed that IVIM-DWI parameters were significantly lower in medulla than cortex for both patients and controls (P < 0.01). Regardless of whether eGFR was reduced, ANOVA revealed that f values of renal parenchyma were significantly lower in patients than controls (P < 0.05). Spearman correlation analysis revealed that there were positive correlations between eGFR and D (cortex, r = 0.466, P < 0.001; medulla, r = 0.491, P < 0.001), and between eGFR and f (cortex, r = 0.713, P < 0.001; medulla, r = 0.512, P < 0.001). Negative correlations were found between f and glomerular injury (cortex, r = -0.773, P < 0.001; medulla, r = -0.629, P < 0.001), and between f and tubulointerstitial lesion (cortex, r = -0.728, P < 0.001; medulla, r = -0.547, P < 0.001). IVIM-DWI might be feasible for noninvasive evaluation of renal function and pathology of CKD, especially in detection of renal insufficiency at an early stage. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1251-1259. © 2017 International Society for Magnetic Resonance in Medicine.

The relationship between nephron number, kidney size and body weight in two inbred mouse strains.

PubMed

Murawski, Inga J; Maina, Rita W; Gupta, Indra R

2010-01-01

While some reports in humans have shown that nephron number is positively correlated with height, body weight or kidney weight, other studies have not reproduced these findings. To understand the impact of genetic and environmental variation on these relationships, we examined whether nephron number correlates with body weight, kidney planar surface area, or kidney weight in two inbred mouse strains with contrasting kidney sizes but no overt renal pathology: C3H/HeJ and C57BL/6J. C3H/HeJ mice had smaller kidneys at birth and larger kidneys by adulthood, however there was no significant difference in nephron number between the two strains. We did observe a correlation between kidney size and body weight at birth and at adulthood for both strains. However, there was no relationship between nephron number and body weight or between nephron number and kidney size. From other studies, it appears that a greater than two-fold variation is required in each of these parameters in order to demonstrate these relationships, suggesting they are highly dependent on scale. Our results are therefore not surprising since there was a less than two-fold variation in each of the parameters examined. In summary, the relationship between nephron number and body or kidney size is most likely to be demonstrated when there is greater phenotypic variation either from genetic and/or environmental factors.

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

PubMed

Rassaf, Tienush; Balzer, Jan; Rammos, Christos; Zeus, Tobias; Hellhammer, Katharina; v Hall, Silke; Wagstaff, Rabea; Kelm, Malte

2015-04-01

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Sub-chronic safety evaluation of aqueous extract of Alangium salvifolium (L.f.) Wangerin leaves in rats

PubMed Central

Kapoor, Bhupinder; Kaur, Gagandeep; Gupta, Mukta; Gupta, Reena

2017-01-01

Conventionally, the juice and extract of Alangium salvifolium leaves have been used for the treatment of diabetes, wound healing, dog bite, and as a poultice in rheumatism. To carry out the sub-chronic toxicity and thereafter safety evaluation of A. salvifolium leaves. The aqueous extract of A. salvifolium leaves was administered orally at the doses of 200, 400, and 800 mg/kg/day for 90 days. All the animals were observed daily for general behavior, changes in body weight, food, and water consumption. At the end of the treatment period, biochemical and hematological parameters were analyzed; and the animals were sacrificed for histopathological examination of heart, lungs, liver, and kidney. The general behavior and water intake were normal in all the rats. The increase in body weight was observed in female rats of all the groups while body weight was decreased in high dose group animals of both sexes. Hematological parameters were not disturbed by the continuous use of extract. A significant decrease in glucose level was observed in intermediate- and high-dose group animals while urea and creatinine level were significantly high in animals of high-dose group. Although histopathological examination of most of the organs exhibited no structural changes, some tubal damage in kidneys was observed in high-dose group animals. The high dose of extract has shown mild signs of toxicity on kidney function test, but no toxic response was observed on hematological and liver biochemical parameters. The extract also exhibited hypoglycemic potential. PMID:28795025

The HALT Polycystic Kidney Disease Trials – Analysis of baseline parameters

PubMed Central

Torres, Vicente E.; Chapman, Arlene B.; Perrone, Ronald D.; Bae, K. Ty; Abebe, Kaleab Z.; Bost, James E.; Miskulin, Dana C.; Steinman, Theodore I.; Braun, William; Winklhofer, Franz T.; Hogan, Marie C.; Oskoui, Frederic Rahbari; Kelleher, Cass; Masoumi, Amirali; Glockner, James; Halin, Neil J; Martin, Diego; Remer, Erick; Patel, Nayana.; Pedrosa, Ivan; Wetzel, Louis H.; Thompson, Paul A.; Miller, J. Philip; Meyers, Catherine M.; Schrier, Robert W.

2013-01-01

HALT-PKD consists of two randomized trials comparing treatment with an angiotensin converting inhibitor (ACEI)-angiotensin receptor blocker (ARB) combination vs ACEI alone and standard vs low blood pressure target in Study A (eGFR >60 ml/min/1.73 m2) and ACEI-ARB vs ACEI alone in Study B (eGFR 25-60 ml/min/1.73 m2). It includes the largest cohort of systematically studied ADPKD patients (558 A and 486 B) to date. We used correlation and multiple regression cross-sectional analyses to ascertain associations of baseline parameters with total kidney (TKV) and liver (TLV) or liver cyst (LCV) volumes measured by MRI in Study A and with eGFR in both studies. Lower eGFR and higher natural log transformed urine albumin excretion are independently associated with larger natural log transformed TKV adjusted for height (HtTKV). Higher BSA is independently associated with higher ln(HtTKV) and lower eGFR. Men have larger HtTKV and smaller LCV than women. A weak correlation was found between ln(HtTKV) and ln(HtTLV) or ln(LCV) in women only. Women have higher urine aldosterone excretions and lower plasma potassium levels. In summary, this analysis 1) confirms a strong association between renal volume and functional parameters, 2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and 3) suggests an association between anthropomorphic measures reflecting preand/or post-natal growth and the severity of the disease. PMID:22205355

Pre- and post-operative evaluations of eight dogs following right nephrectomy due to Dioctophyma renale.

PubMed

Mesquita, L R; Rahal, S C; Faria, L G; Takahira, R K; Rocha, N S; Mamprim, M J; Oliveira, H S

2014-01-01

Dioctophyma renale is a large nematode distributed worldwide that may cause progressive and severe destruction of renal parenchyma. The present study aimed to evaluate pre- and post-operatively dogs submitted to right nephrectomy due to D. renale and to assess the histopathological damage of the removed kidney. Eight crossbred dogs, aged from 12 to 48 months that were unilaterally nephrectomized due to the presence of D. renale were evaluated. Physical examination, urinalysis, complete blood count, serum biochemistry, and abdominal ultrasound were performed immediately before and one month after nephrectomy. The nephrectomized right kidneys were submitted to macroscopic and microscopic evaluations. Urinalysis preoperatively detected occult blood in all dogs and D. renale eggs in five cases. Complete blood count showed all parameters within the reference range, except one dog post-operatively. Serum biochemistry performed before and after surgery verified that urea, creatinine and sodium were within the reference range values in all dogs. Other findings varied among the dogs. The length and arterial resistive index mean values of the left kidney were similar pre- and post-operatively. Thus, the inconsiderable change in laboratory findings pre- and post-operatively was attributable to compensation by left kidney function for the removed abnormal right kidney. Right kidney histology revealed chronic nephropathy due to D. renale. Imaging diagnosis should be performed on dogs suspected as carrying the disease or on those from an enzootic area since the laboratory findings are not specific except eggs in the urine.

Mercury levels, reproduction, and hematology in western grebes from three California Lakes, USA

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

Elbert, R.A.; Anderson, D.W.

1998-02-01

Twenty-three healthy adult western and Clark`s grebes (Aechmorphorus occidentalis and Aechmorphorus clarkii) were collected at three study sites in California, USA, in 1992: Clear Lake, Lake County; Eagle Lake, Lassen County; and Tule Lake, Siskiyou County. Liver, kidney, breast muscle, and brain were analyzed for total mercury (Hg) concentration (ppm wet weight), and blood was analyzed for various blood parameters. Clear Lake birds had greater Hg concentrations in kidney, breast muscle, and brain than birds from the other two lakes whereas liver concentrations were not statistically different. Average concentrations for Clear Lake birds were 2.74 ppm for liver, 2.06 ppmmore » for kidney, 1.06 ppm for breast muscle, and 0.28 ppm for brain. The tissue levels of kidney, breast muscle, and brain at the other two study sites were one half the levels found at Clear Lake. These mean tissue levels were near, but below, those known to cause adverse effects. When data from all sites were merged, kidney, breast muscle, and brain concentrations are positively correlated to each other. Liver concentrations were not correlated to any other value. Brain Hg concentrations were also negatively correlated to blood potassium and blood phosphorus levels. Kidney Hg levels were positively correlated to percent blood heterophils and negatively correlated to percent eosinophils, suggesting that mercury levels might be affecting immune function. These biomarkers could not be related to any obvious ecological effects.« less

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

A strain-hardening bi-power law for the nonlinear behaviour of biological soft tissues.

PubMed

Nicolle, S; Vezin, P; Palierne, J-F

2010-03-22

Biological soft tissues exhibit a strongly nonlinear viscoelastic behaviour. Among parenchymous tissues, kidney and liver remain less studied than brain, and a first goal of this study is to report additional material properties of kidney and liver tissues in oscillatory shear and constant shear rate tests. Results show that the liver tissue is more compliant but more strain hardening than kidney. A wealth of multi-parameter mathematical models has been proposed for describing the mechanical behaviour of soft tissues. A second purpose of this work is to develop a new constitutive law capable of predicting our experimental data in the both linear and nonlinear viscoelastic regime with as few parameters as possible. We propose a nonlinear strain-hardening fractional derivative model in which six parameters allow fitting the viscoelastic behaviour of kidney and liver tissues for strains ranging from 0.01 to 1 and strain rates from 0.0151 s(-1) to 0.7s(-1). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

PubMed Central

Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

2017-01-01

Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

Effects of feline hyperthyroidism on kidney function: a review.

PubMed

Vaske, Heather H; Schermerhorn, Thomas; Grauer, Gregory F

2016-02-01

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function. © ISFM and AAFP 2015.

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

Influence of low-level laser radiation on kidney functions

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1998-12-01

Most of all renal diseases are accompanied by lowering of kidney functions. That makes the quality of the treatment worse. On an example 69 patients receiving Low-Level Laser Therapy (LLLT), the influence of the laser radiation on a contracting system of blood, on current of an active and inactive tubercular inflammation and on partial functions of kidneys were investigated. Is established, that LLLT does not render influence to a contracting system; promotes stopping of unspecific and moderate peaking of a specific inflammation of kidneys. Is proved, that after a rate of laserotherapy the improving of a blood micricirculation in kidney occurs in 57.9% of patients; a secretion - in 63.1% of the patients; a stimulation of urodynamic is fixed in 79% of cases. Magnification of diuresis, improving filtration and concentration functions of kidneys also is marked.

Effect of mercury chloride to number of melano-macrophage centers on the kidney of carp fish (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Mubarokah, L.; Tjahjaningsih, W.; Sulmartiwi, L.

2018-04-01

Mercury chloride can cause immunotoxic effects on fish. The accumulation or aggregate of melano-macrophages centers (MMCs) in the kidney is a feature of cellular immune response, so it can be used as a bioindicator of heavy metal toxicity in waters. This research aims to determine an effect of heavy metal exposure concentration of mercury chloride (HgCl2) on a number of MMCs from common carp kidney. This research using four treatments of mercury chloride: 0 ppm, 0.01 ppm, 0.05 ppm and 0.1 ppm. The main parameters were the number of MMCs in kidney common carp. Supporting parameter was behavior change, water quality and concentration of mercury in the water and kidney. The results of the research showed that the concentration the heavy metal exposure concentration of mercury chloride (HgCl2) affected the number of MMCs from common carp (Cyprinus carpio) kidney. The number of MMCs in the kidney of common carp exposed to mercury chloride 0.01 ppm, 0.05 ppm and 0.1 ppm increased compared to carp was not exposed to mercury chloride (0 ppm).

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice.

PubMed

Calvo-Rubio, Miguel; Burón, M Isabel; López-Lluch, Guillermo; Navas, Plácido; de Cabo, Rafael; Ramsey, Jon J; Villalba, José M; González-Reyes, José A

2016-06-01

Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age-related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

PubMed

Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

2011-03-01

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of acute versus prolonged exercise and dehydration on kidney function and injury.

PubMed

Bongers, Coen C W G; Alsady, Mohammad; Nijenhuis, Tom; Tulp, Anouk D M; Eijsvogels, Thijs M H; Deen, Peter M T; Hopman, Maria T E

2018-06-01

Exercise and dehydration may be associated with a compromised kidney function and potential signs of kidney injury. However, the kidney responses to exercise of different durations and hypohydration levels are not yet known. Therefore, we aimed to compare the effects of acute versus prolonged exercise and dehydration on estimated glomerular filtration rate (eGFR) and kidney injury biomarkers in healthy male adults. A total of 35 subjects (23 ± 3 years) were included and invited for two study visits. Visit 1 consisted of a maximal cycling test. On Visit 2, subjects performed a submaximal exercise test at 80% of maximal heart rate until 3% hypohydration. Blood and urine samples were taken at baseline, after 30 min of exercise (acute effects; low level of hypohydration) and after 150 min of exercise or when 3% hypohydration was achieved (prolonged effects, high level of hypohydration). Urinary outcome parameters were corrected for urinary cystatin C, creatinine, and osmolality. Subjects dehydrated on average 0.6 ± 0.3% and 2.9 ± 0.7% after acute and prolonged exercise, respectively (P < 0.001). The eGFR cystatin C did not differ between baseline and acute exercise (118 ± 11 vs. 116 ± 12 mL/min/1.73 m 2 , P = 0.12), whereas eGFR cystatin C was significantly lower after prolonged exercise (103 ± 16 mL/min/1.73 m 2 , P < 0.001). We found no difference in osmolality corrected uKIM1 concentrations after acute and prolonged exercise (P > 0.05), and elevated osmolality corrected uNGAL concentrations after acute and prolonged exercise (all P-values < 0.05). In conclusion, acute exercise did barely impact on eGFR cystatin C and kidney injury biomarkers, whereas prolonged exercise is associated with a decline in eGFR cystatin C and increased biomarkers for kidney injury. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

PubMed

Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya

2018-05-30

Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renoprotective and blood pressure-lowering effect of dietary soy protein via protein kinase C beta II inhibition in a rat model of metabolic syndrome.

PubMed

Palanisamy, Nallasamy; Viswanathan, Periyasamy; Ravichandran, Mambakkam Katchapeswaran; Anuradha, Carani Venkataraman

2010-01-01

We studied whether substitution of soy protein for casein can improve insulin sensitivity, lower blood pressure (BP), and inhibit protein kinase C betaII (PKCbetaII) activation in kidney in an acquired model of metabolic syndrome. Adult male rats were fed 4 different diets: (i) starch (60%) and casein (20%) (CCD), (ii) fructose (60%) and casein (20%) (FCD), (iii) fructose (60%) and soy protein (20%) (FSD), and (iv) starch (60%) and soy protein (20%) (CSD). Renal function parameters, BP, pressor mechanisms, PKCbetaII expression, oxidative stress, and renal histology were evaluated after 60 days. FCD rats displayed insulin resistance and significant changes in body weight, kidney weight, urine volume, plasma and urine electrolytes accompanied by significant changes in renal function parameters compared with CCD rats. Elevated BP, plasma angiotensin-converting enzyme (ACE) activity, renal oxidative stress, and reduced nitrite (NO) and kallikrein activity were observed. Western blot analysis revealed enhanced renal expression of membrane-associated PKCbetaII in the FCD group. Histology showed fatty infiltration and thickening of glomeruli while urinary protein profile revealed a 5-fold increase in albumin. Substitution of soy protein for casein improved insulin sensitivity, lowered BP and PKCbetaII activation and restored renal function. Antioxidant action, inhibitory effect on ACE and PKCbetaII activation, and increased availability of kinins and NO could be contributing mechanisms for the benefits of dietary soy protein.

Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

PubMed

Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

2013-03-01

Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model.

PubMed

La Manna, Gaetano; Bianchi, Francesca; Cappuccilli, Maria; Cenacchi, Giovanna; Tarantino, Lucia; Pasquinelli, Gianandrea; Valente, Sabrina; Della Bella, Elena; Cantoni, Silvia; Claudia, Cavallini; Neri, Flavia; Tsivian, Matvey; Nardo, Bruno; Ventura, Carlo; Stefoni, Sergio

2011-01-01

Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

PubMed

Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

PubMed

Ali, Mana; Mwendwa, Denée T; Sims, Regina; Ricks, Madia; Sumner, Anne E

2016-02-01

Kidney disease disparately affects those of African descent. Age trends have generally been established for kidney function in the overall US population, but the contribution of age at the time of immigration for African immigrants is unknown. To examine the independent and joint effects of age and age at the time of immigration, and kidney function. Estimated glomerular filtration rate (eGFR) was calculated for 93 African immigrants (60 % male; mean age = 33.5). Hierarchical regression and post hoc analyses revealed a significant age × age at the time of immigration interaction after accounting for traditional risk factors among those who immigrated at age ≤21. Younger age at the time of immigration to the US may exacerbate an inverse relationship between age and kidney function in a self-identified healthy African immigrant sample. Investigation of biopsychosocial factors associated with kidney health among African immigrants is warranted.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

PubMed

Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

2018-06-01

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

PubMed Central

Sweeney, William E; Frost, Philip; Avner, Ellis D

2017-01-01

AIM To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation. We administered TSV by oral gavage in the same doses to the orthologous PCK model (from PN30 to PN90) to assess efficacy and toxicity in animals where developmental processes are complete. The following parameters were assessed: Body weight, total kidney weight; kidney weight to body weight ratios; and morphometric determination of a cystic index and a measure of hepatic disease. Renal function was assessed by: Serum BUN; creatinine; and a 12 h urinary concentrating ability. Validation of reported targets including the level of angiogenesis and inhibition of angiogenesis (active VEGFR2/KDR) was assessed by Western analysis. RESULTS This study demonstrates that: (1) in vivo pharmacological inhibition of multiple kinase cascades with TSV reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src and KDR; and (2) this reduction of kinase activity resulted in significant reduction of renal and biliary disease in both bpk and PCK models of ARPKD. The amelioration of disease by TSV was not associated with any apparent toxicity. CONCLUSION The data supports the hypothesis that this multi-kinase inhibitor TSV may provide an effective clinical therapy for human ARPKD. PMID:28729967

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats.

PubMed

Maia, R C A; Sousa, L E; Santos, R A S; Silva, M E; Lima, W G; Campagnole-Santos, M J; Alzamora, A C

2015-11-01

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150-180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

PubMed

Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

2018-05-01

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Experimental model for acute kidney injury caused by uropathogenic Escherichia coli.

PubMed

Skowron, Beata; Baranowska, Agnieszka; Kaszuba-Zwoińska, Jolanta; Więcek, Grażyna; Malska-Woźniak, Anna; Heczko, Piotr; Strus, Magdalena

2017-06-19

Acute kidney injury (AKI) is the rapid deterioration of renal function, diagnosed on the basis of an increase in serum creatinine and abnormal urinary parameters. AKI is associated with increased risk of mortality or chronic kidney disease (CKD). The aim of the study was to develop an experimental model for AKI resulting from Escherichia coli-induced pyelonephritis. E. coli was isolated from a patient with clinical symptoms of urinary tract infection (UTI). The study included three groups of female Wistar rats (groups 1, 2 and 3), in which pyelonephritis was induced by transurethral inoculation with highly virulent E. coli (105, 107 and 109 cfu/ml, respectively). Urine and blood samples for analysis were obtained prior to the inoculation (day 0), as well as 7, 14 and 21 days thereafter. Aside from a microbiological examination of urine samples, daily urine output, serum creatinine (CreaS), creatinine clearance (CrCl), interleukin 6 (IL-6), fractional excretion of sodium (FENa) and fractional excretion of urea (FEUrea) were determined. A histopathological examination of kidney and urinary bladder specimens was conducted as well. While UTI-related pyelonephritis developed irrespective of E. coli inoculum size, AKI was observed only following transurethral administration of E. coli at the intermediate and high dose, i.e. 107 and 109 cfu/ml, respectively (group 2 and 3). An increase in CreaS and abnormal diuresis were accompanied by changes in parameters specific for various forms of AKI, i.e. FENa and FEUrea. Based on these changes, administration of E. coli at 107 cfu/ml was demonstrated to induce renal AKI, whereas inoculation with 109 cfu/ml seemed to cause not only ascending pyelonephritis, but perhaps also bacteremia and urosepsis (prerenal component of AKI).

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

PubMed

Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

2011-08-01

Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

PubMed Central

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Soy-based renoprotection

PubMed Central

McGraw, Nancy J; Krul, Elaine S; Grunz-Borgmann, Elizabeth; Parrish, Alan R

2016-01-01

Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function. PMID:27152261

The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of Acute Kidney Injury.

PubMed

Lim, Sung Yoon; Ko, Yoon Sook; Lee, Hee Young; Yang, Ji Hyun; Kim, Myung Gyu; Jo, Sang Kyung; Cho, Won Yong

2018-04-12

Recent observational studies have shown that in chronic kidney disease (CKD) patients, a significantly smaller percentage of patients with an episode of acute kidney injury (AKI) have full recovery of renal function compared to those without CKD. However, precise mechanisms involved in the incomplete repair after AKI with preexisting CKD have not been completely ascertained. Here, we assessed the impact of preexisting CKD on the severity and recovery of AKI in a mouse model of 5/6 nephrectomy. Male CD-1 mice underwent 5/6 nephrectomy (Nx). Six weeks post surgery, ischemia reperfusion injury (IRI) or a sham operation was performed and functional, histological, and various molecular parameters were compared between them. Serum creatinine level on day 1 after IRI was comparable between control and Nx mice. However, serum creatinine remained significantly higher throughout the recovery phase in Nx mice compared to control mice. mRNA and protein expression of the cell cycle regulatory proteins were persistently elevated in Nx mice and this was associated with significantly increased levels of the G1 cell cycle arrest markers. Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD. Taken together, reduced nephron mass have a negative effect on the repair process that is partially mediated by the disruption of the cell cycle regulation. © 2018 S. Karger AG, Basel.

When Your Child Needs a Kidney Transplant

MedlinePlus

... Search English Español When Your Child Needs a Kidney Transplant KidsHealth / For Parents / When Your Child Needs ... to monitor their new kidney function. About the Kidneys Kidneys are bean-shaped organs located near the ...

Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation.

PubMed

Barros, Xoana; Fuster, David; Paschoalin, Raphael; Oppenheimer, Federico; Rubello, Domenico; Perlaza, Pilar; Pons, Francesca; Torregrosa, Jose V

2015-05-01

Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

PubMed

Artunc, F; Yildiz, S; Rossi, C; Boss, A; Dittmann, H; Schlemmer, H P; Risler, T; Heyne, N

2010-06-01

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Effect of Euterpe oleracea Mart. Seeds Extract on Chronic Ischemic Renal Injury in Renovascular Hypertensive Rats.

PubMed

da Costa, Cristiane Aguiar; Ognibene, Dayane Teixeira; Cordeiro, Viviane Silva Cristino; de Bem, Graziele Freitas; Santos, Izabelle Barcellos; Soares, Ricardo Andrade; de Melo Cunha, Letícia L; Carvalho, Lenize C R M; de Moura, Roberto Soares; Resende, Angela Castro

2017-10-01

Previously, we have demonstrated that the seeds of Euterpe oleracia Mart. (açaí) are rich in polyphenols with antihypertensive and antioxidant properties. This study evaluated the renal protective effects of the hydroalcoholic extract obtained from the seeds of açaí (ASE) fruits in two-kidney, one-clip (2K1C) renovascular hypertension. Young male Wistar rats were used to obtain 2K1C and sham groups. Animals received ASE (200 mg/(kg·day) in drinking water) or vehicle for 40 days. We evaluated serum and urinary parameters, renal structural changes, and oxidative status. The increase in systolic blood pressure of the 2K1C group was accompanied by a decrease in left kidney volume and number of glomeruli, as well as an increase in glomerular volume and collagen deposition. ASE prevented the alterations of these parameters, except the reduced kidney volume. Serum levels of urea and creatinine and urinary protein excretion were increased in the 2K1C group and treatment with ASE improved all these functional parameters. The increased oxidative damage in the 2K1C group, assessed by lipid and protein oxidation, was prevented by ASE. The nitrite content and both expression and activity of antioxidant enzymes (superoxide dismutase-1, catalase, and glutathione peroxidase) were lower in the 2K1C group and restored by ASE. ASE substantially reduced renal injury and prevented renal dysfunction in 2K1C rats probably through its antihypertensive and antioxidant effects, providing a natural resource for treatment and prevention of renovascular hypertension-related abnormalities.

The use of group sequential, information-based sample size re-estimation in the design of the PRIMO study of chronic kidney disease.

PubMed

Pritchett, Yili; Jemiai, Yannis; Chang, Yuchiao; Bhan, Ishir; Agarwal, Rajiv; Zoccali, Carmine; Wanner, Christoph; Lloyd-Jones, Donald; Cannata-Andía, Jorge B; Thompson, Taylor; Appelbaum, Evan; Audhya, Paul; Andress, Dennis; Zhang, Wuyan; Solomon, Scott; Manning, Warren J; Thadhani, Ravi

2011-04-01

Chronic kidney disease is associated with a marked increase in risk for left ventricular hypertrophy and cardiovascular mortality compared with the general population. Therapy with vitamin D receptor activators has been linked with reduced mortality in chronic kidney disease and an improvement in left ventricular hypertrophy in animal studies. PRIMO (Paricalcitol capsules benefits in Renal failure Induced cardia MOrbidity) is a multinational, multicenter randomized controlled trial to assess the effects of paricalcitol (a selective vitamin D receptor activator) on mild to moderate left ventricular hypertrophy in patients with chronic kidney disease. Subjects with mild-moderate chronic kidney disease are randomized to paricalcitol or placebo after confirming left ventricular hypertrophy using a cardiac echocardiogram. Cardiac magnetic resonance imaging is then used to assess left ventricular mass index at baseline, 24 and 48 weeks, which is the primary efficacy endpoint of the study. Because of limited prior data to estimate sample size, a maximum information group sequential design with sample size re-estimation is implemented to allow sample size adjustment based on the nuisance parameter estimated using the interim data. An interim efficacy analysis is planned at a pre-specified time point conditioned on the status of enrollment. The decision to increase sample size depends on the observed treatment effect. A repeated measures analysis model, using available data at Week 24 and 48 with a backup model of an ANCOVA analyzing change from baseline to the final nonmissing observation, are pre-specified to evaluate the treatment effect. Gamma-family of spending function is employed to control family-wise Type I error rate as stopping for success is planned in the interim efficacy analysis. If enrollment is slower than anticipated, the smaller sample size used in the interim efficacy analysis and the greater percent of missing week 48 data might decrease the parameter estimation accuracy, either for the nuisance parameter or for the treatment effect, which might in turn affect the interim decision-making. The application of combining a group sequential design with a sample-size re-estimation in clinical trial design has the potential to improve efficiency and to increase the probability of trial success while ensuring integrity of the study.

Association of Kidney Function and Albuminuria With Prevalent and Incident Hypertension: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Huang, Minxuan; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Astor, Brad C.; Coresh, Josef

2014-01-01

Background Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results. Study Design Cross-sectional for prevalent and prospective observational study for incident hypertension. Setting & Participants 9,593 participants from the Atherosclerosis Risk in Communities (ARIC) Study, aged 53-75 years during 1996-1998. Predictors Several markers of kidney function (estimated glomerular filtration rate [eGFR] using serum creatinine and/or cystatin C and two novel markers [β-trace protein and β2-microglobulin]) and one marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for eGFRs and bottom quintile for the rest). Outcomes Prevalent and incident hypertension. Measurements Prevalence and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively. Results There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. While all five kidney function markers were significantly associated with prevalent hypertension, prevalent hypertension was most notably associated with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was consistently associated with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0 mg/g) was significantly associated with incident hypertension. Limitations Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range. Conclusions Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was consistently associated with incident hypertension, suggesting that kidney damage is more closely related to hypertension than moderate reduction in overall kidney function. PMID:25151408

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats.

PubMed

Nyengaard, J R; Chang, K; Berhorst, S; Reiser, K M; Williamson, J R; Tilton, R G

1997-01-01

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen-associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

PubMed

Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

2009-07-01

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

PubMed

Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

2017-12-01

Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultrasonographic anatomy of the healthy southern tigrina ( Leopardus guttulus) abdomen: comparison with domestic cat references.

PubMed

Müller, Thiago R; Marcelino, Raquel S; de Souza, Livia P; Teixeira, Carlos R; Mamprim, Maria J

2017-02-01

Objectives The aim of the study was to describe the normal abdominal echoanatomy of the tigrina and to compare it with the abdominal echoanatomy of the domestic cat. Reference intervals for the normal abdominal ultrasonographic anatomy of individual species are important for accurate diagnoses and interpretation of routine health examinations. The hypothesis was that the echoanatomy of the tigrina was similar to that of the domestic cat. Methods Eighteen clinically healthy tigrina were selected for abdominal ultrasound examination, in order to obtain normal parameters of the bladder, spleen, adrenal gland, kidney, gastrointestinal tract, liver and gall bladder, and Doppler parameters of liver and kidney vessels. Results The splenic parenchyma was consistently hyperechoic to the kidneys and liver. The liver, kidneys and spleen had similar echotexture, shape and dimensions when compared with the domestic cat. The gall bladder was lobulated and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The adrenal glands had a bilobulated shape. The urinary bladder had a thin echogenic wall. The Doppler parameters of the portal vein and renal artery were similar to the domestic cat. Conclusions and relevance The results support the hypothesis that the ultrasonographic parameters of the abdominal viscera of the southern tigrina are similar to those of the domestic cat.

Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy.

PubMed

Qiu, Yuan-Ye; Tang, Li-Qin; Wei, Wei

2017-03-05

In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine. In vitro, berberine inhibited mesangial cell proliferation. Cells treated with berberine showed reduced levels of AGEs, accompanied by decreased RAGE, p-PKC and TGF-β1 levels soon afterwards. Berberine exhibited renoprotective effects in diabetic nephropathy rats, and the molecular mechanism was associated with changes in the levels and regulation of the AGEs-RAGE-PKC-β-TGF-β1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors.

PubMed

Courbebaisse, Marie; Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-08-08

The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m(2) before donation and 63.8±9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m(2) (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. Copyright © 2016 by the American Society of Nephrology.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. 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.

Use of intravoxel incoherent motion diffusion-weighted imaging to detect early changes in diabetic kidneys.

PubMed

Deng, Yi; Yang, Biran; Peng, Yan; Liu, Zhiqiang; Luo, Jinwen; Du, Guoxin

2018-03-14

The purpose of the study was to examine differences in kidney intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in early-stage diabetic patients versus healthy controls. Nineteen type 2 diabetic patients (group A) with a urinary albumin-to-creatinine ratio (ACR) < 30 mg/g and an estimated glomerular filtration rate (eGFR) of 80-120 mL/(min 1.73 m 2 ) and twelve healthy volunteers (group B) were recruited. Kidneys were scanned with 1.5-Tesla IVIM-DWI. Nine b values (0, 50, 100, 150, 200, 300, 400, 600, and 800 s/mm 2 ) were used. The parameters derived from IVIM-DWI were calculated for each kidney by two radiologists and included the perfusion fraction (f), diffusion coefficient (D), and pseudo-diffusion coefficient (D*). The mean values of f, D, and D* were calculated by selecting multiple regions of interest in the kidney. The diagnostic performance of the f, D, and D* values for the diagnosis of early diabetic kidney changes was determined by receiver operating characteristic analysis. Three radiologists independently measured the parameters derived from IVIM-DWI in the two groups by free-hand placing regions of interest, and the interclass coefficients (ICCs) were analyzed by SPSS.16.0 software. The f values of the kidneys were significantly higher in diabetic patients than in healthy volunteers. The D value of the kidneys was significantly lower in diabetic patients than in healthy volunteers. No significant differences in the D* values of the kidneys were observed between diabetic patients and healthy volunteers. The D values of the right kidneys were significantly higher than those of the left kidneys in both groups. The results of the receiver operating characteristic analysis were as follows: left kidney-f value AUC = 0.650 (cutoff point ≥ 27.49%) and D value AUC = 0.752 (cutoff point ≤ 1.68 × 10 -3  mm 2 /s); and right kidney-f value AUC = 0.650 (cutoff point ≥ 28.24%) and D value AUC = 0.752 (cutoff point ≤ 1.81 × 10 -3 mm 2 /s). The diagnostic performance of the D* value was very low (AUC < 0.6). No significant differences were present between the areas under the curves of the f and D values (P > 0.05). The ICCs of the f value and D value were between 0.637 and 0.827. The ICC of the D* value was less than 0.3. The results of our study suggest that changes in kidneys detected by IVIM-DWI may serve as indicators of early diabetic kidney disease.

Hydration Status, Kidney Function, and Kidney Injury in Florida Agricultural Workers.

PubMed

Mix, Jacqueline; Elon, Lisa; Vi Thien Mac, Valerie; Flocks, Joan; Economos, Eugenia; Tovar-Aguilar, Antonio J; Stover Hertzberg, Vicki; McCauley, Linda A

2018-05-01

Recent findings suggest that laboring in hot occupational environments is related to kidney damage in agricultural workers. We examined hydration status and kidney function in 192 Florida agricultural workers. Blood and urine samples were collected over 555 workdays during the summers of 2015 and 2016. Urine-specific gravity (USG), serum creatinine, and other kidney function markers were examined pre- and post-shift on each workday. Multivariable mixed modeling was used to examine the association of risk factors with hydration status and acute kidney injury (AKI). Approximately 53% of workers were dehydrated (USG ≥1.020) pre-shift and 81% post-shift; 33% of participants had AKI on at least one workday. The odds of AKI increased 47% for each 5-degree (°F) increase in heat index. A strikingly high prevalence of dehydration and AKI exists in Florida agricultural workers.

Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

PubMed

Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

2017-04-01

The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other potential confounding variables. Most participants showed impaired kidney function. The factors that were found to relate significantly to this impairment include being overweight, having hyperlipidemia, having hypertension, having high fasting blood glucose, and having an unhealthy lifestyle. Because of the lack of symptoms during the early stages of chronic kidney disease, a community-based health promotion program for these factors is an important element in health advocacy for this vulnerable population.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

PubMed

Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara

2018-06-14

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Cardiorenal Syndrome: New Developments in the Understanding and Pharmacologic Management

PubMed Central

2013-01-01

Summary Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. PMID:23929925

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

PubMed

Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Comparison of Recipient Outcomes After Kidney Transplantation: In-House Versus Imported Deceased Donors.

PubMed

Lim, S Y; Gwon, J G; Kim, M G; Jung, C W

2018-05-01

Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P = .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys. Copyright © 2018 Elsevier Inc. All rights reserved.

Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

PubMed

Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

2016-06-01

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

PubMed

Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

Periodontal treatment in patients with chronic kidney disease: a pilot study.

PubMed

Almeida, S; Figueredo, C M; Lemos, C; Bregman, R; Fischer, R G

2017-04-01

This pilot cohort study evaluated the effect of periodontal treatment on renal function, metabolic markers and asymmetric dimethylarginine (ADMA) in patients with pre-dialysis chronic kidney disease (CKD) presenting chronic periodontitis. Twenty-six patients with CKD and severe chronic periodontitis were selected. Periodontal parameters included plaque index, bleeding on probing, probing pocket depth and clinical attachment level. Estimated glomerular filtration rate (eGFR), triglycerides, total cholesterol, albumin and ADMA levels were evaluated at baseline, 90 and 180 d after periodontal therapy. eGFR was evaluated by the Modification of Diet in Renal Disease equation. All periodontal clinical parameters significantly improved (p < 0.05) 180 d after periodontal therapy. There was a significant improvement on the median values (25%; 75% percentiles) of eGFR from 34.6 (27; 44.7) mL/min/1.73 m 2 on baseline to 37.6 (29.7; 57) mL/min/1.73 m 2 on day 90, and to 37.6 (28.6; 56) mL/min/1.73 m 2 (p < 0.05) on day 180. ADMA levels significantly reduced 180 d after periodontal treatment. No significant differences were observed at the median values of metabolic markers comparing baseline and 180 d after periodontal treatment. The results point to a link of kidney disease with endothelium dysfunction and periodontitis, suggesting that periodontal treatment may be beneficial to the course of CKD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

PubMed Central

Yasuda, Hideo; Leelahavanichkul, Asada; Tsunoda, Shinichiro; Dear, James W.; Takahashi, Yoshiyuki; Ito, Shuichi; Hu, Xuzhen; Zhou, Hua; Doi, Kent; Childs, Richard; Klinman, Dennis M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development. PMID:18305095

Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress.

PubMed

Jabri, Mohamed-Amine; Sakly, Mohsen; Marzouki, Lamjed; Sebai, Hichem

2017-03-01

The present study aimed to investigate the inhibitory effect of chamomile decoction extract (CDE) on intestinal glucose absorption as well as its protective role against high fat diet (HFD)-induced obesity and lipotoxicity in rats. We used the Ussing chamber system to investigate the effect of CDE on intestinal transport of glucose. Male Wistar rats were fed HFD for six weeks to provoke obesity. CDE (100mg/kg, b.w. p.o.) has been per orally administered to HFD fed rats. Ex vivo, we found that CDE significantly and dose-dependently increased intestinal absorption of glucose. In vivo, HFD increased the body, liver and kidney weights, while CDE treatment showed a significant protective effects. High fat diet induced also a lipid profiles disorder and a disturbances in kidney and liver function parameters. Moreover liver and kidney lipotoxicity is accompanied by an oxidative stress status characterized by increased lipoperoxidation, depletion of antioxidant enzymes activity and non-enzymatic antioxidant (-SH groups and GSH) levels as well as increased levels of free iron, hydrogen peroxide (H 2 O 2 ) and calcium. However, treatment with CDE alleviated all the deleterious effects of HFD feed. These findings suggest that chamomile decoction extract can be used as functional beverage against obesity, hyperglycemia and hyperlipidemia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

PubMed

Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

2016-01-12

The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60-89.9, and ≥90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

A bioartificial environment for kidney epithelial cells based on a supramolecular polymer basement membrane mimic and an organotypical culture system.

PubMed

Mollet, Björne B; Bogaerts, Iven L J; van Almen, Geert C; Dankers, Patricia Y W

2017-06-01

Renal applications in healthcare, such as renal replacement therapies and nephrotoxicity tests, could potentially benefit from bioartificial kidney membranes with fully differentiated and functional human tubular epithelial cells. A replacement of the natural environment of these cells is required to maintain and study cell functionality cell differentiation in vitro. Our approach was based on synthetic supramolecular biomaterials to mimic the natural basement membrane (BM) on which these cells grow and a bioreactor to provide the desired organotypical culture parameters. The BM mimics were constructed from ureidopyrimidinone (UPy)-functionalized polymer and bioactive peptides by electrospinning. The resultant membranes were shown to have a hierarchical fibrous BM-like structure consisting of self-assembled nanofibres within the electrospun microfibres. Human kidney-2 (HK-2) epithelial cells were cultured on the BM mimics under organotypical conditions in a custom-built bioreactor. The bioreactor facilitated in situ monitoring and functionality testing of the cultures. Cell viability and the integrity of the epithelial cell barrier were demonstrated inside the bioreactor by microscopy and transmembrane leakage of fluorescently labelled inulin, respectively. Furthermore, HK-2 cells maintained a polarized cell layer and showed modulation of both gene expression of membrane transporter proteins and metabolic activity of brush border enzymes when subjected to a continuous flow of culture medium inside the new bioreactor for 21 days. These results demonstrated that both the culture and study of renal epithelial cells was facilitated by the bioartificial in vitro environment that is formed by synthetic supramolecular BM mimics in our custom-built bioreactor. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

PubMed

Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C

2014-07-01

Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function?

PubMed

Marchini, Giovanni S; Vicentini, Fabio C; Mazzucchi, Eduardo; Brito, Arthur; Ebaid, Gustavo; Srougi, Miguel

2012-02-01

To report our experience with silent ureteral stones and expose their true influence on renal function. We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%±12.1% vs 20%±11.8%; P=.83) and serum creatinine (0.8±0.13 mg/dL vs 1.0±0.21 mg/dL; P=.45). Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. Copyright © 2012 Elsevier Inc. All rights reserved.

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model.

PubMed

Aksu, Ugur; Guner, Ibrahim; Yaman, Onur M; Erman, Hayriye; Uzun, Duygu; Sengezer-Inceli, Meliha; Sahin, Ahmet; Yelmen, Nermin; Gelisgen, Remisa; Uzun, Hafize; Sahin, Gulderen

2014-12-01

Ischemia-reperfusion (IR) has been reported to be associated with augmented reactive oxygen radicals and cytokines. Currently, we aimed to examine the influence of fluoxetine, which is already used as a preoperative anxiolytic, in the context of IR induced by occlusion of infrarenal abdominal aorta (60 min of ischemia) and its effects on renal oxidative status, inflammation, renal function, and cellular integrity in reperfusion (120 min post-ischemia). Male rats were randomly assigned as control, IR, and pretreated groups. The pretreated group animals received fluoxetine (20 mg/kg, i.p.) once daily for 3 days. Renal tissue oxidative stress, myeloperoxidase activity, proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6), histology, and function were assessed. As an anti-inflammatory cytokine, interleukin-10 was also assessed. IR led to a significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant antioxidant balance and decrease in superoxide dismutase activity and ferric reducing/antioxidant power level (p < 0.05), but fluoxetine was able to restore these parameters. High concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase activity caused by IR were significantly decreased in kidney tissue with fluoxetine. In addition, interleukin-10 levels were high in fluoxetine pretreated group. IR resulted in disrupted cellular integrity, infiltration of tissue with leukocytes, and decreased serum creatinine-urea levels (p < 0.05). Fluoxetine significantly restored impaired redox balance and inflammation parameters of rats subjected to IR to baseline values. This beneficial effect of fluoxetine on redox balance might be addressed to an improvement in renal function.

Assessing Intrarenal Non-perfusion and Vascular Leakage in Acute Kidney Injury withzz 19F MRI and Perfluorocarbon Nanoparticles

PubMed Central

Hu, Lingzhi; Chen, Junjie; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Yanaba, Noriko; Caruthers, Shelton D.; Lanza, Gregory M.; Hammerman, Marc R.; Wickline, Samuel A.

2014-01-01

Purpose We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles (PFC NPs) and 19F MRI. Methods Because the detected 19F signal intensity directly reflects local blood volume, and the 19F R1 is linearly proportional to local blood oxygen content (pO2), 19F spin density weighted and T1 weighted images were utilized to generate quantitative functional mapping in both healthy and ischemia-reperfusion (acute kidney injury, AKI) injured mouse kidneys. 1H Blood-Oxygenation-Level-Dependant (BOLD) MRI was also employed as a supplementary approach to facilitate the compressive analysis of renal circulation and its pathological changes in AKI. Results Heterogeneous blood volume distribution and intrarenal oxygenation gradient were confirmed in healthy kidneys by 19F MRI. In a mouse model of AKI, 19F MRI, in conjunction with BOLR MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary (CM) junction region, we observed 25% lower 19F signal (p<0.05) and 70% longer 1H T2* (p<0.01) in injured kidneys compared to contralateral kidneys at 24 hours after initial ischemia-reperfusion injury. We also detected 71% higher 19F signal (p<0.01) and 40% lower 1H T2* (p<0.05) in the renal medulla region of injured kidneys compared to contralateral kidneys. Conclusion With demonstrated superior diagnostic capability, functional kidney 19F MRI using PFC NPs could serve as a new diagnostic measures for comprehensive evaluation of renal function and pathology. PMID:23929727

Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization

PubMed Central

Uzarski, Joseph S.; Bijonowski, Brent M.; Wang, Bo; Ward, Heather H.; Wandinger-Ness, Angela

2015-01-01

Analysis of perfusion-based bioreactors for organ engineering and a detailed evaluation of physical and biochemical parameters that measure dynamic changes within maturing cell-laden scaffolds are critical components of ex vivo tissue development that remain understudied topics in the tissue and organ engineering literature. Intricately designed bioreactors that house developing tissue are critical to properly recapitulate the in vivo environment, deliver nutrients within perfused media, and monitor physiological parameters of tissue development. Herein, we provide an in-depth description and analysis of two dual-purpose perfusion bioreactors that improve upon current bioreactor designs and enable comparative analyses of ex vivo scaffold recellularization strategies and cell growth performance during long-term maintenance culture of engineered kidney or liver tissues. Both bioreactors are effective at maximizing cell seeding of small-animal organ scaffolds and maintaining cell survival in extended culture. We further demonstrate noninvasive monitoring capabilities for tracking dynamic changes within scaffolds as the native cellular component is removed during decellularization and model human cells are introduced into the scaffold during recellularization and proliferate in maintenance culture. We found that hydrodynamic pressure drop (ΔP) across the retained scaffold vasculature is a noninvasive measurement of scaffold integrity. We further show that ΔP, and thus resistance to fluid flow through the scaffold, decreases with cell loss during decellularization and correspondingly increases to near normal values for whole organs following recellularization of the kidney or liver scaffolds. Perfused media may be further sampled in real time to measure soluble biomarkers (e.g., resazurin, albumin, or kidney injury molecule-1) that indicate degree of cellular metabolic activity, synthetic function, or engraftment into the scaffold. Cell growth within bioreactors is validated for primary and immortalized cells, and the design of each bioreactor is scalable to accommodate any three-dimensional scaffold (e.g., synthetic or naturally derived matrix) that contains conduits for nutrient perfusion to deliver media to growing cells and monitor noninvasive parameters during scaffold repopulation, broadening the applicability of these bioreactor systems. PMID:25929317

Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization.

PubMed

Uzarski, Joseph S; Bijonowski, Brent M; Wang, Bo; Ward, Heather H; Wandinger-Ness, Angela; Miller, William M; Wertheim, Jason A

2015-10-01

Analysis of perfusion-based bioreactors for organ engineering and a detailed evaluation of physical and biochemical parameters that measure dynamic changes within maturing cell-laden scaffolds are critical components of ex vivo tissue development that remain understudied topics in the tissue and organ engineering literature. Intricately designed bioreactors that house developing tissue are critical to properly recapitulate the in vivo environment, deliver nutrients within perfused media, and monitor physiological parameters of tissue development. Herein, we provide an in-depth description and analysis of two dual-purpose perfusion bioreactors that improve upon current bioreactor designs and enable comparative analyses of ex vivo scaffold recellularization strategies and cell growth performance during long-term maintenance culture of engineered kidney or liver tissues. Both bioreactors are effective at maximizing cell seeding of small-animal organ scaffolds and maintaining cell survival in extended culture. We further demonstrate noninvasive monitoring capabilities for tracking dynamic changes within scaffolds as the native cellular component is removed during decellularization and model human cells are introduced into the scaffold during recellularization and proliferate in maintenance culture. We found that hydrodynamic pressure drop (ΔP) across the retained scaffold vasculature is a noninvasive measurement of scaffold integrity. We further show that ΔP, and thus resistance to fluid flow through the scaffold, decreases with cell loss during decellularization and correspondingly increases to near normal values for whole organs following recellularization of the kidney or liver scaffolds. Perfused media may be further sampled in real time to measure soluble biomarkers (e.g., resazurin, albumin, or kidney injury molecule-1) that indicate degree of cellular metabolic activity, synthetic function, or engraftment into the scaffold. Cell growth within bioreactors is validated for primary and immortalized cells, and the design of each bioreactor is scalable to accommodate any three-dimensional scaffold (e.g., synthetic or naturally derived matrix) that contains conduits for nutrient perfusion to deliver media to growing cells and monitor noninvasive parameters during scaffold repopulation, broadening the applicability of these bioreactor systems.

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.

Cyclosporine A-induced nephrotoxicity is ameliorated by dose reduction and conversion to sirolimus in the rat.

PubMed

Sereno, J; Vala, H; Nunes, S; Rocha-Pereira, P; Carvalho, E; Alves, R; Teixeira, F; Reis, F

2015-04-01

Side-effect minimization strategies to avoid serious side-effects of cyclosporine A (CsA), such as nephrotoxicity, have been mainly based on dose reduction and conversion to other putatively less nephrotoxic drugs, such as sirolimus (SRL), an inhibitor of the mammalian target of rapamycin. This study intended to evaluate the impact of protocols based on CsA dose reduction and further conversion to SRL on kidney function and lesions, based on serum, urine and renal tissue markers. The following 3 groups (n=6) were tested during a 9-week protocol: control (vehicle); CsA (5 mg/kg/day) and Red + Conv (CsA 30 mg/kg/day during 3 weeks + 3 weeks with CsA 5 mg/kg/day + SRL 1 mg/kg/day during the last 3 weeks). The following parameters were analysed: blood pressure, heart rate and biochemical data; serum and urine contents and clearances of creatinine, urea and neutrophil gelatinase-associated lipocalin (NGAL), as well as, glomerular filtration rate; kidney lipid peroxidation and clearance; kidney lesions were evaluated and protein expression was performed by immunohistochemistry. After the first 3 weeks of CsA (30 mg/kg/day) treatment animals showed body weight loss, hypertension, tachycardia, as well as, increased serum levels of non-HDL cholesterol, glucose, triglycerides, creatinine and urea, accompanied by decreased GFR and insulin levels. In addition, a significant increase in the expression of connective tissue growth factor, kidney injury molecule-1 (KIM-1), mammalian target of rapamycin, nuclear factor-κβ1 and transforming growth factor-β was found in the kidney, accompanied by extensive renal damage. The following 3 weeks with CsA dose reduction revealed amelioration of vascular and glomerular lesions, but without significant tubular improvement. The last 3 weeks with the conversion to sirolimus revealed high serum and urine NGAL contents but the CsA-evoked renal damage was substantially ameliorated, by reduced of connective tissue growth factor, mammalian target of rapamycin, nuclear factor-κβ1 protein expression. In conclusion, CsA nephrotoxicity is dose dependent and moderate dysfunction could be ameliorated/prevented by SRL conversion, which could be pivotal for the preservation of kidney function and structure.

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

Marques da Silva, A; Narciso, L

Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in themore » liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve limitations in the segmentation step, mainly when background region has higher activity compared to kidneys. Financial support by CAPES.« less

Low serum bicarbonate and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Driver, Todd H; Shlipak, Michael G; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J; Hoofnagle, Andrew N; Siscovick, David S; Kestenbaum, Bryan; de Boer, Ian H; Ix, Joachim H

2014-10-01

Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Retrospective cohort study. 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Serum bicarbonate concentrations. Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Cause of metabolic acidosis cannot be determined in this study. Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2). Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney transplantation: a systematic review of interventional and observational studies of physical activity on intermediate outcomes.

PubMed

Macdonald, Jamie Hugo; Kirkman, Danielle; Jibani, Mahdi

2009-11-01

Kidney transplant patients have decreased quality and longevity of life. Whether exercise can positively affect associated outcomes such as physical functioning, metabolic syndrome, kidney function, and immune function, has only been addressed in relatively small studies. Thus the aim of this systematic review was to determine effects of physical activity level on these intermediate outcomes in kidney transplant patients. We electronically and hand searched to identify 21 studies (6 retrospective assessments of habitual physical activity and 15 intervention studies including 6 controlled trials). After study quality assessment, intermediate outcomes associated with quality and longevity of life were expressed as correlations or percentage changes in addition to effect sizes. Habitual physical activity level was positively associated with quality of life and aerobic fitness and negatively associated with body fat (medium to large effect sizes). Exercise interventions also showed medium to large positive effects on aerobic capacity (10%-114% increase) and muscle strength (10%-22% increase). However, exercise programs had minimal or contradictory effects on metabolic syndrome and immune and kidney function. In kidney transplant patients, physical activity intervention is warranted to enhance physical functioning. Whether exercise impacts on outcomes associated with longevity of life requires further study.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

PubMed

Liu, Xue-Jing; Wu, Xiao-Yue; Wang, Huan; Wang, Su-Xia; Kong, Wei; Zhang, Ling; Liu, George; Huang, Wei

2018-05-08

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease.

PubMed

Łukaszyk, Ewelina; Łukaszyk, Mateusz; Koc-Żórawska, Ewa; Tobolczyk, Jolanta; Bodzenta-Łukaszyk, Anna; Małyszko, Jolanta

2015-01-01

One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency. © 2015 S. Karger AG, Basel.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

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

MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation.

PubMed

Ulbing, M; Kirsch, A H; Leber, B; Lemesch, S; Münzker, J; Schweighofer, N; Hofer, D; Trummer, O; Rosenkranz, A R; Müller, H; Eller, K; Stadlbauer, V; Obermayer-Pietsch, B

2017-02-01

Chronic kidney disease (CKD) is associated with a multifactorial dysregulation of bone and vascular calcification and closely linked to increased cardiovascular mortality and concomitant bone disease. We aimed to investigate specific microRNA (miRNA) signatures in CKD patients to find indicators for vascular calcification and/or bone mineralization changes during CKD and after kidney transplantation (KT). A miRNA array was used to investigate serum miRNA profiles in CKD patients, then selected miRNAs were quantified in a validation cohort comprising 73 patients in CKD stages 3 to 5, 67 CKD patients after KT, and 36 healthy controls. A spectrum of biochemical parameters including markers for kidney function, inflammation, glucose, and mineral metabolism was determined. The relative expression of miR-223-3p and miR-93-5p was down-regulated in patients with CKD stage 4 and 5 compared to healthy controls. This down-regulation disappeared after kidney transplantation even when lower glomerular filtration rates (eGFR) persisted. MiR-223-3p and miR-93-5p were associated with interleukin-6 (IL-6) and eGFR levels, and by trend with interleukin-8 (IL-8), C-peptide, hematocrit, and parathyroid hormone (PTH). This study contributes new knowledge of serum miRNA expression profiles in CKD, potentially reflecting pathophysiological changes of bone and calcification pathways associated with inflammation, vascular calcification, mineral and glucose metabolism. Identified miRNA signatures can contribute to future risk markers or future therapeutic targets in bone and kidney disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products.

PubMed

Liu, Kai; Xu, Huiqin; Lv, Gaohong; Liu, Bin; Lee, Maxwell Kim Kit; Lu, Chunhong; Lv, Xing; Wu, Yunhao

2015-02-15

Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo. We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney. Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion.

PubMed

Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin

2013-03-01

On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors

PubMed Central

Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-01-01

Background and objectives The predictors of long–term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. Design, setting, participants, & measurements We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for 51Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. Results For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m2 before donation and 63.8±9.4 ml/min per 1.73 m2 at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m2 (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: −0.4 [95% confidence interval (95% CI), −0.5 to −0.1]; body mass index: −0.3 [95% CI, −0.6 to −0.1]; rk-GFR/vol: −55.1 [95% CI, −92.3 to −17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: −0.1 [95% CI, −0.5 to 0.3]; body mass index: −0.9 [95% CI, −1.8 to −0.1]; rk-GFR/vol: −97.6 [95% CI, −137.5 to −57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. Conclusions For given age and body mass index, the long–term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. PMID:27189317

Chinese Minimally Invasive Percutaneous Nephrolithotomy for Intrarenal Stones in Patients with Solitary Kidney: A Single-Center Experience

PubMed Central

Huang, Zhichao; Fu, Fajun; Zhong, Zhaohui; Zhang, Lei; Xu, Ran; Zhao, Xiaokun

2012-01-01

Objective To report our experience with Chinese minimally invasive percutaneous nephrolithotomy (Chinese MPCNL) to manage patients with intrarenal stones in solitary kidney, and evaluate the safety, efficiency and feasibility of this technique. Methods Forty-one patients with intrarenal stones in solitary kidney underwent Chinese MPCNL in our department from March 2009 to February 2011. Demographic characteristics, operative parameters, number of tracts, stone-free rates (SFRs), stone analyses, hemoglobin levels, nephrostomy tube removal time, hospitalization time, and complications were evaluated. Serum creatinine (Scr) and glomerular filtration rate (GFR) were measured preoperatively, postoperatively at 1 month, and each follow-up visit. The 5-stage classification of chronic kidney disease (CKD) was used according to the National Kidney Foundation guidelines. Results The initial stone-free status was achieved in 35 (85.4%) patients after Chinese MPCNL. The mean follow-up time was 16.9±4.7 months (range: 12–24), and the final SFR improved to 97.6% after auxiliary procedures. Among all patients, complex stones were detected in 26 (63.4%) patients, and 9 (22.0%) required multiple tracts. The mean operative time and mean hospitalization time were 71.3±23.5 min (range: 40–139) and 6.1±0.5 days (range: 5–11), respectively. During preoperative period and postoperative period (1 month), Scr were 132.1±41.3 umol/L (range: 78.2–231.4) and 108.9±30.7 umol/L (range: 71.6–136.9), respectively (P<0.05), while GFR were 74.9±24.2 ml/min (range: 35–110) and 83.9±27.4 ml/min (range: 65–110), respectively (P<0.05). According to CKD classification, the renal function was stable, improved, and worse in 29 (70.7%), 11 (26.8%), and 1 (2.5%) patients, compared with the preoperative levels. No patient progressed to end-stage renal disease requiring dialysis. Conclusions Our experience with Chinese MPCNL demonstrates that it is safe, feasible and efficient for managing the intrarenal calculi in solitary kidney with a low complication rate. At long-term follow-up, renal function stabilized or even improved in the majority of patients with solitary kidney. PMID:22808197

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

PubMed

Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

2017-12-01

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

Changes in urine volume and serum albumin in incident hemodialysis patients.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Rhee, Connie M; Chou, Jason A; Tortorici, Amanda R; Mathew, Anna T; Kim, Taehee; Soohoo, Melissa; Streja, Elani; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-10-01

Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (P trend  < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels. © 2016 International Society for Hemodialysis.

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

PubMed

Selamet, Umut; Katz, Ronit; Ginsberg, Charles; Rifkin, Dena E; Fried, Linda F; Kritchevsky, Stephen B; Hoofnagle, Andrew N; Bibbins-Domingo, Kirsten; Drew, David; Harris, Tamara; Newman, Anne; Gutiérrez, Orlando M; Sarnak, Mark J; Shlipak, Michael G; Ix, Joachim H

2018-06-06

Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. Case-cohort study. Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function. Published by Elsevier Inc.

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

PubMed

Verdelli, C; Corbetta, S

2017-01-01

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

PubMed

Hussain, Tajamul; Al-Attas, Omar S; Alrokayan, Salman A; Ahmed, Mukhtar; Al-Daghri, Nasser M; Al-Ameri, Salman; Pervez, Shamsh; Dewangan, Shippi; Mohammed, Arif; Gambhir, Dikshit; Sumague, Terrance S

2016-07-01

Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease.

PubMed

Rajani, Roshan; Pastor-Soler, Nuria M; Hallows, Kenneth R

2017-09-01

AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins. These new studies have focused on the role of AMPK in the kidney in the setting of various diseases such as diabetes, which include evaluation of the effects of the hyperglycemic state on podocyte and tubular cell function. Other recent studies have investigated how reduced kidney mass, polycystic kidney disease (PKD), and fibrosis affect AMPK activation status. A general theme of several conditions that lead to chronic kidney disease (CKD) is that AMPK activity is abnormally suppressed relative to that in normal kidneys. Thus, the idea that AMPK activation may be a therapeutic strategy to slow down the progression of CKD has emerged. In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD. AMPK in the kidney plays a unique role at the crossroads of energy metabolism, ion and water transport, inflammation, and stress. Its potential role in modulating recovery from vs. progression of acute and chronic kidney injury has been the topic of recent research findings. The continued study of AMPK in kidney physiology and disease has improved our understanding of these physiological and pathological processes and offers great hope for therapeutic avenues for the increasing population at risk to develop kidney failure.

Measuring and Assessing Kidney Function.

PubMed

Vart, Priya; Grams, Morgan E

2016-07-01

Assessment of kidney function is important for the detection and management of chronic kidney disease. The glomerular filtration rate (GFR) and level of albuminuria are two frequently used indices of kidney function assessment. Administration of an exogenous filtration marker to measure GFR and collection of urine for 24 hours to measure albumin excretion generally are considered the gold standard for GFR and albuminuria, respectively, but they are time consuming and onerous for the patient. Thus, in routine clinical practice, other methods are used more frequently to assess GFR and albuminuria. In this review, we discuss the role of GFR and albuminuria in staging of chronic kidney disease as well as the pros and cons and prognostic implications of various methods of assessment of GFR and albuminuria. Copyright © 2016 Elsevier Inc. All rights reserved.

Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

PubMed Central

2012-01-01

Introduction To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. Results There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial. Conclusions The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI. Trial Registration www.clinicaltrials.gov: NCTNCT00511186 PMID:22269279

Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation.

PubMed

Patankar, Khalil; Low, Ronny Su-Tong; Blakeway, Darryn; Ferrari, Paolo

2014-07-01

Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. nSRF derived from the renal scintigram, expressed as the right kidney's function in percent of the total, was 50.2 ± 3.3 (range, 44.1-54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4-52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )= 0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Creatinine blood test

MedlinePlus

Serum creatinine; Kidney function - creatinine; Renal function - creatinine ... kidney damage or failure, infection, or reduced blood flow Loss of ... medicine overdose. Your provider will tell you more, if needed.

THE KNOCKED-OUT UNILATERAL KIDNEY! CAUSES AND PRESENTATION.

PubMed

Bangash, Kashif; Alam, Asaf; Amin, Mohammed; Anwar, Khursheed

2015-01-01

Due to lack of awareness and non-availability of proper medical facilities in Pakistan, patients with kidney problems tend to seek urological consultation very late when their kidney has already knocked-out. The aim of the study was to find the various presenting complaints of patients having unilateral loss of kidney function and their aetiologies. The study also targeted the patient's awareness regarding their disease. This descriptive case-series of 103 consecutive patients who were diagnosed as having less than 20% of function on DTPA Renal Scan were evaluated. The aetiology of the non-functioning kidney (NFK) was made on either imaging findings or during the exploration, and/or on histopathology if necessary. The results were analysed using SPSS 16.0. Results: The aetiology of the unilateral renal failure included those that were secondary to nephro-pelvic stones in 39.8% and ureteric stones in 14.6%. Of the other aetiologies culminating in a unilateral NFK, 7.8% of the patients had chronic pyelonephritis, 20.4% had PUJO and 5.8% were Genito-urinary Tuberculosis; 3.9% had VUR and were found incidentally, 3.9% developed non-functioning kidney iatrogenically. About 39.8% of the patients knew about their primary disease causing destruction of renal function since long. The remaining 60.2% were unaware that they had developed NFK already when they presented. Proper education through awareness program both for the public and general practitioners can detect early threats to the kidney and hence decrease the loss of a kidney. This will also decrease the number of nephrectomies carried out for the benign condition.

77 FR 6130 - National Institute of Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Diabetes and Digestive and Kidney Diseases Notice of Closed Meeting Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Cellular Biology of Kidney Function and... Research; 93.849, Kidney Diseases, Urology and Hematology Research, National Institutes of Health, HHS...

Notes on the Problems of the Transplantation of Kidneys in Dogs

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

Puza, A.; Drahovsky, V.; Neubauer, E.

1963-01-01

In a group of 29 mongrel dogs kidney homotransplantation was performed. In five dogs an autograft was performed to check the suitability of the surgical technique. In the remaining 24 dogs kidney homografts were carried out, Five dogs served as controls; in these animals the functioning of the homografted kidney stopped after 8 days on the average, In 12 animals an attempt at the induction of immunological tolerance by exsanguinotransfusion, whole-body irradiation and 6-MP-administration was made. Induction of immunological tolerance by total exsanguinotransfusion immediately after birth may render possible a successful homograft even in adult life. The transplanted organ thenmore » exhibits a permanent take and takes over the function of the recipient's removed kidneys. One dog is alive with its single kidney homograft after almost two years. 6-MP administration may lead to such a degree of induced tolerance that the function of a kidney homograft is prolonged by a factor of two to three. Whole-body irradiation within a range of 400 rad (Co 60 source) does not significantly prolong homograft survival.« less

Xuezhikang ameliorates contrast media-induced nephropathy in rats via suppression of oxidative stress, inflammatory responses and apoptosis.

PubMed

Chu, Shichun; Hu, Liuhua; Wang, Xiaolei; Sun, Shiqun; Zhang, Tuo; Sun, Zhe; Shen, Linghong; Jin, Shuxuan; He, Ben

2016-11-01

The aim of this study was to assess the preventive effect of xuezhikang (XZK) to replace atorvastatin on the contrast media-induced acute kidney injury (CI-AKI). The male Sprague-Dawley rats were divided into five groups: group 1 (sham), injected with normal saline; group 2 (XZK), treated with XZK; group 3 contrast media (CM), injected with CM; group 4 (CM + ATO), injected with CM + pretreatment with atorvastatin; group 5 (CM + XZK), injected with CM + pretreatment with XZK. Twenty-four hours after injection with normal saline or CM, the blood sample and the kidneys were collected for the measurement of biochemical parameters, oxidative stress markers, nitric oxide production, inflammatory parameters, as well as renal histopathology and apoptosis detection. Our results indicated that XZK restored the renal function by reducing serum blood urea nitrogen (BUN) and serum creatinine (Scr), depressing renal malondialdehyde (MDA), increasing renal NO production, decreasing TNF-ɑ and IL-6 expression, attenuating renal pathological changes and inhibiting the apoptosis of renal tubular cells. XZK's therapeutic effect is similar, or even better than atorvastatin at the same effectual dose in some parts.

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

Effects of RAAS Inhibitors in Patients with Kidney Disease.

PubMed

Zhang, Fan; Liu, Hong; Liu, Di; Liu, Yexin; Li, Huiqiong; Tan, Xia; Liu, Fuyou; Peng, Youming; Zhang, Hongqing

2017-08-08

Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

Aluminum exacerbates cyclosporin induced nephrotoxicity in rats.

PubMed

Tariq, M; Morais, C; Sujata, B; Sobki, S; al Sulaiman, M; al Khader, A

1999-01-01

Cyclosporin (CSA) has been universally used as an immunosuppressant for the management of allotransplantation and autoimmune diseases. However, nephrotoxicity of CSA limits its use to optimum level. Aluminum (Al) is an extensively distributed element in the environment and human exposure to this metal is unavoidable. Recent studies suggest that even a slight impairment of renal function may increase the Al body burden significantly, which may lead to neurotoxicity, nephrotoxicity, osteodystrophy or hypochromic anemia. In the present study, an attempt was made to study the effect of concomitant use of Al and CSA on structure and function of kidney in rats. This study was undertaken in two steps. In the first set of experiments, the effect of single dose of Al (1% Al2(SO4)3 18H2O) on the nephrotoxicity of multiple doses of CSA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) was studied, where as in the second set of experiments the effect of multiple doses of Al (0.25%, 0.5% and 1%) on single dose of CSA (50 mg/kg) was undertaken. Male Sprague-Dawley rats (weighing 230 +/- 20 g) were used in this study. CSA was given once a day by gavage for seven days, where as Al was given in drinking water for the same period. Twenty four hours after the last dose of CSA, animals were sacrificed and blood and kidney were collected for biochemical and histopathological studies. The bio-chemical parameters included blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Al levels. The kidney homogenates were assayed for malondialdehyde (MDA) and lipid hydroperoxides (LPH). Treatment of rats with CSA alone produced dose-dependent structural and functional changes in kidney. Although Al alone failed to produce any deleterious effect on renal function, it significantly increased the bioavailability and nephrotoxicity of CSA. Al also exacerbated CSA induced increase in oxidative stress (as evident by increased MDA and LPH). Thus, the exacerbation of CSA nephrotoxicity by Al may be attributed to increased bioavailability of CSA and excessive generation of free radicals following concomitant use of these drugs.

Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study.

PubMed

Jetton, Jennifer G; Guillet, Ronnie; Askenazi, David J; Dill, Lynn; Jacobs, Judd; Kent, Alison L; Selewski, David T; Abitbol, Carolyn L; Kaskel, Fredrick J; Mhanna, Maroun J; Ambalavanan, Namasivayam; Charlton, Jennifer R

2016-01-01

Acute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes. The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly "snapshots"; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values. AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences. The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few "lessons learned." The AWAKEN database includes ~325 unique variables and >4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease.

Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney Disease.

PubMed

Gao, Jing; Perlman, Alan; Kalache, Safa; Berman, Nathaniel; Seshan, Surya; Salvatore, Steven; Smith, Lindsey; Wehrli, Natasha; Waldron, Levi; Kodali, Hanish; Chevalier, James

2017-11-01

To evaluate the value of multiparametric quantitative ultrasound imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic findings as reference standards. We prospectively measured multiparametric quantitative ultrasound markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD before kidney biopsy and 10 healthy volunteers. Based on all pathologic (glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and edema) scores, the patients with CKD were classified into mild (no grade 3 and <2 of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD groups. Multiparametric quantitative ultrasound parameters included kidney length, cortical thickness, pixel intensity, parenchymal shear wave velocity, intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index. We tested the difference in quantitative ultrasound parameters among mild CKD, moderate to severe CKD, and healthy controls using analysis of variance, analyzed correlations of quantitative ultrasound parameters with pathologic scores and the estimated glomerular filtration rate (GFR) using Pearson correlation coefficients, and examined the diagnostic performance of quantitative ultrasound parameters in determining moderate CKD and an estimated GFR of less than 60 mL/min/1.73 m 2 using receiver operating characteristic curve analysis. There were significant differences in cortical thickness, pixel intensity, PSV, and EDV among the 3 groups (all P < .01). Among quantitative ultrasound parameters, the top areas under the receiver operating characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated GFR of less than 60 mL/min/1.73 m 2 . Moderate to good correlations were found for PSV, EDV, and pixel intensity with pathologic scores and estimated GFR. The PSV, EDV, and pixel intensity are valuable in determining moderate to severe CKD. The value of shear wave velocity in assessing CKD needs further investigation. © 2017 by the American Institute of Ultrasound in Medicine.

Time-integrated activity coefficient estimation for radionuclide therapy using PET and a pharmacokinetic model: A simulation study on the effect of sampling schedule and noise

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

Hardiansyah, Deni

2016-09-15

Purpose: The aim of this study was to investigate the accuracy of PET-based treatment planning for predicting the time-integrated activity coefficients (TIACs). Methods: The parameters of a physiologically based pharmacokinetic (PBPK) model were fitted to the biokinetic data of 15 patients to derive assumed true parameters and were used to construct true mathematical patient phantoms (MPPs). Biokinetics of 150 MBq {sup 68}Ga-DOTATATE-PET was simulated with different noise levels [fractional standard deviation (FSD) 10%, 1%, 0.1%, and 0.01%], and seven combinations of measurements at 30 min, 1 h, and 4 h p.i. PBPK model parameters were fitted to the simulated noisymore » PET data using population-based Bayesian parameters to construct predicted MPPs. Therapy simulations were performed as 30 min infusion of {sup 90}Y-DOTATATE of 3.3 GBq in both true and predicted MPPs. Prediction accuracy was then calculated as relative variability v{sub organ} between TIACs from both MPPs. Results: Large variability values of one time-point protocols [e.g., FSD = 1%, 240 min p.i., v{sub kidneys} = (9 ± 6)%, and v{sub tumor} = (27 ± 26)%] show inaccurate prediction. Accurate TIAC prediction of the kidneys was obtained for the case of two measurements (1 and 4 h p.i.), e.g., FSD = 1%, v{sub kidneys} = (7 ± 3)%, and v{sub tumor} = (22 ± 10)%, or three measurements, e.g., FSD = 1%, v{sub kidneys} = (7 ± 3)%, and v{sub tumor} = (22 ± 9)%. Conclusions: {sup 68}Ga-DOTATATE-PET measurements could possibly be used to predict the TIACs of {sup 90}Y-DOTATATE when using a PBPK model and population-based Bayesian parameters. The two time-point measurement at 1 and 4 h p.i. with a noise up to FSD = 1% allows an accurate prediction of the TIACs in kidneys.« less

Biochemical assays on plasminogen activators and hormones from kidney sources

NASA Technical Reports Server (NTRS)

Barlow, Grant H.; Lewis, Marian L.; Morrison, Dennis R.

1988-01-01

Investigations were established for the purpose of analyzing the conditioned media from human embryonic kidney cell subpopulations separated in space by electrophoresis. This data is based on the experiments performed on STS-8 on the continuous flow electrophoresis system. The primary biological activity that was analyzed was plasminogen activator activity, but some assays for erythropoeitin and human granulocyte colony stimulating activity were also performed. It is concluded that a battery of assays are required to completely define the plasminogen activator profile of a conditioned media from cell culture. Each type of assay measures different parts of the mixture and are influenced by different parameters. The functional role of each assay is given along with an indication of which combination of assays are required to answer specific questions. With this type of information it is possible by combinations of assays with mathematical analysis to pinpoint a specific component of the system.

Grape seed and skin extract protects kidney from doxorubicin-induced oxidative injury.

PubMed

Mokni, Meherzia; Hamlaoui, Sonia; Kadri, Safwen; Limam, Ferid; Amri, Mohamed; Marzouki, Lamjed; Aouani, Ezzedine

2016-05-01

The study investigated the protective effect of grape seed and skin extract (GSSE) against doxorubicin-induced renal toxicity in healthy rats. Animals were treated with GSSE or not (control), for 8 days, administered with doxorubicin (20mg/kg) in the 4th day, and renal function as well as oxidative stress parameters were evaluated. Data showed that doxorubicin induced renal toxicity by affecting renal architecture and plasma creatinine. Doxorubicin also induced an oxidative stress characterized by an increase in malondialdehyde (MDA), calcium and H(2)O(2) and a decrease in catalase (CAT) and superoxide dismutase (SOD). Unexpectedly doxorubicin increased peroxidase (POD) and decreased carbonyl protein and plasma urea. Treatment with GSSE counteracted almost all adverse effects induced by doxorubicin. Data suggest that doxorubicin induced an oxidative stress into rat kidney and GSSE exerted antioxidant properties, which seem to be mediated by the modulation of intracellular calcium.

Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking.

PubMed

Stangenberg, Stefanie; Nguyen, Long T; Chen, Hui; Al-Odat, Ibrahim; Killingsworth, Murray C; Gosnell, Martin E; Anwer, Ayad G; Goldys, Ewa M; Pollock, Carol A; Saad, Sonia

2015-07-01

An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developmental Programming of Branching Morphogenesis in the Kidney

PubMed Central

Schneider, Laura; Al-Awqati, Qais

2015-01-01

The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases. PMID:25644110

Developmental Programming of Branching Morphogenesis in the Kidney.

PubMed

Sampogna, Rosemary V; Schneider, Laura; Al-Awqati, Qais

2015-10-01

The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases. Copyright © 2015 by the American Society of Nephrology.

Cystatin C– and Creatinine-Based Estimated Glomerular Filtration Rate, Vascular Disease, and Mortality in Persons With Diabetes in the U.S.

PubMed Central

Tsai, Ching-Wei; Grams, Morgan E.; Inker, Lesley A.; Coresh, Josef; Selvin, Elizabeth

2014-01-01

OBJECTIVE Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetes complications. RESEARCH DESIGN AND METHODS We analyzed data from adult participants from the 1999–2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ≥60 mL/min/1.73 m2) or reduced (eGFR <60 mL/min/1.73 m2) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations. RESULTS Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (odds ratio 3.1 [95% CI 1.9–4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality. CONCLUSIONS More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetes complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study. PMID:24271191

Kidney transplantation: evaluation and clinical outcome of 237 recipients at low, medium, high, or strong immunological risk of rejection.

PubMed

Nascimento, E; Fabreti de Oliveira, R A; Maciel, M D; Pereira, A B; das Mercêz de Lucas, F; Salomão-Filho, A; Pereira, W A; Moreira, J B; Vilaça, S S; de Castro Gontijo, R; Lasmar, M F; Vianna, H R; Magalhâes, A; Calazans, C A C; Simão-Filho, C; Vilela, B

2014-01-01

Donor-specific antibodies (DSAs) play a fundamental role in kidney transplantation. The identification of DSAs is an essential rejection parameter. We evaluated a protocol in 237 patients receiving kidneys from living (LDs) and deceased donors (DDs). Recipients were classified as being at low (LR), medium (MR), high (HR), or strong (SR) risk of rejection based on Luminex panel reactive antibody (PRA)-single antigen beads (SABs). Grafts that survived for 1 year were evaluated. Of the 237 transplanted patients, 129 (54.43%) received a kidney from an LD and 108 (45.57%) from a DD. Of 95 LR recipients receiving kidneys from LDs, 2 patients lost the graft due to non-immunological causes. Of 34 MR recipients, 13 had rejection episodes, and 2 lost the graft by AMR and one by cellular rejection (CR). Of 108 recipients receiving a kidney from a DD, 59 (54.63%) were LR, 31 (28.70%) MR, 11 (10.19%) HR, and 7 (6.48%) SR. Twenty of all transplanted recipients lost their grafts; 4 were due to clinical causes, 4 by cellular rejection, and 12 by antibody-mediated rejection (AMR) with PRA-SAB mean fluorescent intensity of 530 to 12,591. One-year graft survival for LD transplanted LR and MR patients was 97.6% and 94.1%, respectively (P = .004). In DD recipients, the LR vs MR SD was P = .011, and for LR vs HR + SR it was P = .001. For MR vs HR+SR no SD was found (P = .323). Rejections were detected in 51 patients (21.52%). Graft failure occurred in 16 patients (6.75%). A total of 218 (91.98%) recipients maintained good kidney function after 1 year. This protocol based on fluxogram risk assessment of AMR provided fast and precise immunological evaluation of recipients and donors and stratification by immunological risk of AMR. Copyright © 2014 Elsevier Inc. All rights reserved.

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

PubMed

Bissolati, Massimiliano; Gazzetta, Paolo Giovanni; Caldara, Rossana; Guarneri, Giovanni; Adamenko, Olga; Giannone, Fabio; Mazza, Michele; Maggi, Giulia; Tomanin, Deborah; Rosati, Riccardo; Secchi, Antonio; Socci, Carlo

2018-03-30

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The renin-angiotensin-aldosterone system blockade in patients with advanced diabetic kidney disease.

PubMed

Bermejo, Sheila; García, Carles Oriol; Rodríguez, Eva; Barrios, Clara; Otero, Sol; Mojal, Sergi; Pascual, Julio; Soler, María José

Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. Non-RAAS blockade patients had worse renal function and older age (p<0.05) at baseline compared to RAAS blockade patients. Patients who received RAAS blockade were not found to have greater toxicity or chronic kidney disease progression and no differences in renal prognosis were identified. Mortality was higher in non-RAAS blockade patients, older patients and patients with worse renal function (p<0.05). In the multivariate analysis, older age and worse renal function were risk factors for mortality. Treatment with RAAS blockade is more common in diabetic kidney disease patients with eGFR≥30ml/min/1.73m 2 . In our study, there were no differences in the evolution of renal function between the three groups. Older age and worse renal function were associated with higher mortality in patients who did not receive RAAS blockade. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

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

Feng, Tao; Tsui, Benjamin M. W.; Li, Xin

Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method inmore » pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.« less

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

[Pharmacological study on Tianxiong (tuber of Aconitum carmichaeli Debx.), a Chinese drug for reinforcing the kidney yang retail in Hong Kong market].

PubMed

Cao, H; Wang, S T; Wu, L Y; Wang, X T; Jiang, A P

2001-06-01

To explore the pharmacodynamic mechanism of Tianxiong (Aconitum carmichaeli) in tonifying the kidney and supporting Yang, so as to provide evidences for further development of new drugs treating Yang-eficiency of the kidney. Observing parameters such as visceral index, survival time of low-temperature swimming for hydrocortisone-induced Yang-deficiency model mouse and testis-removed kidney-deficiency model rat. The decoction of processed Tianxiong could strengthen the antifatigual ability and prolong the survival time of low-temperature swimming for mice, and promote immunization in rats. Tianxiong is able to reinforce the kidney Yang, which reconforms the conclusion of "replenishing the fire of vital gate and the Qi of kidney" recorded in Chinese historical literature and proved by overseas clinical practice.

Supplementation of arachidonic acid rich oil in European sea bass juveniles (Dicentrarchus labrax) diets: Effects on leucocytes and plasma fatty acid profiles, selected immune parameters and circulating prostaglandins levels.

PubMed

Torrecillas, S; Román, L; Rivero-Ramírez, F; Caballero, M J; Pascual, C; Robaina, L; Izquierdo, M S; Acosta, F; Montero, D

2017-05-01

The main objective of this study was to assess the effects of graded levels of dietary arachidonic acid (ARA), supplemented from alternative sources, on fatty acid composition of plasma and head kidney leucocytes of European sea bass (Dicentrarchus labrax). For that purpose, sea bass juveniles were fed four diets containing graded levels of ARA as follows: 0.5% (ARA0.5), 1% (ARA1), 2% (ARA2) and 4% (ARA4) during 60 days. At the end of the feeding trial fatty acid profiles of plasma and head kidney leucocytes were analyzed. Besides, plasma prostaglandins levels, head kidney leucocytes respiratory burst activity; peroxidase activity and phagocytic index were assayed. Reducing dietary ARA levels below 1% markedly reduced European sea bass growth performance. However, fish fed diet ARA0.5 tried to compensate this dietary ARA deficiency by a selective deposition of ARA on plasma and head kidney leucocytes, reaching similar levels to those fish fed diet ARA1 after 60 days of feeding. Nevertheless, head kidney phagocytic capacity was reduced as dietary ARA content in relation not only to variations on membrane composition but also to changes on fish basal prostaglandins levels. Results obtained demonstrated the importance to supply the necessary quantity n-6 LC-PUFA, and not only n-3 LC-PUFA levels, in European sea bass diets, in relation to not only growth performance but also immune system function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Driver, Todd H.; Shlipak, Michael G.; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J.; Hoofnagle, Andrew N.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.; Ix, Joachim H.

2014-01-01

Background Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Study Design Retrospective cohort study. Setting & Participants 6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year). Results The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR. Limitations Etiology of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role in the development of an eGFR <60 mL/min/1.73 m2. PMID:24953891

Kidney Disease Measures and Left Ventricular Structure and Function: The Atherosclerosis Risk in Communities Study.

PubMed

Matsushita, Kunihiro; Kwak, Lucia; Sang, Yingying; Ballew, Shoshana H; Skali, Hicham; Shah, Amil M; Coresh, Josef; Solomon, Scott

2017-09-22

Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR). Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66-90 years during 2011-2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6-87.0] g/m 2 for eGFR <30 mL/min per 1.73 m 2 , 80.9 [95% CI, 77.3-84.6] g/m 2 for eGFR 30-44 mL/min per 1.73 m 2 , and 80.1 [95% CI, 76.7-83.5] g/m 2 for eGFR 45-59 mL/min per 1.73 m 2 compared with 78.7 [95% CI, 75.3-82.1] g/m 2 for eGFR 75-89 mL/min per 1.73 m 2 ; trend P <0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m 2 . For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6-96.5] g/m 2 for ACR ≥300 mg/g and 82.9 [95% CI, 79.4-86.3] g/m 2 for ACR 30-299 mg/g compared with 77.7 [95% CI, 74.4-81.1] g/m 2 for ACR <10 mg/g [trend P <0.001]; left arterial volume index, 24.9 [95% CI, 22.9-26.8] and 24.7 [95% CI, 23.4-26.1] mL/m 2 compared with 23.4 [95% CI, 22.1-24.7] mL/m 2 , respectively [trend P =0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident. LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Suramin protects from cisplatin-induced acute kidney injury

PubMed Central

Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Combining the LKB NTCP model with radiosensitivity parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.

PubMed

Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying

2012-06-01

The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of radiosensitivity parameters. This work replaces the generalized mean equivalent uniform dose (gEUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various radiosensitivity parameters such as intrinsic radiosensitivity α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different radiosensitivity of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different radiosensitivity and different radionuclides. The influence of various radiobiological parameters should be taken into consideration in the NTCP model.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Novel in vivo techniques to visualize kidney anatomy and function.

PubMed

Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

2015-07-01

Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

PubMed

Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

2011-01-01

Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

Sectorial technetium-99m-dimercaptosuccinic acid scintigraphy for monitoring the effect of extracorporeal piezoelectric lithotripsy for calyceal calculi on regional renal function.

PubMed

Al-Tawheed, A; Al-Awadi, K A; Kehinde, E O; Loutfi, I; Abdul-Haleem, H; Al-Mohannadi, S

2003-01-01

To apply a semiquantitative method for analysis of technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy for monitoring the effect of extracorporeal piezoelectric lithotripsy (EPL) in patients with calyceal stones on regional kidney function and to check whether EPL had caused any deleterious effect on the target calyceal renal parenchymal function. Forty patients (mean age 35 years) suffering from calyceal stones documented by abdominal plain radiography, intravenous urogram or abdominal ultrasound were studied. All patients were treated by EPL. (99m)Tc-DMSA scan was performed before and 4 weeks after EPL. Sector analysis involved calculation of the relative function of the target calyx to the function of the ipsilateral kidney and the relative function of the treated kidney to global renal function. The stone sizes were 6-11 mm in diameter and 11 were located in the upper, 13 in the middle and 16 in the lower calyx. After EPL, the overall stone clearance rate was 85% (100% for calculi in the upper and middle calyces, 62% for lower calyces). The sector analysis did not show statistically significant change of the relative regional (calyceal) or whole kidney function between the pre- and post-EPL (99m)Tc-DMSA scans. Using sector analysis, EPL appeared to be a safe modality and its usage was not associated with any untoward effect on calyceal or whole kidney function. Sector analysis of (99m)Tc-DMSA renal scan is a simple semiquantitative method for monitoring regional changes of kidney function after EPL for treatment of calyceal stone. Copyright 2003 S. Karger AG, Basel

The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney.

PubMed

Dankers, Patricia Y W; Boomker, Jasper M; Huizinga-van der Vlag, Ali; Smedts, Frank M M; Harmsen, Martin C; van Luyn, Marja J A

2010-11-10

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

The Aristotelian kidney.

PubMed

Marandola, P; Musitelli, S; Jallous, H; Speroni, A; de Bastiani, T

1994-01-01

Aristotle incorrectly observed the absence of the kidney in fish and birds and deduced that it was not essential for the existence of a living organism. This underlies his observations on structure and function of the kidney. From examination of rhesus monkeys he generalized that the right kidney is higher than the left. Aristotle did not consider that the renal pelvis is divided by a filter membrane into 2 chambers, and wrote that no blood reaches the renal pelvis. The theory of the 'filter kidney' cannot thus be attributed to Aristotle. The function of the kidney was described as being to separate the surplus liquid from the blood inside the renal meat (not in the renal pelvis) and to transform this liquid into what Aristotle called residuum, i.e. the urine. Aristotle also considered that the kidneys acted to anchor the blood vessels to the body. He only briefly considered renal pathology.

Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

PubMed Central

Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

2010-01-01

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

PubMed

Johnson, Richard J; Bakris, George L; Borghi, Claudio; Chonchol, Michel B; Feldman, David; Lanaspa, Miguel A; Merriman, Tony R; Moe, Orson W; Mount, David B; Sanchez Lozada, Laura Gabriella; Stahl, Eli; Weiner, Daniel E; Chertow, Glenn M

2018-06-01

Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cyclosporine A and azathioprine are equipotent in chronic kidney allograft rejection.

PubMed

Hamar, P; Liu, S; Viklický, O; Szabó, A; Múller, V; Heemann, U

2000-04-15

Chronic rejection is the major cause of graft loss after kidney transplantation. Various immunosuppressive protocols have been used to ameliorate this process. We investigated whether cyclosporin A- (CyA) or azathioprine- (Aza) based immunosuppression is better able to slow the progression of chronic rejection. Fisher kidneys were transplanted into bilaterally nephrectomized Lewis rats. Recipients received CyA (1.5 mg/kg/day, s.c.) for 10 days, and were treated from day 11 with either CyA (1.5 mg/kg)+pred (0.15 mg/kg) (C+P),Aza (2 mg/kg)+pred (A+P), vehicle+pred (P), or vehicle alone (controls) (n = 8/group). Proteinuria was regularly assessed and grafts were harvested for morphological, immunohistological, and molecular biological analysis at week 24. By week 12 proteinuria had increased to significant levels. At week 24, proteinuria was significantly lower and creatinine clearance was significantly higher in C+P and A+P, than in P or controls. Morphological analysis supported these functional results: at week 24, glomerulopathy, tubular atrophy and intimal proliferation (as assessed according to the BANFF score) were less pronounced in C+P and A+P, as compared with P or controls. These morphological parameters were accompanied by a reduced infiltration of ED-1+ macrophages and CD-5+ T lymphocytes. In P or controls the synthesis of IL-2Ralpha mRNA was markedly elevated at this time. In parallel to the reduced cellular infiltration, IL-2Ralpha mRNA expression was markedly inhibited, both, in C+P and A+P. There were no significant differences between C+P and A+P regarding the parameters studied. In conclusion, both C+P and A+P reduced the infiltration of activated T lymphocytes, and the pace of chronic kidney allograft rejection. The outcome of C+P and A+P based therapy did not differ significantly.

Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease.

PubMed

Ranganathan, Natarajan; Ranganathan, Pari; Friedman, Eli A; Joseph, Anthony; Delano, Barbara; Goldfarb, David S; Tam, Paul; Rao, A Venketeshwer; Anteyi, Emmanuel; Musso, Carlos Guido

2010-09-01

Uremic syndrome consists of nitrogenous waste retention, deficiency in kidney-derived hormones, and reduced acid excretion, and, if untreated, may progress to coma and eventual death. Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4. This report presents preliminary data from a pilot study. This was a 6-month prospective, randomized, double-blind, placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries, at five institutions, on 46 outpatients with CKD stages 3 an nd 4: USA (n=10), Canada (n=113), Nigeria (n=115), and Argentina (n=8). Outcomes were compared using biochemical parameters:blood urea nitrogen (BUN), serum creatinine, and uric acid. General well-being was assessed as a secondary parameter by a quality of life (QQOL) questionnaire on a subjective scale of 1-10. Oral ingestion of probiotics (90 billion colony forming units [CFUs]/day) was well tolerated and safe during the entire trial period at all sites. BUN levels decreased in 29 patients (63%, P<0.05), creatinine levels decreased in 20 patients (43%, no statistical significance), and uric acid levels decreased in 15 patients (33%, no statistical significance). Almost all subjects expressed a perceived substantial overall improvement in QOL (86%, P<0.05). The main outcomes of this preliminary trial include a significant reduction of BUN, enhanced well-being, and absence of serious adverse effects, thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction. QOL and BUN levels showed statistically significant differences in outcome (P<0.05) between placebo and probiotic treatment periods at all four sites (46 patients). A major limitation of this trial is the small sample size nd elated inconsistencies.

Physiologically based pharmacokinetic modeling of a homologous series of barbiturates in the rat: a sensitivity analysis.

PubMed

Nestorov, I A; Aarons, L J; Rowland, M

1997-08-01

Sensitivity analysis studies the effects of the inherent variability and uncertainty in model parameters on the model outputs and may be a useful tool at all stages of the pharmacokinetic modeling process. The present study examined the sensitivity of a whole-body physiologically based pharmacokinetic (PBPK) model for the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen, gut, muscle, adipose, skin, bone, heart, brain, testes) after i.v. bolus administration to rats. The aims were to obtain new insights into the model used, to rank the model parameters involved according to their impact on the model outputs and to study the changes in the sensitivity induced by the increase in the lipophilicity of the homologues on ascending the series. Two approaches for sensitivity analysis have been implemented. The first, based on the Matrix Perturbation Theory, uses a sensitivity index defined as the normalized sensitivity of the 2-norm of the model compartmental matrix to perturbations in its entries. The second approach uses the traditional definition of the normalized sensitivity function as the relative change in a model state (a tissue concentration) corresponding to a relative change in a model parameter. Autosensitivity has been defined as sensitivity of a state to any of its parameters; cross-sensitivity as the sensitivity of a state to any other states' parameters. Using the two approaches, the sensitivity of representative tissue concentrations (lung, liver, kidney, stomach, gut, adipose, heart, and brain) to the following model parameters: tissue-to-unbound plasma partition coefficients, tissue blood flows, unbound renal and intrinsic hepatic clearance, permeability surface area product of the brain, have been analyzed. Both the tissues and the parameters were ranked according to their sensitivity and impact. The following general conclusions were drawn: (i) the overall sensitivity of the system to all parameters involved is small due to the weak connectivity of the system structure; (ii) the time course of both the auto- and cross-sensitivity functions for all tissues depends on the dynamics of the tissues themselves, e.g., the higher the perfusion of a tissue, the higher are both its cross-sensitivity to other tissues' parameters and the cross-sensitivities of other tissues to its parameters; and (iii) with a few exceptions, there is not a marked influence of the lipophilicity of the homologues on either the pattern or the values of the sensitivity functions. The estimates of the sensitivity and the subsequent tissue and parameter rankings may be extended to other drugs, sharing the same common structure of the whole body PBPK model, and having similar model parameters. Results show also that the computationally simple Matrix Perturbation Analysis should be used only when an initial idea about the sensitivity of a system is required. If comprehensive information regarding the sensitivity is needed, the numerically expensive Direct Sensitivity Analysis should be used.

[The kidney transplantation from the ABO-incompatible donors].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Shishlo, L A; Morozova, M M; Ragimov, A A; Dashkova, N G; Salimov, É L

2012-01-01

The experience of 28 allotransplantations of ABO-incompatible kidneys was compared with the treatment results of 38 ABO-compatible renal transplantations. The transplanted kidney function, morphological changes of the transplanted kidney and the comparative analysis of actuary survival in both groups showed no significant difference. The results of the study prove the validity of the kidney transplantation from the ABO-incompatible donors.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

A case of unilateral nephrectomy performed for autosomal dominant polycystic kidney disease with marked unilateral enlargement.

PubMed

Makabe, Shiho; Kataoka, Hiroshi; Kondo, Tsunenori; Tanabe, Kazunari; Tsuchiya, Ken; Nitta, Kosaku; Mochizuki, Toshio

2018-05-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the occurrence of multiple cysts that increase the size of both kidneys, progressively reducing kidney function. Usually the cysts occur bilaterally, and there is no difference in the degree of cyst enlargement between the left and right. Here, we report a case of ADPKD in which kidney size increased markedly on the left side and was accompanied by severe abdominal distension and discomfort. Renal dynamic scintigraphy revealed a severe reduction in function of the left kidney compared with the right. Open left nephrectomy was performed. No change in renal function was observed postoperatively [preoperative estimated glomerular filtration rate (eGFR): 57.6 mL/min/1.73 m 2 , 3-month postoperative eGFR: 56.4 mL/min/1.73 m 2 ], and the abdominal symptoms subsided. When one kidney is markedly larger than the other, the cause and status of the laterality should be evaluated by using renal dynamic scintigraphy in addition to other examinations such as computed tomography or magnetic resonance imaging. Unilateral nephrectomy should be considered as a potential treatment.

Protective Effect of Sorrel Extract on Adult Rats Treated by Carbon Tetrachloride

PubMed Central

Alkushi, Abdullah Glil

2017-01-01

Context: Heart, kidneys, and liver are the vital organs present in vertebrates and some other animals. They have a wide range of functions, such as maintaining homeostasis, detoxification, protein synthesis, and production of biochemical, that are necessary for digestion and maintaining circulation. These organs are necessary for the survival, and currently, there are no means to compensate for the absence of their functionalities in a long term. The damage of liver can affect other vital organs, including kidneys and heart. Aims: This study aimed at investigating the effect of sorrel extract in the treatment of some of the diseases of liver, kidneys, and heart using experimental animals. Settings and Design: This study is a randomized, controlled clinical trial. Materials and Methods: Forty mature male albino rats, weighing 150–160 g, were used and divided into four equal groups. One group was kept as negative control (C −ve) group whereas the other three groups were injected subcutaneously (s/c) with carbon tetrachloride in 50% V/V paraffin oil (2 ml/kg b.wt.). Tissue specimens were obtained from all the groups and fixed in 10% formalin for histopathological examination. Statistical Analysis Used: The obtained data were statistically analyzed using computerized Superior Performing Statistical Software (SPSS) at SAS Institute, Cary, NC, USA. Effects of different treatments were analyzed by one-way analysis of variance test using Duncan's multiple range test, and P < 0.05 was also used to indicate the significance level between different groups (Snedecor and Cochran, 1967). Results: The resulting data showed that the sorrel extract demonstrated a significant enhancement in liver intoxication and all other tested parameters. In addition, it also helped in minimizing the structural tissue damages in the vital organs. Conclusions: According to these results, sorrel can impair the liver function and maintain the functions of the vital organs. SUMMARY All rats, poisoned with carbon tetrachloride (CCl4) and administrated with all tested herbs, showed a significant increase in BWG as compared to the control (+ve) groupSorrel extract demonstrates a significant enhancement in liver intoxication and all other tested parameters and can reduce the lipid peroxidation in CCl4-induced liver damageAll rats, poisoned with CCl4 and orally fed with all tested herbs, showed a significant decrease in the mentioned parameters when compared to control (+ve) group. Abbreviations Used: ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; ALB: Albumin; BWG%: Body weight gain percentage; CCl4: Carbon tetrachloride; CAT: Catalase; GGT: Gamma-glutamyl transferase; GSH-Px: Glutathione peroxidase; GLOB: Globulin; iNOS: Inducible nitric oxide synthase; MDA: Malondialdehyde; RP: Rumex patientia; SOD: Superoxide dismutase; TP: Total protein; TC: Total cholesterol; TGs: Riglycerides. PMID:28539746

Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

PubMed Central

Mohammod Mostakim, Golam; Zahangir, Md. Mahiuddin; Monir Mishu, Mahbuba; Rahman, Md. Khalilur; Islam, M. Sadiqul

2015-01-01

Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p < 0.05) at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations. PMID:26635877

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

[Paired kidneys in transplant].

PubMed

Regueiro López, Juan C; Leva Vallejo, Manuel; Prieto Castro, Rafael; Anglada Curado, Francisco; Vela Jiménez, Francisco; Ruiz García, Jesús

2009-02-01

Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver. We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple. The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors. This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation

PubMed Central

Stratta, Robert J.; Rohr, Michael S.; Sundberg, Aimee K.; Farney, Alan C.; Hartmann, Erica L.; Moore, Phillip S.; Rogers, Jeffrey; Iskandar, Samy S.; Gautreaux, Michael D.; Kiger, David F.; Doares, William; Anderson, Teresa K.; Hairston, Gloria; Adams, Patricia L.

2006-01-01

Objective: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants. PMID:16632993

Evaluation of Renal Function after Percutaneous Nephrolithotomy-Does the Number of Percutaneous Access Tracts Matter?

PubMed

Gorbachinsky, Ilya; Wood, Kyle; Colaco, Marc; Hemal, Sij; Mettu, Jayadev; Mirzazadeh, Majid; Assimos, Dean G; Gutierrez-Aćeves, Jorge

2016-07-01

Renal function following percutaneous nephrolithotomy has long been a concern to urologists, especially in the setting of multi-tract access. We determined whether the risk of renal injury after multi-tract percutaneous nephrolithotomy was greater than after a single access approach. We retrospectively reviewed the records of 307 consecutive patients treated with percutaneous nephrolithotomy from 2011 to 2012 at Wake Forest Health. Perioperative (99m)Tc-mercaptoacetyltriglycine nuclear renogram parameters along with serum creatinine values were assessed within 1 year of the procedure. Patients were stratified by single access vs multi-access (2 or more). We identified 110 cases in which renography was done before and after percutaneous nephrolithotomy. A total of 74 patients (67.3%) underwent single access percutaneous nephrolithotomy while 36 (32.7%) underwent multi-access percutaneous nephrolithotomy. Serum creatinine did not significantly differ between the 2 cohorts postoperatively (p = 0.09). There was a significant 2.28% decrease in renal function based on mercaptoacetyltriglycine nuclear renogram results after percutaneous nephrolithotomy of the affected kidney in patients with multiple accesses (p <0.01). This relationship was not observed when patients were stratified by multiple comorbidities associated with nephrolithiasis. Multi-access percutaneous nephrolithotomy is associated with a small reduction in the function of the targeted kidney compared to a single access approach. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sleep disorders, depressive symptoms and health-related quality of life--a cross-sectional comparison between kidney transplant recipients and waitlisted patients on maintenance dialysis.

PubMed

Kovacs, Agnes Zsofia; Molnar, Miklos Zsolt; Szeifert, Lilla; Ambrus, Csaba; Molnar-Varga, Marta; Szentkiralyi, Andras; Mucsi, Istvan; Novak, Marta

2011-03-01

Kidney transplantation is believed to improve health-related quality of life (HRQoL) of patients requiring renal replacement therapy (RRT). Recent studies suggested that the observed difference in HRQoL between kidney transplant recipients (Tx) vs patients treated with dialysis may reflect differences in patient characteristics. We tested if Tx patients have better HRQoL compared to waitlisted (WL) patients treated with dialysis after extensive adjustment for covariables. Eight hundred and eighty-eight prevalent Tx patients followed at a single outpatient transplant clinic and 187 WL patients treated with maintenance dialysis in nine dialysis centres were enrolled in this observational cross-sectional study. Data about socio-demographic and clinical parameters, self-reported depressive symptoms and the most frequent sleep disorders assessed by self-reported questionnaires were collected at enrollment. HRQoL was assessed by the Kidney Disease Quality of Life Questionnaire. Patient characteristics were similar in the Tx vs WL groups: the proportion of males (58 vs 60%), mean ± SD age (49 ± 13 vs 49 ± 12) and proportion of diabetics (17 vs 18%), respectively, were all similar. Tx patients had significantly better HRQoL scores compared to the WL group both in generic (Physical function, General health perceptions, Energy/fatigue, Emotional well-being) and in kidney disease-specific domains (Symptoms/problems, Effect- and Burden of kidney disease and Sleep). In multivariate regression models adjusting for clinical and socio-demographic characteristics, sleep disorders and depressive symptoms, the modality of RRT (WL vs Tx) remained independently associated with three (General health perceptions, Effect- and Burden of kidney disease) out of the eight HRQoL dimensions analysed. Kidney Tx recipients have significantly better HRQoL compared to WL dialysis patients in some, but not all, dimensions of quality of life after accounting for differences in patient characteristics. Utilizing multidimensional disease-specific questionnaires will allow better understanding of treatment, disease and patient-related factors potentially affecting quality of life in patients with chronic medical conditions.

Inhibition property of green tea extract in relation to reserpine-induced ribosomal strips of rough endoplasmic reticulum (rER) of the rat kidney proximal tubule cells.

PubMed

Abdel-Majeed, Safer; Mohammad, Afzal; Shaima, Al-Bloushi; Mohammad, Rafique; Mousa, Shaker A

2009-12-01

The aim of this study was to evaluate the effect of green tea in inhibiting and reversing the nephrotoxicity of reserpine--a potent oxidative stress inducer--which induced cellular kidney damage. Serum biochemical parameters, antioxidant enzyme levels, thiobarbituric acid reactive substances (TBARS) and serum transaminases (glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) values and histopathology were systematically evaluated. Reserpine exposure led to increase the oxidative stress and organ injury was significantly observed through biochemical parameters and ultrastructural evaluation. Sprague-Dawely (S.D.) rats were intraperitonealy administered reserpine to induce oxidative kidney damage. Experimental rats were given green tea extract according to the protocol given below. Sixty rats were randomly divided into six groups, with 10 rats in each group. Reserpine was found to cause kidney proximal tubule damage, such as stripping and clustering of ribosomes from the rough endoplasmic reticulum (rER) and demolishing of mitochondrial christae with elevated level of oxidative stress markers, such as TBARS. While the ultrastructural study showed a revival of kidney proximal tubule cells as a result of the administration of green tea extract to rats. We suggest that green tea might elevate antioxidant defense system, clean up free radicals, lessen oxidative damages and protect kidney against reserpine-induced toxicity and thus had a potential protective effect.

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease.

PubMed

Nowak, Albina; Koch, Gilbert; Huynh-Do, Uyen; Siegenthaler, Martin; Marti, Hans-Peter; Pfister, Marc

2017-01-01

Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males. A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function. © 2017 The Author(s)Published by S. Karger AG, Basel.

A study on evaluation of the dependences of the function and the shape in a 99 m Tc-DMSA renal scan on the difference in acquisition count

NASA Astrophysics Data System (ADS)

Dong, Kyung-Rae; Shim, Dong-Oh; Kim, Ho-Sung; Park, Yong-Soon; Chung, Woon-Kwan; Cho, Jae-Hwan

2013-02-01

In a nuclear medicine examination, methods to acquire a static image include the preset count method and the preset time method. The preset count method is used mainly in a static renal scan that utilizes 99 m Tc-DMSA (dimoercaptosuccinic acid) whereas the preset time method is used occasionally. When the preset count method is used, the same number of acquisition counts is acquired for each time, but the scan time varies. When the preset time method is used, the scan time is constant, but the number of counts acquired is not the same. Therefore, this study examined the dependence of the difference in information on the function and the shape of both sides of the kidneys on the counts acquired during a renal scan that utilizes 99 m Tc-DMSA. The study involved patients who had 40-60% relative function of one kidney among patients who underwent a 99 m Tc-DMSA renal scan in the Nuclear Medicine Department during the period from January 11 to March 31, 2012. A gamma camera was used to obtain the acquisition count continuously using 100,000 counts and 300,000 counts, and an acquisition time of 7 minutes (exceeding 300,000 counts). The function and the shape of the kidney were evaluated by measuring the relative function of both sides of the kidneys, the geometric mean, and the size of kidney before comparative analysis. According to the study results, neither the relative function nor the geometric mean of both sides of the kidneys varied significantly with the acquisition count. On the other hand, the size of the kidney tended to be larger with increasing acquisition count.

4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice

PubMed Central

Xie, Luke; Qi, Yi; Subashi, Ergys; Liao, Grace; Miller DeGraff, Laura; Jetten, Anton M.; Johnson, G. Allan

2015-01-01

Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant lose of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that while kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3 to 17 weeks) and applied high spatiotemporal resolution MRI (125×125×125 cubic microns every 7.7 seconds). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements including kidney volume, cyst volume, and cyst-kidney volume ratio changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, while TTP variance increased with age. The treatment of rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, while renal function remained the same. Quantifying renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment. PMID:25810360

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PubMed

Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

2015-01-01

We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

An evaluation of the protective role of α-tocopherol on free radical induced hepatotoxicity and nephrotoxicity due to chromium in rats

PubMed Central

Balakrishnan, Rajendran; Satish Kumar, Chitturi Sree; Rani, Matukumalli Usha; Srikanth, Mylaram Kistaiah; Boobalan, Gopu; Reddy, Alla Gopala

2013-01-01

Aim: To avert the health problems induced by many environmental pollutants, available antioxidants have been evaluated. The present study was aimed to investigate whether α-tocopherol could protect the hexavalent chromium (Cr VI)-induced peroxidation in the liver and kidney and to explore the underlying mechanism of the same. Materials and Methods: A total of 24 Wistar adult female rats were equally divided into four groups. Group 1 served as control while Groups 2 and 3 were administered K2Cr2O7(10 mg/kg b.wt. s.c. single dose). In addition to (Cr VI), Group 3 also received α-tocopherol (125 mg/kg, daily) by oral gavage for 14 days. Group 4 was maintained as α-tocopherol control (dose as above). At the end of 14 days, blood samples were drawn for hematology. Subsequently, all the rats were sacrificed to collect liver and kidney samples for assay of tissue peroxidation markers, antioxidant markers and functional markers and histopathology. Results: Administration of chromium (Cr VI) in Group 2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide dismutase and reduced glutathione along with significant (P < 0.05) increase in peroxidation markers such as malondialdehyde and protein carbonyls in the liver and kidney as compared with other groups. The functional markers in serum such as total protein was decreased significantly (P < 0.05), whereas other functional markers viz. alanine transaminase, blood urea nitrogen and creatinine were increased significantly (P < 0.05) in Group 2 as compared with the other groups. Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total leukocyte count were observed in Cr VI treated Group 2 rats. Prominent pathological changes were observed in the liver and kidney of Group 2. Co-treatment with α-tocopherol in Group 3 rats significantly (P < 0.05) reversed the Cr VI induced changes. The parameters in the study in Group 4 did not differ as compared with Group 1. Conclusions: α–tocopherol exhibited protective effect against Cr VI-induced damage to the liver and kidney by inhibition of lipid peroxidation owing its antioxidant activity. PMID:24130385

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

PubMed

Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

2018-02-01

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study.

PubMed

Banerjee, Tanushree; Tucker, Katherine; Griswold, Michael; Wyatt, Sharon B; Harman, Jane; Young, Bessie; Taylor, Herman; Powe, Neil R

2018-07-01

Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20 years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17 mg/g for men, >25 mg/g for women), reduced kidney function (eGFR <60 mL/minute/1.73 m 2 ), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Association between Delayed graft function (DGF) biomarkers and long-term outcomes after living donor kidney transplantation.

PubMed

Sahraei, Zahra; Mehdizadeh, Mona; Salamzadeh, Jamshid; Nafar, Mohsen; Eshraghi, Azadeh

2018-05-21

The Association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interlukin-18 (uIL-18) with poor 1-year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is any association between these postoperative biomarkers with important recipient outcomes beyond this time in live-donor transplants. NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Also, the association between delayed graft function with clinical outcome and serum creatinine (SrCr) were evaluated during this period. The Mean age for kidney recipients was 23.9 years. There was significant interaction between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). Changes in urine NGAL postoperative is associated with worse outcome 2 years after kidney transplantation, suggesting its potential role for identifying patients that are at high risk for diminished allograft function, outcome and survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.

PubMed

Rudnicki, Michael; Mayr, Johannes A; Zschocke, Johannes; Antretter, Herwig; Regele, Heinz; Feichtinger, René G; Windpessl, Martin; Mayer, Gert; Pölzl, Gerhard

2016-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNA Leu(UUR) . Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m 2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Automatic detection of kidney in 3D pediatric ultrasound images using deep neural networks

NASA Astrophysics Data System (ADS)

Tabrizi, Pooneh R.; Mansoor, Awais; Biggs, Elijah; Jago, James; Linguraru, Marius George

2018-02-01

Ultrasound (US) imaging is the routine and safe diagnostic modality for detecting pediatric urology problems, such as hydronephrosis in the kidney. Hydronephrosis is the swelling of one or both kidneys because of the build-up of urine. Early detection of hydronephrosis can lead to a substantial improvement in kidney health outcomes. Generally, US imaging is a challenging modality for the evaluation of pediatric kidneys with different shape, size, and texture characteristics. The aim of this study is to present an automatic detection method to help kidney analysis in pediatric 3DUS images. The method localizes the kidney based on its minimum volume oriented bounding box) using deep neural networks. Separate deep neural networks are trained to estimate the kidney position, orientation, and scale, making the method computationally efficient by avoiding full parameter training. The performance of the method was evaluated using a dataset of 45 kidneys (18 normal and 27 diseased kidneys diagnosed with hydronephrosis) through the leave-one-out cross validation method. Quantitative results show the proposed detection method could extract the kidney position, orientation, and scale ratio with root mean square values of 1.3 +/- 0.9 mm, 6.34 +/- 4.32 degrees, and 1.73 +/- 0.04, respectively. This method could be helpful in automating kidney segmentation for routine clinical evaluation.

Autosomal Dominant Polycystic Kidney Disease

MedlinePlus

... replacement therapies—hemodialysis and kidney transplantation, developed through fundamental NIH research in the 1960s—were increasingly available ... possible to restore lost kidney function. More aggressive management of diabetes and high blood pressure, as well ...

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ballew, Shoshana H; Chen, Yan; Daya, Natalie R; Godino, Job G; Windham, B Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

2017-02-01

Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR cr ) and serum cystatin C level (eGFR cys ) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR cr <60mL/min/1.73m 2 , 2,480 (50%) had eGFR cys <60mL/min/1.73m 2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR cr and eGFR cys <60mL/min/1.73m 2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR cr and a strong association with eGFR cys and albumin-creatinine ratio. Frail individuals with eGFR cr of 60 to <75mL/min/1.73m 2 were frequently reclassified to lower eGFR categories using eGFR cys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m 2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFR cys versus eGFR cr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Mononuclear phagocyte subpopulations in the mouse kidney.

PubMed

George, James F; Lever, Jeremie M; Agarwal, Anupam

2017-04-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases.

Mild cognitive impairment in older adults with pre-dialysis patients with chronic kidney disease: Prevalence and association with physical function.

PubMed

Otobe, Yuhei; Hiraki, Koji; Hotta, Chiharu; Nishizawa, Hajime; Izawa, Kazuhiro P; Taki, Yasuhiro; Imai, Naohiko; Sakurada, Tsutomu; Shibagaki, Yugo

2017-09-26

Chronic kidney disease (CKD) is a risk factor for declining cognitive and physical function. However, the prevalence of mild cognitive impairment (MCI) and its relationship with physical function is not clear. Therefore, our aim was to evaluate the prevalence of MCI and the relationship between MCI and physical function among older adults with pre-dialysis CKD. We conducted a cross-sectional study of 120 patients, aged ≥ 65 years (mean age, 77.3 years), with pre-dialysis CKD but without probable dementia (Mini Mental State Examination < 24). MCI was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). For analysis, patients were classified into two cognitive function groups: normal (MoCA-J ≥26) and MCI (MoCA-J <26). Physical, clinical, and biochemical parameters were compared between the groups. Logistic and linear regression analyses were used to evaluate the specific association between cognitive and physical function. Seventy-five patients (62.5%) patients belonged to the MCI group. Significant differences between the two groups were identified for gait speed, balance, age, and haemoglobin concentration. After adjustment for covariates, only gait speed was significantly associated with MCI (odds ratio, 0.06; 95% confidence interval, 0.009-0,411). The prevalence of MCI among older adults with pre-dialysis CKD was as high as 62.5%. The association between MCI and reduced gait speed supports the possible interaction between physical and cognitive functions and the need for early screening. This article is protected by copyright. All rights reserved.

The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis".

PubMed

Bricker, N S; Morrin, P A; Kime, S W

1997-09-01

Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.

Supplementing diet with Manitoba lingonberry juice reduces kidney ischemia-reperfusion injury.

PubMed

Isaak, Cara K; Wang, Pengqi; Prashar, Suvira; O, Karmin; Brown, Daniel Cw; Debnath, Samir C; Siow, Yaw L

2017-07-01

Lingonberry (Vaccinium vitis-idaea L.) contains high levels of anthocyanins which are bioavailable in the kidney and may be protective against ischemia-reperfusion (IR)-induced acute kidney injury. This study investigated the effect of lingonberry juice on the IR-induced stress-activated signalling pathway and inflammatory response in the kidney. Sprague-Dawley rats subjected to kidney IR had significantly impaired kidney function, with increased activation of the JNK signalling pathway and increased inflammatory response, measured using a multiplex panel containing an extensive array of inflammatory biomarkers. In rats fed 1 mL lingonberry juice daily for 3 weeks prior to IR, kidney function was protected and attenuation of inflammatory response and JNK signalling was reflected in the reduction of the measured biomarkers. In vitro results in cultured HK-2 cells confirmed that lingonberry anthocyanins reduced JNK signalling and inflammatory gene expression after IR. This study shows, for the first time, that daily supplementation with lingonberry juice may protect against loss of kidney function induced by IR injury by modulating JNK signalling and inhibiting the subsequent inflammatory response. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry.

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

PubMed

Vize, P D; Seufert, D W; Carroll, T J; Wallingford, J B

1997-08-15

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Renal cortical volume: High correlation with pre- and post-operative renal function in living kidney donors.

PubMed

Gardan, Edouard; Jacquemont, Lola; Perret, Christophe; Heudes, Pierre-Marie; Gourraud, Pierre-Antoine; Hourmant, Maryvonne; Frampas, Eric; Limou, Sophie

2018-02-01

CT volumetry has previously been proposed as an alternative to scintigraphy for the evaluation of pre-donation split renal function and the prediction of post-donation renal function in living kidney donors. The aim of our study was to retrospectively assess the relevance of three CT volumetry techniques for estimating pre-donation kidney function and predicting the risk for chronic kidney disease (CKD) at 1-year post-nephrectomy in a French cohort of living donors using isotopic measures of kidney function. Kidney volume was quantified pre-donation for 105 donors using three methods total parenchymal three-dimensional renal volume (3DRV), total parenchymal renal volume contouring (RVCt), and renal cortical volume (RCoV). Subjects also had a 51Cr-EDTA scintigraphy to measure glomerular filtration rate (mGFR) pre-donation and 1-year after donation. For each volume, we tested for association with mGFR using univariate regression models, and computed receiver operating characteristics analyses to assess their predictive potential of post-donation CKD. Our population was composed of healthy subjects, who were predominantly female (69%) with a median age at donation of 51yo. Median mGFR was 102 mL/min/1.73 m 2 at pre-donation and 66 mL/min/1.73 m 2 1-year after nephrectomy. The pre-donation median volume of the preserved kidney was 156 cm 3 , 163 cm 3 and 99 cm 3 for the 3DRV, RVCt and RCoV methods respectively, with a high correlation observed between each technique (R > 0.84). For all methods, total kidney volume was significantly associated with pre-donation mGFR (P < 0.001). Preserved kidney volume was also strongly correlated with post-donation mGFR (P < 0.0001), with the strongest correlation observed for RCoV (R = 0.60 vs. R = 0.39 and R = 0.51 for 3DRV and RVCt, respectively). Finally, the RCoV method yielded the best predictive value of 1-year post-donation CKD (AUC = 0.80 vs. AUC = 0.76 and 0.70 for RVCt and 3DRV, respectively). In our cohort of healthy donors with measured kidney function, cortical volumetry (RCoV) appears as the best volumetric technique to use as a surrogate to scintigraphy for estimating pre-donation split renal function and predicting post-donation renal outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 42716 - Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

...] Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop AGENCY: Food... outcomes in kidney transplantation. This public workshop is intended to obtain information from health care... for the prophylaxis and/or treatment of delayed graft function (DGF) and related conditions in kidney...

[Lithium treatment in patients with impaired kidney function: Between Scylla and Charybdis].

PubMed

Dehning, Julia; Grunze, Heinz; Born, Christoph; Hausmann, Armand

2017-05-01

Introduction In quite a few patients with bipolar disorder there is no real alternative to lithium treatment despite impaired kidney function. Is it possible to continue lithium treatment despite kidney malfunction by changing dosage and/or frequency of administration? Case Report We report on a 65-year-old woman suffering from bipolar-I disorder who had been on lithium treatment for many decades. While on lithium, the glomerular filtration rate (GFR) decreased constantly. A decision had to be made whether to switch to a more tolerable o.d. administration or to taper off lithium. Conclusion With a single dose at bedtime, the serum levels remained stable; however, kidney function unfortunately did not improve. A relevant increase of GFR above the level of 60 mL/min/1,73 m 2 was only achieved after a 50% dose reduction leading also to a substantial decrease of lithium serum levels. A kidney protective lithium application in patients with reduced renal function is like sailing between Scylla and Charybdis. Georg Thieme Verlag KG Stuttgart · New York.

The biomechanics of the kidney: the isothermal function of the capsule adipose renis.

PubMed

Rados, N; Keros, P; Trnski, D; Muftić, O

1993-01-01

The paper describes the research in the field of thermodynamics. It deals with the function of capsule adipose renis. This homogenous tissue of low temperature acts as an independent thermal conductor. In fact, by encapsulating the kidney, it acts as a vacuum-flask, providing insulation for the kidney from two surrounding thermal areas, the warmer being on the interperitoneum and the cooler on the skin surface.

Recurrent clot anuria following laparoscopic pyeloplasty in a solitary functioning kidney: managing with double guide wire technique

PubMed Central

Kumar, Santosh; Singh, Shivanshu; Parmar, Kalpesh Mahesh; Garg, Nitin

2014-01-01

Clot anuria in a solitary functioning kidney is an emergency situation. Haematuria with clot anuria in an early postoperative period represents a challenge, as treatment options are limited. Manipulation of the anastomotic site may lead to anastomotic disruption and urinoma while use of thrombolytic therapy poses the danger of increasing haematuria. We report a case of anuria due to clot retention in the upper tract following laparoscopic dismembered pyeloplasty in a solitary functioning kidney, managed successfully with double guide wire technique. PMID:25540210

Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

PubMed Central

Ohashi, Y.; Thomas, G.; Nurko, S.; Stephany, B.; Fatica, R.; Chiesa, A.; Rule, A. D.; Srinivas, T.; Schold, J. D.; Navaneethan, S. D.; Poggio, E. D.

2013-01-01

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. PMID:23865821

New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

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

Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu

2005-06-17

Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1more » proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.« less

Preeclampsia Risks in Kidney Donors and Recipients.

PubMed

Shah, Pratik B; Samra, Manpreet; Josephson, Michelle A

2018-06-08

To review the studies and practice guidelines on the preeclampsia risks in kidney donors and recipients. There is a small increased risk of gestational hypertension and preeclampsia in pregnancies that follow kidney donation. Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline (2017) and the 2015 American Society of Transplantation (AST) consensus conference statement recommends counseling kidney donors about this increased risk. There is no observed increase in fetal complications or eclampsia post-kidney donation. Preeclampsia is more commonly observed in kidney transplant recipients than the general population and these patients should be co-managed with an obstetrician with experience in managing high risk pregnancies. Although preeclampsia has not been found to have a deleterious effect on renal graft function, it can cause premature delivery. Risk calculators have been proposed and an elevated pre-pregnancy creatinine seems to be an important risk. KDIGO Clinical Practice Guidelines (2009) recommends attempting pregnancy when kidney function is stable with proteinuria of less than 1 g per day. The use of novel biomarkers for preeclampsia has not been published in this population. Preeclampsia is an important concern for female kidney donors and recipients of child-bearing age. These individuals should be appropriately counseled.

Natural killer cell function predicts severe infection in kidney transplant recipients.

PubMed

Dendle, Claire; Gan, Poh-Yi; Polkinghorne, Kevan R; Ngui, James; Stuart, Rhonda L; Kanellis, John; Thursky, Karin; Mulley, William R; Holdsworth, Stephen

2018-04-30

The aim of this study was to determine if natural killer cell number (CD3 - /CD16 ± /CD56 ± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Case Report: First Reported Combined Heart-Liver Transplant in a Patient With a Congenital Solitary Kidney.

PubMed

Hanna, R M; Kamgar, M; Hasnain, H; Khorsan, R; Nsair, A; Kaldas, F; Baas, A; Bunnapradist, S; Wilson, J M

2018-04-01

We report a case of successful combined heart liver transplant in a patient with a congenital solitary kidney. The patient had normal renal function before combined heart-liver transplantation and developed acute kidney injury requiring slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks post transplantation. Her renal function recovered and she remains off dialysis now 7 months post transplantation. She only currently has mild chronic renal insufficiency. We believe this is the first reported case of successful heart liver transplant in a patient with a congenital solitary kidney. Published by Elsevier Inc.

[A computer tomography assisted method for the automatic detection of region of interest in dynamic kidney images].

PubMed

Jing, Xueping; Zheng, Xiujuan; Song, Shaoli; Liu, Kai

2017-12-01

Glomerular filtration rate (GFR), which can be estimated by Gates method with dynamic kidney single photon emission computed tomography (SPECT) imaging, is a key indicator of renal function. In this paper, an automatic computer tomography (CT)-assisted detection method of kidney region of interest (ROI) is proposed to achieve the objective and accurate GFR calculation. In this method, the CT coronal projection image and the enhanced SPECT synthetic image are firstly generated and registered together. Then, the kidney ROIs are delineated using a modified level set algorithm. Meanwhile, the background ROIs are also obtained based on the kidney ROIs. Finally, the value of GFR is calculated via Gates method. Comparing with the clinical data, the GFR values estimated by the proposed method were consistent with the clinical reports. This automatic method can improve the accuracy and stability of kidney ROI detection for GFR calculation, especially when the kidney function has been severely damaged.

The impact of gut microbiota on kidney function and pathogenesis.

PubMed

Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

2017-09-01

Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

PubMed Central

Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

2013-01-01

Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

What happens to the heart in chronic kidney disease?

PubMed

Rutherford, E; Mark, P B

2017-03-01

Cardiovascular disease is common in patients with chronic kidney disease. The increased risk of cardiovascular disease seen in this population is attributable to both traditional and novel vascular risk factors. Risk of sudden cardiac or arrhythmogenic death is greatly exaggerated in chronic kidney disease, particularly in patients with end stage renal disease where the risk is roughly 20 times that of the general population. The reasons for this increased risk are not entirely understood and while atherosclerosis is accelerated in the presence of chronic kidney disease, premature myocardial infarction does not solely account for the excess risk. Recent work demonstrates that the structure and function of the heart starts to alter early in chronic kidney disease, independent of other risk factors. The implications of cardiac remodelling and hypertrophy may predispose chronic kidney disease patients to heart failure, arrhythmia and myocardial ischaemia. Further research is needed to minimise cardiovascular risk associated with structural and functional heart disease associated with chronic kidney disease.

The endoderm indirectly influences morphogenetic movements of the zebrafish head kidney through the posterior cardinal vein and VegfC.

PubMed

Chou, Chih-Wei; Hsu, Hsiao-Chu; You, May-Su; Lin, Jamie; Liu, Yi-Wen

2016-08-01

Integration of blood vessels and organ primordia determines organ shape and function. The head kidney in the zebrafish interacts with the dorsal aorta (DA) and the posterior cardinal vein (PCV) to achieve glomerular filtration and definitive hematopoiesis, respectively. How the head kidney co-develops with both the axial artery and vein remains unclear. We found that in endodermless sox32-deficient embryos, the head kidney associated with the PCV but not the DA. Disrupted convergent migration of the PCV and the head kidney in sox32-deficient embryos was rescued in a highly coordinated fashion through the restoration of endodermal cells. Moreover, grafted endodermal cells abutted the host PCV endothelium in the transplantation assay. Interestingly, the severely-disrupted head kidney convergence in the sox32-deficient embryo was suppressed by both the cloche mutation and the knockdown of endothelial genes, indicating that an interaction between the endoderm and the PCV restricts the migration of the head kidney. Furthermore, knockdown of either vegfC or its receptor vegfr3 suppressed the head kidney convergence defect in endodermless embryos and perturbed the head kidney-PCV association in wild-type embryos. Our findings thus underscore a role for PCV and VegfC in patterning the head kidney prior to organ assembly and function.

Two-as-one monolateral dual kidney transplantation.

PubMed

Veroux, Pierfrancesco; Giuffrida, Giuseppe; Cappellani, Alessandro; Caglià, Pietro; Palmucci, Stefano; Sorbello, Massimiliano; Puzzo, Lidia; Veroux, Massimiliano

2011-01-01

Dual kidney transplantation (DKT) of marginal kidneys could offer transplant candidates a very satisfactory kidney transplantation in terms of renal function. However, DKT might be considered a major surgical procedure and, in older recipients, has a potentially greater risk of surgical complications compared with single kidney transplantation. Because of these findings, some transplant centers have replaced the classic bilateral placement of 2 kidneys with the monolateral placement of both kidneys. In a group of 35 DKTs performed during a 5-year period, we applied a new technique of monolateral placement of DKT in 10 recipients. In these 10 patients, the arteries and veins of the 2 kidneys were joined through a running suture, and the joined kidneys were anastomosed into the external iliac vessels in the recipient. The delayed graft function rate was 20%. No surgical complications developed in the entire series. One patient experienced late rejection with ureteral stricture. The graft and patient survival rate at a median follow-up of 30 months was 90%. To reduce the surgical risk and morbidity rate, the monolateral placement of both kidneys seems the safest method to perform DKT. The joined monolateral DKT, by reducing the cold ischemia time and the surgical trauma, could represent a step forward in the delicate treatment of these patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Association between kidney function and telomere length: the Heart and Soul Study

PubMed Central

Bansal, Nisha; Whooley, Mary A.; Regan, Mathilda; McCulloch, Charles E.; Ix, Joachim H.; Epel, Elissa; Blackburn, Elizabeth; Lin, Jue; Hsu, Chi-yuan

2013-01-01

Background Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods The Heart and Soul study is a longitudinal study of patients with stable coronary heart disease (CHD). Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (N=954) and 5 years later (N=608). Linear regression models were used to test the association of kidney function with i) baseline telomere length and ii) change in telomere length over 5 years. Results At baseline, mean eGFRCKD-EPI was 72.6 (± 21.5) ml/min/1.73 m2, eGFRcys was 71.0 (± 23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/gm. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 [95% CI 1.2–16.9] fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 [95% CI 4.3–17.3] decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant. Conclusions In patients with CHD, reduced kidney function is associated with i) shorter baseline telomere length and ii) more rapid telomere shortening over 5 years, however these associations are entirely explained by older age. PMID:23108000

Arterial wave reflections and kidney function decline among persons with preserved estimated glomerular filtration rate: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Hsu, Jeffrey J; Katz, Ronit; Chirinos, Julio A; Jacobs, David R; Duprez, Daniel A; Peralta, Carmen A

2016-05-01

Differences in arterial wave reflections have been associated with increased risk for heart failure and mortality. Whether these measures are also associated with kidney function decline is not well established. Reflection magnitude (RM, defined as the ratio of the backward wave [Pb] to that of the forward wave [Pf]), augmentation index (AIx), and pulse pressure amplification (PPA) were derived from radial tonometry measures among 5232 participants free of cardiovascular disease who were enrolled in the Multiethnic Study of Atherosclerosis. Kidney function was estimated by creatinine and cystatin C measurements, as well as albumin-to-creatinine ratio. We evaluated the associations of Pb, Pf, RM, AIx, and PPA with annualized estimated glomerular filtration rate (eGFR) change and rapid kidney function decline over 5 years, using generalized linear mixed models and logistic regression, respectively. Of the study participants, 48% were male, mean age was 62 years, mean eGFR and median albumin-to-creatinine ratio at baseline were 84 mL/min/1.73 m(2) and 5.3 mg/g, respectively. In demographically adjusted models, both Pb and Pf had similarly strong associations with kidney function decline; compared to those in the lowest tertiles, the persons in the highest tertiles of Pb and Pf had a 1.01 and 0.99 mL/min/1.73 m(2)/year faster eGFR decline, respectively (P < .05). However, these associations were attenuated after adjustment for systolic blood pressure. We found no significant associations between RM, AIx, or PPA and kidney function decline. In conclusion, the reflected and forward wave components were similarly associated with kidney function decline, and these associations were explained by differences in systolic blood pressure. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

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

Arfian, Nur; Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp; Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe

Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secretedmore » by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and ET{sub A} receptor expression. This was accompanied by tubular injury, wall thickening and reduction of lumen area/wall area ratio of small renal arteries, increased oxidative stress and inflammation. These parameters were attenuated in VEETKO mice. Conclusion: Our results suggest that suppression of ET-1 from the endothelial cells attenuates IRI kidney injury. Blocking ET-1 effects may represent a therapeutic strategy in the management of AKI.« less

Primary Hyperparathyroidism

MedlinePlus

... blood calcium (above a certain level) • Impaired kidney function Non-surgical treatment: checkups and medicines For some patients without signs or symptoms, doctors recommend regular checkups instead of surgery. ... to check kidney function, and checks of bone density. A doctor may ...

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

PubMed Central

Herrero, Esther; Torras, Joan; Ripoll, Elia; Flaquer, Maria; Gomà, Montse; Lloberas, Nuria; Anegon, Ignacio; Cruzado, Josep M.; Grinyó, Josep M.; Herrero-Fresneda, Immaculada

2012-01-01

In solid organ transplantation, mesenchymal stem cell (MSC) therapy is strongly emerging among other cell therapies due to the positive results obtained in vitro and in vivo as an immunomodulatory agent and their potential regenerative role. We aimed at testing whether a single dose of MSCs, injected at 11 weeks after kidney transplantation for the prevention of chronic mechanisms, enhanced regeneration and provided protection against the inflammatory and fibrotic processes that finally lead to the characteristic features of chronic allograft nephropathy (CAN). Either bone marrow mononuclear cells (BMCs) injection or no-therapy (NT) were used as control treatments. A rat kidney transplantation model of CAN with 2.5 h of cold ischemia was used, and functional, histological, and molecular parameters were assessed at 12 and 24 weeks after transplantation. MSC and BMC cell therapy preserves renal function at 24 weeks and abrogates proteinuria, which is typical of this model (NT24w: 68.9±26.5 mg/24 h, MSC24w: 16.6±2.3 mg/24 h, BMC24w: 24.1±5.3 mg/24 h, P<0.03). Only MSC-treated animals showed a reduction in interstitial fibrosis and tubular atrophy (NT24w: 2.3±0.29, MSC24w: 0.4±0.2, P<0.03), less T cells (NT: 39.6±9.5, MSC: 8.1±0.9, P<0.03) and macrophages (NT: 20.9±4.7, MSC: 5.9±1.7, P<0.05) infiltrating the parenchyma and lowered expression of inflammatory cytokines while increasing the expression of anti-inflammatory factors. MSCs appear to serve as a protection from injury development rather than regenerate the damaged tissue, as no differences were observed in Ki67 expression, and kidney injury molecule-1, Clusterin, NGAL, and hepatocyte growth factor expression were only up-regulated in nontreated animals. Considering the results, a single delayed MSC injection is effective for the long-term protection of kidney allografts. PMID:22494435

Acute Knockdown of Uncoupling Protein-2 Increases Uncoupling via the Adenine Nucleotide Transporter and Decreases Oxidative Stress in Diabetic Kidneys

PubMed Central

Friederich-Persson, Malou; Aslam, Shakil; Nordquist, Lina; Welch, William J.; Wilcox, Christopher S.; Palm, Fredrik

2012-01-01

Increased O2 metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O2 consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (−30–50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT. PMID:22768304

Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

PubMed

Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun

2017-09-11

To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

Investigation of aquaporins and apparent diffusion coefficient from ultra-high b-values in a rat model of diabetic nephropathy.

PubMed

Wang, Yu; Zhang, Heng; Zhang, Ruzhi; Zhao, Zhoushe; Xu, Ziqian; Wang, Lei; Liu, Rongbo; Gao, Fabao

2017-01-01

To assess kidney damage in a rat model of type-2 diabetic nephropathy based on apparent diffusion coefficient (ADC) data obtained from ultra-high b-values and discuss its relationship to the expression of aquaporins (AQPs). This study was approved by the institutional Animal Care and Use Committee. Thirty male Sprague-Dawley rats were randomised into two groups: (1) untreated controls and (2) diabetes mellitus (DM). All rats underwent diffusion-weighted imaging (DWI) with 18 b-values (0-4500 s/mm 2 ). Maps of low ADC (ADC low ), standard ADC (ADC st ) and ultra-high ADC (ADC uh ) were calculated from low b-values (0-200 s/mm 2 ), standard b-values (300-1500 s/mm 2 ) and ultra-high b-values (1700-4500 s/mm 2 ), respectively. The expression of AQPs in the kidneys was studied using immunohistochemistry. Laboratory parameters of diabetic and kidney functions, ADC low , ADC st , ADC uh , and the optical density (OD) of AQP expression in the two groups were compared using an independent t test. Correlations between ADCs and the OD of AQP expression were evaluated by Pearson's correlation analysis. ADC uh were significantly higher in the cortex (CO), outer stripe of the outer medulla (OS) and inner stripe of the outer medulla (IS), and the OD values of AQ-2 were significantly higher in the OS, IS and inner medulla (IM) in DM animals compared with control animals. ADC uh and OD values of AQP-2 expression were positively correlated in the OS, IS and IM of the kidney. ADC uh may work as useful metrics for early detection of kidney damage in diabetic nephropathy and may be associated with AQP-2 expression.

Korean red ginseng extract alleviates advanced glycation end product-mediated renal injury

PubMed Central

Quan, Hai Yan; Kim, Do Yeon; Chung, Sung Hyun

2013-01-01

The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-α (TNF-α), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-α and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy. PMID:23717171

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

PubMed

Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

2016-11-01

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Toxic effects of lambda-cyhalothrin, a synthetic pyrethroid pesticide, on the rat kidney: Involvement of oxidative stress and protective role of ascorbic acid.

PubMed

Fetoui, Hamadi; Makni, Mohamed; Garoui, El Mouldi; Zeghal, Najiba

2010-11-01

Lambda-cyhalothrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress, changes in biochemical parameters and enzyme activities in the kidney of male rats and its possible attenuation by Vitamin C (vit C). Renal function, histopathology, tissue malondialdehyde (MDA), protein carbonyl (PCO) levels, antioxidant enzyme activities and reduced glutathione (GSH) levels were evaluated. Exposure of rats to lambda-cyhalothrin, during 3 weeks, caused a significant increase in kidney MDA and protein carbonyl levels (p<0.01) as compared to controls. Co-administration of vitamin C was effective in reducing MDA and PCO levels. The kidney of LTC-treated rats exhibited severe vacuolations, cells infiltration and widened tubular lumen. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were significantly decreased due to lambda-cyhalothrin exposure. Co-administration of vitamin C ameliorated the increase in enzymatic activities of aminotransferases (AST and ALT), lactate dehydrogenase (LDH), creatinine and urea levels and improved the antioxidant status. These data indicated the protective role of ascorbic acid against lambda-cyhalothrin-induced nephrotoxicity and suggested a significant contribution of its antioxidant property to these beneficial effects. Copyright © 2009 Elsevier GmbH. All rights reserved.

Intermediate filament protein expression pattern and inflammatory response changes in kidneys of rats receiving doxorubicin chemotherapy and quercetin.

PubMed

Khalil, Samah R; Mohammed, Amany Tharwat; Abd El-Fattah, Amir H; Zaglool, Asmaa W

2018-05-15

The aim of this study was to explore the potential effects of quercetin (QUR) on doxorubicin (DOX)-induced nephrotoxicity. Fifty male rats were assigned to five groups (10 rats each): a control group, a DOX-treated group (total dose, 15 mg/kg bw, intraperitoneally), a QUR-treated group (50 mg/kg bw/day, orally), a prophylaxis co-treated group, and a therapeutic co-treated group. Biochemical parameters and renal function were measured. Moreover, kidney tissues were homogenized for inflammatory marker evaluation and real-time qPCR analysis to determine the changes in intermediate filament protein mRNA levels (desmin, vimentin, connexin 43 and nestin). QUR exhibited a significant nephroprotective effect, particularly when it was administered prior to and simultaneously with DOX treatment (prophylaxis co-treated group). This role was biochemically demonstrated by the significant modulation of DOX-induced body weight loss, hypoproteinemia, and elevated serum creatinine and urea. Moreover, QUR attenuated the inflammatory response as shown by decreased renal nitric oxide, tumor necrosis factor-α production and myeloperoxidase activity elicited by DOX injection. These biochemical improvements were accompanied by a significant histopathological restoration of rat kidney tissue and successful down-regulation of the intermediate filament protein mRNA levels, indicating amelioration of DOX-induced podocyte injury. Taken together, these results conclusively demonstrated that QUR administration has a prophylactic effect on DOX-induced injury in the rat kidney. Copyright © 2018 Elsevier B.V. All rights reserved.

Retinopathy and chronic kidney disease in the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Grunwald, Juan E; Alexander, Judith; Ying, Gui-Shuang; Maguire, Maureen; Daniel, Ebenezer; Whittock-Martin, Revell; Parker, Candace; McWilliams, Kathleen; Lo, Joan C; Go, Alan; Townsend, Raymond; Gadegbeku, Crystal A; Lash, James P; Fink, Jeffrey C; Rahman, Mahboob; Feldman, Harold; Kusek, John W; Xie, Dawei; Jaar, Bernard G

2012-09-01

To investigate the association between retinopathy and chronic kidney disease. In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of chronic kidney disease, were offered participation. Nonmydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. The photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and nontraditional risk factors for decreased kidney function were obtained from the CRIC study. Greater severity of retinopathy was associated with lower estimated glomerular filtration rate after adjustment for traditional and nontraditional risk factors. The presence of vascular abnormalities usually associated with hypertension was also associated with lower estimated glomerular filtration rate. We found no strong direct relationship between estimated glomerular filtration rate and average arteriolar or venular calibers. Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and nontraditional risk factors for chronic kidney disease, suggesting that retinovascular pathology reflects renal disease.

Kidney regeneration by xeno-embryonic nephrogenesis.

PubMed

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Kawamura, Tetsuya

2008-03-01

Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

Combined heart-kidney transplantation after total artificial heart insertion.

PubMed

Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-01-01

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Kidney Response to the Spectrum of Diet-Induced Acid Stress

PubMed Central

Goraya, Nimrit; Wesson, Donald E.

2018-01-01

Chronic ingestion of the acid (H+)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H+ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H+ excretion is less than the cumulative increment in dietary H+, consistent with H+ retention. This H+ retention associated with the described high dietary H+ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H+ retention does not measurably change plasma acid–base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H+ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H+ injury, which we characterize as “H+ stress”, and the emerging evidence that high dietary H+ constitutes a threat to long-term kidney health. PMID:29751620

Impact of a Pharmacy-Cardiology Collaborative Practice on Dofetilide Safety Monitoring.

PubMed

Quffa, Lieth H; Panna, Mark; Kaufmann, Michael R; McKillop, Matthew; Dietrich, Nicole Maltese; Franck, Andrew J

2017-01-01

Limited studies have been published examining dofetilide's postmarketing use and its recommended monitoring. To evaluate the impact of a collaborative pharmacy-cardiology antiarrhythmic drug (AAD) monitoring program on dofetilide monitoring. This retrospective cohort study was performed to assess if a novel monitoring program improved compliance with dofetilide-specific monitoring parameters based on the Food and Drug Administration's Risk Evaluation and Mitigation Strategy. A total of 30 patients were included in the analysis. The monitoring parameters evaluated included electrocardiogram, serum potassium, serum magnesium, and kidney function. The primary outcome evaluated was the composite of these dofetilide monitoring parameters obtained in each cohort. In the standard cohort, 245 of 352 (69.6%) monitoring parameters were completed versus 134 of 136 (98.5%) in the intervention group ( P < 0.05). A collaborative pharmacy-cardiology AAD monitoring program was associated with a significant improvement in dofetilide monitoring. This improvement could potentially translate into enhanced patient safety outcomes, such as prevention of adverse drug reactions and decreased hospitalizations.

Kidney Transplantation Is Superior to Hemodialysis and Peritoneal Dialysis in Terms of Cognitive Function, Anxiety, and Depression Symptoms in Chronic Kidney Disease.

PubMed

Ozcan, H; Yucel, A; Avşar, U Z; Cankaya, E; Yucel, N; Gözübüyük, H; Eren, F; Keles, M; Aydınlı, B

2015-06-01

Cognitive impairment, anxiety and depression are important problems for patients with chronic kidney failure. Cognitive impairment, anxiety, and depression may be related to various factors, such as complications of hemo/peritoneal dialysis, uremic encephalopathy, psychosocial burden of the disease, and various comorbidities in patients with chronic kidney failure. Successful kidney transplantation (KT) improves kidney, endocrine, metabolic, and vascular systems, mental functions, and the quality of life of the patients. A total of 181 patients with chronic kidney failure were studied: 54 currently on hemodialysis, 58 on peritoneal dialysis, and 69 with KT. All participants were given a detailed sociodemographic form, including data about the reason of kidney failure, duration of treatment (hemodialysis, peritoneal dialysis, and KT), and comorbid illnesses. Participants were evaluated with the use of the Hospital Anxiety and Depression Scale (HADS) for evaluating depressive and anxiety symptoms and the Brief Cognitive State Examination (BCSE) for detecting possible cognitive impairment. Patients with KT had lower levels of anxiety and depression symptoms than patients with hemodialysis and peritoneal dialysis. The KT group scored better than the hemodialysis and peritoneal dialysis groups on the BCSE. The peritoneal dialysis group scored higher on the BCSE than the hemodialysis group. The hemodialysis group scored higher on the HADS than the peritoneal dialysis group. In this study it was found that KT patients have better cognitive and mood regulation outcomes than hemodialysis and peritoneal dialysis patients with chronic kidney failure. With this knowledge we suggest that patients with kidney failure should have KT for having better cognitive functions and mood state as soon as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.

PubMed

Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid

2017-03-01

The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm 3 , respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm 3 . The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm 3 and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm 3 and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

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

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

DOE PAGES

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

2017-05-03

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Radiologic imaging of the renal parenchyma structure and function.

PubMed

Grenier, Nicolas; Merville, Pierre; Combe, Christian

2016-06-01

Radiologic imaging has the potential to identify several functional and/or structural biomarkers of acute and chronic kidney diseases that are useful diagnostics to guide patient management. A renal ultrasound examination can provide information regarding the gross anatomy and macrostructure of the renal parenchyma, and ultrasound imaging modalities based on Doppler or elastography techniques can provide haemodynamic and structural information, respectively. CT is also able to combine morphological and functional information, but the use of CT is limited due to the required exposure to X-ray irradiation and a risk of contrast-induced nephropathy following intravenous injection of a radio-contrast agent. MRI can be used to identify a wide range of anatomical and physiological parameters at the tissue and even cellular level, such as tissue perfusion, oxygenation, water diffusion, cellular phagocytic activity, tissue stiffness, and level of renal filtration. The ability of MRI to provide valuable information for most of these parameters within a renal context is still in development and requires more clinical experience, harmonization of technical procedures, and an evaluation of reliability and validity on a large scale.

Revisiting double kidney transplantation: two kidneys provide better graft survival than one.

PubMed

Cruzado, J M; Fernandez, L; Riera, L; Bestard, O; Carrera, M; Torras, J; Gil Vernet, S; Melilli, E; Ngango, L; Grinyó, J M

2011-01-01

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Mononuclear phagocyte subpopulations in the mouse kidney

PubMed Central

George, James F.; Lever, Jeremie M.

2017-01-01

Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. Although the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the present knowledge regarding classification of these cells in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases. PMID:28100500

Ultrasonographic evaluation of the renal dimensions in captive tigers.

PubMed

Huaijantug, Somkiat; Manatpreprem, Komsan; Manatpreprem, Sukhumarn; Yatmark, Paranee

2017-01-10

Ultrasonographic measurements of kidney size are useful in the practical diagnosis of kidney diseases in animals. In tigers, there is a lack of information regarding the ultrasonography methods used to measure the kidney size of the tiger. Thirty-three healthy captive tigers (Panthera tigris) were placed in lateral recumbency for ultrasonography. The measurements obtained from the ultrasonography were computed, and the results showed that there was a statistically significant difference between genders in terms of body weight and renal length. The length of the right kidney was significantly different from that of the left kidney (10.23 ± 0.76 cm in males versus 9.94 ± 0.80 cm in females; P<0.05). Interestingly, this study demonstrated that kidney length was statistically significantly associated with the body weight, and it also had a positive linear relationship with the body weight. Therefore, ultrasonographic renal dimensions could prove to be beneficial and modality for use in the evaluation of kidneys in unconscious tigers. However, kidney size evaluation must be performed using not only ultrasound but other clinical forms of technology and parameters.

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

PubMed

He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

2013-06-01

Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

Diuretic renography in hydronephrosis: delayed tissue tracer transit accompanies both functional decline and tissue reorganization.

PubMed

Schlotmann, Andreas; Clorius, John H; Rohrschneider, Wiltrud K; Clorius, Sandra N; Amelung, Folker; Becker, Kristianna

2008-07-01

The significance of delayed tissue tracer transit (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Twenty 2- to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with (99m)Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both follow-ups. In these 12 kidneys, the SKF declined from 51% +/- 4% to 18% +/- 14%, and the THS was 9.0 +/- 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 +/- 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 +/- 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. In hydronephrosis, a delayed TTT of (99m)Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.

Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

PubMed

Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

2017-05-01

Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

PubMed Central

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

PubMed

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

PubMed

Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

2018-01-01

Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

PubMed

Girerd, Sophie; Jaisser, Frédéric

2018-04-17

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

Clinical case report: a rare cause of acute kidney failure - tissue is the issue.

PubMed

Heggermont, Ward A; Verhoef, Gregor; Evenepoel, Pieter; Sprangers, Ben; Lerut, Evelyn; Tousseyn, Thomas; Claes, Kathleen

2017-06-01

A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.

Polycystin-1 Binds Par3/aPKC and Controls Convergent Extension During Renal Tubular Morphogenesis

PubMed Central

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-01-01

Several organs, including lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintanance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1 (PC-1), a large receptor of unknown function. Here we demonstrate that PC-1 plays an essential role in establishment of correct tubular diameter during nephron development. PC-1 associates with Par3 favoring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a program of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis and in renal cyst formation. Our data define PC-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis. PMID:24153433

Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

NASA Astrophysics Data System (ADS)

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-10-01

Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.

Is percutaneous nephrolithotomy in solitary kidneys safe?

PubMed

Wong, Kathie Alexina; Sahai, Arun; Patel, Amit; Thomas, Kay; Bultitude, Matthew; Glass, Jonathan

2013-11-01

To review our experience from a high volume stone center with a focus on efficacy, safety, and renal function. Stones requiring percutaneous nephrolithotomy (PCNL) in patients with solitary kidneys can pose significant anxiety to the urologist. Limited data are available in published reports in this setting. A comprehensive retrospective review of medical records was performed on patients who underwent PCNL and had a solitary kidney or a single functioning renal unit. Data were collected on patient demographics, stone burden, outcomes, complications, and renal function. Of 378 PCNLs performed between January 2003 and September 2011, 22 were performed in 17 patients with a single functioning kidney. Three procedures were performed in a transplanted kidney. In those with solitary calculus, the longest mean length and stone surface area were 37 mm and 825 mm(2), respectively. Stone-free rate was 59%. Auxiliary procedures were required in 6 cases, resulting in a stone-free rate of 77%. Median inpatient stay was 4 days. Serum creatinine values improved from 144 to 126 umol/L before and after the procedure and mean estimated glomerular filtration rate improved similarly from 51 to 59 mls/minute, respectively. Blood transfusion was required in 1 patient, sepsis developed in 3, and 2 patients required a stent for obstruction. PCNL in solitary kidneys is safe with an acceptable complication rate if performed in a high volume center. Outcomes are good, although auxiliary procedures may be necessary. Renal function remains stable or improves after procedure. Copyright © 2013 Elsevier Inc. All rights reserved.

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

Analysis of the Results of ABO-Incompatible Kidney Transplantation: In Comparison with ABO-Compatible Kidney Transplantation

PubMed Central

Jeon, Byung Joo; Seong, Youl Keun; Han, Bo Hyun

2010-01-01

Purpose The number of patients waiting for kidney transplantation is incessantly increasing, but the number of cadaveric kidney transplantations or ABO-compatible donors is so insufficient that ABO-incompatible kidney transplantation is being performed as an alternative. There are overseas studies and research showing that the 5-year survival rate and 5-year graft survival rate of ABO-incompatible kidney transplantation are not much different from those of ABO-compatible kidney transplantation. However, domestic research on the subject is rare. Therefore, we report the results of 22 ABO-incompatible kidney transplantation cases performed in our hospital. Materials and Methods This research was from 22 patients in our hospital who underwent ABO-incompatible kidney transplantation from 15 February 2007 to 20 May 2010. Results As yet, there have been no donor graft losses and no deaths after transplantation. The results of the two groups were analyzed by analysis of covariance of the creatinine value of the recipients at 6 months after the operation, corrected for the preoperative value in order to statistically identify whether there were differences in renal function after the operation between ABO-compatible and ABO-incompatible kidney transplantation. The results of the analysis of covariance showed no statistical difference in renal function after the operation between the two groups. Conclusions Even though there were not many cases, our initial results for ABO-incompatible kidney transplantation were positive. Considering the increasing number of patients waiting for kidney transplantation, longer-term domestic research studies of ABO-incompatible kidney transplantation are necessary. PMID:21221208

Development of an in situ perfused kidney preparation for elasmobranch fish: action of arginine vasotocin.

PubMed

Wells, Alan; Anderson, W Gary; Hazon, Neil

2002-06-01

Acclimation of the European lesser-spotted dogfish Scyliorhinus canicula to reduced environmental salinity [85-70% seawater (SW)] induced a significant diuresis in addition to a significant decrease in plasma osmolality in vivo. The threshold for this diuresis was determined to be 85% SW. Therefore, S. canicula acclimated to 85% SW was selected for further study as a diuretic model in the development of an in situ perfused kidney preparation. The renal role of arginine vasotocin (AVT) in the in situ perfused trunk preparation was investigated. In SW, perfusion of 10(-9) and 10(-10) M AVT resulted in a glomerular antidiuresis and decreases in tubular transport maxima for glucose and perfusate flow. In 85% SW, 10(-10) M AVT had no significant effect on these renal parameters with the exception of transport maxima for glucose and perfusate flow. Tubular parameters remained unchanged by either 10(-9) or 10(-10) M AVT. The results demonstrate that the perfused kidney preparation was a viable tool for the investigation of renal parameters in elasmobranch fish and that AVT induced a glomerular antidiuresis.

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PubMed

Geist, Barbara Katharina; Dobrozemsky, Georg; Samal, Martin; Schaffarich, Michael P; Sinzinger, Helmut; Staudenherz, Anton

2015-12-01

The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.

Qiwei granules alleviates podocyte lesion in kidney of diabetic KK-Ay mice.

PubMed

Zhou, Jingxin; Sun, Wen; Yoshitomi, Hisae; Li, Linyi; Qin, Lingling; Guo, Xiangyu; Wu, Lili; Zhang, Yan; Wu, Xinli; Xu, Tunhai; Gao, Ming; Liu, Tonghua

2015-03-31

Chinese medicine comprised of all natural herbs is widespread used in the treatment of diabetic nephropathy (DN). Podocyte contributes to the integrity of glomerular filtration barrier whose injury plays an important role in the initiation and progression of DN. Our study aimed to investigate the effect of Qiwei granules on podocyte lesion in diabetic KK-A(y) mice kidney and its underlying mechanism. Twelve-week-old male KK-A(y) mice were randomly divided in vehicle group and Qiwei granules group, while C57BL/6J mice were used as normal control. The mice were gavage with 1.37 g/kg/day Qiwei granules or water for 10 weeks. We measured water, food intake and body weight (BW) and fasting blood glucose (FBG) every 2 weeks, and urine protein every 4 weeks. At the end of the experiment, all surviving mice were sacrificed. The kidney weight and serum renal parameters were measured, and the renal morphology was observed. To search the underlying mechanism, we examined the podocyte positive marker, slit diaphragm protein expression and some involved cell signal pathway. Qiwei granules treatment significantly improved the metabolic parameters, alleviated the urinary protein, and protected renal function in KK-A(y) mice. In addition, the glomerular injuries and podocyte lesions were mitigated with Qiwei granules treatment. Furthermore, Qiwei granules increased expression of nephrin, CD2AP, and integrin alpha3beta1 in the podocytes of KK-A(y) mice. Qiwei granules improved the phosphoration of Akt and inhibited cleaved caspase-3 protein expression. These finding suggest that Qiwei granules protects the podocyte from the development of DN via improving slit diaphragm (SD) molecules expression and likely activating Akt signaling pathway in KK-A(y) mice.

Dietary fiber intake is associated with chronic kidney disease (CKD) progression and cardiovascular risk, but not protein nutritional status, in adults with CKD.

PubMed

Lu, Lu; Huang, Yan-Feng; Wang, Ming-Qing; Chen, De-Xiu; Wan, Heng; Wei, Lian-Bo; Xiao, Wei

Evidence suggests that dietary fiber benefits patients with chronic kidney disease (CKD); however, this conclusion requires further validation. In this study, we examined the effects of dietary fiber on kidney function, inflammation, indoxyl sulfate, nutritional status, and cardiovascular risk in patients with advanced CKD. We performed linear regressions to assess the association between dietary fiber intake and CKD parameters. The aforementioned parameters were compared over an 18-month follow- up period. Kaplan-Meier analysis was used to investigate the association between fiber intake and Cardiac vascular disease (CVD). In total, 157 patients were included in this study. Dietary fiber and inflammatory indices were associated (interleukin [IL]-6: β=-0.024, p=0.035). The differential estimated glomerular filtration rate (ΔeGFR) as well as levels of C-reactive protein, IL-6, indoxyl sulfate, and serum cholesterol in the higher fiber intake (>=25 g/day) group were lower than those in the lower fiber intake (<25 g/day) group (p<0.05). Differences in IL-6 and indoxyl sulfate levels were more significant in patients in the higher protein intake group (p<0.05). Dietary fiber intake may be a protective factor associated with CVD (hazard ratio=0.537 and 0.305- 0.947). The protein nutritional status was not different between the two groups (p>0.05). Our results suggest that increasing fiber intake can retard the decrease in the eGFR; can reduce the levels of proinflammatory factors, indoxyl sulfate, and serum cholesterol; and is negatively associated with cardiovascular risk, but does not disrupt the nutritional status of patients with CKD.

A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication.

PubMed

Räsänen, M; Helanterä, I; Kalliomäki, J; Savikko, J; Parry, M; Lempinen, M

Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after acute kidney injury, designed to interdict renal tubular damage. Magn Reson Med 79:3144-3153, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

PubMed Central

Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

2009-01-01

Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

Estimated Nephron Number of the Donor Kidney: Impact on Allograft Kidney Outcomes.

PubMed

Schachtner, T; Reinke, P

Low birth weights have been associated with a reduction in nephron number with compensatory hypertrophy of existing glomeruli. The impact of donor birth weight as an estimate of nephron number on allograft function, however, has not been examined. We collected donor birth weight, kidney weight, and volume from 91 living kidney donor-recipient pairs before nephrectomy and after 12, 36, and 60 months. Nephron number was calculated from donor birth weight and age. Donor birth weight, kidney weight/body surface area (BSA), and kidney volume showed a moderate positive correlation with allograft estimated glomerular filtration rate (eGFR) at 12 months (P < .05). Donor age showed a negative moderate correlation with allograft eGFR at 12 months (P = .015). The strongest correlation with allograft eGFR was observed for calculated donor kidney nephron number at 12, 36, and 60 months (R, 0.340, 0.305, and 0.476, respectively; P < .05). No impact was observed on allograft daily proteinuria of any investigated marker (P > .05). Recipients of donors with birth weight <2.5 kg had need of a significantly greater number of antihypertensive drugs (P < .05). Calculated nephron number from donor birth weight and age is suggested to be superior to donor kidney weight/BSA and volume regarding allograft function. Calculated nephron number could estimate expected eGFR and guide decision making in cases of impaired allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiographic kidney measurements in captive cheetahs (Acinonyx jubatus).

PubMed

Hackendahl, Nicole C; Citino, Scott B

2005-06-01

The prevalence of chronic renal disease is substantial among captive cheetahs (Acinonyx jubatus). The purpose of this study was to determine kidney measurements from radiographs of captive cheetahs (n = 15) with normal renal function. The ratio of kidney length to length of the body of the second lumbar vertebrae has been established for domestic cats with normal renal function. The mean ratio of renal length to length of the second lumbar vertebra was 1.81 +/- 0.14 in cheetahs. This baseline data may allow an objective evaluation of radiographic kidney size in cheetahs. However, evaluation of a small number of cheetahs with confirmed renal failure resulted in a similar ratio.

Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

PubMed

Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

2017-11-01

Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

PubMed

Cunard, Robyn

2015-04-20

Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Ballew, Shoshana H.; Chen, Yan; Daya, Natalie R.; Godino, Job G.; Windham, B. Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E.

2016-01-01

Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. PMID:27884475

Prognostic Value of Residual Urine Volume, GFR by 24-hour Urine Collection, and eGFR in Patients Receiving Dialysis.

PubMed

Lee, Mi Jung; Park, Jung Tak; Park, Kyoung Sook; Kwon, Young Eun; Oh, Hyung Jung; Yoo, Tae-Hyun; Kim, Yong-Lim; Kim, Yon Su; Yang, Chul Woo; Kim, Nam-Ho; Kang, Shin-Wook; Han, Seung Hyeok

2017-03-07

Residual kidney function can be assessed by simply measuring urine volume, calculating GFR using 24-hour urine collection, or estimating GFR using the proposed equation (eGFR). We aimed to investigate the relative prognostic value of these residual kidney function parameters in patients on dialysis. Using the database from a nationwide prospective cohort study, we compared differential implications of the residual kidney function indices in 1946 patients on dialysis at 36 dialysis centers in Korea between August 1, 2008 and December 31, 2014. Residual GFR calculated using 24-hour urine collection was determined by an average of renal urea and creatinine clearance on the basis of 24-hour urine collection. eGFR-urea, creatinine and eGFR β 2 -microglobulin were calculated from the equations using serum urea and creatinine and β 2 -microglobulin, respectively. The primary outcome was all-cause death. During a mean follow-up of 42 months, 385 (19.8%) patients died. In multivariable Cox analyses, residual urine volume (hazard ratio, 0.96 per 0.1-L/d higher volume; 95% confidence interval, 0.94 to 0.98) and GFR calculated using 24-hour urine collection (hazard ratio, 0.98; 95% confidence interval, 0.95 to 0.99) were independently associated with all-cause mortality. In 1640 patients who had eGFR β 2 -microglobulin data, eGFR β 2 -microglobulin (hazard ratio, 0.98; 95% confidence interval, 0.96 to 0.99) was also significantly associated with all-cause mortality as well as residual urine volume (hazard ratio, 0.96 per 0.1-L/d higher volume; 95% confidence interval, 0.94 to 0.98) and GFR calculated using 24-hour urine collection (hazard ratio, 0.97; 95% confidence interval, 0.95 to 0.99). When each residual kidney function index was added to the base model, only urine volume improved the predictability for all-cause mortality (net reclassification index =0.11, P =0.01; integrated discrimination improvement =0.01, P =0.01). Higher residual urine volume was significantly associated with a lower risk of death and exhibited a stronger association with mortality than GFR calculated using 24-hour urine collection and eGFR-urea, creatinine. These results suggest that determining residual urine volume may be beneficial to predict patient survival in patients on dialysis. Copyright © 2017 by the American Society of Nephrology.

Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment.

PubMed

Mahfoudh-Boussaid, Asma; Zaouali, Mohamed Amine; Hauet, Thierry; Hadj-Ayed, Kaouther; Miled, Abdel-Hédi; Ghoul-Mazgar, Sonia; Saidane-Mosbahi, Dalila; Rosello-Catafau, Joan; Ben Abdennebi, Hassen

2012-08-01

Endoplasmic reticulum (ER) and mitochondria have been implicated in the pathology of renal ischemia/reperfusion (I/R). In the present study, we investigated whether the use of ischemic postconditioning (IPostC) and trimetazidine (TMZ) separately or combined could reduce ER stress and mitochondria damage after renal ischemia. Kidneys of Wistar rats were subjected to 60-min of warm ischemia followed by 120-min of reperfusion (I/R group, n = 6), or to 6 cycles of ischemia/reperfusion (10-s each cycle) just after 60-min of warm ischemia (IPostC group, n = 6), or to i.p. injection of TMZ (3 mg/kg) 30-min before ischemia (TMZ group, n = 6), or to the combination of both treatments (IPostC+TMZ group, n = 6). The results of these experimental groups were compared to those of a sham-operated group in which rat renal pedicles were only dissected. Sodium reabsorption rate, creatinine clearance lactate deshydrogenase (LDH) activity in plasma, and concentration of malonedialdehyde (MDA) in tissue were determined. In addition, Western blot analysis was performed to identify the amounts of cytochrome c, c-JunNH2-terminal kinase (JNK), voltage-dependent anion channel (VDAC), glycogen synthase kinase 3-beta (GSK3-β), and ER stress parameters. IPostC or/and TMZ significantly decreased cytolysis, oxidative stress and improved renal function in comparison to I/R group. IPostC but not TMZ significantly attenuated ER stress parameters versus I/R group. Indeed, it down-regulated the glucose-regulated protein 78 (GRP78), the activating transcription factor 4 (ATF4), the RNA activated protein kinase (PKR)-like ER kinas (PERK), the X box binding protein-1 (XBP-1) and the caspase12 protein levels. TMZ treatment significantly augmented GSK3-β phosphorylation and reduced levels of cytochrome c and VDAC phosphorylation in comparison to IPostC application. The combination of both treatments gave a synergetic effect. It significantly improved the survival rate, attenuated cytolysis, oxidative stress and improved renal function. This study revealed that IPostC protects kidney from I/R injury by suppressing ER stress while the beneficial effects of TMZ are mediated by mitochondria protection. The combination of both treatments ameliorated functional recovery.

A Soft Computing Approach to Kidney Diseases Evaluation.

PubMed

Neves, José; Martins, M Rosário; Vilhena, João; Neves, João; Gomes, Sabino; Abelha, António; Machado, José; Vicente, Henrique

2015-10-01

Kidney renal failure means that one's kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient's history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the sensitivity and the specificity exhibited values range between 93.1 and 94.9 and 91.9-94.2 %, respectively.

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

PubMed

Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

PubMed

Scheen, André J

2015-07-01

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results in animal models.

Chronic kidney disease among high school students of Kinshasa

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a major worldwide health problem. However, its burden among adolescents and young adults is unknown, especially in sub-Saharan Africa. The aim of this study was to investigate its prevalence in the school environment. The concordance of usual formulas used to estimate renal function was also assessed. Methods In an epidemiological cross sectional study, a random sample of 524 pupils (263 boys, mean age of 18.7 ± 1.4 years) from school environment of Kinshasa were studied. Recorded parameters of interest were anthropometric, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) according to the Schwartz formula using uncalibrated creatinine levels from one random measurement. CKD was defined as the presence of kidney damage (daily proteinuria ≥ 300 mg) and/or reduced kidney function (eGFR < 60 ml/min/1.73 m2). Concordances between eGFR according to Schwartz, Cockcroft-Gault (C-G) indexed for BSA and modification of diet in renal disease (MDRD) study equations were computed using the kappa coefficient. Results The prevalence of CKD by the Schwartz formula was 1.5%. By stage, 0.8% had CKD stage 1 (proteinuria with normal eGFR) and 0.8% had CKD stage 3 (eGFR, 30 to 59 ml/min/1.73 m2). The prevalence of proteinuria ≥ 300 mg/day was 1% (one case had 2.7g/day). Agreement between eGFR according to Schwartz formula and the MDRD formula was excellent (kappa: 88.8%). Although correlations between all formulas were excellent (0.99; 0.87, and 0.89), agreement was poor between eGFR according to Schwartz and C-G indexed BSA equation (kappa: 52.7%) and, poorer with C-G unadjusted for BSA (kappa: 26.9%). Conclusion In the large African city of Kinshasa, 2% of high school students have CKD. This high prevalence rate emphasizes the need for appropriate detection and prevention measures in this vulnerable young age population group. PMID:22559052

odd skipped related1 reveals a novel role for endoderm in regulating kidney vs. vascular cell fate

PubMed Central

Mudumana, Sudha P.; Hentschel, Dirk; Liu, Yan; Vasilyev, Aleksandr; Drummond, Iain A.

2009-01-01

Summary The kidney and vasculature are intimately linked functionally and during development, where nephric and blood/vascular progenitor cells occupy adjacent bands of mesoderm in zebrafish and frog embryos. Developmental mechanisms underlying the differentiation of kidney vs. blood/vascular lineages remain unknown. The odd skipped related1 (osr1) gene encodes a zinc finger transcription factor that is expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood/vascular markers. Knockdown of osr1 in zebrafish embryos resulted in a complete, segment-specific loss of anterior kidney progenitors and a compensatory increase in the number of angioblast cells in the same trunk region. Histology revealed a subsequent absence of kidney tubules, enlarged cardinal vein, and expansion of the posterior venous plexus. Altered kidney vs. vascular development correlated with expanded endoderm development in osr1 knockdowns. Combined osr1 loss of function and blockade of endoderm development by knockdown of sox32/casanova rescued anterior kidney development. The results indicate that osr1 activity is required to limit endoderm differentiation from mesendoderm and, in the absence of osr1, excess endoderm alters mesoderm differentiation, shifting the balance from kidney toward vascular development. PMID:18787069

Tolvaptan and Kidney Pain in Patients With Autosomal Dominant Polycystic Kidney Disease: Secondary Analysis From a Randomized Controlled Trial

PubMed Central

Casteleijn, Niek F.; Blais, Jaime D.; Chapman, Arlene B.; Czerwiec, Frank S.; Devuyst, Olivier; Higashihara, Eiji; Leliveld, Anna M.; Ouyang, John; Perrone, Ronald D.; Torres, Vicente E.; Gansevoort, Ron T.

2017-01-01

Background Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is difficult to measure, the incidence of kidney pain leading to objective medical interventions was used in the present study to assess pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney pain events defined by objective medical interventions. Measurements Kidney pain events were recorded and independently adjudicated. Incidence of a first kidney pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39 ± 7 [SD] years; mean estimated glomerular filtration rate, 81 ± 22 mL/min/1.73 m2; median total kidney volume, 1,692 [IQR, 750–7,555] mL), 50.9% reported a history of kidney pain at baseline. History of urinary tract infections, kidney stones, or hematuria (all P < 0.001) and female sex (P < 0.001) were significantly associated with history of kidney pain. Tolvaptan use resulted in a significantly lower incidence of kidney pain events when compared to placebo: 10.1% versus 16.8% (P < 0.001), with a risk reduction of 36% (HR, 0.64; 95% CI, 0.48–0.86). The reduction in pain event incidence by tolvaptan was found in all groups irrespective of pain severity and was independent of predisposing factors (P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total kidney volume and kidney function. Conclusions Tolvaptan decreased the incidence of kidney pain events independent of patient characteristics predisposing for kidney pain and possibly in part due to reductions in ADPKD-related complications. PMID:27856088

Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

PubMed

Barr, Maureen M

2005-02-01

The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.

PubMed

Zhang, Bo; Tran, Uyen; Wessely, Oliver

2018-03-22

The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in polycystic kidney disease (PKD), resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein-coupled signaling in the Xenopus pronephric kidney, we discovered that loss of the G-protein α subunit, Gnas, results in a PKD phenotype. Polycystin 1, one of the genes mutated in human PKD, encodes a protein resembling a G-protein-coupled receptor. Furthermore, deletion of the G-protein-binding domain present in the intracellular C terminus of polycystin 1 impacts functionality. A comprehensive analysis of all the G-protein α subunits expressed in the Xenopus pronephric kidney demonstrates that polycystin 1 recruits a select subset of G-protein α subunits and that their knockdown - as in the case of Gnas - results in a PKD phenotype. Mechanistically, the phenotype is caused by increased endogenous G-protein β/γ signaling and can be reversed by pharmacological inhibitors as well as knocking down Gnb1. Together, our data support the hypothesis that G proteins are recruited to the intracellular domain of PKD1 and that this interaction is crucial for its function in the kidney. © 2018. Published by The Company of Biologists Ltd.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

PubMed

Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

2013-09-01

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Kidney allotransplantation from alive related donor in patients with Alport syndrome].

PubMed

Goriaĭnov, V A; Kaabak, M M; Babenko, N N; Morozova, M M; Aganesov, A P; Panin, V V; Platova, E N; Dymova, O V

2016-01-01

To evaluate the results of kidney transplantation from alive related donor in patients with Alport syndrome and to compare with those in patients with kidney hypoplasia. We have analyzed 8 and 27 medical records of patients with Alport syndrome and kidney hypoplasia respectively. Following parameters were used - Kaplan-Meier survival analysis, Wilcox overall risk, percentage of transplants loss and mortality (Fisher's exact test calculation). It is concluded that percentage of transplants loss and mortality rate as well as overall survival and risk were similar in both groups. Despite risk of anti-GBM nephritis development in patients with Alport syndrome results are comparable with those after transplatation for chronic renal failure caused by other reasons.

Optical Coherence Tomography in Kidney Transplantation

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

Hand-assisted Laparoscopic Nephrectomy in Living-donor Kidneys With Multiple Arteries: Experience of a Transplant Center.

PubMed

Bandín Musa, Alfonso Ricardo; Montes de Oca, Jorge

2016-04-01

Hand-assisted laparoscopic nephrectomy is a relatively new procedure in our country. This article reports on one of the largest number of this procedure in kidneys with multiple vessels. We reviewed all cases of hand-assisted laparoscopic nephrectomy from July 2002 to February 2009. Results were then descriptive, with statistical analyses performed with SPSS software (SPSS: An IBM Company, version 10.0, IBM Corporation, Armonk, NY, USA). From July 2002 to February 2009, 165 patients had hand-assisted laparoscopic nephrectomy, with 96.9% being the left kidney. We found a prevalence of 18.7% (n = 31) of kidneys with multiple arteries, with 8 of these having multiple principal arteries, 9 with superior polar artery, and 14 with inferior polar artery. Twenty-nine donors (17.57%) presented with more than 1 principal vein. Warm ischemia was longer in kidneys with multiple arteries (4.16 vs 3.96 min); recipient renal function (evaluated by creatinine levels at day 5 after transplant) was 1.63 mg/dL in kidneys with single artery versus 1.27 mg/dL in kidneys with multiple arteries. There were no significant differences for time of surgery, bleeding, and discharge of the donor. We found no differences in kidney function between single and multiple artery kidneys, resulting in the conclusion that hand-assisted laparoscopic nephrectomy offers an effective option for kidney donors, including those with multiple arteries.

Final Year Nursing Students in Nigeria; How Knowledgeable and Prepared are They to Offer Medical Care to Patients with Chronic Kidney Disease?

PubMed Central

Okwuonu, Chimezie Godswill; Kanu, Hannah Sylvanus; Odigie, Ojeh-Oziegbe

2017-01-01

Background: Nurses play an important role in the management of chronic kidney disease (CKD) patients at primary, secondary, and tertiary levels of care. In other to perform their functions, it is pertinent that they have a good understanding of kidney functions and CKD. We do not know if the current educational curriculum prepares them adequately for this role. Aim: To assess the knowledge level of kidney functions and diseases among final year nursing students in Abia State Nigeria. Materials and Methods: This was a cross sectional study involving final year diploma and Bachelor of nursing (B. Nursing) students who were randomly chosen. Structured, self-administered questionnaire containing 18 items was the tool for data collection. A score of one was given for each correctly answered question on functions of the kidney, symptoms, signs, causes, and complications of CKD. A score of 50% and above was regarded as good knowledge. Results: Two hundred questionnaires were distributed, but 186 were returned (response rate of 93%). Male:female ratio was 1:14.5. One hundred and seventeen (62.9%) knew the correct definition of CKD, but only 69 (37.1%) knew the normal range of glomerular filtration rate. Eighty-one percent had good knowledge of kidney functions while 39 (21%) had good knowledge of CKD. Overall, 42 (22.6%) had good knowledge of kidney functions and CKD. Students who rotated through the dialysis unit during their clinical posting had higher mean knowledge score than others (P = 0.03). There was no significant difference in the mean knowledge scores of the diploma and B. Nursing students (P = 0.76). Conclusion: The majority of the final year students had poor knowledge of CKD. There is need to expand the current teaching curriculum so as to increase the knowledge of these future nurses on the basic concepts of CKD to improve outcomes of patient management. PMID:28300046

Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline.

PubMed

Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim H; Shlipak, Michael G; Newman, Anne B; Hoofnagle, Andy; Fried, Linda; Sarnak, Mark J; Gutierrez, Orlando M

2018-01-01

Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82-1.19] for ≥30% decline and OR 1.17 [95% CI 1.00-1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91-1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02-1.58] for highest vs. lowest quartile). Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults. © 2018 S. Karger AG, Basel.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

PubMed Central

de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

2015-01-01

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

PubMed

Bouzenna, Hafsia; Samout, Noura; Amani, Etaya; Mbarki, Sakhria; Tlili, Zied; Rjeibi, Ilhem; Elfeki, Abdelfattah; Talarmin, Hélène; Hfaiedh, Najla

2016-08-01

Aromatic and medicinal plants are sources of natural antioxidants thanks to their secondary metabolites. Administration of Pinus halepensis L. (Pinaceae family) in previous studies was found to alleviate deleterious effects of aspirin-induced damage on liver and kidney. The present study, carried out on female rats, evaluates the effects of P. halepensis L. essential oil (EOP) on aspirin (A)-induced damage to liver and kidney. The animals used in this study were rats (n=28) divided into 4 groups of 7 each: (1) a control group (C); (2) a group given NaCl for 56 days then treated with (A) (600 mg/kg) for 4 days (A); (3) a group fed with (EOP) for 56 days then (A) for 4 days; and a group fed with only (EOP) for 56 days and given NaCl for 4 days. Estimations of biochemical parameters in blood were determined using kit methods (Spinreact). Lipid peroxidation levels (TBARS), superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) activities were determined. Histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin embeddeding and hematoxylin-eosin staining. Under our experimental conditions, Aspirin at dose 600 mg/kg body weight induced an increase of serum biochemical parameters as well as an oxidative stress in both organs. An increase occurred in TBARS by 108% and 55%, a decrease in SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively, compared to control. Administration of EOP given to rats enabled correction in these parameters. It could be concluded that the treatment with P. halepensis L. essential oil inhibited aspirin-induced liver and kidney damage.

Intrinsic factors, adrenal gland morphology, and disease burden in captive cheetahs (Acinonyx jubatus) in South Africa.

PubMed

Gillis-Germitsch, Nina; Vybiral, Pamela-Rose; Codron, Daryl; Clauss, Marcus; Kotze, Antoinette; Mitchell, Emily P

2017-01-01

Adrenal gland weight (AW) and corticomedullary ratio (ACMR) are used as indicators of stress in animals. Captive cheetahs (Acinonyx jubatus) have higher ACMRs than free-ranging ones and stress has been linked to gastritis, amyloidosis, glomerulosclerosis, and myocardial fibrosis. We reviewed age, sex, body weight (BW), kidney weight (KW), and left AW and ACMR with necropsy findings in 51 South African captive cheetahs. Eleven common histopathologic lesions were counted for each animal as measure of its disease burden. Adrenal corticomedullary hyperplasia was significantly correlated with left AW and ACMR. Males had significantly higher AWs than females; other parameters showed no difference between the sexes. Disease burden, gastritis, and myocardial fibrosis were moderately correlated with adrenal morphology supporting prior evidence that gastritis and myocardial fibrosis are linked to stress. Glomerulosclerosis was not correlated with adrenal morphology and neither kidney nor liver amyloidosis contributed significantly to variation in AW or ACMR on multivariate analyses. Interstitial nephritis showed much stronger correlations with kidney and liver amyloidosis than gastritis. All three adrenal parameters were correlated with age; age was the only significant variable affecting ACMR on the multivariate analyses; and disease burden as well as systemic amyloidosis and kidney disease (except for fibrosis) showed moderate correlations with age. Age may, therefore, be important in the pathogenesis of disease in captive cheetahs, particularly of amyloidosis and kidney disease. None of the intrinsic measurements or adrenal parameters were sufficiently closely linked to disease to be used as ante-mortem proxies for disease burden or specific diseases. Zoo Biol. 36:40-49, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Sequential monitoring of renal transplant with aspiration cytology].

PubMed

Manfro, R C; Gonçalves, L F; de Moura, L A

1998-01-01

To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

Magnesium and cardiovascular complications of chronic kidney disease.

PubMed

Massy, Ziad A; Drüeke, Tilman B

2015-07-01

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Abundant experimental evidence suggests a physiological role of magnesium in cardiovascular function, and clinical evidence suggests a role of the cation in cardiovascular disease in the general population. The role of magnesium in CKD-mineral and bone disorder, and in particular its impact on cardiovascular morbidity and mortality in patients with CKD, is however not well understood. Experimental studies have shown that magnesium inhibits vascular calcification, both by direct effects on the vessel wall and by indirect, systemic effects. Moreover, an increasing number of epidemiologic studies in patients with CKD have shown associations of serum magnesium levels with intermediate and hard outcomes, including vascular calcification, cardiovascular events and mortality. Intervention trials in these patients conducted to date have had small sample sizes and have been limited to the study of surrogate parameters, such as arterial stiffness, vascular calcification and atherosclerosis. Randomized controlled trials are clearly needed to determine the effects of magnesium supplementation on hard outcomes in patients with CKD.

Pulmonary vein isolation alone and combined with renal sympathetic denervation in chronic kidney disease patients with refractory atrial fibrillation.

PubMed

Kiuchi, Márcio G; Chen, Shaojie; E Silva, Gustavo R; Paz, Luis M R; Kiuchi, Tetsuaki; de Paula Filho, Ary G; Souto, Gladyston L L

2016-12-01

Atrial fibrillation (AF) commonly occurs in association with chronic kidney disease (CKD), resulting in adverse outcomes. Combining pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may reduce the recurrence of AF in patients with CKD and hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. Our goal was to compare the impact of PVI + RSD with that of PVI alone in patients with concurrent AF and CKD. This was a single-center, prospective, longitudinal, randomized, double-blind study. Forty-five patients with controlled hypertension, symptomatic paroxysmal AF and/or persistent AF, stage 2 or 3 CKD, and a dual-chamber pacemaker were enrolled from January 2014 to January 2015. We assessed the 30-second recurrence of AF recorded by the pacemaker, 24-hour ambulatory blood pressure measurements, estimated glomerular filtration rate, albuminuria, echocardiographic parameters, and safety of RSD. No patient developed procedural or other complications. The ambulatory blood pressure measurements did not differ within the PVI + RSD group or between the PVI + RSD and PVI groups throughout the study. Significantly more patients in the PVI + RSD group than in the PVI group were free of AF at the 12-month follow-up evaluation. The PVI group had an unacceptable response to ablation with respect to changes in echocardiographic parameters, whereas these parameters improved in the PVI + RSD group. PVI + RSD were associated with a lower AF recurrence rate than PVI alone; it also improved renal function and some echocardiographic parameters. These encouraging data will serve as baseline information for further long-term studies on larger patient populations.

Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study.

PubMed

Mazzeffi, Michael; Jonna, Srikar; Blanco, Natalia; Mavrothalassitis, Orestes; Odekwu, Obi; Fontaine, Magali; Rock, Peter; Tanaka, Kenichi; Thom, Kerri

2018-06-01

Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI  0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI  1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

Graft function assessment in mouse models of single- and dual- kidney transplantation.

PubMed

Wang, Lei; Wang, Ximing; Jiang, Shan; Wei, Jin; Buggs, Jacentha; Fu, Liying; Zhang, Jie; Liu, Ruisheng

2018-05-23

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher GFR than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.

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

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

PubMed Central

Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

2018-01-01

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

PubMed

Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Kaneko, Tetsuji; Hibi, Yoshiko; Yamasaki, Yasuhito; Yamamoto, Masaki; Nakano, Masaru; Iwata, Naoyuki; Hibino, Satoshi

2016-06-01

Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation.

PubMed

Diuwe, Piotr; Domagala, Piotr; Durlik, Magdalena; Trzebicki, Janusz; Chmura, Andrzej; Kwiatkowski, Artur

2017-08-01

One of the most important problems in transplantation medicine is the ischemia/reperfusion injury of the organs to be transplanted. The aim of the present study was to assess the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitor etanercept on the machine perfusion hypothermia of renal allograft kidney function and organ perfusion. No statistically significant differences were found in the impact of the applied intervention on kidney machine perfusion during which the average flow and vascular resistance were evaluated. There were no statistically significant differences in the occurrence of delayed graft function (DGF). Fewer events in patients who received a kidney from the etanercept treated Group A compared to the patients who received a kidney from the control Group B were observed when comparing the functional DGF and occurrence of acute rejection episodes, however, there was no statistically significant difference. In summary, no effect of treatment with etanercept an inhibitor of TNF-alpha in a hypothermic machine perfusion on renal allograft renal survival and its perfusion were detected in this study. However, treatment of the isolated organ may be important for the future of transplantation medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

PubMed

Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

2017-01-01

The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

PubMed

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

PubMed

Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

2018-03-01

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

Bardoxolone: augmenting the Yin in chronic kidney disease.

PubMed

Thomas, Merlin C

2011-10-01

Nrf-2 (NF-E2-related factor 2) is a regulator of anti-oxidant, anti-inflammatory and detoxification pathways. Coordinated augmentation of these key defence pathways via Nrf-2 signalling is being investigated for the treatment of chronic diseases, including diabetes and its complications. The first to reach commercial development is the triterpenoid, bardoxolone methyl. In recent clinical trial, bardoxolone rapidly improved kidney function on average by 5-10 ml/min within 4 weeks of therapy. Importantly, this improvement was sustained during one year of active treatment. This suggests that rather that overworking a failing system, bardoxolone appeared to safely augment renal function, at least to one year. If similar improvements in kidney function can be reproduced in the upcoming BEACON trial, it will represent a major advance on conventional therapy and new way to bring balance to the failing kidney.

Application of ureterorenoscope and flexible ureterorenoscope lithotripsy in removing calculus from extracorporeal living donor renal graft: a single-center experience.

PubMed

Lin, Chun-Hua; Zhang, Zuo-Fu; Wang, Jiahui; Yu, Lu-Xin; Wang, Wen-Ting; Shi, Lei; Lin, Xiang-Nan

2017-11-01

Here, we reported our clinical application of ureterorenoscope (URS) and flexible URS lithotripsy in stone removal on 10 cases of excised living donor kidney graft. After the extraction of donor kidney by retroperitoneal laparoscopy, the donor graft was perfused with 4 °C HCA solution. Calculus between 2-4 mm were removed intact with lithotomy forceps under direct vision of URS. Larger calculi of >4 mm were fractured with flexible URS combining holmium laser lithotripsy. Fragments of the calculus were extracted with basket extractor and lithotomy forceps. All operations were successful. The operation time was 14-31 min (average 21.2 ± 6.3 min). The kidneys were then transplanted to the recipients using routine procedure. The transplanted kidneys functioned well after transplantation. Gross hematuria resolved 1-4 d after operation (average 2.6 ± 0.9 d). The transplanted kidneys functioned well without early complications such as functional recovery delay and acute graft rejection. The donors and recipients were followed for 12 months. The size of the transplanted kidneys was normal and new stones or urinary obstruction was not seen upon urinary color Doppler ultrasound examination. In conclusion, we believe it is feasible, safe and effective to use URS or flexible URS combining holmium laser lithotripsy on extracorporeal living donor kidney.

Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

PubMed

Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

2017-12-01

To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle.

PubMed

Chang, C-Hong; Davies, Jamie A

2012-01-01

Tissue engineering of functional kidney tissue is an important goal for clinical restoration of renal function in patients damaged by infectious, toxicological, or genetic disease. One promising approach is the use of the self-organizing abilities of embryonic kidney cells to arrange themselves, from a simply reaggregated cell suspension, into engineered organs similar to fetal kidneys. The previous state-of-the-art method for this results in the formation of a branched collecting duct tree, immature nephrons (S-shaped bodies) beside and connected to it, and supportive stroma. It does not, though, result in the significant formation of morphologically detectable loops of Henle - anatomical features of the nephron that are critical to physiological function. We have combined the best existing technique for renal tissue engineering from cell suspensions with a low-volume culture technique that allows intact kidney rudiments to make loops of Henle to test whether engineered kidneys can produce these loops. The result is the formation of loops of Henle in engineered cultured 'fetal kidneys', very similar in both morphology and in number to those formed by intact organ rudiments. This brings the engineering technique one important step closer to production of a fully realistic organ. Copyright © 2012 S. Karger AG, Basel.

Comparison of the Physiology of the Spaceflight and Hindlimb Suspended Rat

NASA Technical Reports Server (NTRS)

Grindeland, R. E.; Booth, F. W.

1994-01-01

The suspended rat has been used extensively as a simulation of the spaceflight animal. In suspension, hindlimbs are unloaded from the acceleration of gravity, much as they are in spaceflight. Comparisons of data from spaceflight (microgravity) and suspended (1G) rats have suggested that suspension my be an appropriate model, but no direct comparisons had been made between the spaceflight and suspended rat. Cosmos 2044 afforded the first opportunity to directly compare the effects of hindlimb suspension (HS) and spaceflight (SF) on a broad range of physiological and histological parameters. This paper reports on the comparison of skelton, skeletal muscle, heart, neural, pulmonary, kidney, liver, intestine, blood plasma, immune function, red blood cells, and endocrine and reproductive functions and systems.

An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

PubMed

Hanson, Camilla S; Chapman, Jeremy R; Gill, John S; Kanellis, John; Wong, Germaine; Craig, Jonathan C; Teixeira-Pinto, Armando; Chadban, Steve J; Garg, Amit X; Ralph, Angelique F; Pinter, Jule; Lewis, Joshua R; Tong, Allison

2018-06-07

Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings. Copyright © 2018 by the American Society of Nephrology.

Kidney-inspired algorithm for optimization problems

NASA Astrophysics Data System (ADS)

Jaddi, Najmeh Sadat; Alvankarian, Jafar; Abdullah, Salwani

2017-01-01

In this paper, a population-based algorithm inspired by the kidney process in the human body is proposed. In this algorithm the solutions are filtered in a rate that is calculated based on the mean of objective functions of all solutions in the current population of each iteration. The filtered solutions as the better solutions are moved to filtered blood and the rest are transferred to waste representing the worse solutions. This is a simulation of the glomerular filtration process in the kidney. The waste solutions are reconsidered in the iterations if after applying a defined movement operator they satisfy the filtration rate, otherwise it is expelled from the waste solutions, simulating the reabsorption and excretion functions of the kidney. In addition, a solution assigned as better solution is secreted if it is not better than the worst solutions simulating the secreting process of blood in the kidney. After placement of all the solutions in the population, the best of them is ranked, the waste and filtered blood are merged to become a new population and the filtration rate is updated. Filtration provides the required exploitation while generating a new solution and reabsorption gives the necessary exploration for the algorithm. The algorithm is assessed by applying it on eight well-known benchmark test functions and compares the results with other algorithms in the literature. The performance of the proposed algorithm is better on seven out of eight test functions when it is compared with the most recent researches in literature. The proposed kidney-inspired algorithm is able to find the global optimum with less function evaluations on six out of eight test functions. A statistical analysis further confirms the ability of this algorithm to produce good-quality results.

Identification and characterization of kidney transplants with good glomerular filtration rate at 1 year but subsequent progressive loss of renal function.

PubMed

Park, Walter D; Larson, Timothy S; Griffin, Matthew D; Stegall, Mark D

2012-11-15

After the first year after kidney transplantation, 3% to 5% of grafts fail each year but detailed studies of how grafts progress to failure are lacking. This study aimed to analyze the functional stability of kidney transplants between 1 and 5 years after transplantation and to identify initially well-functioning grafts with progressive decline in allograft function. The study included 788 adult conventional kidney transplants performed at the Mayo Clinic Rochester between January 2000 and December 2005 with a minimum graft survival and follow-up of 2.6 years. The modification of diet in renal disease equation for estimating glomerular filtration rate (eGFR(MDRD)) was used to calculate the slope of renal function over time using all available serum creatinine values between 1 and 5 years after transplantation. Most transplants demonstrated good function (eGFR(MDRD) ≥40 mL/min) at 1 year with positive eGFR(MDRD) slope between 1 and 5 years after transplantation. However, a subset of grafts with 1-year eGFR(MDRD) ≥40 mL/min exhibited strongly negative eGFR(MDRD) slope between 1 and 5 years suggestive of progressive loss of graft function. Forty-one percent of this subset reached graft failure during follow-up, accounting for 69% of allograft failures occurring after 2.5 years after transplantation. This pattern of progressive decline in estimated glomerular filtration rate despite good early function was associated with but not fully attributable to factors suggestive of enhanced antidonor immunity. Longitudinal analysis of serial estimated glomerular filtration ratemeasurements identifies initially well-functioning kidney transplants at high risk for subsequent graft loss. For this subset, further studies are needed to identify modifiable causes of functional decline.

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year.

PubMed

Taner, Timucin; Gustafson, Michael P; Hansen, Michael J; Park, Walter D; Bornschlegl, Svetlana; Dietz, Allan B; Stegall, Mark D

2018-06-01

Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes. Mixed cell cultures with donor or third party cells were used to measure cell proliferation and interferon gamma production. Despite a significant overlap, simultaneous liver-kidney transplant recipients had a lower overall frequency of circulating CD8 + , activated CD4 + and effector memory T cells, compared to solitary kidney transplant recipients. Simultaneous liver-kidney transplant recipient T cells had a significantly lower proliferative response to the donor cells compared to solitary kidney recipients (11.9 vs. 42.9%), although their response to third party cells was unaltered. The frequency of interferon gamma producing alloreactive T cells in simultaneous liver-kidney transplant recipients was significantly lower than that of solitary kidney transplant recipients. Flow cytometric analysis of the mixed cultures demonstrated that both alloreactive CD4 + and CD8 + compartments of the simultaneous liver-kidney transplant recipient circulating blood cells were smaller. Thus, the phenotypic and functional characteristics of the circulating blood cells of the simultaneous liver-kidney transplant recipients resembled those of solitary liver transplant recipients, and appear to be associated with donor-specific hypo-alloresponsiveness. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease.

PubMed

Toth, Peter P; Dwyer, Jamie P; Cannon, Christopher P; Colhoun, Helen M; Rader, Daniel J; Upadhyay, Ashish; Louie, Michael J; Koren, Andrew; Letierce, Alexia; Mandel, Jonas; Banach, Maciej

2018-06-01

Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.

PubMed

van Daalen, Emma E; Jennette, J Charles; McAdoo, Stephen P; Pusey, Charles D; Alba, Marco A; Poulton, Caroline J; Wolterbeek, Ron; Nguyen, Tri Q; Goldschmeding, Roel; Alchi, Bassam; Griffiths, Meryl; de Zoysa, Janak R; Vincent, Beula; Bruijn, Jan A; Bajema, Ingeborg M

2018-01-06

Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 ( P =0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated ( P <0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3. Copyright © 2018 by the American Society of Nephrology.

First successful combined heart and kidney transplant in Iran: a case report.

PubMed

Ahmadi, Zargham-Hossein; Mirhosseini, Seyed Mohsen; Fakhri, Mohammad; Mozaffary, Amirhossein; Lotfaliany, Mojtaba; Nejatollahi, Seyed Mohammad Reza; Marashi, Seyed-Ali; Behzadnia, Neda; Sharif-Kashani, Babak

2013-08-01

Combined heart and kidney transplant has become an accepted therapy for patients with coexisting heart and kidney failure. This method, compared with single-organ transplant, has a better outcome. Here, we report the first successful combined heart and kidney transplant in Iran. The patient was a 36-year-old man with end-stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to concurrent heart and kidney end-stage diseases, combined cardiorenal transplant was done. Eight months after his transplant, routine follow-ups have not shown any signs of acute rejection. He is now New York Heart Association functional class I. Both cardiac and renal functions are within normal ranges. Good outcome during follow-up for this case justifies simultaneous heart plus kidney transplants as an alternate treatment for patients with advanced disease of both organs.

TECHNIQUES FOR COMBINED PROCUREMENT OF HEARTS AND KIDNEYS WITH SATISFACTORY EARLY FUNCTION OF RENAL ALLOGRAFTS

PubMed Central

Shaw, Byers W.; Rosenthal, J. Thomas; Griffith, Bartley F.; Haresty, Robert L.; Broznik, Brian; Hakala, Thomas; Bahnson, Henry T.; Starzl, Thomas E.

2009-01-01

SUMMARY Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance. PMID:6351307

Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

PubMed

Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

2013-08-01

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

PubMed

Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2008-06-03

A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.

Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

PubMed Central

Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2010-01-01

Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single center. Few kidney biopsies were performed. Conclusion A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes. PMID:18519927

Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

PubMed

Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

2016-11-01

Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of 24-Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking.

PubMed

Liakos, Charalampos I; Karpanou, Eva A; Markou, Maria I; Grassos, Charalampos A; Vyssoulis, Gregory P

2015-12-01

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross-sectional study sought to determine the association of 24-hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never-treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24-hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV =standard deviation×100/mean value) derived from ambulatory recording. The CV SBP-to-CV HR ratio (CV R) was used as a marker of the interplay between 24-hour SBP and HR variability. Renal function was estimated via 24-hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and 24-hour urine α1 -microglobulin. After adjustment for age, sex, and smoking, CV SBP was found to be weakly correlated to eGFR (r=-0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1 -microglobulin (r=-0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CV HR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1 -microglobulin (r=0.185, 0.134, -0.306, -0.247; all P<.001, respectively). CV R also showed equally good adjusted correlations (r=-0.175, -0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CV HR and CV R were even better in smokers (r=0.213, 0.158, -0.332, -0.272 and -0.183, -0.118, 0.351, 0.275, respectively; all P<.001). CV HR and CV R emerge as better related to kidney function than CV SBP, especially in smokers. The correlation of CV HR and CV SBP to renal function is inverse to each other. ACR and α1 -microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved. © 2015 Wiley Periodicals, Inc.

Understanding alterations on blood and biochemical parameters in athletes that use dietary supplements, steroids and illicit drugs.

PubMed

Bordin, Dayanne Mozaner; Bettim, Bárbara Beltrame; Perdona, Gleici Castro; de Campos, Eduardo Geraldo; De Martinis, Bruno Spinosa

2017-02-01

In recent years it was verified there are an alarming growing number of teenagers and young adults using a combination of dietary supplements (DS) anabolic androgenic steroids (AAS) and drugs of abuse. This practice is used to improve physical fitness and appearance, may cause serious side effects. This article shows the alterations in the hematological and renal function parameters associate with these substances in 40 athletes. This research involved three steps: 1-the administration of a self-completion questionnaire ; 2-the assessment of hematological and biochemical parameters of renal function and; 3-toxicological urinalysis. Hematological and biochemical tests were conducted in an accredited laboratory and the toxicological urinalysis was validated in our laboratory using liquid-liquid extraction (LLE) and gas chromatography-mass spectrometry (GC-MS). The testosterone levels in the participants who consumed steroids increased 20-60% and alterations in serum creatinine, urea and uric reached values of up to 1.9; 60.6 and 7.5mg/dL, respectively. The toxicological urinalysis supports self-reports confirming the use of AAS and recreational drugs, putting at risk the health of those athletes increasing the chances of kidney diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Kidney Response to the Spectrum of Diet-Induced Acid Stress.

PubMed

Goraya, Nimrit; Wesson, Donald E

2018-05-11

Chronic ingestion of the acid (H⁺)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H⁺ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H⁺ excretion is less than the cumulative increment in dietary H⁺, consistent with H⁺ retention. This H⁺ retention associated with the described high dietary H⁺ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H⁺ retention does not measurably change plasma acid⁻base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H⁺ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H⁺ injury, which we characterize as “H⁺ stress”, and the emerging evidence that high dietary H⁺ constitutes a threat to long-term kidney health.

Novel biomarkers of acute kidney injury and failure: clinical applicability.

PubMed

Mårtensson, J; Martling, C-R; Bell, M

2012-12-01

Acute kidney injury (AKI) has a number of triggers, including ischaemia, nephrotoxins, radiocontrast, and bacterial endotoxins. It occurs in around one-third of patients treated in intensive care unit (ICU) and is even more prevalent in cardiac surgery patients. There is a higher mortality in patients with AKI compared with non-AKI counterparts, and in severe AKI requiring renal support, the 6 month mortality is >50%. Unlike the progressive development of biomarkers in cardiology, there have been few changes in kidney diagnostic markers. Creatinine is still used as an indicator of kidney function but not of the parenchymal kidney injury. Serum creatinine (sCr) concentration does not change until around 50% of kidney function is lost, and varies with muscle mass, age, sex, medications, and hydration status. The lag time between injury and loss of function, risks missing a therapeutic opportunity, and may explain the high associated mortality. Novel biomarkers of AKI- and failure include neutrophil gelatinase-associated lipocalin, N-acetyl-β-d-glucosaminidase, kidney injury molecule-1, interleukin-18, and cystatin C. The pathophysiology associated with accumulation of these markers in plasma and urine is not clear, but a common denominator is inflammation. Some of these new AKI biomarkers may have clinical applicability in anaesthesia and intensive care in the future. It is possible that a 'kidney biomarker panel' will become standard before and after major surgery. If elevated or positive, the anaesthetist must take special care to optimize the patients after operation on the surgical wards or ICU to avoid further nephrotoxic insults and initiate supplementary care.

A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney.

PubMed

Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus

2017-05-01

Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation.

PubMed

Snanoudj, R; Rabant, M; Timsit, M O; Karras, A; Savoye, E; Tricot, L; Loupy, A; Hiesse, C; Zuber, J; Kreis, H; Martinez, F; Thervet, E; Méjean, A; Lebret, T; Legendre, C; Delahousse, M

2009-11-01

It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR.