Inhibition of WISE preserves renal allograft function.

PubMed

Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

2013-01-01

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

SIMULTANEOUS LIVER KIDNEY TRANSPLANTATION IN LIVER TRANSPLANT CANDIDATES WITH RENAL DYSFUNCTION: IMPORTANCE OF CREATININE LEVELS, DIALYSIS, AND ORGAN QUALITY IN SURVIVAL

PubMed Central

Tanriover, Bekir; MacConmara, Malcolm P.; Parekh, Justin; Arce, Cristina; Zhang, Song; Gao, Ang; Mufti, Arjmand; Levea, Swee-Ling; Sandikci, Burhaneddin; Ayvaci, Mehmet U.S.; Ariyamuthu, Venketash K.; Hwang, Christine; Mohan, Sumit; Mete, Mutlu; Vazquez, Miguel A.; Marrero, Jorge A.

2016-01-01

Background The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature. Methods The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality. Results On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62–0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5). Conclusions Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients. PMID:27942610

Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers.

PubMed

Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

2005-01-01

Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

PubMed

Hoskote, Aparna; Burch, Michael

2015-06-01

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis.

PubMed

Daoussis, Dimitrios; Panoulas, Vasileios; Toms, Tracey; John, Holly; Antonopoulos, Ioannis; Nightingale, Peter; Douglas, Karen M J; Klocke, Rainer; Kitas, George D

2009-01-01

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA. Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results. UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

PubMed

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in most RCTs. The RIFLE, AKIN and KDIGO classification systems were infrequently used; renal dysfunction was generally defined using the SOFA score.

The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

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

Provoost, A.P.; Van Aken, M.

1984-01-01

In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. Themore » accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.« less

Prevalence and Factors Associated with Renal Dysfunction Among HIV-Infected Patients

DTIC Science & Technology

2010-01-01

cross-sectional study at two military clinics with open access to care to determine the impact of HIV factors, including antiretroviral therap¥, on...clinics with open access to care to determine the impact of HIV factors, including antiretroviral therapi, on renal function. Renal dysfunction was...measurement for determination of renal dysfunction rather than measurements over a 3-month or greater period used to establish chronic kidney disease.21

Long-Term Outcomes of Renal Transplant in Recipients With Lower Urinary Tract Dysfunction.

PubMed

Wilson, Rebekah S; Courtney, Aisling E; Ko, Dicken S C; Maxwell, Alexander P; McDaid, James

2018-01-02

Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower urinary tract dysfunction is not a barrier to successful renal transplant.

Prevalence of Hyponatremia, Renal Dysfunction, and Other Electrolyte Abnormalities Among Runners Before and After Completing a Marathon or Half Marathon

PubMed Central

Mohseni, Michael; Silvers, Scott; McNeil, Rebecca; Diehl, Nancy; Vadeboncoeur, Tyler; Taylor, Walt; Shapiro, Shane; Roth, Jennifer; Mahoney, Sherry

2011-01-01

Background: Prior reports on metabolic derangements observed in distance running frequently have small sample sizes, lack prerace laboratory measures, and report sodium as the sole measure. Hypothesis: Metabolic abnormalities—hyponatremia, hypokalemia, renal dysfunction, hemoconcentration—are frequent after completing a full or half marathon. Clinically significant changes occur in these laboratory values after race completion. Study Design: Observational, cross-sectional study. Methods: Consenting marathon and half marathon racers completed a survey as well as finger stick blood sampling on race day of the National Marathon to Fight Breast Cancer (Jacksonville, Florida, February 2008). Parallel blood measures were obtained before and after race completion (prerace, n = 161; postrace, n = 195). Results: The prevalence of prerace and postrace hyponatremia was 8 of 161 (5.0%) and 16 of 195 (8.2%), respectively. Hypokalemia was not present prerace but was present in 1 runner postrace (1 of 195). Renal dysfunction occurred prerace in 14 of 161 (8.7%) and postrace in 83 of 195 (42.6%). Among those with postrace renal dysfunction, 45.8% (38 of 83) were classified as moderate or severe. Hemoconcentration was present in 2 of 161 (1.2%) prerace and 6 of 195 (3.1%) postrace. The mean changes in laboratory values were (postrace minus prerace): sodium, 1.6 mmol/L; potassium, −0.2 mmol/L; blood urea nitrogen, 2.8 mg/dL; creatinine, 0.2 mg/dL; and hemoglobin, 0.3 g/dL for 149 pairs (except blood urea nitrogen, n = 147 pairs). Changes were significant for all comparisons (P < 0.01) except potassium (P = 0.08) and hemoglobin (P = 0.01). Conclusions: Metabolic abnormalities are common among endurance racers, and they may be present prerace, including hyponatremia. The clinical significance of these findings is unknown. Clinical relevance: It is unclear which runners are at risk for developing clinically important metabolic derangements. Participating in prolonged endurance exercise appears to be safe in the majority of racers. PMID:23016001

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

PubMed

Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

2017-03-20

Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

PubMed

Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal dysfunction patients had 8.5-fold increased risk for adverse outcomes. Although IC is often self-limited, our data warrants special attention and aggressive therapy in treating these patients.

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

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

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

Renal dysfunction after total body irradiation: Dose-effect relationship

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

Kal, Henk B.; Kempen-Harteveld, M. Loes van

2006-07-15

Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated.more » Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.« less

Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database.

PubMed

Cooper, William A; O'Brien, Sean M; Thourani, Vinod H; Guyton, Robert A; Bridges, Charles R; Szczech, Lynda A; Petersen, Rebecca; Peterson, Eric D

2006-02-28

Although patients with end-stage renal disease are known to be at high risk for mortality after coronary artery bypass graft (CABG) surgery, the impact of lesser degrees of renal impairment has not been well studied. The purpose of this study was to compare outcomes in patients undergoing CABG with a range from normal renal function to dependence on dialysis. We reviewed 483,914 patients receiving isolated CABG from July 2000 to December 2003, using the Society of Thoracic Surgeons National Adult Cardiac Database. Glomerular filtration rate (GFR) was estimated for patients with the use of the Modification of Diet in Renal Disease study formula. Multivariable logistic regression was used to determine the association of GFR with operative mortality and morbidities (stroke, reoperation, deep sternal infection, ventilation >48 hours, postoperative stay >2 weeks) after adjustment for 27 other known clinical risk factors. Preoperative renal dysfunction (RD) was common among CABG patients, with 51% having mild RD (GFR 60 to 90 mL/min per 1.73 m2, excludes dialysis), 24% moderate RD (GFR 30 to 59 mL/min per 1.73 m2, excludes dialysis), 2% severe RD (GFR <30 mL/min per 1.73 m2, excludes dialysis), and 1.5% requiring dialysis. Operative mortality rose inversely with declining renal function, from 1.3% for those with normal renal function to 9.3% for patients with severe RD not on dialysis and 9.0% for those who were dialysis dependent. After adjustment for other covariates, preoperative GFR was one of the most powerful predictors of operative mortality and morbidities. Preoperative RD is common in the CABG population and carries important prognostic importance. Assessment of preoperative renal function should be incorporated into clinical risk assessment and prediction models.

Directed Retrograde Cerebral Protection during Moderate Hypothermic Circulatory Arrest

PubMed Central

Yacoubian, Vahe; Jyrala, Aarne; Kay, Gregory L.

2006-01-01

There are many choices for neurologic protection for aortic arch surgery. Although numerous investigators have challenged the efficacy of retrograde cerebral perfusion, we have had good results with our application of this technique. We performed a retrospective review of 8 consecutive patients who underwent surgery from 1 June 2001 through 31 March 2003; the age range was 33 to 97 years. All patients required circulatory arrest and underwent retrograde cerebral perfusion with use of a tourniquet on the patients' left and right arms above the elbow to direct retrograde flow to the brain. Moderate hypothermia (around 24 °C nasopharyngeal) was used; circulatory arrest time ranged from 27 to 63 minutes. There was 1 late hospital death due to multiple-organ system failure. There were no neurologic complications (stroke or temporary neurologic dysfunction). There was no substantive neurologic or renal dysfunction in this cohort, in which moderate hypothermia was used. These results are comparable to those reported in the literature for similar patients. We conclude that, for patients who require circulatory arrest, directed retrograde cerebral perfusion at moderate nasopharyngeal hypothermia gives results comparable to those reported with other techniques. PMID:17215968

Transient renal tubulopathy in a racing Greyhound.

PubMed

Abraham, L A; Tyrrell, D; Charles, J A

2006-11-01

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Intra-operative hemodialysis during liver transplantation: an expanded role of the nephrology nurse.

PubMed

Henson, Angela; Carpenter, Sally

2010-01-01

Hemodialysis is widely acknowledged as a treatment option to stabilize acute medical conditions where biochemistry management is paramount. One of the most challenging situations is during liver transplantation, when patients with moderate renal dysfunction are likely to become acutely acidotic. For nephrology nurses, this extended role requires increased knowledge, advanced skills, and a high level of communication with unfamiliar team members. With appropriate procedures and a supportive environment, delivering such a service is feasible.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert

2008-05-01

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

PubMed Central

Nishijima, Takeshi; Komatsu, Hirokazu; Gatanaga, Hiroyuki; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Tanuma, Junko; Yazaki, Hirohisa; Tsukada, Kunihisa; Honda, Miwako; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi

2011-01-01

Background Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. Methods In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. Results The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m2 decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058). Conclusion The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir. PMID:21799928

Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

PubMed Central

Marckmann, Peter; Logager, Vibeke B.

2007-01-01

Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation

PubMed Central

Habib, Shahid; Khan, Khalid; Hsu, Chiu-Hsieh; Meister, Edward; Rana, Abbas; Boyer, Thomas

2017-01-01

Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated. PMID:28496531

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.

[Psychosocial profile and family support perception in adults].

PubMed

Landeros-Herrera, Jesús Ernesto; Simental-Mendía, Luis E; Rodríguez-Durán, Juan Luis

2015-01-01

Psychosocial profile disturbances are the basis of personality disorders, which are frequent in México. Thus, the objective of this study was to determine if the family support perception is associated with the psychosocial profile in adults. A total of 450 men and non-pregnant women aged 18 to 60 years were enrolled in a population-based cross-sectional study. According psychosocial profile individuals were allocated into groups altered and unaltered. The presences of psychiatric illness, renal, hepatic, and cardiovascular disease, malignancy or any kind of disability were exclusion criteria. The family support perception was determined by family APGAR and the psychosocial profile using the Dr. Víctor Chávez test. A logistic regression analysis was used to compute the association between family support perception and psychosocial profile. A total of 344 (76.4 %) and 106 (23.5 %) subjects were included into the groups with altered and unaltered psychosocial profile, respectively. Both, moderate family dysfunction (OR = 1.80 95 % CI 1.01-3.23 p = 0.04), and high family dysfunction (OR = 3.88 95 % CI 1.09-12.09 p = 0.02) were significantly associated with altered psychosocial profile. Both, moderate and high family dysfunctions are associated with altered psychosocial profile in adults.

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.

Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.

PubMed

Liu, Licette C Y; Schutte, Elise; Gansevoort, Ron T; van der Meer, Peter; Voors, Adriaan A

2015-01-01

The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone. This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of finerenone. The selectivity and greater binding affinity of finerenone to the MR may reduce the risk of hyperkalemia and renal dysfunction and thereby overcome the reluctance to start and uptitrate MRAs in patients with HF and diabetic kidney disease. Studies conducted in patients with HFrEF and moderate chronic kidney disease and diabetic kidney disease, showed promising results. Phase III trials will have to show whether finerenone might become the third-generation MRA for the treatment of HF and diabetic kidney disease.

Methoxyflurane revisited: tale of an anesthetic from cradle to grave.

PubMed

Mazze, Richard I

2006-10-01

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

PubMed

Kostrubiec, Maciej; Łabyk, Andrzej; Pedowska-Włoszek, Justyna; Pacho, Szymon; Dzikowska-Diduch, Olga; Dul, Przemysław; Ciurzyński, Michał; Bienias, Piotr; Pruszczyk, Piotr

2012-09-01

Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.

PubMed

Sho, Takuya; Suda, Goki; Nagasaka, Atsushi; Yamamoto, Yoshiya; Furuya, Ken; Kumagai, Kenichi; Uebayashi, Minoru; Terashita, Katsumi; Kobayashi, Tomoe; Tsunematsu, Izumi; Onodera, Manabu; Meguro, Takashi; Kimura, Megumi; Ito, Jun; Umemura, Machiko; Izumi, Takaaki; Kawagishi, Naoki; Ohara, Masatsugu; Ono, Yuji; Nakai, Masato; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Sakamoto, Naoya

2018-06-01

The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction. © 2018 The Japan Society of Hepatology.

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

PubMed Central

Legrand, Matthieu; Mik, Egbert G; Johannes, Tanja; Payen, Didier; Ince, Can

2008-01-01

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium–leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed. PMID:18488066

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

PubMed Central

Adhikari, Neill K. J.; Ostermann, Marlies; Heels-Ansdell, Diane; Douketis, James D.; Skrobik, Yoanna; Qushmaq, Ismael; Meade, Maureen; Guyatt, Gordon; Geerts, William; Walsh, Michael W.; Crowther, Mark A.; Friedrich, Jan O.; Burry, Lisa; Bellomo, Rinaldo; Brandão da Silva, Nilton; Costa Filho, Rubens; Cox, Michael J.; Alves Silva, Suzana; Cook, Deborah J.

2018-01-01

Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. Results In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone. PMID:29856817

Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment

PubMed Central

Breen, Des; Wilmer, Alexander; Bodenham, Andrew; Bach, Vagn; Bonde, Jan; Kessler, Paul; Albrecht, Sven; Shaikh, Soraya

2004-01-01

Introduction This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care. Methods A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain. Results There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use. Conclusion Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours. PMID:14975051

Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

PubMed

Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

2015-12-01

Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease

PubMed Central

Edwards, Nicola C; Steeds, Richard P; Chue, Colin D; Stewart, Paul M; Ferro, Charles J; Townend, Jonathan N

2012-01-01

AIM Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic early stage CKD (eGFR 30–89 ml/min/1.73m2) received 25 mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. RESULTS After 40 weeks of treatment the incidence of serious hyperkalaemia (K+≥6.0 mmol/L) was <1%. A potassium 5.5–5.9 mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0 mmol/L and eGFR ≤45 ml/min/1.73m2. Over follow-up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. CONCLUSION Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. PMID:21950312

The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease.

PubMed

Edwards, Nicola C; Steeds, Richard P; Chue, Colin D; Stewart, Paul M; Ferro, Charles J; Townend, Jonathan N

2012-03-01

Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic early stage CKD (eGFR 30-89ml/min/1.73m(2) ) received 25mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. After 40 weeks of treatment the incidence of serious hyperkalaemia (K(+) ≥6.0mmol/L) was <1%. A potassium 5.5-5.9mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0mmol/L and eGFR ≤45 ml/min/1.73m(2) . Over follow-up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End‐Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects

PubMed Central

Dymond, Angela W.; Martin, Paul; Huang, Yifan; Severin, Paul; Holmes, Victoria; Mariani, Gabriella; Marbury, Thomas

2016-01-01

Abstract Two phase I open‐label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end‐stage renal disease (ESRD) undergoing hemodialysis and subjects with varying degrees of hepatic impairment; both studies included a matched control group comprised of healthy individuals. In the renal impairment study, subjects received single doses of selumetinib 50 mg; those with ESRD received selumetinib before and after dialysis (with a between‐treatment washout period of ≥7 days). In the hepatic impairment study, subjects received varying single doses of selumetinib (20‐50 mg) depending on liver dysfunction (mild, moderate, or severe as per Child‐Pugh classification). PK, safety, and tolerability data were collected from both studies. Overall, 24 subjects were included in the renal impairment study (ESRD, N = 12; healthy subjects, N = 12). Selumetinib exposure (AUC and Cmax) was not increased in the ESRD group vs healthy subjects. Selumetinib exposure was lower when selumetinib was dosed before vs after dialysis, although individual exposure was variable. Overall, 32 subjects were included in the hepatic impairment study (mild, moderate, and severe impairment, N = 8 per group; healthy subjects, N = 8). Generally, dose‐normalized total selumetinib exposure was increased by 25% to 59% in subjects with moderate and severe hepatic impairment compared with healthy subjects. Increasing Child‐Pugh score, decreasing serum albumin, and increasing prothrombin time correlated with increasing unbound selumetinib exposure. In both studies, selumetinib was well tolerated with no new safety concerns. These studies will inform dose adjustment considerations in patients. PMID:28019010

Association between in-hospital mortality and renal dysfunction in 186,219 patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.

PubMed

Fabbian, Fabio; Gallerani, Massimo; Pala, Marco; De Giorgi, Alfredo; Salmi, Raffaella; Dentali, Francesco; Ageno, Walter; Manfredini, Roberto

2014-11-01

Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186,219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n=32,189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF. © The Author(s) 2013.

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.

Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

PubMed

Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

2013-12-01

High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

Renal tubular function in children with tyrosinaemia type I treated with nitisinone.

PubMed

Santra, S; Preece, M A; Hulton, S-A; McKiernan, P J

2008-06-01

Tyrosinaemia type I (TTI) is an inherited deficiency in the enzyme fumarylacetoacetate hydrolase and is frequently complicated by renal tubular dysfunction which may persist in some patients after hepatic transplantation. Nitisinone has revolutionized the management of TTI but its effect on renal tubular dysfunction has not been described in a large cohort of patients. To document the incidence and progression of renal tubular dysfunction in children with TTI treated with nitisinone at a single centre. Twenty-one patients with TTI from a single centre were treated with nitisinone for at least 12 months. Median age at first treatment was 17 weeks (range 1 week to 27 months). Nine patients (43%) presented in acute liver failure, seven (33%) had a chronic presentation and five (24%) were detected pre-clinically. A retrospective case analysis of plasma phosphate, urinary protein/creatinine ratio and tubular reabsorption of phosphate was performed for all patients as markers of tubular function. Renal ultrasounds were examined for evidence of nephrocalcinosis and where available, skeletal radiographs for rickets. All patients had biochemical evidence of renal tubular dysfunction at presentation. After nitisinone and dietary treatment were started, all three markers normalized within one year. Four children had clinical rickets at presentation (which improved), of whom one had nephrocalcinosis, which did not reverse on nitisinone. No child redeveloped tubular dysfunction after commencing nitisinone. All patients with TTI had evidence of tubular dysfunction at presentation and in all cases this resolved with nitisinone and dietary control. The tubulopathy associated with TTI is reversible.

Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

PubMed

Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

2012-01-13

To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation.

PubMed Central

Weinstein, M J; Chute, L E; Schmitt, G W; Hamburger, R H; Bauer, K A; Troll, J H; Janson, P; Deykin, D

1985-01-01

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments. Images PMID:3932466

Chronic Kidney Disease in Pregnancy.

PubMed

Koratala, Abhilash; Bhattacharya, Deepti; Kazory, Amir

2017-09-01

With the increasing prevalence of chronic kidney disease (CKD) worldwide, the number of pregnant women with various degrees of renal dysfunction is expected to increase. There is a bidirectional relation between CKD and pregnancy in which renal dysfunction negatively affects pregnancy outcomes, and the pregnancy can have a deleterious impact on various aspects of kidney disease. It has been shown that even mild renal dysfunction can increase considerably the risk of adverse maternal and fetal outcomes. Moreover, data suggest that a history of recovery from acute kidney injury is associated with adverse pregnancy outcomes. In addition to kidney dysfunction, maternal hypertension and proteinuria predispose women to negative outcomes and are important factors to consider in preconception counseling and the process of risk stratification. In this review, we provide an overview of the physiologic renal changes during pregnancy as well as available data regarding CKD and pregnancy outcomes. We also highlight the important management strategies in women with certain selected renal conditions that are seen commonly during the childbearing years. We call for future research on underexplored areas such as the concept of renal functional reserve to develop a potential clinical tool for prognostication and risk stratification of women at higher risk for complications during pregnancy.

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

Evaluation of clinical outcomes among nonvalvular atrial fibrillation patients treated with rivaroxaban or warfarin, stratified by renal function
.

PubMed

Weir, Matthew R; Haskell, Lloyd; Berger, Jeffrey S; Ashton, Veronica; Laliberté, François; Crivera, Concetta; Brown, Kip; Lefebvre, Patrick; Schein, Jeffrey

2018-05-01

Renal dysfunction increases the risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF). Adult NVAF patients with ≥ 6 months prior to first warfarin or rivaroxaban dispensing were selected from the IMS Health Real-World Data Adjudicated Claims database (05/2011 - 06/2015) with electronic medical records. Ischemic stroke events, thromboembolic events (venous thromboembolism, myocardial infarction, or ischemic stroke), and major bleeding events were compared between patients by renal function identified by 1) relevant ICD-9-CM diagnosis codes and 2) estimated creatinine clearance (eCrCl). Baseline confounders were adjusted using inverse probability of treatment weights. The diagnosis-based analysis included 39,872 rivaroxaban and 48,637 warfarin users (3,572 and 8,230 with renal dysfunction, respectively). The eCrCl-based analysis included 874 rivaroxaban and 1,069 warfarin users (66 and 208 with eCrCl < 60 mL/min, respectively). In the diagnosis-based analysis, rivaroxaban users with renal dysfunction had a significantly lower stroke rate (HR = 0.55, p = 0.0004) compared to warfarin users; rivaroxaban users with and without renal dysfunction had significantly lower thromboembolic event rates (HR = 0.62, p < 0.0001; and HR = 0.64, p < 0.0001, respectively), and similar major bleeding rates to warfarin users. In the eCrCl-based analysis, rivaroxaban users with eCrCl ≥ 60 mL/min had a significantly lower thromboembolic event rate, but other outcomes were not statistically significant. Rivaroxaban-treated NVAF patients with diagnosed renal dysfunction had a significantly lower stroke rate compared to warfarin-treated patients. Regardless of renal dysfunction diagnoses, rivaroxaban users had lower thromboembolic event rates compared to warfarin users, and a similar rate of major bleeding. eCrCl-based analysis was limited by a small sample size.
.

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

PubMed

Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

2008-02-01

The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered significant. Overall, 32% and 41% of patients had acute perioperative renal dysfunction measured by CrCl and SCr, respectively. Seven patients required HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB were significantly associated with acute perioperative renal dysfunction. Acute perioperative renal dysfunction was associated with increased intensive care unit and hospital stays, postoperative blood transfusion, dialysis, and major infection. Aprotinin patients were significantly older (75.2 v 70.2 years, p < 0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v 96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005) were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group. Baseline renal function and renal outcomes were not significantly different between the aprotinin and EACA groups. Six of the 7 patients who required HD received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

Assessment of Nephroprotective Potential of Histochrome during Induced Arterial Hypertension.

PubMed

Agafonova, I G; Bogdanovich, R N; Kolosova, N G

2015-12-01

Magnetic resonance tomography was employed to verify endothelial dysfunction of renal arteries in Wistar and OXYS rats under conditions of induced arterial hypertension. Angiography revealed changes in the size and form of renal arteries of hypertensive animals. In hypertensive rats, histochrome exerted a benevolent therapeutic effect in renal arteries: it decreased BP, diminished thrombus formation in fi ne capillaries and arterioles, demonstrated the anticoagulant properties, partially improved endothelial dysfunction of small renal arteries, and up-regulated the glomerular filtration.

Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy

PubMed Central

Mukhopadhyay, Partha; Horváth, Béla; Zsengellér, Zsuzsanna; Zielonka, Jacek; Tanchian, Galin; Holovac, Eileen; Kechrid, Malek; Patel, Vivek; Stillman, Isaac E.; Parikh, Samir M.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

2011-01-01

Cisplatin is a widely used anti-neoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show that mitochondrial dysfunction is not only a feature of cisplatin nephrotoxicity, but that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin’s anti-neoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Since similar compounds appear to be safe in humans, mitochondrially-targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. PMID:22120494

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery.

PubMed

Shahin, Jason; DeVarennes, Benoit; Tse, Chun Wing; Amarica, Dan-Alexandru; Dial, Sandra

2011-07-07

Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery.

Cardiovascular Disease in Patients with End-Stage Renal Disease on Hemodialysis

PubMed Central

Aoki, Jiro; Ikari, Yuji

2017-01-01

Cardiovascular disease is a major concern for patients with end-stage renal disease (ESRD), especially those on hemodialysis. ESRD patients with coronary artery disease often do not have symptoms or present with atypical symptoms. Coronary lesions in ESRD patients are characterized by increased media thickness, infiltration and activation of macrophages, and marked calcification. Several studies showed worsened clinical outcomes after coronary revascularization, which were dependent on the severity of renal dysfunction. ESRD patients on hemodialysis have the most severe renal dysfunction; thus, the clinical outcomes are worse in these patients than in those with other types of renal dysfunction. Medications for primary or secondary cardiovascular prevention are also insufficient in ESRD patients. Efficacy of drug-eluting stents is inferior in ESRD patients, compared to the excellent outcomes observed in patients with normal renal function. Unsatisfactory outcomes with trials targeting cardiovascular disease in patients with ESRD emphasize a large potential to improve outcomes. Thus, optimal strategies for diagnosis, prevention, and management of cardiovascular disease should be modified in ESRD patients. PMID:29515692

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2011-05-01

in urine output and decreased urine osmolality as compared to dextrose-infused and no infusion controls; however, at the completion of the infusion...levels of alanine amino transferase (ALT) and blood urea nitrogen (BUN), markers of hepatic and renal damage and dysfunction respectively. To examine...hepatic injury and dysfunction, as well as blood urea nitrogen (BUN) and creatinine, makers of renal dysfunction, were elevated following delayed

Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

PubMed Central

Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

2013-01-01

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

Pharmacokinetics of the novel oral prostacyclin receptor agonist selexipag in subjects with hepatic or renal impairment

PubMed Central

Cruz, Hans G.; Krause, Andreas; Ulč, Ivan; Halabi, Atef; Dingemanse, Jasper

2016-01-01

Aim The aim of the present study was to explore the effect of hepatic or renal dysfunction on the pharmacokinetics (PK), tolerability and safety of selexipag, an orally active prostacyclin receptor agonist. Methods Two prospective, open‐label studies evaluated the PK of selexipag and its active metabolite ACT‐333679 in healthy subjects and in subjects with mild, moderate and severe hepatic impairment or severe renal function impairment (SRFI). A single dose of 200 μg or 400 μg was administered. The PK parameters were derived from plasma concentration–time profiles. Results Exposure increased with the severity of hepatic impairment. Geometric mean ratios and 90% confidence intervals of the area under the concentration–time curve from time zero to infinity (AUC0–∞) for selexipag and ACT‐333679 increased 2.1‐fold (1.7–2.6) and 1.2‐fold (0.9–1.6) in subjects with mild hepatic impairment, and 4.5‐fold (3.4–5.8) and 2.2‐fold (1.7–2.8) in subjects with moderate hepatic impairment when compared with healthy subjects. The two subjects with severe hepatic impairment showed similar dose‐normalized exposure to that of subjects with moderate hepatic impairment. A 1.7‐fold increase in the AUC0–∞ of selexipag and ACT‐333679 was observed with SRFI compared with healthy subjects. Although exposure to selexipag and/or ACT‐333679 was higher in subjects with mild or moderate hepatic impairment or SRFI vs. healthy subjects, no safety concerns were raised in these groups. Conclusions Based on these observations, the PK data suggest that the clinically used starting dose needs no adjustments in patients with mild or moderate hepatic impairment or SRFI. However, doses should be up‐titrated with caution in these patients. The small number of subjects limits the interpretation of selexipag PK in subjects with severe hepatic impairment. PMID:27062188

Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

2010-10-28

Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.

PubMed

Bilbao, Itxarone; Salcedo, Magdalena; Gómez, Miguel Angel; Jimenez, Carlos; Castroagudín, Javier; Fabregat, Joan; Almohalla, Carolina; Herrero, Ignacio; Cuervas-Mons, Valentín; Otero, Alejandra; Rubín, Angel; Miras, Manuel; Rodrigo, Juan; Serrano, Trinidad; Crespo, Gonzalo; De la Mata, Manuel; Bustamante, Javier; Gonzalez-Dieguez, M Luisa; Moreno, Antonia; Narvaez, Isidoro; Guilera, Magda

2015-08-01

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy. © 2015 American Association for the Study of Liver Diseases.

Renal Tubular Cell Mitochondrial Dysfunction Occurs Despite Preserved Renal Oxygen Delivery in Experimental Septic Acute Kidney Injury

PubMed Central

Pollen, Sean; Greco, Elisabetta; Courtneidge, Holly; Hall, Andrew M.; Duchen, Michael R.; Tam, Frederick W. K.; Unwin, Robert J.; Singer, Mervyn

2018-01-01

Objective: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Intervention: Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6–10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum. Measurements and Main Results: By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl. Conclusions: Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism. PMID:29293148

Reversible renal allograft dysfunction and proteinuria from nutcracker-like syndrome: a case report.

PubMed

Krishnan, S G S; Pritsiolas, J; Susin, M; Linden, E; Beil-Levi, E; Gitman, M; Mossey, R; Bhaskaran, M

2007-06-01

A 27-year-old Hispanic man with hypertension and renal failure was on hemodialysis for 4 years prior to receiving a living donor renal transplant from his 19-year-old sister. His serum creatinine decreased to 1.7 mg/dL at 3 weeks posttransplant with a urine protein creatinine ratio (UP) of 0.1 (g/g). Over the next 2 months, he experienced repeated episodes of allograft dysfunction with elevation of creatinine and proteinuria levels, associated with a lymphocele. Doppler studies of the allograft revealed renal vein compression. His symptoms responded to aspiration of the fluid collection, resolving completely with surgical drainage. We believe that the episodes of allograft dysfunction and proteinuria were related to recurrent lymphocele, causing a nutcracker-like syndrome.

PHARMACOLOGIC PROBING OF AMPHOTERICIN B-INDUCED RENAL DYSFUNCTION IN THE NEONATAL RAT

EPA Science Inventory

Pharmacologic Probing of Amphotericin B-Induced Renal Dysfunction in the Neonatal Rat. Gray, J.A., and Kavlock, R.J. (1988). Toxicol. Appl. Pharmacol. 93, 360-368. Acetazolamide, furosemide, chlorothiazide, and amiloride pharmacologic agents that act primarily in the proximal tub...

Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

PubMed

Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

2001-01-01

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

PubMed

Kusaba, T; Hatta, T; Tanda, S; Kameyama, H; Tamagaki, K; Okigaki, M; Inaba, T; Shimazaki, C; Sasaki, S

2006-03-01

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

γ-Tocotrienol Protects against Mitochondrial Dysfunction and Renal Cell Death

PubMed Central

Bakajsova, Diana; Hayes, Corey; Hauer-Jensen, Martin; Compadre, Cesar M.

2012-01-01

Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine whether γ-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidants. Primary cultures of RPTCs were injured by using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or α-tocopherol (AT). Reactive oxygen species (ROS) production increased 300% in TBHP-injured RPTCs. State 3 respiration, oligomycin-sensitive respiration, and respiratory control ratio (RCR) decreased 50, 63, and 47%, respectively. The number of RPTCs with polarized mitochondria decreased 54%. F0F1-ATPase activity and ATP content decreased 31 and 65%, respectively. Cell lysis increased from 3% in controls to 26 and 52% at 4 and 24 h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycin-sensitive respirations and F0F1-ATPase activity, and maintained RCR and mitochondrial membrane potential (ΔΨm) in injured RPTCs. GT3 maintained ATP content, blocked RPTC lysis at 4 h, and reduced it to 13% at 24 h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, ΔΨm, and F0F1-ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTCs against oxidant injury and may prove therapeutically valuable for preventing renal injury associated with oxidative stress. PMID:22040679

Kidney disease in heart failure: the importance of novel biomarkers for type 1 cardio-renal syndrome detection.

PubMed

Palazzuoli, Alberto; McCullough, Peter A; Ronco, Claudio; Nuti, Ranuccio

2015-08-01

Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.

Right ventricular systolic dysfunction and vena cava dilatation precede alteration of renal function in adult patients undergoing cardiac surgery: An observational study.

PubMed

Guinot, Pierre Grégoire; Abou-Arab, Osama; Longrois, Dan; Dupont, Herve

2015-08-01

Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients. We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms. A single-centre, prospective observational study. Amiens University Hospital, France. All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed. Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1. All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI). These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

Different antidiabetic regimens and the development of renal dysfunction in US Veterans with type 2 diabetes mellitus.

PubMed

Gosmanova, Elvira O; Canada, Robert B; Wan, Jim; Mangold, Therese A; Wall, Barry M

2012-10-01

The aim of this study was to evaluate the development of renal dysfunction in veterans with type 2 diabetes mellitus (T2DM) treated with different antidiabetic regimens. A retrospective cohort study involving 1715 patients with T2DM and baseline serum creatinine (SCr) of 1.5 mg/dL or lesser. The development of renal dysfunction, defined as 0.5 mg/dL or greater increase from baseline SCr during 4.8 years of follow-up with monotherapy metformin (M), 2 combination therapy groups: metformin + insulin (MI) and metformin + sulfonylurea (MS) users were compared with changes observed in sulfonylurea monotherapy users (S). Both MI and MS groups had higher mean baseline hemoglobin A1C (HbA1C) (9.0 and 8.6%, respectively) and higher rates of baseline macroalbuminuria (17.3 and 12.1%, respectively) as compared with M and S groups (mean HbA1C7.7% in both groups, and proteinuria M-5.1% and S-7.4%). In unadjusted analysis, the development of renal dysfunction was more frequent in MI and MS but not in M group as compared with sulfonylurea monotherapy (unadjusted HRs and [95% confidence interval (CI), 2.1[1.4-3.0], 1.4[1.1-1.9], and 1.0[0.6-1.7], respectively). However, differences in the development of renal dysfunction were not significant between the 4 groups after adjusting for baseline variables. Baseline macroalbuminuria was a strong predictor of Scr elevation of 0.5 mg/dL or greater during follow-up (adjusted HR, 3.1[1.9-4.7]). Unexpectedly, baseline use of renin-angiotensin-aldosterone system blockers was also associated with the development of renal dysfunction (adjusted HR, 1.9[1.3-2.8]). In this retrospective cohort study involving US predominantly male veterans with T2DM, baseline macroalbuminuria and use of RAAS blockers were associated with increased risk of development of renal dysfunction, whereas different antidiabetic regimens were not.

Acquired Bartter syndrome following gentamicin therapy

PubMed Central

Singh, J.; Patel, M. L.; Gupta, K. K.; Pandey, S.; Dinkar, A.

2016-01-01

Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management. PMID:27942182

Acquired Bartter syndrome following gentamicin therapy.

PubMed

Singh, J; Patel, M L; Gupta, K K; Pandey, S; Dinkar, A

2016-01-01

Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7 th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

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

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrialmore » NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. - Highlights: • Naringin ameliorated gentamicin-induced nephrotoxicity in rats. • Naringin treatment attenuated gentamicin-induced renal apoptosis in rats. • Naringin ameliorated gentamicin-induced renal mitochondrial dysfunction in rats. • Naringin decreased NF-κB activation and pro-inflammatory cytokine release. • U-HPLC-MS data revealed that naringin did not alter the renal uptake of gentamicin.« less

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery

PubMed Central

2011-01-01

Introduction Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. Material and methods A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Results Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Conclusions Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery. PMID:21736726

The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries.

PubMed

Calvier, Laurent; Martinez-Martinez, Ernesto; Miana, Maria; Cachofeiro, Victoria; Rousseau, Elodie; Sádaba, J Rafael; Zannad, Faiez; Rossignol, Patrick; López-Andrés, Natalia

2015-01-01

This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. Aldosterone is involved in cardiac and renal fibrosis that is associated with the development of cardiorenal injury. However, the mechanisms of these interactions remain unclear. Gal-3, a β-galactoside-binding lectin, is increased in heart failure and kidney injury. Rats were treated with aldosterone-salt combined with spironolactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gal-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with aldosterone for 3 weeks. Hemodynamic, cardiac, and renal parameters were analyzed. Hypertensive aldosterone-salt-treated rats presented cardiac and renal hypertrophy (at morphometric, cellular, and molecular levels) and dysfunction. Cardiac and renal expressions of Gal-3 as well as levels of molecular markers attesting fibrosis were also augmented by aldosterone-salt treatment. Spironolactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, aldosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymal transition. Gal-3 knockout mice were resistant to aldosterone effects. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac and renal fibrosis and dysfunction but was prevented by pharmacological inhibition (modified citrus pectin) or genetic disruption of Gal-3. These data suggest a key role for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

A2B Adenosine Receptor–Mediated Induction of IL-6 Promotes CKD

PubMed Central

Dai, Yingbo; Zhang, Weiru; Wen, Jiaming; Zhang, Yujin; Kellems, Rodney E.

2011-01-01

Chronic elevation of adenosine, which occurs in the setting of repeated or prolonged tissue injury, can exacerbate cellular dysfunction, suggesting that it may contribute to the pathogenesis of CKD. Here, mice with chronically elevated levels of adenosine, resulting from a deficiency in adenosine deaminase (ADA), developed renal dysfunction and fibrosis. Both the administration of polyethylene glycol–modified ADA to reduce adenosine levels and the inhibition of the A2B adenosine receptor (A2BR) attenuated renal fibrosis and dysfunction. Furthermore, activation of A2BR promoted renal fibrosis in both mice infused with angiotensin II (Ang II) and mice subjected to unilateral ureteral obstruction (UUO). These three mouse models shared a similar profile of profibrotic gene expression in kidney tissue, suggesting that they share similar signaling pathways that lead to renal fibrosis. Finally, both genetic and pharmacologic approaches showed that the inflammatory cytokine IL-6 mediates adenosine-induced renal fibrosis downstream of A2BR. Taken together, these data suggest that A2BR-mediated induction of IL-6 contributes to renal fibrogenesis and shows potential therapeutic targets for CKD. PMID:21511827

Prevalence, correlates, and impact of coronary calcification on adverse events following PCI with newer-generation DES: Findings from a large multiethnic registry.

PubMed

Copeland-Halperin, Robert S; Baber, Usman; Aquino, Melissa; Rajamanickam, Anitha; Roy, Swathi; Hasan, Choudhury; Barman, Nitin; Kovacic, Jason C; Moreno, Pedro; Krishnan, Prakash; Sweeny, Joseph M; Mehran, Roxana; Dangas, George; Kini, Annapoorna S; Sharma, Samin K

2018-04-01

We sought to determine the prevalence, predictors, and clinical impact of target lesion calcification in patients undergoing percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES) and devices. Coronary calcification is independently associated with adverse outcomes following PCI. While newer DES and contemporary devices are considered safer and more efficacious, their influence on outcomes following PCI of heavily calcified lesions is unknown. We performed a retrospective analysis of a large, multiethnic cohort of patients undergoing PCI with new generation DES at an academic center between 2009 and 2013. Coronary calcification was qualitatively assessed as none/mild, moderate, or severe. Independent demographic, clinical, and anatomic predictors of moderate/severe calcification were identified using logistic regression. Associations between coronary calcification and 1-year MACE (death, myocardial infarction, or target vessel revascularization) were examined using Cox modeling. Compared to patients with none/mild (n = 10,180; 82.0%), those with moderate (n = 1,271; 10.0%) or severe (n = 994; 8.0%) calcification were older, more often Caucasian, had more complex target lesions, and worse renal function. The strongest demographic, clinical, and anatomic correlates of moderate/severe calcification were age, Caucasian race, renal dysfunction, lesion length, and left main location. Unadjusted MACE rates among those with none/mild, moderate, and severe calcification were 8.3, 14.6, and 17.8%, respectively (P < 0.001). After multivariable adjustment, the hazard ratio (95% CI) for MACE associated with moderate or severe coronary calcification was 1.63. Target lesion calcification remains independently associated with adverse outcomes in patients treated with newer generation DES and modern devices. © 2017 Wiley Periodicals, Inc.

Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network

PubMed Central

Rowan, Christopher G.; Brunelli, Steven M.; Munson, Jeffrey; Flory, James; Reese, Peter P.; Hennessy, Sean; Lewis, James; Mines, Daniel; Barrett, Jeffrey S.; Bilker, Warren; Strom, Brian L.

2014-01-01

Objective To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. Background Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. Methods Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. Results The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362 809 patients and 792 665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90–1.66). There were 1449 renal dysfunction events among 272,099 patients and 574 584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58–1.44). There were 1434 hepatic dysfunction events among 367 612 patients and 815 945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45–1.31). Conclusions Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy. PMID:22422642

Cognitive Dysfunction in Patients with Renal Failure Requiring Hemodialysis

PubMed Central

Thimmaiah, Rohini; Murthy, K. Krishna; Pinto, Denzil

2012-01-01

Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis. PMID:23439613

[Usefulness of FDG-PET/CT for the diagnosis of intravascular large B-cell lymphoma presenting with fever of unknown origin and renal dysfunction].

PubMed

Yago, Kazuhiro; Yanagita, Soshi; Aono, Maki; Matsuo, Ken; Shimada, Hideto

2009-06-01

A 76-year-old man presented with fever of unknown origin and renal dysfunction. Laboratory examination revealed anemia, thrombocytopenia, hypoalbuminemia, proteinuria, and elevations of C-reactive protein, lactic dehydrogenase, creatinine and ferritin. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging showed FDG accumulation in the renal cortex and spleen. Based on the imaging study, renal biopsy was performed and histological diagnosis of intravascular large B-cell lymphoma (IVLBCL) was made. Renal impairment due to IVLBCL is uncommon and is often difficult to diagnose early. FDG-PET/CT may be a useful tool for the early diagnosis of IVLBCL.

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.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features.

PubMed

Zhou, Yaoyao; Zhang, Junfeng

2014-09-20

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare but fatal autosomal recessive multisystem disorder caused by mutations in the VPS33B or VIPAR gene. The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. Diagnosis of ARC syndrome relies on clinical features, organ biopsy, and mutational analysis. However, no specific treatment currently exists for this syndrome. This is an overview of the latest knowledge regarding the genetic features and clinical manifestations of ARC syndrome. Greater awareness and understanding of this syndrome should allow more timely intervention with potential for improving long-term outcome.

Optical monitoring of kidney oxygenation and hemodynamics using a miniaturized near-infrared sensor

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Nigro, Mark; Nguan, Christopher

2017-02-01

Background: Following human renal allograft transplant primary graft dysfunction can occur early in the postoperative period as a result of acute tubular necrosis, acute rejection, drug toxicity, and vascular complications. Successful treatment of graft dysfunction requires early detection and accurate diagnosis so that disease-specific medical and/or surgical intervention can be provided promptly. However, current diagnostic methods are not sensitive or specific enough, so that identifying the cause of graft dysfunction is problematic and often delayed. Near-infrared spectroscopy (NIRS) is an established optical method that monitors changes in tissue hemodynamics and oxygenation in real time. We report the feasibility of directly monitoring kidney the kidney in an animal model using NIRS to detect renal ischemia and hypoxia. Methods: In an anesthetized pig, a customized continuous wave spatially resolved (SR) NIRS sensor was fixed directly to the surface of the surgically exposed kidney. Changes in the concentration of oxygenated (O2Hb) deoxygenated (HHb) and total hemoglobin (THb) were monitored before, during and after renal artery clamping and reperfusion, and the resulting fluctuations in chromophore concentration from baseline used to measure variations in renal perfusion and oxygenation. Results: On clamping the renal artery THb and O2Hb concentrations declined progressively while HHb rose. With reperfusion after releasing the artery clamp O2Hb and THb rose while HHb fell with all parameters returning to its baseline. This pattern was similar in all three trials. Conclusion: This pilot study indicates that a miniaturized NIRS sensor applied directly to the surface of a kidney in an animal model can detect the onset of renal ischemia and tissue hypoxia. With modification, our NIRS-based method may contribute to early detection of renal vascular complications and graft dysfunction following renal transplant.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

PubMed

Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2017-01-01

Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.

Advances in the Care of Adults With Congenital Heart Disease.

PubMed

Nasr, Viviane G; Kussman, Barry D

2015-09-01

The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. © The Author(s) 2014.

COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

PubMed

Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

2015-07-01

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay.

PubMed

Yeruva, Sri L H; Paul, Yonette; Oneal, Patricia; Nouraie, Mehdi

2016-09-01

Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan ® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Impact of moderate functional mitral insufficiency in patients undergoing surgical revascularization.

PubMed

Grossi, Eugene A; Crooke, Gregory A; DiGiorgi, Paul L; Schwartz, Charles F; Jorde, Ulrich; Applebaum, Robert M; Ribakove, Greg H; Galloway, Aubrey C; Grau, Juan B; Colvin, Stephen B

2006-07-04

Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expbeta = 1.49; P=0.007) and mild MR (expbeta = 1.34; P=0.033). Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.

Effects of Renal Transplantation on Female Sexual Dysfunction: Comparative Study With Hemodialysis and a Control Group.

PubMed

Kurtulus, F O; Salman, M Y; Fazlioglu, A; Fazlioglu, B

2017-11-01

Sexual dysfunction occurs commonly in individuals with end-stage renal disease. Chronic renal failure as well as the treatments used for it generally has a negative impact on sexual function with a subsequent increase in the risk of depression. There is scarcity of published data on female sexual dysfunction and the degree of improvement in patients on hemodialysis (HD) and transplant (Tx) recipients. The aim of this study was to compare the sexual function and degree of depression in HD and Tx patients with control group. For this purpose, we used the validated Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI). A total of 23 renal Tx, 29 HD, and 30 control patients were enrolled in the study. HD patients were required to be undergoing HD for ≥6 months, and for renal Tx recipients, the Tx had to be performed ≥6 months before study entry. All women underwent a general and urogynecologic examination. Demographic and clinical variables were documented. FSFI and BDI scale scores were compared among groups. The rates of female sexual dysfunction were 56.7%, 89.7%, and 73.9% in the control, HD, and Tx, patients respectively. Total FSFI scores in HD group were significantly lower than those in Tx and control patients (P < .05). FSFI scores improved significantly in the Tx group. BDI scores in HD and control subjects were 23.24 and 14.17, respectively, with a significant difference between the 2 groups (P < .005). BDI score in the Tx group was 16.65 and the difference was statistically insignificant. This preliminary study documented that successful Tx may positively affect sexual life in women with chronic renal failure. A diagnosis of female sexual dysfunction should be made routinely in patients with chronic renal failure. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.

PubMed

Kress, Hans G

2009-03-01

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.

[Oliguria and acute renal dysfunction in a six-month-old infant].

PubMed

Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

2017-02-01

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Cardio-renal syndrome: an entity cardiologists and nephrologists should be dealing with collegially.

PubMed

Palazzuoli, Alberto; Ronco, Claudio

2011-11-01

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus.

PubMed

Sreekutty, M S; Mini, S

2016-01-01

Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus.

Nephrotoxicity of Natural Products.

PubMed

Nauffal, Mary; Gabardi, Steven

2016-01-01

The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.

Factors determining extreme brain natriuretic peptide elevation.

PubMed

Guglin, Maya; Hourani, Rayan; Pitta, Sridevi

2007-01-01

Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects its severity. It is unknown why some patients have extremely high BNP levels. The authors retrospectively reviewed data on 179 consecutive patients whose BNP levels fell within one of several predetermined ranges: mild elevation, 500 to 1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted with the unpaired t test and Pearson's correlation coefficient. Adjustments were made for age, sex, and serum creatinine level. Patients with moderate BNP elevation were more symptomatic and had more advanced structural and hemodynamic changes than did patients with lower BNP elevation. Characteristics of the high BNP level group did not differ from those of the moderate BNP level group. Serum creatinine level correlated with BNP level, but neither age nor sex did. High BNP level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the severity of heart failure.

Cardiovascular risk reduction by reversing endothelial dysfunction:ARBs, ACE inhibitors, or both? Expectations from The ONTARGET Trial Programme

PubMed Central

Ruilope, Luis Miguel; Redón, Josep; Schmieder, Roland

2007-01-01

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008. PMID:17583170

Meta-analysis of Renal Function Following Infrarenal EVAR using Suprarenal or Infrarenal Fixation Devices.

PubMed

Stather, Philip W; Ferguson, James; Awopetu, Ayoola; Boyle, Jonathan R

2018-03-03

The effect of suprarenal (SR) as opposed to infrarenal (IR) fixation on renal outcomes post-endovascular aneurysm repair (EVAR) remains controversial. This meta-analysis aims to update current understanding of this issue. A prior meta-analysis was updated through a Preferred Reporting Items for Systematic reviews and Meta-Analyses search for additional studies published in the last 3 years reporting on renal dysfunction or related outcomes post-EVAR. Random effects meta-analysis was undertaken using SPSS. A total of 25 non-randomised studies comparing SR with IR fixation were included, totalling 54,832 patients. In total, 16,634 underwent SR and 38,198 IR. Baseline characteristics, including age, baseline estimated glomerular filtration rate, diabetes, cardiac disease, and smoking, were similar between the groups. There was a small but significant difference in outcomes for renal dysfunction at the study end point (SR 5.98% vs. IR 4.83%; odds ratio [OR] 1.29, 95% confidence interval [CI] 1.18-1.40 [p < .001]); however, at 30 days and 12 months there was no significant difference, and this did not hold up to sensitivity analysis. Incidence of renal infarcts (SR 6.6% vs. IR 2.3%; OR 2.78, 95% CI 1.46-5.29 [p = .002]), renal stenosis (SR 2.4% vs. IR 0.8%; OR 2.89, 95% CI 1.00-8.38 [p = .05]), and renal artery occlusion (SR 2.4% vs. IR 1.2%; OR 2.21, 95% CI 1.15-4.25 [p = 0.02]) favoured IR fixation; however, there was no difference in haemodialysis rates. This meta-analysis has identified small but significantly worse renal outcomes in patients having SR fixation devices compared with IR; however, there was no difference in dialysis rates and a small effect on renal dysfunction, which did not stand up to rigorous sensitivity analysis. This should be taken into consideration during graft selection, and further studies must assess renal outcomes in the longer term, and in those with pre-existing renal dysfunction. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

PubMed

Esquirol, Yolande; Tully, Mark; Ruidavets, Jean-Bernard; Fogarty, Damian; Ferrieres, Jean; Quinn, Michael; Hughes, Maria; Kee, Frank

2014-12-20

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain. We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease. From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years. For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease. Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Stanojevic, Natasa Bogavac; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-11-01

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor. © 2013 Wiley Periodicals, Inc.

Pharmacokinetics of cefotaxime and its active metabolite in children with renal dysfunction.

PubMed Central

Paap, C M; Nahata, M C; Mentser, M A; Mahan, J D; Puri, S K; Hubbard, J W

1991-01-01

We studied cefotaxime (CTX) and desacetylcefotaxime (dCTX) pharmacokinetics in 19 children (ages, 7 to 16 years) with various degrees of renal function. The patients were stratified into three groups according to 24-h urinary creatinine clearance (CLCR) values: group I, CLCR greater than 80 ml/min/1.73 m2 (n = 7); group II, CLCR from 30 to 80 ml/min/1.73 m2 (n = 6); and group III, CLCR less than 30 ml/min/1.73 m2 (n = 6). A single 50-mg/kg dose of CTX was given intravenously to each patient after which blood and urine samples were collected and analyzed for CTX and dCTX by high-performance liquid chromatography. Safety was assessed by pre- and poststudy blood chemistries and urinalysis. The mean values for total body clearance of CTX for groups I, II, and III were 158.1 +/- 38.8, 118.3 +/- 50.8, and 84.8 +/- 11.7 ml/min/1.73 m2, respectively (P less than 0.01). Renal clearance also decreased across groups, I, II, and III, with values of 77.5 +/- 20.2, 41.3 +/- 18.5, and 11.4 +/- 7.7 ml/min/1.73 m2 respectively (P less than 0.0001). Both the CTX fraction nonrenally cleared and elimination half-life increased with decreasing renal function. The CTX volume of distribution at steady state was not affected by renal disease. The renal clearance values of dCTX were 146.4 +/- 71.4, 64.5 +/- 32.1, and 14.4 +/- 8.7 ml/min/1.73 m2 for groups I, II, and III, respectively (P less than 0.0004). Elimination half-life values were 2.04 +/- 0.39, 3.87 +/- 1.93, and 6.19 +/- 3.22 h for the respective groups (P less than 0.006). Both the maximum concentration of dCTX in plasma and time to reach the maximum concentration of dCTX in plasma were increased with decreased CLCR. The results of this study indicate that dosage adjustment may be necessary for CTX in children with renal dysfunction. On the basis of the pharmacokinetics and antimicrobial activities of the parent drug and its metabolite, dosage reductions of 25 to 50% in children with moderate renal impairment (CLCR from 30 to 80 ml/min/1.73 m2) and 50 to 75% in children with severe renal impairment (CLCR < 30 ml/min/1.73 m2) are recommended. PMID:1952862

Gender Differences in Left Ventricular Function Following Percutaneous Coronary Intervention for First Anterior Wall ST-Segment Elevation Myocardial Infarction.

PubMed

Weissler-Snir, Adaya; Kornowski, Ran; Sagie, Alexander; Vaknin-Assa, Hana; Perl, Leor; Porter, Avital; Lev, Eli; Assali, Abid

2014-11-15

Little is known regarding gender differences in left ventricular (LV) function after anterior wall ST-segment elevation myocardial infarction (STEMI), despite it being a major determinant of patients' morbidity and mortality. We therefore sought to investigate the impact of gender on LV function after primary percutaneous coronary intervention (PCI) for first anterior wall STEMI. Seven hundred eighty-nine consecutive patients (625 men) with first anterior STEMI were included in the analysis. All patients underwent an echocardiographic study within 48 hours of PCI. Women were older and more likely to have diabetes, hypertension, chronic renal failure, and a higher Killip score. Women had prolonged ischemic time, which was driven by prolonged symptom-to-presentation time (2.75 [interquartile range 1.5 to 4] vs 2 [interquartile range 1 to 3.5] hours, p = 0.005). A higher percentage of women had moderate or worse LV dysfunction (LV ejection fraction <40%; 61.6% vs 48%, p = 0.002). In a univariable analysis female gender was associated with moderate or worse LV function (p = 0.002). However, after accounting for variable baseline risk profiles between the 2 groups using multivariable and propensity score techniques, ischemic time >3.5 hours, leukocytosis, and pre-PCI Thrombolysis In Myocardial Infarction flow grade <2 were independent predictors of moderate or worse LV dysfunction, whereas female gender was not. Data on LV function recovery at 6 months, which were available for 45% of female and male patients with moderate or worse LV dysfunction early after PCI, showed no significant gender related difference in LV function recovery. In conclusion, women undergoing PCI for the first event of anterior STEMI demonstrate worse LV function than that of men, which might be partially attributed to delay in presentation. Hence greater efforts should be devoted to increasing women's awareness of cardiac symptoms during the prehospital course of STEMI. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction.

PubMed

Pires, María J; Rodríguez-Peña, Ana B; Arévalo, Miguel; Cenador, Begoña; Evangelista, Stefano; Esteller, Alejandro; Sánchez-Rodríguez, Angel; Colaço, Aura; López-Novoa, José M

2007-12-01

D/L-Nebivolol is a lypophilic beta1-adrenergic antagonist which is devoid of intrinsic sympathomimetic activity and can increase nitric oxide (NO) bioavailability with its subsequent vasodilating properties. The purpose of the present work was to assess the effect of long-term nebivolol administration on both renal damage and endothelial dysfunction induced by renal mass reduction (RMR) in rats. Atenolol, which does not increase NO bioavailability, was included in the study as a comparative beta-adrenoceptor antagonist. Rats were subjected to both right nephrectomy and surgical removal of two-thirds of the left kidney in order to retain approximately one-sixth of the total renal mass. One week after ablation, rats were distributed randomly according to the following experimental groups: control group containing RMR rats without treatment; RMR rats treated daily with nebivolol for 6 months (drinking water, 8 mg/kg per day); and RMR rats treated daily with atenolol for 6 months (drinking water, 80 mg/kg per day). A group of sham-operated animals was also included. Administration of either nebivolol or atenolol similarly reduced arterial pressure in comparison with RMR untreated animals; however, animals receiving nebivolol presented lower levels of collagen type I expression as well as lower glomerular and interstitial fibrosis than those receiving atenolol. Urinary excretion of oxidative stress markers were also lower in animals receiving nebivolol than in rats treated with atenolol. Furthermore, nebivolol prevented RMR-induced endothelial dysfunction more efficiently than atenolol. Nebivolol protects against renal fibrosis, oxidative stress and endothelial dysfunction better than equivalent doses, in terms of arterial pressure reduction, of atenolol in a hypertensive model of renal damage induced by RMR.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

PubMed

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R; Shyam Sunder, R; Sistla, Ramakrishna

2014-05-15

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of pressure ulcers in patients with declining renal function using arginine, glutamine and ß-hydroxy-ß-methylbutyrate.

PubMed

Ogura, Y; Yuki, N; Sukegane, A; Nishi, T; Miyake, Y; Sato, H; Miyamoto, C; Mihara, C

2015-10-01

The aim of this study is to examine the efficacy on healing pressure ulcers (PU) of using a supplement combination containing arginine, glutamine and ß-hydroxy-ß-methylbutyrate, which was given to two elderly patients with renal dysfunction. The PU was surgically opened, decompressed and treated by drugs. A half quantity of the defined dose of the supplement combination, with an enteral nutrition product, was administered to the patients twice a day. This combination improved the PUs, with no effect on renal function. This novel finding may provide a nutritional rationale of arginine, glutamine and ß-hydroxy-ß-methylbutyrate for PUs associated with renal dysfunction.

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

PubMed

Runde, Joseph; Rivera-Rivera, Edgardo; Pompeii-Wolfe, Cecelia; Clardy, Christopher; Sentongo, Timothy

2018-05-10

Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome. © 2018 American Society for Parenteral and Enteral Nutrition.

Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats.

PubMed

Sugiura, Takahiro; Tsutsui, Hidenobu; Takaoka, Masanori; Kobuchi, Shuhei; Hayashi, Kentaro; Fujii, Toshihide; Matsumura, Yasuo

2008-03-01

Enhanced renal sympathetic nerve activity (RSNA) during ischemic period and the renal venous norepinephrine (NE) overflow after reperfusion play important roles in the development of ischemic/reperfusion (I/R)-induced acute renal failure (ARF) in rats. This study evaluated whether agmatine, which is known to reduce sympathetic nerve activity and NE overflow by electrical stimulation, would prevent the I/R-induced renal dysfunction. Ischemic ARF was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous (IV) injection of agmatine (100 and 300 micromol/kg) to ischemic ARF rats dose-dependently suppressed the enhanced RSNA and attenuated the I/R-induced renal dysfunction and histological damage. Intracerebroventricular (ICV) injection of agmatine (600 nmol/kg) to ischemic ARF rats suppressed the enhanced RSNA during the ischemic period and attenuated the I/R-induced renal injury. Furthermore, both IV and ICV injection of agmatine significantly suppressed the renal venous NE overflow after the reperfusion. These results indicate that agmatine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppression of the enhanced RSNA during ischemic period and NE overflow from renal sympathetic nerve endings.

Renal dysfunction in patients with thalassaemia.

PubMed

Quinn, Charles T; Johnson, Valerie L; Kim, Hae-Young; Trachtenberg, Felicia; Vogiatzi, Maria G; Kwiatkowski, Janet L; Neufeld, Ellis J; Fung, Ellen; Oliveri, Nancy; Kirby, Melanie; Giardina, Patricia J

2011-04-01

Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine. We calculated creatinine clearance and urine calcium-to-creatinine ratio and measured urinary β(2) -microglobulin, albumin, and protein. We used multivariate modelling to identify clinical, therapeutic, and laboratory predictors of renal dysfunction. One-third of thalassaemia patients who were not regularly transfused had abnormally high creatinine clearance. Regular transfusions were associated with a decrease in clearance (P = 0·004). Almost one-third of patients with thalassaemia had hypercalciuria, and regular transfusions were associated with an increase in the frequency and degree of hypercalciuria (P < 0·0001). Albuminuria was found in over half of patients, but was not consistently associated with transfusion therapy. In summary, renal hyperfiltration, hypercalciuria, and albuminuria are common in thalassaemia. Higher transfusion intensity is associated with lower creatinine clearance but more frequent hypercalciuria. The transfusion effect needs to be better understood. Awareness of underlying renal dysfunction in thalassaemia can inform decisions now about the use and monitoring of iron chelation. © 2011 Blackwell Publishing Ltd.

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

Pharmacokinetics of Dalfampridine Extended Release 7.5-mg Tablets in Healthy Subjects and Individuals With Mild and Moderate Renal Impairment: An Open-Label Study

PubMed Central

Samara, Emil; Winkle, Peter; Pardo, Patricia; Henney, Herbert R; Way, Susan L; Brown, Eppie; Lee, Angela; Blight, Andrew R

2014-01-01

Dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) are available to improve walking in patients with multiple sclerosis (MS). D-ER is mainly renally eliminated; the approved 10-mg twice daily dose is contraindicated in the United States in patients with moderate or severe renal impairment. This study evaluated single-dose and steady-state pharmacokinetics of a 7.5-mg dose of D-ER in healthy subjects (n = 13) and subjects with mild (n = 17) and moderate (n = 12) renal impairment. D-ER plasma concentrations were consistently higher in subjects with renal impairment relative to healthy individuals with a significant (P < .0001) inverse linear relationship between creatinine clearance and drug exposure. Steady-state AUC0–12 among healthy subjects, 167.0 ± 55.3 ng h/mL, increased 74% and 151% with mild and moderate renal impairment, respectively. The overall incidence of adverse events was 61.5%, 47.1%, and 33.3% in healthy subjects, and subjects with mild and moderate renal impairment, respectively, and for treatment-related adverse events the rates were 0%, 17.6%, and 8.3%, respectively. The most common adverse events were headache, dizziness, and arthralgia. The pharmacokinetics of D-ER 7.5-mg twice daily in subjects with mild renal impairment was comparable to 10-mg twice daily in patients with MS who had normal renal function. Exposure was significantly higher in moderate renal impairment. PMID:24150835

Dose-response analysis of heavy metal toxicants in man. Direct in vivo assessment of body burden

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

Ellis, K.J.

Differences in uptake, metabolism, and excretion of heavy metals makes selection of a suitable biological media as a monitor of body burden very difficult. Exposure assessments based on body fluid levels can provide, at best, only general population estimates. The most frequently monitored media are blood, urine, nail or hair clippings, sweat, and saliva. Unfortunately each of these tissues can be influenced by recent exposure conditions and are not accurate indices of the total dose or body burden. However, direct in vivo measurements of body burden in humans, have recently been performed. This nuclear technique has focused on the measurementsmore » of kidney and liver cadmium (Cd) by neutron activation analysis and bone lead (Pb) determinations using x-ray fluorescence. The dose-response relationship for renal dysfunction based on the direct in vivo body burden for Cd is presented. The most probable Cd value for the kidney associated with renal impairment is approximately 35 mg. Approximately 10% of the subjects with 20 mg Cd in the kidney will have moderately elevated ..beta../sub 2/-microglobulin, an early indicator of potential renal functional changes. 11 refs., 5 figs., 2 tabs.« less

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction.

PubMed

Hamamura, Kengo; Matsunaga, Naoya; Ikeda, Eriko; Kondo, Hideaki; Ikeyama, Hisako; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Yoshida, Yuya; Matsuda, Masaki; Yasuda, Kaori; Doi, Atsushi; Yokota, Yoshifumi; Amamoto, Toshiaki; Aramaki, Hironori; Irino, Yasuhiro; Koyanagi, Satoru; Ohdo, Shigehiro

2016-03-04

Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-β1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Relationship between age, renal function and bone mineral density in the US population.

PubMed

Klawansky, Sidney; Komaroff, Eugene; Cavanaugh, Paul F; Mitchell, David Y; Gordon, Matthew J; Connelly, Janet E; Ross, Susan D

2003-07-01

Bisphosphonate drugs for treating osteoporosis are excreted by the kidney. However, many of the major trials on efficacy and safety of the bisphophonates for treating osteoporosis excluded patients with significant renal compromise. Since both osteoporosis and renal insufficiency become more prevalent with age, it seems prudent for physicians to be aware of the prevalence of renal dysfunction in patients with osteoporosis who are candidates for treatment with bisphosphonates. Data on 13,831 men and women aged 20+ from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) were used to study the occurrence of compromise in renal clearance function in men and women with osteopenia and osteoporosis. To estimate creatinine clearance (CCr), a measure of renal function, serum creatinine (sCr), weight and age were inserted into the Cockcoft-Gault (C-G) formula. The World Health Organization gender specific bone mineral density (BMD) cut-offs were used to define the populations with osteopenia and osteoporosis. For women ages 20-80+ with osteoporosis, the percent prevalence (95% CI) for mild to moderate compromise of CCr

Pathophysiology of Cardiopulmonary Bypass: Current Strategies for the Prevention and Treatment of Anemia, Coagulopathy, and Organ Dysfunction.

PubMed

Esper, Stephen A; Subramaniam, Kathirvel; Tanaka, Kenichi A

2014-06-01

The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over the past 60 years, and numerous numbers of cardiac surgical procedures are conducted around the world using CPB. Despite more widespread applications of percutaneous coronary and valvular interventions, the need for cardiac surgery using CPB remains the standard approach for certain cardiac pathologies because some patients are ineligible for percutaneous procedures, or such procedures are unsuccessful in some. The ageing patient population for cardiac surgery poses a number of clinical challenges, including anemia, decreased cardiopulmonary reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal insufficiency. The use of CPB is associated with inductions of systemic inflammatory responses involving both cellular and humoral interactions. Inflammatory pathways are complex and redundant, and thus, the reactions can be profoundly amplified to produce a multiorgan dysfunction that can manifest as capillary leak syndrome, coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive decline. In this review, pathophysiological aspects of CPB are considered from a practical point of view, and preventive strategies for hemodilutional anemia, coagulopathy, inflammation, metabolic derangement, and neurocognitive and renal dysfunction are discussed. © The Author(s) 2014.

Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X-Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions.

PubMed

Li, Zhan; Tian, Longlong; Liu, Jianli; Qi, Wei; Wu, Qiang; Wang, Haijing; Ali, Mohammad Chand; Wu, Wangsuo; Qiu, Hongdeng

2017-09-01

Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast-enhanced computed tomography (CT) is proposed. In order to serve as contrast-enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X-ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs. It is found that GO/AgNPs can enhance the imaging of CT into the lung, liver, and kidney of mice for a long circulation time (≈24 h) and a safety profile in vivo in the presence of simvastatin. Interestingly, the lower dose of GO/AgNPs (≈0.5 mg per kg bw) shows an excellent performance for CT imaging of renal perfusion, and visually exhibits the right renal dysfunction in model mice. Hence, this work suggests that graphene nanoparticles will play a vital role for the future medical translational development including drug carrier, biosensing, and disease therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of 80-kVp scan and raw data-based iterative reconstruction for reduced iodine load abdominal-pelvic CT in patients at risk of contrast-induced nephropathy referred for oncological assessment: effects on radiation dose, image quality and renal function.

PubMed

Nagayama, Yasunori; Tanoue, Shota; Tsuji, Akinori; Urata, Joji; Furusawa, Mitsuhiro; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Yoshida, Eri; Yoshida, Morikatsu; Kidoh, Masafumi; Tateishi, Machiko; Yamashita, Yasuyuki

2018-05-01

To evaluate the image quality, radiation dose, and renal safety of contrast medium (CM)-reduced abdominal-pelvic CT combining 80-kVp and sinogram-affirmed iterative reconstruction (SAFIRE) in patients with renal dysfunction for oncological assessment. We included 45 patients with renal dysfunction (estimated glomerular filtration rate  <45 ml per min per 1.73 m 2 ) who underwent reduced-CM abdominal-pelvic CT (360 mgI kg -1 , 80-kVp, SAFIRE) for oncological assessment. Another 45 patients without renal dysfunction (estimated glomerular filtration rate >60 ml per lmin per 1.73 m 2 ) who underwent standard oncological abdominal-pelvic CT (600 mgI kg -1 , 120-kVp, filtered-back projection) were included as controls. CT attenuation, image noise, and contrast-to-noise ratio (CNR) were compared. Two observers performed subjective image analysis on a 4-point scale. Size-specific dose estimate and renal function 1-3 months after CT were measured. The size-specific dose estimate and iodine load of 80-kVp protocol were 32 and 41%,, respectively, lower than of 120-kVp protocol (p < 0.01). CT attenuation and contrast-to-noise ratio of parenchymal organs and vessels in 80-kVp images were significantly better than those of 120-kVp images (p < 0.05). There were no significant differences in quantitative or qualitative image noise or subjective overall quality (p > 0.05). No significant kidney injury associated with CM administration was observed. 80-kVp abdominal-pelvic CT with SAFIRE yields diagnostic image quality in oncology patients with renal dysfunction under substantially reduced iodine and radiation dose without renal safety concerns. Advances in knowledge: Using 80-kVp and SAFIRE allows for 40% iodine load and 32% radiation dose reduction for abdominal-pelvic CT without compromising image quality and renal function in oncology patients at risk of contrast-induced nephropathy.

Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

PubMed Central

Borelli, Flavio Antonio de Oliveira; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R.

2013-01-01

Background Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. Objective To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. Methods In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). Results The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Conclusion Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. PMID:24061685

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.

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

PubMed

Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

2012-01-01

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

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

PubMed

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

2018-05-01

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

A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia

PubMed Central

Wang, Winfred C; Ware, Russell E; Miller, Scott T; Iyer, Rathi V; Casella, James F; Minniti, Caterina P; Rana, Sohail; Thornburg, Courtney D; Rogers, Zora R; Kalpatthi, Ram V; Barredo, Julio C; Brown, R Clark; Sarnaik, Sharada A; Howard, Thomas H; Wynn, Lynn W; Kutlar, Abdullah; Armstrong, F Daniel; Files, Beatrice A; Goldsmith, Jonathan C; Waclawiw, Myron A; Huang, Xiangke; Thompson, Bruce W

2011-01-01

Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA. PMID:21571150

Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload.

PubMed

Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

2016-08-22

Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD.

Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms.

PubMed

du Moulin, Marcel; Thies, Bastian; Blohm, Martin; Oh, Jun; Kemper, Markus J; Santer, René; Mühlhausen, Chris

2018-01-01

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral organic aciduria" in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

Early renal dysfunction after contrast media administration despite prophylactic hydration.

PubMed

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

2013-06-01

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

Worsening renal function and prognosis in pulmonary hypertension patients hospitalized for right heart failure.

PubMed

Mielniczuk, Lisa M; Chandy, George; Stewart, Duncan; Contreras-Dominguez, Vladamir; Haddad, Haissam; Pugliese, C; Davies, Ross A

2012-01-01

Increased central venous pressures have been associated with the development of worsening renal function (WRF), an important marker of prognosis. We sought to determine the incidence and prognostic significance of WRF in pulmonary hypertension patients (PH) with isolated right HF. A prospective study of PH clinic patients admitted to hospital for right HF. WRF was defined as a rise in creatinine of 26 μmol/L (0.3 mg/dL) within the first 48 hours of admission. A total of 32 patients were enrolled in this study, 67% of patients had moderate-severe chronic kidney disease with an eGFR ≤ 60 mL/min and 34% (n=11) developed WRF during their admission. The mean right atrial pressure was higher in patients with WRF (19 ± 7 mm Hg vs 12 ± 6 mm Hg, P=.05). A total of 36% of patients with WRF died in hospital compared to 5% in the group that did not develop WRF (OR for hospital death 13.3 ± 16, P=.03). The combined endpoint of death or readmission at 6 months was 45% in the WRF group and 43% in the group without WRF (P=.89). Significant renal dysfunction is common in patients with PH and an acute decline in renal function is an important marker of in hospital death and short term mortality in right heart failure. © 2012 Wiley Periodicals, Inc.

Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.

PubMed

Dare, Anna J; Bolton, Eleanor A; Pettigrew, Gavin J; Bradley, J Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P

2015-08-01

Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Protection against renal ischemia–reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ

PubMed Central

Dare, Anna J.; Bolton, Eleanor A.; Pettigrew, Gavin J.; Bradley, J. Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P.

2015-01-01

Ischemia–reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24 h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. PMID:25965144

Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium

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

Zhang, Chen; Liang, Yihuai; Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032

2013-08-15

Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidneymore » parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23–13.22 μg/L; UCd, 8.65–32.90 μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P < 0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease. - Highlights: • A long term heavily Cd exposure induced renal dysfunction. • Cd exposure correlated positively with DNA methylation in RASAL1 and KLOTHO. • Hypermethylation of RASAL1 correlated with adjusted renal function indicators.« less

The effects of heart failure on renal function.

PubMed

Udani, Suneel M; Koyner, Jay L

2010-08-01

Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. 2010 Elsevier Inc. All rights reserved.

The Effects of Heart Failure on Renal Function

PubMed Central

Udani, Suneel M; Koyner, Jay L

2010-01-01

Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

PubMed Central

Wang, K.; Blotner, S.; Magnusson, M. O.; Wilkins, J. J.; Martin, P.; Solsky, J.; Nieforth, K.; Wat, C.; Grippo, J. F.

2013-01-01

Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0–12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0–12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients. PMID:24080649

Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury.

PubMed

Zhao, Chuanyan; Chen, Zhuyun; Xu, Xueqiang; An, Xiaofei; Duan, Suyan; Huang, Zhimin; Zhang, Chengning; Wu, Lin; Zhang, Bo; Zhang, Aihua; Xing, Changying; Yuan, Yanggang

2017-01-15

Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

PubMed Central

Liu, Yong; Zhou, Simon; Assaf, Mahmoud; Nissel, Jim

2016-01-01

Abstract The pharmacokinetics of apremilast and its major metabolite M12 were evaluated in subjects with varying degrees of renal impairment. Men and women with renal impairment (estimated glomerular filtration rate, 60‒89 mL/min [mild, n = 8], 30‒59 mL/min [moderate, n = 8], or <30 mL/min [severe, n = 8]) or demographically healthy matched (control) subjects (n = 24) received a single oral dose of apremilast 30 mg. Plasma apremilast and metabolite M12 concentrations were determined, and pharmacokinetic parameters were calculated from samples obtained predose and up to 72 hours postdose. In subjects with mild to moderate renal impairment, apremilast pharmacokinetic profiles were similar to healthy matched subjects. In subjects with severe renal impairment, apremilast elimination was significantly slower, and exposures based on area under the plasma concentration‐versus‐time curve from time zero extrapolated to infinity and maximum observed plasma concentration were increased versus healthy matched subjects. Metabolite M12 pharmacokinetic profiles for subjects with mild renal impairment were similar to those of the healthy matched subjects; however, they were increased in both the moderate and severe renally impaired subjects. Dose reduction of apremilast is recommended in individuals with severe renal impairment, but not in those with mild to moderate renal impairment. PMID:27870479

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

PubMed

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

RenalGuard system to prevent contrast-induced acute kidney injury in Japanese patients with renal dysfunction; RESPECT KIDNEY study.

PubMed

Katoh, Hiromasa; Nozue, Tsuyoshi; Horie, Kazuki; Sozu, Takashi; Inoue, Naoto; Michishita, Ichiro

2018-05-05

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 ] undergoing catheter procedures. Baseline eGFR and Mehran's CIN (contrast-induced nephropathy) risk score were 35.1 ± 8.5 mL/min/1.73 m 2 and 11.7 ± 4.3, respectively. Regardless of this high-risk profile, the incidence of CI-AKI was 8.6% (5/58) compared with the 26.1% incidence estimated by the CIN risk score. Moreover, two-sided 95% (Fisher's) exact confidence interval was 2.9-19.0 and its upper limit (i.e., 19.0) was less than the prespecified threshold incidence of 25.0. Univariate logistic regression analysis demonstrated that the UFR during catheter procedure was one of the most important factor associated with CI-AKI (odds ratio 0.99, confidence interval 0.98-1.00, p = 0.03). In conclusion, RenalGuard therapy may prevent CI-AKI development in Japanese patients with renal dysfunction. Further large-scale prospective multicenter studies are necessary to confirm our findings.

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

PubMed

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S; Januzzi, James L

2014-01-01

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

PubMed Central

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

2014-01-01

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

PubMed

Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

2016-01-01

Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.

PubMed

Heinig, Roland; Kimmeskamp-Kirschbaum, Nina; Halabi, Atef; Lentini, Silvia

2016-11-01

Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CL CR ] 50-80 mL/min; n = 8), moderate (CL CR 30 to < 50 mL/min; n = 8), or severe (CL CR < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CL CR > 80 mL/min; n  = 8) over 96 hours postdose. Exposure to finerenone was not affected by mild renal impairment. In participants with moderate or severe renal impairment, exposure to finerenone was increased compared with those with normal renal function (increase in area under the curve for unbound finerenone, 57.1% [outlier excluded] and 46.5%, respectively), with moderate to high interindividual variability. Renal impairment had no consistent effect on the maximum plasma concentration, C max (differences in C max for unbound finerenone of +12% and -7% with moderate [outlier excluded] and severe impairment vs normal renal function, respectively). Renal elimination of finerenone is minimal. However, changes in exposure may occur because of the effects of renal impairment on nonrenal routes of elimination. © 2016, The American College of Clinical Pharmacology.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

PubMed

Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

Cardiac and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Reduced NO production rapidly aggravates renal function through the NF-κB/ET-1/ETA receptor pathway in DOCA-salt-induced hypertensive rats.

PubMed

Kimura, Kimihiro; Ohkita, Mamoru; Koyama, Maki; Matsumura, Yasuo

2012-10-15

It has been reported that endothelin-1 (ET-1) overproduction and reduced nitric oxide (NO) production are closely related to the progression of renal diseases. In the present study, we examined the interrelation between ET-1 and NO system using rats treated with the combination of deoxycorticosterone acetate (DOCA)-salt and a non selective NO synthase inhibitor N(ω)-nitro-L-arginine (NOARG). Rats were treated with DOCA-salt (15 mg/kg, plus drinking water containing 1% NaCl) for two weeks, and then additional treatment of NOARG (0.6 mg/ml in the drinking water) was performed for three days. Combined treatment of DOCA-salt and NOARG drastically developed the severe renal dysfunction and tissue injury. This treatment additionally enhanced renal ET-1 production compared to the rats treated with DOCA-salt alone, whereas a selective ET(A) receptor antagonist ABT-627 completely prevented renal dysfunction and tissue injury. On the other hand, combined treatment of DOCA-salt and NOARG induced the phosphorylation of inhibitory protein kappa B (IκB), followed by the activation of nuclear factor-kappa B (NF-κB) in the kidney. In addition, pyrrolidine-dithiocarbamate completely suppressed not only NF-κB activation but also renal dysfunction and ET-1 overproduction. These results suggest that NF-κB/ET-1/ET(A) receptor-mediated actions are responsible for the increased susceptibility to DOCA-salt induced renal injuries in the case of reduced NO production. Copyright © 2012 Elsevier Inc. All rights reserved.

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

PubMed

Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

2013-12-18

Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. clinicaltrials.gov Identifier: NCT01132846.

Tailored dialysis start may allow persistence of residual renal function after graft failure: a case report.

PubMed

Piccoli, G B; Motta, D; Gai, M; Mezza, E; Maddalena, E; Bravin, M; Tattoli, F; Consiglio, V; Burdese, M; Bilucaglia, D; Ferrari, A; Segoloni, G P

2004-11-01

Restarting dialysis after kidney transplantation is a critical step with psychological and clinical implications. Maintenance of residual renal function a known factor affecting survival in chronic kidney disease, has so far not been investigated after a kidney transplantation. A 54-year-old woman who started dialysis in 1974 (first graft, 1975-1999) received a second "marginal" kidney graft in February 2001 (donor age, 65 years). Her chronic therapy was tacrolimus and steroids. She had a clinical history as follows: nadir creatinine level of 1.5 mg/dL, moderate-severe hypertension, progressive graft dysfunction, nonresponsiveness to addition of mycophenolate, tapering FK levels, and a rescue switch from tacrolimus to rapamycin. From October to December 2003, the creatinine level increased from 2-2.8 to 7 mg/dL. Biopsy specimen showed malignant and "benign" nephrosclerosis, posttransplantation glomerulopathy, and tacrolimus toxicity. Chronic dialysis was started (GFR <3 mL/min). Rapamycin was discontinued. Dialysis was tailored to reach an equivalent renal clearance of >15 mL/min (2 sessions/wk). Blood pressure control improved, nephrotoxic drugs were avoided, and fluid loss was minimized (maximum 500 mL/hr). By this policy, renal function progressively increased to GFR >10 mL/min in May 2004, allowing a once or twice weekly dialysis schedule, with good clinical balance, and obvious advantages for the quality of life. This long-term patient, who restarted dialysis with severely reduced renal function, regained sufficient renal function to allow once weekly dialysis. Thus, careful tailoring of dialysis sessions at the restart of dialysis may allow preservation of residual kidney function, at least in individuals for whom a subsequent graft is unlikely.

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.

Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

PubMed Central

Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

2015-01-01

Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

Bardet-Biedl syndrome: A rare cause of end stage renal disease.

PubMed

Hemachandar, R

2015-01-01

Bardet-Biedl syndrome is a rare autosomal recessive disorder, recently categorized as ciliopathy characterized by dysfunction of primary cilia which results in myriad manifestations in various organ systems. Though renal abnormalities can occur in this syndrome, renal failure is a rare presentation. The author reports a case of 18-year-old female who presented with polydactyly, obesity, retinitis pigmentosa, learning disability and renal failure.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

PubMed Central

Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

2016-01-01

Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

Renal function outcomes in pediatric patients with symptomatic reflux into the transplanted kidney treated with redo ureteroneocystostomy.

PubMed

Wang, Mary K; Chuang, Kai-Wen; Li, Yi; Gaither, Thomas; Brakeman, Paul; Gonzalez, Lynette; Brennan, Jessica; Baskin, Laurence S

2018-03-14

Asymptomatic post-renal transplant reflux is common but only 5-10% patients are diagnosed with vesico-ureteral reflux in the setting of post-transplant febrile urinary tract infections, requiring redo ureteroneocystostomy (redo-UNC). Here we report the renal function outcomes of 37 such patients, stratified by lower urinary tract (LUT) status. We hypothesized that those with pre-transplant LUT dysfunction would have lower glomerular filtration rate (GFR) on follow-up. Using procedure codes, 37 patients who underwent renal transplant followed by redo-UNC for transplant reflux at our institution between 1991 and 2014 were identified. Patient characteristics and GFR levels from four different time points were recorded. Comparisons were made between those with and without LUT dysfunction, using Fisher's exact, Wilcoxon rank sum, or signed-rank tests. Generalized estimating equations were constructed to account for the clustered nature of GFR within each LUT group and to assess their change over time. Twelve patients (32%) had pre-transplant LUT dysfunction. The proportion of males in this group was significantly higher (75% vs. 32%, p = 0.032), and there was no statistical difference towards presenting earlier with post-transplant reflux (1.4 vs. 2.3 years, p = 0.087). After an average of 4.9 years, the median GFRs were similar between the two groups (53 mg/dL vs. 58 mg/dL, p = 0.936). There was no significant difference in GFR at this last follow-up time point in patients with and without LUT dysfunction. Vesicoureteral reflux in the setting of renal transplantation is common and doesn't often require repair. In our series, we found that those with LUT dysfunction did not present statistically sooner with symptomatic transplant reflux. Longer-term follow-up did show a decline in GFR but did not reveal a difference in GFR in patients' with and without LUT dysfunction. Pediatric post-transplant GFR after open redo ureteral reimplant decreases over time in similar fashion in patients with symptomatic reflux regardless of whether they have LUT dysfunction or normal anatomy. Vigilance should apply to the recognition, treatment, and follow-up of all symptomatic transplant reflux regardless of LUT status. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

PubMed Central

Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

2013-01-01

Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

PubMed

Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

2018-05-02

We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Pulmonary-renal crosstalk in the critically ill patient].

PubMed

Donoso F, Alejandro; Arriagada S, Daniela; Cruces R, Pablo

2015-01-01

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31.

PubMed

Zhao, Hao; Liu, Yan-Jun; Liu, Zong-Rui; Tang, Dong-Dong; Chen, Xiao-Wen; Chen, Yi-Hua; Zhou, Ru-Ning; Chen, Si-Qi; Niu, Hong-Xin

2017-06-05

Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure (CRF). Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury.

PubMed

Nowak, Grazyna; Takacsova-Bakajsova, Diana; Megyesi, Judit

2017-01-01

Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44 and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. Copyright © 2017 the American Physiological Society.

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury

PubMed Central

Takacsova-Bakajsova, Diana; Megyesi, Judit

2016-01-01

Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44 and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. PMID:27760765

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PubMed

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

2016-01-01

To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

RAAS inhibition and cardiorenal syndrome.

PubMed

Onuigbo, Macaulay Amechi C

2014-01-01

The consensus conference on cardio-renal syndromes (2008) defined 'cardio-renal syndromes' as 'disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other' and identified five subtypes of the syndromes. Various pathophysiologic mechanisms underlie cardiorenal syndrome including hemodynamic derangements, reduced cardiac output leading to impaired renal perfusion, reduced stroke volume, raised atrial filling pressures, elevated atrial pressures, sodium and water retention, venous congestion, right ventricular dysfunction and venous hypertension causing increased renal venous pressure, intra-abdominal hypertension, various neurohormonal adaptations including activation of the renin-angiotensin-aldosterone system, adaptive activation of the sympathetic nervous system, cytokine release and oxidative stress. Although there are standardized clinical guidelines for the management of heart failure, and chronic kidney disease, respectively, there are no similar consensus clinical guidelines for the management of the cardiorenal syndromes. RAAS inhibition is advocated in treating systolic heart failure. There is evidence that RAAS inhibition is also useful in cardiorenal syndrome. However, RAAS inhibition, while potentially useful in the management of cardiorenal syndrome, is not the 'magic bullet', is sometimes limited by adverse renal events, is not applicable to all patients, and must be applied by physicians with due diligence and caution. Nevertheless, a more comprehensive multidisciplinary multipronged approach to managing patients with cardiorenal syndrome is even more pragmatic and commonsense given the multiple mechanisms and pathogenetic pathways implicated in the causation and perpetuation of cardiorenal syndrome.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Clinical outcomes in overweight heart transplant recipients.

PubMed

Jalowiec, Anne; Grady, Kathleen L; White-Williams, Connie

2016-01-01

Few studies have examined the impact of patient weight on heart transplant (HT) outcomes. Nine outcomes were compared in 2 groups of HT recipients (N = 347) based on their mean body mass index (BMI) during the first 3 years post-HT. Group 1 consisted of 108 non-overweight patients (BMI <25; mean age 52; 29.6% females; 16.7% minorities). Group 2 consisted of 239 overweight patients (BMI ≥25; mean age 52; 15.9% females; 13.8% minorities). Outcomes were: survival, re-hospitalization, rejections, infections, cardiac allograft vasculopathy (CAV), stroke, renal dysfunction, diabetes, and lymphoma. Non-overweight patients had shorter survival, were re-hospitalized more days after the HT discharge, and had more lymphoma and severe renal dysfunction. Overweight patients had more CAV, steroid-induced diabetes, and acute rejections. Overweight HT patients had better survival, but more rejections, CAV, and diabetes. Non-overweight HT patients had worse survival, plus more re-hospitalization time, lymphoma, and renal dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B.

PubMed

Tanaka, Mio; Suzuki, Fumitaka; Seko, Yuya; Hara, Tasuku; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Akuta, Norio; Kobayashi, Masahiro; Suzuki, Yoshiyuki; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kobayashi, Mariko; Kumada, Hiromitsu

2014-03-01

Renal dysfunction and Fanconi's syndrome associated with hypophosphatemia caused by long-term administration of low-dose adefovir dipivoxil (ADV) has been reported in recent years. The aim of this retrospective study was to determine the incidence and factors associated with renal dysfunction and hypophosphatemia in patients with hepatitis B infection on long-term treatment with ADV and lamivudine (LAM). The study subjects were 292 patients treated with 10 mg/day ADV and 100 mg/day LAM for more than 6 months. We evaluated estimated glomerular filtration rate (eGFR), serum creatinine and serum phosphate level at the start of ADV and every 6 months. During a median treatment duration of 64 months, 28 (9.6 %) patients developed renal impairment (defined as eGFR < 50 ml/min/1.73 m(2)), and 73 (27.1 %) developed hypophosphatemia, including 14 with persistent hypophosphatemia. The cumulative incidences of renal impairment at 1, 3, and 5 years were 1.4, 7.5, 10.5 %, respectively, and those of hypophosphatemia were 6.8, 20.6, 26.7 %, respectively. Multivariate analysis identified old age, liver cirrhosis and hypertension as determinants of renal impairment, and male sex, HCC, low baseline serum phosphate as determinants of hypophosphatemia. Three of the 14 patients with persistent hypophosphatemia developed Fanconi's syndrome; their serum creatinine level remained normal, but eGFR was lower than at baseline. Long-term treatment of hepatitis B with low-dose (10 mg/day) ADV and LAM can potentially cause renal impairment and hypophosphatemia. We advocate regular monitoring of serum phosphate and evaluation of eGFR, in addition to serum creatinine, in such patients.

Outcomes of cryptococcosis in renal transplant recipients in a less-resourced health care system.

PubMed

Ponzio, Vinicius; Camargo, Luis F A; Medina-Pestana, José O; Perfect, John R; Colombo, Arnaldo L

2018-04-20

Cryptococcosis is the second most common cause of invasive fungal infections in renal transplant recipients in many countries, and data on graft outcome after treatment for this infection is lacking in less-resourced health care settings. Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss and mortality rates were evaluated. Predictors of mortality and graft loss were estimated. A total of 38 (97.4%) patients treated with amphotericin B deoxycholate (AMBd) showed graft dysfunction after antifungal initiation and 8 (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels and graft dysfunction concomitant to AMBd therapy and an additional nephrotoxic condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high CSF opening pressure, positive CSF India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with AMBd and an additional nephrotoxic condition and graft loss within 30 days. Graft dysfunction was common in renal transplant recipients with cryptococcosis treated with AMBd. The rate of graft loss rate was high, most frequently in patients with concomitant nephrotoxic conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population requiring a polyene induction regimen for treatment of severe cryptococcosis in all health care systems caring for transplantation recipients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Tricuspid valve regurgitation : Indications and operative techniques].

PubMed

Lange, R; Piazza, N; Günther, T

2017-11-01

Functional tricuspid valve (TV) regurgitation secondary to left heart disease (e.g. mitral insufficiency and stenosis) is observed in 75% of the patients with TV regurgitation and is thus the most common etiology; therefore, the majority of patients who require TV surgery, undergo concomitant mitral and/or aortic valve surgery. Uncorrected moderate and severe TV regurgitation may persist or even worsen after mitral valve surgery, leading to progressive heart failure and death. Patients with moderate to severe TV regurgitation show a 3-year survival rate of 40%. Surgery is indicated in patients with severe TV regurgitation undergoing left-sided valve surgery and in patients with severe isolated primary regurgitation without severe right ventricular (RV) dysfunction. For patients requiring mitral valve surgery, tricuspid valve annuloplasty should be considered even in the absence of significant regurgitation, when severe annular dilatation (≥40 mm or >21 mm/m 2 ) is present. Functional TV regurgitation is primarily treated with valve reconstruction which carries a lower perioperative risk than valve replacement. Valve replacement is rarely required. Tricuspid valve repair with ring annuloplasty is associated with better survival and a lower reoperation rate than suture annuloplasty. Long-term results are not available. The severity of the heart insufficiency and comorbidities (e.g. renal failure and liver dysfunction) are the essential determinants of operative mortality and long-term survival. Tricuspid valve reoperations are rarely necessary and associated with a considerable mortality.

Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis.

PubMed

Noyan, Aytul; Parmaksiz, Gonul; Dursun, Hasan; Ezer, Semire Serin; Anarat, Ruksan; Cengiz, Nurcan

2015-10-01

The clinical tests currently in use for obstructive nephropathy (such as renal ultrasonography, differential radionuclide renal scans and urinary creatinine concentration data) are not efficient predictors of the subsequent clinical course. Novel and simple biomarkers are required which, if proven, could be clinically beneficial in determining if a patient is eligible for surgery or reno-protective therapy. More recently, the interest of clinicians has focused on the potential of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1) and urinary liver-type fatty acid-binding proteins (uL-FABP) as biomarkers for renal function in children with hydronephrosis (HN). The purpose of this study was to investigate possible clinical applications of uNGAL, uKIM-1 and uL-FABP as beneficial non-invasive biomarkers to determine whether or not surgical intervention is required in children with HN. Renal ultrasonography and radionuclide renal scans were used as diagnostic tools to detect HN. Patients were divided into two groups based on the antero-posterior diameter of their renal pelvis and the presence of dysfunction. Group 1 included 26 children with severe HN (with dysfunction), and group 2 consisted of 36 children with mild HN (without dysfunction). Urine samples were collected from 62 children with HN and 20 healthy children. Hydronephrosis was more common in males than in females, with a male to female ratio of 9:1 in the study sample. The incidence of left kidney involvement (32 patients) was slightly higher than right kidney involvement (28 patients). Compared with controls and group 2, the ratio of uNGAL to creatinine was significantly higher in group 1 (p < 0.05). The biomarker uNGAL/Cr exhibited fairly good diagnostic accuracy, with an area under the curve of 0.68 [95% confidence interval 0.6-0.7] and an optimal cut-off value of 0.16 ng/mg Cr (sensitivity 58%, specificity 75%) (p < 0.05). There was a positive correlation between the uNGAL/Cr ratio and the uKIM-1/Cr ratio (r = 0.582, p < 0.05) and uL-FABP/Cr ratio (r = 0675, p < 0.05) in group 1. The results clearly demonstrated that children with hydronephrosis and dysfunction had significantly increased uNGAL, and uNGAL/Cr concentrations. However, uKIM-1, uKIM-1/Cr, uL-FABP and uL-FABP/Cr concentrations were not significantly different when compared with controls. These results support the use of uNGAL concentrations as an early marker for renal dysfunction in HN. The study clearly demonstrated that pediatric patients with hydronephrosis and dysfunction had significantly higher uNGAL to creatinine concentrations as compared with controls. Copyright © 2015 Journal of Pediatric Urology Company. All rights reserved.

Inhibition of NA+/H+ Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats

PubMed Central

Li, Peng; Chen, Geng-Rong; Wang, Fu; Xu, Ping; Liu, Li-Ying; Yin, Ya-Ling; Wang, Shuang-Xi

2016-01-01

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1. PMID:26697498

Borderline Changes on Dysfunctional Renal Allograft Biopsies: Clinical Relevance in a Living Related Renal Transplant Setting.

PubMed

Mubarak, Muhammed; Shakeel, Shaheera; Abbas, Khawar; Aziz, Tahir; Zafar, Mirza Naqi; Naqvi, Syed Anwer; Rizvi, Syed Adibul Hasan

2017-02-01

Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria. Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment. The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Spironolactone Treatment and Effect on Survival in Chronic Heart Failure Patients with Reduced Renal Function: A Propensity-Matched Study

PubMed Central

Stubnova, Viera; Os, Ingrid; Grundtvig, Morten; Atar, Dan; Waldum-Grevbo, Bård

2017-01-01

Background/Aims Spironolactone may be hazardous in heart failure (HF) patients with renal dysfunction due to risk of hyperkalemia and worsened renal function. We aimed to evaluate the effect of spironolactone on all-cause mortality in HF outpatients with renal dysfunction in a propensity-score-matched study. Methods A total of 2,077 patients from the Norwegian Heart Failure Registry with renal dysfunction (eGFR <60 mL/min/1.73 m2) not treated with spironolactone at the first visit at the HF clinic were eligible for the study. Patients started on spironolactone at the outpatient HF clinics (n = 206) were propensity-score-matched 1:1 with patients not started on spironolactone, based on 16 measured baseline characteristics. Kaplan-Meier and Cox regression analyses were used to investigate the independent effect of spironolactone on 2-year all-cause mortality. Results Propensity score matching identified 170 pairs of patients, one group receiving spironolactone and the other not. The two groups were well matched (mean age 76.7 ± 8.1 years, 66.4% males, and eGFR 46.2 ± 10.2 mL/min/1.73 m2). Treatment with spironolactone was associated with increased potassium (delta potassium 0.31 ± 0.55 vs. 0.05 ± 0.41 mmol/L, p < 0.001) and decreased eGFR (delta eGFR −4.12 ± 12.2 vs. −0.98 ± 7.88 mL/min/1.73 m2, p = 0.006) compared to the non-spironolactone group. After 2 years, 84% of patients were alive in the spironolactone group and 73% of patients in the non-spironolactone group (HR 0.59, 95% CI 0.37-0.92, p = 0.020). Conclusion In HF outpatients with renal dysfunction, treatment with spironolactone was associated with improved 2-year survival compared to well-matched patients not treated with spironolactone. Favorable survival was observed despite worsened renal function and increased potassium in the spironolactone group. PMID:28611786

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

PubMed Central

Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

2015-01-01

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure

PubMed Central

Zhang, Sijie; Wang, Zhiqian

2016-01-01

Abstract Background: This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). Methods: The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Results: Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I2 = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). Conclusions: The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF. PMID:27858837

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

Yin, Qingqiao; Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com; Wang, Guan

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression inmore » HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.« less

Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies.

PubMed

Zhang, Jin; Qiu, Jiang; Chen, Guo-Dong; Wang, Chang-Xi; Wang, Chang; Yu, Shuang-Jin; Chen, Li-Zhong

2018-11-01

The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes. We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema. Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively. A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure: A systematic review and meta-analysis.

PubMed

Zhang, Sijie; Wang, Zhiqian

2016-11-01

This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

[Heart involvement in Anderson-Fabry disease: Italian recommendations for diagnostic, follow-up and therapeutic management].

PubMed

Pieruzzi, Federico; Pieroni, Maurizio; Zachara, Elisabetta; Marziliano, Nicola; Morrone, Amelia; Cecchi, Franco

2015-11-01

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations of the GLA gene that encodes alpha-galactosidase A. It is characterized by a multisystemic involvement: the renal, neurological, heart, cochleovestibular and cutaneous systems are the most damaged. Morbidity and mortality of Anderson-Fabry disease depend on renal insufficiency, heart failure and nervous system involvement. Left ventricular hypertrophy is the most common cardiac manifestation followed by conduction system disease, valve dysfunction, and arrhythmias. Mild to moderate left ventricular hypertrophy may simulate a non-obstructive hypertrophic cardiomyopathy. Management of Anderson-Fabry disease starting from the diagnosis of cardiac involvement, the prevention of complications, the therapeutic aspects, up to appropriate clinical follow-up, requires a multidisciplinary approach. According to recent management guidelines, only few evidence-based data are available to guide the clinical and therapeutic approach to this rare disease. An Italian Board, composed by nephrologists, cardiologists, geneticists, pediatricians and neurologists has been established in order to approve by consensus a diagnostic and therapeutic management protocol. The authors report the results of this cardiologic management consensus.

Pharmacological Management of Cardiorenal Syndromes

PubMed Central

House, Andrew A.; Haapio, Mikko; Lassus, Johan; Bellomo, Rinaldo; Ronco, Claudio

2011-01-01

Cardiorenal syndromes 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 pharmacological management of Cardiorenal syndromes may be complicated by unanticipated or unintended effects of agents targeting one organ on the other. Hence, a thorough understanding of the pathophysiology of these disorders is paramount. The treatment of cardiovascular diseases and risk factors may affect renal function and modify the progression of renal injury. Likewise, management of renal disease and associated complications can influence heart function or influence cardiovascular risk. In this paper, an overview of pharmacological management of acute and chronic Cardiorenal Syndromes is presented, and the need for high-quality future studies in this field is highlighted. PMID:21660311

Implementation of Get with the Guideline Acute Myocardial Infarction Program at Johns Hopkins Hospital and Its Effect on Core Measures

DTIC Science & Technology

2007-05-25

allergy E Patient is discharged on hydralazine/nitrate therapy* E Hypotension* El Moderate or severe aortic stenosis El Worsening renal function* E...Hypotension* E Moderate or severe aortic stenosis El Worsening renal function* E Hyperkalemia* E Bilateral renal artery stenosis * E Pregnancy* E Other...Hyperkalemia* El Bilateral renal artery stenosis * E Pregnancy* El Other - must be documented in medical record Angiotension Receptor Blocker (ARB

Inpatient Coronary Angiography and Revascularisation following Non-ST-Elevation Acute Coronary Syndrome in Patients with Renal Impairment: A Cohort Study Using the Myocardial Ischaemia National Audit Project

PubMed Central

Shaw, Catriona; Nitsch, Dorothea; Steenkamp, Retha; Junghans, Cornelia; Shah, Sapna; O’Donoghue, Donal; Fogarty, Damian; Weston, Clive; Sharpe, Claire C.

2014-01-01

Background International guidelines support an early invasive management strategy (including early coronary angiography and revascularisation) for non-ST-elevation acute coronary syndrome (NSTE-ACS) in patients with renal impairment. However, evidence from outside the UK suggests that this approach is underutilised. We aimed to describe practice within the NHS, and to determine whether the severity of renal dysfunction influenced the provision of angiography and modified the association between early revascularisation and survival. Methods We performed a cohort study, using multivariable logistic regression and propensity score analyses, of data from the Myocardial Ischaemia National Audit Project for patients presenting with NSTE-ACS to English or Welsh hospitals between 2008 and 2010. Findings Of 35 881 patients diagnosed with NSTE-ACS, eGFR of <60 ml/minute/1.73 m2 was present in 15 680 (43.7%). There was a stepwise decline in the odds of undergoing inpatient angiography with worsening renal dysfunction. Compared with an eGFR>90 ml/minute/1.73 m2, patients with an eGFR between 45–59 ml/minute/1.73 m2 were 33% less likely to undergo angiography (adjusted OR 0.67, 95% CI 0.55–0.81); those with an eGFR<30/minute/1.73 m2 had a 64% reduction in odds of undergoing angiography (adjusted OR 0.36, 95%CI 0.29–0.43). Of 16 646 patients who had inpatient coronary angiography, 58.5% underwent inpatient revascularisation. After adjusting for co-variables, inpatient revascularisation was associated with approximately a 30% reduction in death within 1 year compared with those managed medically after coronary angiography (adjusted OR 0.66, 95%CI 0.57–0.77), with no evidence of modification by renal function (p interaction = 0.744). Interpretation Early revascularisation may offer a similar survival benefit in patients with and without renal dysfunction, yet renal impairment is an important determinant of the provision of coronary angiography following NSTE-ACS. A randomised controlled trial is needed to evaluate the efficacy of an early invasive approach in patients with severe renal dysfunction to ensure that all patients who may benefit are offered this treatment option. PMID:24937680

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

New Developments in Hepatorenal Syndrome.

PubMed

Mindikoglu, Ayse L; Pappas, Stephen C

2018-02-01

Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary simultaneous liver-kidney transplantation. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Long-term safety of tiotropium/olodaterol Respimat® in patients with moderate-to-very severe COPD and renal impairment in the TONADO® studies.

PubMed

LaForce, Craig; Derom, Eric; Bothner, Ulrich; Kloer, Isabel M; Trampisch, Matthias; Buhl, Roland

2018-01-01

The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO ® studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat ® ) in patients with moderate-to-very severe COPD. In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60-89 mL/min), moderate (CLcr 30-59 mL/min) or severe (CLcr 15-29 mL/min). Adverse events (AEs) were pooled from both studies. Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups. Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively. There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents. There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment. Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular comorbidity. The safety and tolerability of tiotropium/olodaterol is comparable to the monocomponents, irrespective of the level of renal impairment.

Junctional bradycardia with verapamil in renal failure--care required even with mild hyperkalaemia.

PubMed

Hegazi, M O; Aldabie, G; Al-Mutairi, S; El Sayed, A

2012-12-01

Treatment for hypertension with verapamil has a favourable renoprotective effect and is generally considered safe in patients with mild to moderate renal failure. In this report, we highlight the vulnerability of patients with mild to moderate renal failure to verapamil side effects especially in the presence of hyperkalaemia. We report two cases of junctional bradycardia with slow release (SR) verapamil therapy in the presence of mild hyperkalaemia in patients with mild to moderate chronic renal failure. Verapamil and hyperkalaemia may synergistically increase the vulnerability to atrioventricular conduction delay. Renal failure patients with baseline mild hyperkalaemia are particularly liable to bradyarrhythmias with SR verapamil. In such cases, we would recommend verapamil dose reduction and avoidance of SR formulation. In cases of verapamil toxicity, actively treating any level of hyperkalaemia is recommended. © 2012 Blackwell Publishing Ltd.

Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug.

PubMed

Gervasini, Guillermo; Robles, Nicolas Roberto

2017-05-01

Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system. Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients. We put the focus on the renal data provided by these studies. Data were obtained from English peer-reviewed articles on PubMed and clinical trials registered in ClinicalTrials.gov. Expert opinion: Overall, sacubitril-valsartan might be a promising therapeutic approach in patients with renal dysfunction. Renal conditions with marked CV risk, such as arterionephrosclerosis, could constitute a particular setting where to evaluate the impact of the drug. Nevertheless, large, randomized trials are needed to confirm the beneficial effects and safety profile of the drug in renal patients, as well as to elucidate some concerns observed in HF trials, such as the slight increase in proteinuria.

Effect of first myocardial ischemic event on renal function.

PubMed

Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

2007-07-01

Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome).

PubMed

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

PubMed Central

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

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

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

PubMed Central

Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

Renal preservation in children with neurogenic bladder-sphincter dysfunction followed in a national program.

PubMed

Wide, Peter; Glad Mattsson, Gunilla; Mattsson, Sven

2012-04-01

Neurogenic bladder-sphincter dysfunction (NBSD) constitutes the major reason for morbidity in children with spina bifida. The aim of this study was to identify risk factors for renal damage in children with NBSD followed according to the Swedish national guidelines. Records and cystometries from 6 to 16 years (median 11) follow up of 41 consecutive children born 1993-2003 with NBSD were evaluated. The children were divided into a high pressure group (baseline pressure above 30 cmH(2)O at maximal clean intermittent catheterization volume in at least two cystometries) and a low pressure group. Most children (34/41) were followed from birth. Although renal scarring on DMSA-scintigraphy was found in 5/41 children, all but one had normal renal function. Two already had renal scars on entering the follow-up program at age 2.5 and 3 years. Renal scarring was more frequent in the high pressure group (P < 0.01). Most children with renal scars (4/5) had a combination of low compliant bladder and insufficient compliance with treatment and follow up. High baseline pressure is confirmed as a risk factor that, in combination with complex social issues, creates a demanding situation for families and professionals. A structured early follow up with treatment compliance effectively prevents renal damage. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Cerebro-renal interactions: impact of uremic toxins on cognitive function.

PubMed

Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

2014-09-01

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury.

PubMed

Yeh, Wan-Ju; Yang, Hsin-Yi; Pai, Man-Hui; Wu, Chi-Hao; Chen, Jiun-Rong

2017-01-01

The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study

PubMed Central

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-01-01

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708), and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

PubMed

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-07-16

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394-0.708), and eGFR (β = -0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.

Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula

PubMed Central

Červenka, Luděk; Melenovský, Vojtěch; Husková, Zuzana; Sporková, Alexandra; Bürgelová, Marcela; Škaroupková, Petra; Hwang, Sung Hee; Hammock, Bruce D.; Imig, John D.; Sadowski, Janusz

2016-01-01

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/L in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue. PMID:26047375

Renal sympathetic nerve activity measured by norepinephrine spillover rate in response to changes in blood pressure in conscious rabbits.

PubMed

Sano, N; Way, D; McGrath, B P

1989-04-01

1. Renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) was examined by measuring renal norepinephrine (NE) spillover rate in conscious rabbits. 2. A chronic renal vein catheter was implanted for sampling renal venous blood without stress in conscious animals. 3. RSNA estimated by renal NE spillover rate significantly increased in response to moderate falls in MAP produced by sodium nitroprusside (SNP) infusion and decreased in response to moderate rises in MAP produced by phenylephrine (PE) infusion. 4. The NE spillover method is sufficiently sensitive to detect responses of RSNA to physiological stimuli in conscious rabbits.

Oxidative Stress in Hypertension: Role of the Kidney

PubMed Central

Araujo, Magali

2014-01-01

Abstract Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the renin-angiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O2−• rather than H2O2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renal-damaging effects of hypertension. Antioxid. Redox Signal. 20, 74–101. PMID:23472618

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the lung or pulmonary fibrosis means chronic inflammation and scarring of the pulmonary interstitium... Criteria for Claims by Ore Transporters § 79.61 Definitions. (a) Chronic renal disease means the chronic... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The term includes in situ lung cancers. (m) Readily available documentation means documents in the... injury means structural or functional damage to the kidney tubules that results in renal disease and... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

PubMed

Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

PubMed Central

Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser473-AKT, phosphorylated Thr308-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr308-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr308-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr308-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr308-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr308-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate (UAER) and albumin to creatinine ratio. We conclude that phosphorylated Thr308-AKT regulates VEGF-A expression by interacting with either nephrin in glomeruli or Ang II in renal tubules. Antiangiogenic treatment improves renal injury and function in early experimental diabetes. PMID:24759991

Interaction between renal function and percutaneous edge-to-edge mitral valve repair using MitraClip.

PubMed

Kaneko, Hidehiro; Neuss, Michael; Schau, Thomas; Weissenborn, Jens; Butter, Christian

2017-02-01

MitraClip (MC; Abbott Vascular, Menlo Park, CA, USA) is a treatment option for mitral regurgitation. Renal dysfunction is closely associated with cardiovascular disease. However, the influence of renal function in MC remains not fully understood. In this study, we aimed to clarify the association between renal function and MC. We examined 206 consecutive patients who underwent MC and divided patients into 3 groups according to estimated glomerular filtration rate (eGFR), normal eGFR (≥60mL/min/1.73m 2 ) (n=70), mild chronic kidney disease (CKD) (30-59mL/min/1.73m 2 ) (n=106), and severe CKD (<30mL/min/1.73m 2 ) (n=30). N-terminal pro-B type natriuretic peptide (NT-pro BNP) levels increased with decreasing eGFR. Kaplan-Meier curves revealed that the long-term survival rate significantly decreased with eGFR. After adjustment with the covariates, severe CKD was still associated with mortality. Improved renal function was observed in 30% and associated with baseline lower NT-pro BNP levels. Patients with improved renal function had higher chronic phase survival rate. Renal dysfunction is common in MC patients and the survival rate decreased with eGFR in association with increased NT-pro BNP levels. MC may improve renal function in approximately 30% of MC patients. Improved renal function is associated with lower NT-pro BNP levels and results in satisfactory prognosis. These results implies a close association between renal function and MC treatment. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease.

PubMed

Ogawa-Akiyama, Ayu; Sugiyama, Hitoshi; Kitagawa, Masashi; Tanaka, Keiko; Onishi, Akifumi; Yamanari, Toshio; Morinaga, Hiroshi; Uchida, Haruhito Adam; Nakamura, Kazufumi; Ito, Hiroshi; Wada, Jun

2018-01-01

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

PubMed

Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

2000-04-01

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications?

PubMed Central

Ruiz-Tamayo, Irene; Franch-Nadal, Josep; Mata-Cases, Manel; Mauricio, Dídac; Cos, Xavier; Rodriguez-Poncelas, Antonio; Barrot, Joan; Coll-de-Tuero, Gabriel; Mundet-Tudurí, Xavier

2016-01-01

Aim. To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. Methods. Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. Results. Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. Conclusion. Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM. PMID:26881258

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

[Chronic renal disease as cardiovascular risk factor].

PubMed

Hermans, M M H; Kooman, J P; Stehouwer, C D A

2008-07-19

A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.

Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

PubMed Central

Faga, Teresa; Pisani, Antonio; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

Endothelial Dysfunction Exacerbates Renal Interstitial Fibrosis through Enhancing Fibroblast Smad3 Linker Phosphorylation in the Mouse Obstructed Kidney

PubMed Central

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J.; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation. PMID:24391884

Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

PubMed

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation.

Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

PubMed

Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

2013-09-01

Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

Cardiorenal syndrome in acute heart failure: a vicious cycle?

PubMed

Caetano, Francisca; Barra, Sérgio; Faustino, Ana; Botelho, Ana; Mota, Paula; Costa, Marco; Leitão Marques, António

2014-03-01

Worsening renal function has an unquestionably negative impact on prognosis in patients with acute heart failure (HF). In Portugal there is little information about the importance of this entity in HF patients admitted to hospital. The objective of this work was to assess the prevalence of cardiorenal syndrome and to identify its key predictors and consequences in patients admitted for acute HF. This was a retrospective study of 155 patients admitted for acute HF. Cardiorenal syndrome was defined as an increase in serum creatinine of ≥26.5 μmol/l. Clinical, laboratory and echocardiographic parameters were analyzed and compared. Mortality was assessed at 30 and 90 days. Cardiorenal syndrome occurred in 46 patients (29.7%), 5.4 ± 4.4 days after admission; 66.7% (n=24) did not recover baseline creatinine levels. The factors associated with cardiorenal syndrome were older age, chronic renal failure, moderate to severe mitral regurgitation, higher admission blood urea nitrogen, creatinine and troponin I, and lower glomerular filtration rate. Patients who developed cardiorenal syndrome had longer hospital stay, were treated with higher daily doses of intravenous furosemide, and more often required inotropic support and renal replacement therapy. They had higher in-hospital and 30-day mortality, and multivariate analysis identified cardiorenal syndrome as an independent predictor of in-hospital mortality. Renal dysfunction is common in acute HF patients, with a negative impact on prognosis, which highlights the importance of preventing kidney damage through the use of new therapeutic strategies and identification of novel biomarkers. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.

PubMed

Tao, Rong; Fan, Qin; Zhang, Hang; Xie, Hongyang; Lu, Lin; Gu, Gang; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Niu, Wenquan; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-04-01

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it. This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518]; P =0.001), cardiovascular death (1.347 [1.096-1.655]; P =0.005), HF hospitalization (1.234 [1.018-1.494]; P =0.032), and all-cause mortality (1.343 [1.115-1.618]; P =0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without. IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function.

PubMed

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t(last) ) and C(max) for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C(max) for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. © 2011 UCB Biosciences GmbH. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

PubMed Central

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

AIM To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h−1). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. RESULTS Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. CONCLUSIONS The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. PMID:21707699

The effects of low environmental cadmium exposure on bone density

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

Trzcinka-Ochocka, M., E-mail: ochocka@imp.lodz.pl; Jakubowski, M.; Szymczak, W.

2010-04-15

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9;more » 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.« less

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

PubMed

Park, C W; Lim, J H; Youn, D-Y; Chung, S; Lim, M-H; Kim, Y K; Chang, Y S; Lee, J-H

2011-02-01

Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

Adrenalectomy prevents renal ischemia-reperfusion injury.

PubMed

Ramírez, Victoria; Trujillo, Joyce; Valdes, Rafael; Uribe, Norma; Cruz, Cristino; Gamba, Gerardo; Bobadilla, Norma A

2009-10-01

Spironolactone treatment prevents renal damage induced by ischemia-reperfusion (I/R), suggesting that renoprotection conferred by spironolactone is mediated by mineralocorticoid receptor (MR) blockade. It is possible, however, that this effect is due to other mechanisms. Therefore, this study evaluated whether adrenalectomy prevented renal damage induced by I/R. Three groups of Wistar rats were studied: 1) a group subjected to a sham surgery, 2) a group subjected to bilateral I/R, and 3) a group of rats in which adrenal glands were removed 3 days before induction of I/R. As expected, I/R resulted in renal dysfunction and severe tubular injury that was associated with a significant increase in tubular damage markers. In contrast, there was no renal dysfunction or tubular injury in rats that were adrenalectomized before I/R. These effects were demonstrated by normalization of glomerular filtration rate, markers of oxidative stress, and tubular injury markers in adrenalectomized rats. The renoprotection observed was associated with the reestablishment of nitric oxide metabolites, increased endothelial nitric oxide synthase expression and its activating phosphorylation, as well as normalization of Rho-kinase expression and ET(A) mRNA levels. Our results show that aldosterone plays a central role in the pathogenesis of renal damage induced by I/R and that MR blockade may be a promising strategy that opens a new therapeutic option for preventing acute renal injury.

The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

PubMed

Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not require dosage reduction in accordance with the creatinine clearance FUNDING: Astellas Pharma.

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Renal albumin absorption in physiology and pathology.

PubMed

Birn, H; Christensen, E I

2006-02-01

Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

PubMed

Wang, Xiu-juan; Rao, Xiang-rong; Li, Shen; Wang, Li; Liu, Chang; Zhang, Gai-hua; Han, Dong-yan; Zhao, Yu; Zhang, Nan-nan; Li, Xue-xia; Chen, Shuai

2015-11-01

To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

[Organ damage and cardiorenal syndrome in acute heart failure].

PubMed

Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

2014-03-01

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

The central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.

PubMed

Ince, Can

2014-01-01

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed. 2014 S. Karger AG, Basel.

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.

CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

PubMed

Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

2014-10-01

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

PubMed Central

Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

2016-01-01

Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2012-05-15

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to treat chronic RVD.

Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach

PubMed Central

Kelsen, Silvia

2012-01-01

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to treat chronic RVD. PMID:22357917

Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Verinurad, a Selective Uric Acid Reabsorption Inhibitor.

PubMed

Smith, William B; Hall, Jesse; Berg, Jolene K; Kazimir, Michal; Yamamoto, Amy; Walker, Susan; Lee, Caroline A; Shen, Zancong; Wilson, David M; Zhou, Dongmei; Gillen, Michael; Marbury, Thomas C

2018-06-11

BACKGROUND AND OBJECTIVE: Verinurad (RDEA3170) is a high-affinity, selective URAT1 transporter inhibitor in development for treating gout and asymptomatic hyperuricemia. This Phase I, single-dose study investigated the pharmacokinetics, pharmacodynamics, and safety of verinurad in adults with renal impairment and controls with normal renal function. Males aged 18-85 years were enrolled with serum urate (sUA) 4.5-10 mg/dl and creatinine clearance 60- < 90, 30- < 60, 15- < 30, or ≥ 90 ml/min (mild, moderate, severe renal impairment and controls, respectively; n = 7/8). Verinurad 15 mg was administered orally under fasted conditions. Serial plasma/serum and urine samplings were 30 min pre-dose to 72 h post-dose. Compared to controls, verinurad maximum observed plasma concentration increased by 53, 73, and 128% and area under the concentration-time curve increased by 24, 148, and 130%, in subjects with mild, moderate, and severe renal impairment, respectively; renal clearance decreased by 5, 42, and 79%. Exposures of major verinurad metabolites also increased with increasing renal impairment. Verinurad decreased sUA in all groups, with greater maximal changes in control and mild renal impairment than moderate and severe impairment groups (- 38.3, - 36.9, - 20.5, - 12.6%, respectively). There were no adverse event-related withdrawals or clinically meaningful changes in laboratory values. Exposures of verinurad and metabolites increased with decreasing renal function. Consistent with the renal-dependent mechanism of action of verinurad, increasing severity of renal impairment was associated with decreased sUA lowering. Verinurad safety assessments were similar regardless of renal impairment. Continued investigation of verinurad is warranted in patients with gout and renal impairment. CLINICALTRIALS. NCT02219516.

Effect of renal impairment on the pharmacokinetics of exenatide

PubMed Central

Linnebjerg, Helle; Kothare, Prajakti A; Park, Soomin; Mace, Kenneth; Reddy, Shobha; Mitchell, Malcolm; Lins, Robert

2007-01-01

What is already known about this subject Nonclinical studies have shown that exenatide is primarily cleared by the renal system. It was not known to what degree the clinical pharmacokinetics and tolerability would be affected by increasing renal impairment (RI). What this study adds Patients with mild to moderate RI adequately tolerate current therapeutic doses of exenatide.However, exenatide is not recommended in patients with severe RI or end-stage renal disease. Aims To evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI). Methods Exenatide (5 or 10 µg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft–Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min−1, n = 8), mild RI (51–80 ml min−1, n = 8), moderate RI (31–50 ml min−1, n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL. Results Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively. After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h−1, respectively. Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting. Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 µg q.d.). Conclusions Since tolerability and PK changes were considered clinically acceptable in patients with mild to moderate RI, it would be appropriate to administer exenatide to these patients without dosage adjustment. However, poor tolerability and significant changes in PK make the currently available therapeutic doses (5 and 10 µg) unsuitable in severe RI or ESRD. PMID:17425627

Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine.

PubMed

de Cavanagh, Elena M V; Toblli, Jorge E; Ferder, León; Piotrkowski, Bárbara; Stella, Inés; Inserra, Felipe

2006-06-01

Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg.kg-1.day-1, SHR+Los), amlodipine (3 mg.kg-1.day-1, SHR+Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo, mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT1-receptor antagonists.

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

PubMed

Marcus, Julia L; Neugebauer, Romain S; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

2016-04-01

Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

ClinicalTrials.gov

2018-04-24

Metastatic Urothelial Carcinoma; Recurrent Bladder Urothelial Carcinoma; Recurrent Urethral Urothelial Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Renal Failure; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7

Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

PubMed

Futrakul, Narisa; Butthep, Punnee; Vongthavarawat, Varaphon; Futrakul, Prasit; Sirisalipoch, Sasitorn; Chaivatanarat, Tawatchai; Suwanwalaikorn, Sompongse

2006-01-01

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal tubular epithelial cells by improving mitochondrial function

PubMed Central

Qi, Jia; Duan, Suyan; Huang, Zhimin; Zhang, Chengning; Wu, Lin; Zeng, Ming; Zhang, Bo; Wang, Ningning; Mao, Huijuan; Zhang, Aihua; Xing, Changying; Yuan, Yanggang

2017-01-01

Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking. Furthermore, several evidences have shown that mitochondrial fission coordinates with mitophagy. The aim of this study was to investigate whether activation of mitophagy protects against mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. The effect of mitochondrial fission on mitophagy was also investigated. In cultured human renal proximal tubular cells, we observed that 3-methyladenine, a pharmacological inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced mitochondrial dysfunction and cells injury. In contrast, autophagy activator rapamycin enhanced mitophagy and protected against the harmful effects of cisplatin on mitochondrial function and cells viability. Suppression of mitochondrial fission by knockdown of its main regulator dynamin-related protein-1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1 suppression protected against cisplatin-induced cells injury by inhibiting mitochondrial dysfunction. Our results provide evidence that Drp1-depedent mitophagy has potential as renoprotective targets for the treatment of cisplatin-induced AKI. PMID:28423497

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

PubMed

Stafford-Smith, Mark; Podgoreanu, Mihai; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P; Hauser, Elizabeth H; Winn, Michelle P; Milano, Carmelo; Nielsen, Dahlia M; Smith, Mike; Morris, Richard; Newman, Mark F; Schwinn, Debra A

2005-03-01

Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

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

Sun, Yuan; Fujigaki, Yoshihide, E-mail: yf0516@hama-med.ac.j; Sakakima, Masanori

Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PTmore » cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.« less

Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

2017-07-01

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

[Left ventricular dysfunction measured in diabetic patients with chronic renal failure on continuous ambulatory peritoneal dialysis].

PubMed

Díaz-Arrieta, Gustavo; Mendoza-Hernández, María Elsa; Pacheco-Aranda, Erika; Rivas-Duro, Miguel; Robles-Parra, Héctor Manuel; Espinosa-Vázquez, Raúl Arturo; Hernández-Cabrera, Jorge

2010-01-01

In diabetic patients with chronic renal failure (CRF) treated with dialysis, the diastolic and systolic left ventricular dysfunction is frequent. The aim was to assess by echocardiography the prevalence of diastolic and systolic ventricular dysfunction in diabetic patients with CRF treated with continuous ambulatory peritoneal dialysis (CAPD). Sixty diabetic patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78 years). The left ventricular filling pattern (LVFP) as a diastolic function parameter and left ventricular ejection fraction (LVEF) as a systolic function parameter were measured by transthoracic echocardiography. Descriptive statistical analysis was used. 27 (45 %) patients were women and 33 (55 %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed. Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal or greater than 0.55. The prevalence of diastolic left ventricular dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction was 18.3%.

Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

NASA Astrophysics Data System (ADS)

Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

2014-06-01

We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate (UAER) and albumin to creatinine ratio. We conclude that phosphorylated Thr³⁰⁸-AKT regulates VEGF-A expression by interacting with either nephrin in glomeruli or Ang II in renal tubules. Antiangiogenic treatment improves renal injury and function in early experimental diabetes.

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

PubMed Central

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A. J.; Murphy, Michael P.

2011-01-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ∼2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. PMID:21159749

The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

PubMed

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A J; Murphy, Michael P; MacMillan-Crow, Lee Ann

2011-03-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

2009-02-01

Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Effects of palmitoylethanolamide and silymarin combination treatment in an animal model of kidney ischemia and reperfusion.

PubMed

Impellizzeri, Daniela; Bruschetta, Giuseppe; Ahmad, Akbar; Crupi, Rosalia; Siracusa, Rosalba; Di Paola, Rosanna; Paterniti, Irene; Prosdocimi, Marco; Esposito, Emanuela; Cuzzocrea, Salvatore

2015-09-05

The aim of this study was to investigate the efficacy of PEA+silymarin as a combination treatment in a mouse model of renal I/R and to verify whether PEA+silymarin could exert more potent effects compared to the single substances even if administered at lower doses. Mice were subjected to bilateral renal artery occlusion (30min) and reperfusion (6h) and received intraperitoneally silymarin (100, 30 and 10mg/kg) or PEA (1mg/kg) or PEA (1mg/kg)+silymarin (10mg/kg) 15min before release of clamps. Specific indicators of renal dysfunction, tubular injury, myeloperoxidase activity and malondialdehyde levels were measured. The nuclear factor κB pathway and apoptotic mechanisms were also investigated. The treatment with silymarin reduced kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress in a dose dependent manner. Furthermore, PEA+silymarin showed a significant potentiated effect. Therefore, NF-κB and apoptosis pathways were also significantly inhibited. Our results clearly demonstrate that PEA+silymarin treatment attenuated the degree of renal inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

Zinc deficiency during growth: influence on renal function and morphology.

PubMed

Tomat, Analía Lorena; Costa, María Angeles; Girgulsky, Luciana Carolina; Veiras, Luciana; Weisstaub, Adriana Ruth; Inserra, Felipe; Balaszczuk, Ana María; Arranz, Cristina Teresa

2007-03-13

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.

The Activation of Incompetence Schemas in Response to Negative Sexual Events in Heterosexual and Lesbian Women: The Moderator Role of Personality Traits and Dysfunctional Sexual Beliefs.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-01-01

Personality traits and dysfunctional sexual beliefs have been described as vulnerability factors for sexual dysfunction in women, and have also been proposed as dispositional variables for the activation of incompetence schemas in response to negative sexual events. However, no study has tested the role of personality traits and dysfunctional sexual beliefs in the activation of incompetence schemas. The current study aimed to assess the moderator role of neuroticism, extraversion, and dysfunctional sexual beliefs in the association between frequency of unsuccessful sexual episodes and activation of incompetence schemas in heterosexual and lesbian women. An online survey was completed by 1,121 women (831 heterosexual; 290 lesbian). Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Sexual Dysfunctional Beliefs Questionnaire-Female Version (SDBQ), and the Questionnaire of Cognitive Schemas Activated in Sexual Context (QCSASC). Findings indicate that neuroticism moderates the association between frequency of negative sexual events and activation of incompetence schemas in heterosexual women. Moreover, several sexual beliefs also act as moderators of the relationship between negative sexual episodes and the activation of cognitive schemas in both heterosexual and lesbian women. Overall, findings support the cognitive-emotional model of sexual dysfunctions, emphasizing the role of personality traits and dysfunctional sexual beliefs as facilitators of the activation of incompetence schemas in response to negative events in women.

Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement.

PubMed

Gholampour, Hanieh; Moezi, Leila; Shafaroodi, Hamed

2017-10-15

Renal ischemia/reperfusion (I/R) injury is strongly related to morbidity and mortality. Oxidative stress, inflammation, and apoptosis play key roles in renal dysfunction following renal I/R. Aripiprazole is an atypical antipsychotic which used for the treatment of schizophrenia and bipolar disorder. Recent studies have reported aripiprazole as displaying certain anti-inflammatory effects. Regarding the underlying mechanisms of renal ischemia-reperfusion, therefore, nephroprotective effects might be predicted to be seen with aripiprazole. I/R injury was induced by bilateral clamping of the renal pedicles (45min) followed by reperfusion (24h). The mechanism of aripiprazole-mediated nephroprotection was explored by a combined use of aripiprazole and L-NAME (non-selective nitric oxide synthase inhibitor). Animals were given aripiprazole (2.5, 5, 10 and 20mg/kg) intraperitoneally, 30min before ischemia. L-NAME was administered before the aripiprazole injection. Serum creatinine and blood urea nitrogen were assessed after 24h of reperfusion. Serum levels of malondialdehyde (MDA), TNF-α and IL-1β were measured for rats treated with aripiprazole. The extent of necrosis was measured by the stereology method. Ischemia/reperfusion caused significant renal dysfunction and marked renal injury. Aripiprazole reduced creatinine and blood urea nitrogen. Serum levels of MDA, IL-1β and TNF-α were significantly lower in the aripiprazole group. Aripiprazole treatment also decreased the volume of kidney necrosis. The administration of L-NAME reversed the renoprotective effect of aripiprazole on BUN and creatinine, but enhanced the anti-necrotic effect of aripiprazole. The results show that a single dose of aripiprazole significantly improved renal function following ischemia/reperfusion injury - probably through the involvement of nitric oxide. Copyright © 2017 Elsevier B.V. All rights reserved.

EET Enhances Renal Function in Obese Mice Resulting in Restoration of Mfn1/2 -HO-1 Signaling, and Decrease in Hypertension through Inhibition of Sodium Chloride Co-Transporter.

PubMed

Schragenheim, Joseph; Bellner, Lars; Cao, Jian; Singh, Shailendra P; Bamshad, David; McClung, John A; Maayan, Omri; Meissner, Aliza; Grant, Ilana; Stier, Charles T; Abraham, Nader G

2018-05-19

We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity-induced renal dysfunction by improving sodium excretion, reducing the sodium-chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1α dependent mice. EET-agonist treatment normalized glucose metabolism, renal ENaC and NCC protein expression, urinary sodium excretion and blood pressure in obese (db/db) mice. A marked improvement in mitochondrial integrity, thermogenic genes, and PGC-1α-HO-1-adiponectin signaling occurred. Knockout of PGC-1α in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in sodium excretion, elevation of blood pressure and an increase in the pro-inflammatory adipokine nephroblastoma overexpressed gene (NOV). In the elucidation of the effects of EET on peri-renal adipose tissue, EET increased adiponectin, mitochondrial integrity, thermogenic genes and decreased NOV, i.e. "Browning' peri-renal adipose phenotype that occurs under high fat diets. Taken together, these data demonstrate a critical role of an EET agonist in the restoration of healthy adipose tissue with reduced release of inflammatory molecules, such as AngII and NOV, thereby preventing their detrimental impact on sodium absorption and NCC levels and the development of obesity-induced renal dysfunction. Copyright © 2018. Published by Elsevier Inc.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

PubMed

Ishihara, Hiroki; Kondo, Tsunenori; Fukuda, Hironori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2017-12-01

The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point - pre-treatment eGFR)/pre-treatment eGFR] × 100. ΔeGFR was compared between SU- and SO users using a mixed-effects model for repeated measures data with two or greater. Additionally, predictors for ΔeGFR ≤ -10% at 6 months after therapy initiation were evaluated using multivariate logistic regression analysis. Throughout the 24 months after therapy initiation, ΔeGFR was negatively greater in SU users, compared with that in SO users (P < 0.0001). In SU users, renal dysfunction was observed regardless of pre-treatment chronic kidney disease (CKD) status, whereas the magnitude of renal dysfunction was milder in SO users. In SO users without pre-treatment CKD, renal function did not significantly deteriorate. Moreover, ΔeGFR ≤ -10% was more frequently observed in SU users after 3 months (P = 0.0121) and 6 months (P = 0.0009). Finally, SU usage was an independent predictor for ΔeGFR ≤ -10% at 6 months (odds ratio 8.87, P = 0.0053), along with pre-treatment hypertension (odds ratio 4.69, P = 00072). Deterioration of renal function was stronger with SU than SO. During SU therapy, renal function should be monitored and pre-treatment kidney function should be taken into consideration for therapy selection. © The Author 2017. Published by Oxford University Press.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

PubMed

Li, Yizhun; Yang, Liangle; Wang, Hao; Jiang, Haijing; Qiu, Gaokun; Liu, Yiyi; Xiao, Yang; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin

2018-03-01

Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m 2 /year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

PubMed

Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan

2010-09-01

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

The kidney in congestive heart failure: 'are natriuresis, sodium, and diuretics really the good, the bad and the ugly?'.

PubMed

Verbrugge, Frederik H; Dupont, Matthias; Steels, Paul; Grieten, Lars; Swennen, Quirine; Tang, W H Wilson; Mullens, Wilfried

2014-02-01

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

PubMed

Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

2014-11-01

The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Modeling and Simulation for Estimating the Influence of Renal Dysfunction on the Hypouricemic Effect of Febuxostat in Hyperuricemic Patients Due to Overproduction or Underexcretion of Uric Acid.

PubMed

Hirai, Toshinori; Kimura, Toshimi; Echizen, Hirotoshi

2016-01-01

Whether renal dysfunction influences the hypouricemic effect of febuxostat, a xanthine oxidase (XO) inhibitor, in patients with hyperuricemia due to overproduction or underexcretion of uric acid (UA) remains unclear. We aimed to address this question with a modeling and simulation approach. The pharmacokinetics (PK) of febuxostat were analyzed using data from the literature. A kinetic model of UA was retrieved from a previous human study. Renal UA clearance was estimated as a function of creatinine clearance (CLcr) but non-renal UA clearance was assumed constant. A reversible inhibition model for bovine XO was adopted. Integrating these kinetic formulas, we developed a PK-pharmacodynamic (PK-PD) model for estimating the time course of the hypouricemic effect of febuxostat as a function of baseline UA level, febuxostat dose, treatment duration, body weight, and CLcr. Using the Monte Carlo simulation method, we examined the performance of the model by comparing predicted UA levels with those reported in the literature. We also modified the models for application to hyperuricemia due to UA overproduction or underexcretion. Thirty-nine data sets comprising 735 volunteers or patients were retrieved from the literature. A good correlation was observed between the hypouricemic effects of febuxostat estimated by our PK-PD model and those reported in the articles (observed) (r=0.89, p<0.001). The hypouricemic effect was estimated to be augmented in patients with renal dysfunction irrespective of the etiology of hyperuricemia. While validation in clinical studies is needed, the modeling and simulation approach may be useful for individualizing febuxostat doses in patients with various clinical characteristics.

Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula.

PubMed

McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi; Squire, Iain; Komajda, Michel; Bayes-Genis, Antoni; Gotsman, Israel; Whalley, Gillian; Earle, Nikki; Poppe, Katrina K; Doughty, Robert N

2012-05-01

Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146-155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation.

PubMed

Virzì, Grazia Maria; Clementi, Anna; Brocca, Alessandra; de Cal, Massimo; Marcante, Stefano; Ronco, Claudio

2016-01-01

Cardiorenal Syndrome Type 5 (CRS Type 5) is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5. We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN) criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA). Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs) and cell death levels were evaluated. Plasma cytokines levels were measured as well. Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA), while 54.5% of patients showed high endotoxin activity (positive EAA). RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA. Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity. © 2017 S. Karger AG, Basel.

Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

PubMed

Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

2017-07-01

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess. © 2017 American Heart Association, Inc.

Pregnancy in women with renal disease. Yes or no?

PubMed Central

Edipidis, K

2011-01-01

Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients. PMID:21897751

Impact of impaired renal function on the pharmacokinetics of the antiepileptic drug lacosamide.

PubMed

Cawello, Willi; Fuhr, Uwe; Hering, Ursula; Maatouk, Haidar; Halabi, Atef

2013-10-01

The antiepileptic drug lacosamide is eliminated predominantly via the kidneys. Therefore, an evaluation of the impact of renal impairment on its pharmacokinetic profile is an important component of its safety assessment. The objective of this study was to evaluate the pharmacokinetic profile of lacosamide among individuals with renal impairment (mild, moderate, or severe) and among patients with end-stage renal disease (ESRD), including those on hemodialysis. This was an open-label, Phase I trial. The pharmacokinetics of a single oral 100-mg lacosamide dose were evaluated in five groups of participants: healthy controls, patients with mild, moderate, or severe renal impairment, and patients with ESRD (with and without hemodialysis). Forty participants completed the trial, eight in each group. In healthy volunteers, renal clearance accounted for approximately 30 % of total body clearance [geometric mean 0.5897 l/h (coefficient of variation 37.9 %) vs 2.13 l/h (20.8 %)]. With severe renal impairment, renal clearance was approximately 11 % of total body clearance [0.1428 l/h (31.8 %) vs 1.34 l/h (26.9 %)]. Terminal half-life and systemic exposure were increased with renal impairment, while total body clearance, renal clearance, and urinary excretion were decreased. Strong positive correlations between creatinine clearance, renal clearance, and urinary excretion were observed. Among patients with ESRD, approximately 50 % of lacosamide was cleared from systemic circulation by 4-h hemodialysis. In patients with essentially no renal clearance, nonrenal clearance was still present (1.1 l/h). Lacosamide was well tolerated by healthy volunteers and patients. In patients with mild-to-moderate renal impairment, lacosamide dose adjustment is not necessary, because total body clearance decreased by only approximately 20 %. Dose adjustment, however, is required for patients with severe renal impairment. Hemodialysis removes approximately 50 % of lacosamide from plasma; therefore, dose supplementation following hemodialysis should be considered.

Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

PubMed

Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

2018-01-01

Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Diffuse Interstitial Brain Edema in Patients With End-Stage Renal Disease Undergoing Hemodialysis: A Tract-Based Spatial Statistics Study

PubMed Central

Kong, Xiang; Wen, Ji-qiu; Qi, Rong-feng; Luo, Song; Zhong, Jian-hui; Chen, Hui-juan; Ji, Gong-jun; Lu, Guang Ming; Zhang, Long Jiang

2014-01-01

Abstract To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P < 0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P < 0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P > 0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes. PMID:25526483

Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

PubMed

Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

2017-07-10

BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

MicroRNA-29a Promotion of Nephrin Acetylation Ameliorates Hyperglycemia-Induced Podocyte Dysfunction

PubMed Central

Lin, Chun-Liang; Lee, Pei-Hsien; Hsu, Yung-Chien; Lei, Chen-Chou; Ko, Jih-Yang; Chuang, Pei-Chin; Huang, Yu-Ting; Wang, Shao-Yu; Wu, Shin-Long; Chen, Yu-Shan; Chiang, Wen-Chih; Reiser, Jochen

2014-01-01

Podocyte dysfunction is a detrimental feature in diabetic nephropathy, with loss of nephrin integrity contributing to diabetic podocytopathy. MicroRNAs (miRs) reportedly modulate the hyperglycemia-induced perturbation of renal tissue homeostasis. This study investigated whether regulation of histone deacetylase (HDAC) actions and nephrin acetylation by miR-29 contributes to podocyte homeostasis and renal function in diabetic kidneys. Hyperglycemia accelerated podocyte injury and reduced nephrin, acetylated nephrin, and miR-29a levels in primary renal glomeruli from streptozotocin-induced diabetic mice. Diabetic miR-29a transgenic mice had better nephrin levels, podocyte viability, and renal function and less glomerular fibrosis and inflammation reaction compared with diabetic wild-type mice. Overexpression of miR-29a attenuated the promotion of HDAC4 signaling, nephrin ubiquitination, and urinary nephrin excretion associated with diabetes and restored nephrin acetylation. Knockdown of miR-29a by antisense oligonucleotides promoted HDAC4 action, nephrin loss, podocyte apoptosis, and proteinuria in nondiabetic mice. In vitro, interruption of HDAC4 signaling alleviated the high glucose–induced apoptosis and inhibition of nephrin acetylation in podocyte cultures. Furthermore, HDAC4 interference increased the acetylation status of histone H3 at lysine 9 (H3K9Ac), the enrichment of H3K9Ac in miR-29a proximal promoter, and miR-29a transcription in high glucose–stressed podocytes. In conclusion, hyperglycemia impairs miR-29a signaling to intensify HDAC4 actions that contribute to podocyte protein deacetylation and degradation as well as renal dysfunction. HDAC4, via epigenetic H3K9 hypoacetylation, reduces miR-29a transcription. The renoprotective effects of miR-29a in diabetes-induced loss of podocyte integrity and renal homeostasis highlights the importance of post-translational acetylation reactions in podocyte microenvironments. Increasing miR-29a action may protect against diabetic podocytopathy. PMID:24578127

Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy.

PubMed

Puliyanda, Dechu P; Amet, Nurmamet; Dhawan, Archana; Hilo, Lara; Radha, Raju K; Bunnapradist, Suphamai; Czer, Lawrence; Martin, Paul; Jordan, Stanley; Toyoda, Mieko

2006-01-01

BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment.

PubMed

Saag, Kenneth G; Whelton, Andrew; Becker, Michael A; MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo

2016-08-01

Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. © 2016, American College of Rheumatology.

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery.

PubMed

Merath, Katiuscha; Chen, Qinyu; Bagante, Fabio; Akgul, Ozgur; Idrees, Jay J; Dillhoff, Mary; Cloyd, Jordan M; Pawlik, Timothy M

2018-06-18

Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7). Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response.

PubMed

Toorians, A W; Janssen, E; Laan, E; Gooren, L J; Giltay, E J; Oe, P L; Donker, A J; Everaerd, W

1997-12-01

Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psychophysiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and 'Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pharmacokinetics of Diclofenac and Hydroxypropyl‐β‐Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD‐Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment

PubMed Central

Hamilton, Douglas A.; Ernst, Cynthia C.; Kramer, William G.; Madden, Donna; Lang, Eric; Liao, Edward; Lacouture, Peter G.; Ramaiya, Atulkumar

2017-01-01

Abstract Given their established analgesic properties, nonsteroidal anti‐inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl‐β‐cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD‐diclofenac; and (2) the PK of HPβCD following administration of HPβCD‐diclofenac and intravenous itraconazole formulated with HPβCD in healthy adults. Diclofenac clearance (CL) and volume of distribution (Vz) tended to increase with decreasing renal function (moderate insufficiency versus mild insufficiency or healthy controls). Regression analysis demonstrated a significant relationship between Vz (but not CL or elimination half‐life, t½) and renal function. HPβCD CL was significantly decreased in subjects with renal insufficiency, with a corresponding increase in t½. There were no significant differences in diclofenac or HPβCD PK in subjects with mild hepatic impairment versus healthy subjects. Exposure to HPβCD in healthy subjects following HPβCD‐diclofenac administration was ∼12% of that with intravenous itraconazole, after adjusting for dosing schedule and predicted accumulation (<5% without adjustment). With respect to PK properties, these results suggest that HPβCD‐diclofenac might be administered to patients with mild or moderate renal insufficiency or mild hepatic impairment without dose adjustment (NCT00805090). PMID:29197175

Reduction of severe mitral regurgitation with the MitraClip system improves renal function in two patients presenting with acute kidney injury and progressive renal failure due to cardio renal syndrome.

PubMed

Asdonk, T; Nickenig, G; Hammerstingl, C

2014-10-01

Mitral regurgitation (MR) is a frequent valve disorder in elderly patients, often accompanied by multiple comorbidities such as renal impairment. In these patients percutaneous mitral valve (MV) repair has become an established treatment option but the role of MR on renal dysfunction is not yet well defined. We here report on two cases presenting with severe MR and progressive renal failure caused by cardio renal syndrome, in which percutaneous MV treatment with the MitraClip system significantly improved renal function. These findings suggest that interventional MV repair can prevent progression of renal deterioration in patients suffering from combined advanced heart and renal failure. Further clinical studies are necessary to support our finding and to answer the question whether optimizing renal function by implantation of the MitraClip device is also of prognostic relevance in these patients. © 2014 Wiley Periodicals, Inc.

A review of dietary supplement-induced renal dysfunction.

PubMed

Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

2007-07-01

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

Improved mitochondrial function underlies the protective effect of pirfenidone against tubulointerstitial fibrosis in 5/6 nephrectomized rats.

PubMed

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells.

Improved Mitochondrial Function Underlies the Protective Effect of Pirfenidone against Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats

PubMed Central

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells. PMID:24349535

Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction.

PubMed

Chakrabarti, S; Syme, H M; Brown, C A; Elliott, J

2013-01-01

Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

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

PubMed Central

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

2016-01-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. PMID:27216597

A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

PubMed

Rabinowitz, Amanda R; Arnett, Peter A

2009-09-01

Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

Detrimental role of humoral signalling in cardio-renal cross-talk.

PubMed

Cantaluppi, Vincenzo; Dellepiane, Sergio; Quercia, Alessandro D; Ferrario, Silvia

2014-01-22

In critically ill patients, any acute organ injury is associated with a sudden change of circulating factors that may play a role in distant organ dysfunction through a complex cross-talk. In this issue, Virzì and colleagues discuss the relevance of humoral signalling between heart and kidney, focusing on type 1 and type 3 cardio-renal syndrome. We herein review the mechanisms of heart-kidney cross-talk, discussing the role of circulating detrimental mediators in the pathogenetic mechanisms of cardio-renal syndrome.

Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.

PubMed

Shima, Takeru; Matsui, Takashi; Jesmin, Subrina; Okamoto, Masahiro; Soya, Mariko; Inoue, Koshiro; Liu, Yu-Fan; Torres-Aleman, Ignacio; McEwen, Bruce S; Soya, Hideaki

2017-03-01

Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals. The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated. OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats. Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

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

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16more » weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.« less

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.

ASSOCIATIONS OF MACRO- AND MICROVASCULAR ENDOTHELIAL DYSFUNCTION WITH SUBCLINICAL VENTRICULAR DYSFUNCTION IN END-STAGE RENAL DISEASE

PubMed Central

Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita; Mills, Claire; Donovan, Catherine; Beussink, Lauren; Scherzer, Rebecca; Ganz, Peter; Shah, Sanjiv J

2016-01-01

Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. In order to evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral (VTI) of hyperemic blood flow following cuff deflation. Impaired FMD was associated with higher LV mass, independently of age and blood pressure: per two-fold lower FMD, LV mass was 4.1% higher (95%CI [0.49, 7.7], p=0.03). After adjustment for demographics, blood pressure, comorbidities and medications, a two-fold lower VTI was associated with 9.5% higher E/e’ ratio (95% CI [1.0, 16], p=0.03) and 6.7% lower absolute RV longitudinal strain (95% CI [2.0, 12], p=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well-controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. PMID:27550915

Non-Exertional Heatstroke: A Case Report and Review of the Literature

PubMed Central

Mozzini, Chiara; Xotta, Giovanni; Garbin, Ulisse; Pasini, Anna Maria Fratta; Cominacini, Luciano

2017-01-01

Patient: Female, 41 Final Diagnosis: Heatstroke Symptoms: Coma Medication: — Clinical Procedure: Intensive Care Unit-Internal Medicine Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Heatstroke (HS) is a life-threatening condition characterized by an elevation of the core body temperature above 40°C, central nervous system dysfunction, and possible multi-organ failure. HS can trigger systemic inflammation, disseminated intravascular coagulation (DIC), rhabdomyolysis, cerebral edema and seizures, pulmonary edema, heart dysfunctions, and renal and hepatic failure. Case Report: We report the case of a 41-year-old Romanian woman with a history of alcoholism who developed HS after arriving by bus in Verona, Italy in June 2016. The patient developed consecutive multi-organ dysfunction, including liver and renal failure, rhabdomyolysis, DIC, and arrhythmia. The patient was successfully treated with conservative measures. After 17 days, she recovered completely. Conclusions: The exact mechanism of HS-related multiple organ dysfunction is not completely understood and its pathogenesis is complex. It involves inflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Development of a model in which chronic alcohol abuse alters oxidative, inflammatory, and ER stress response could also be a conceivable solution to the positive prognosis of severe HS patients, in which liver failure has a prominent role. PMID:28974669

Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction.

PubMed

Cox, Zachary L; Calcutt, Marion W; Morrison, Thomas B; Akers, Wendell S; Davis, Mary Beth; Lenihan, Daniel J

2013-09-01

To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction We retrospectively identified patients with stage D HF at a single medical center on continuous milrinonein fusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl <30 mL/min), and group 4 (intermittent hemodialysis). Retrospective chart review was performed to quantify the post milrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation. A total of 29 patients were identified: group 1 (n=14), group 2 (n=10), group 3(n=3), and group 4 (n = 2). The mean infusion rate (0.391+0.08 mg/kg/min) did not differ between groups (P=0.14). The mean milrinone concentration was 451+243 ng/mL in group 1, 591+293 ng/mL in group 2, 1575+962 ng/mL in group 3, and 6252+4409 ng/mL in group 4 (P<0.05 compared to groups 1). There was no difference in post milrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 post milrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients. Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.

ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock.

PubMed

Coquerel, David; Chagnon, Frédéric; Sainsily, Xavier; Dumont, Lauralyne; Murza, Alexandre; Côté, Jérôme; Dumaine, Robert; Sarret, Philippe; Marsault, Éric; Salvail, Dany; Auger-Messier, Mannix; Lesur, Olivier

2017-11-01

Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown. Interventional study in a rat model of septic shock (128 adult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function. Experiments were performed in a tertiary care University-based research institute. Polymicrobial sepsis-induced cardiac dysfunction was produced by cecal ligation puncture to assess hemodynamic efficacy, cardioprotection, and biomechanics under acute or continuous infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 µg/kg/hr, respectively) versus normal saline. Apelinergic agonists improved 72-hour survival after sepsis induction, with ELA providing the best clinical outcome after 24 hours. Apelinergic agonist infusion counteracted cecal ligation puncture-induced myocardial dysfunction by improving left ventricular pressure-volume relationship. ELA-treated cecal ligation puncture rats were the only group to 1) display a significant improvement in left ventricular filling as shown by increased E-wave velocity and left ventricular end-diastolic volume, 2) exhibit a higher plasma volume, and 3) limit kidney injury and free-water clearance. These beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a distinctive regulation of pituitary vasopressin release. Activation of the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and survival after cecal ligation puncture-induced sepsis. However, ELA proved better than Apelin-13 by improving fluid homeostasis, cardiovascular hemodynamics recovery, and limiting kidney dysfunction in a vasopressinergic-dependent manner.

zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function

PubMed Central

Herzog, Christian; Yang, Cheng; Holmes, Alexandrea

2012-01-01

Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI. PMID:22896037

Hyperosmolarity induced by high glucose promotes senescence in human glomerular mesangial cells.

PubMed

del Nogal, Maria; Troyano, Nuria; Calleros, Laura; Griera, Mercedes; Rodriguez-Puyol, Manuel; Rodriguez-Puyol, Diego; Ruiz-Torres, María P

2014-09-01

Hyperglycemia is involved in the diabetic complication of different organs and can elevate serum osmolarity. Here, we tested whether hyperosmolarity promoted by high glucose levels induces cellular senescence in renal cells. We treated Wistar rats with streptozotocin to induce diabetes or with consecutive daily injections of mannitol to increase serum osmolarity and analyzed p53 and p16 genes in renal cortex by immunohistochemistry. Both diabetic and mannitol treated rats showed a significant increase in serum osmolarity, without significant signs of renal dysfunction, but associated with increased staining for p53 and p16 in the renal cortex. An increase in p53 and p16 expression was also found in renal cortex slices and glomeruli isolated from healthy rats, which were later treated with 30 mM glucose or mannitol. Intracellular mechanisms involved were analyzed in cultured human glomerular mesangial cells treated with 30 mM glucose or mannitol. After treatments, cells showed increased p53, p21 and p16 expression and elevated senescence-associated β-galactosidase activity. Senescence was prevented when myo-inositol was added before treatment. High glucose or mannitol induced constitutive activation of Ras and ERK pathways which, in turn, were activated by oxidative stress. In summary, hyperosmolarity induced renal senescence, particularly in glomerular mesangial cells, increasing oxidative stress, which constitutively activated Ras-ERK 1/2 pathway. Cellular senescence could contribute to the organ dysfunction associated with diabetes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

PubMed

Marcovecchio, M L; de Giorgis, T; Di Giovanni, I; Chiavaroli, V; Chiarelli, F; Mohn, A

2017-06-01

To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[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.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

PubMed

Ip, Stephen; Hussaini, Trana; Daulat, Aliya; Partovi, Nilufar; Erb, Siegfried R; Yoshida, Eric M; Marquez, Vladimir

2017-01-01

Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. To examine the risk factors in the development of CRF in these patients. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Practice-Based Recommendations from the American Society of Transplantation Liver and Intestine Community of Practice

PubMed Central

Levitsky, J.; O’Leary, J.G.; Asrani, S.; Sharma, P.; Fung, J.; Wiseman, A.; Niemann, C.U.

2016-01-01

Acute and chronic kidney disease after liver transplantation is common and results in significant morbidity and mortality. The introduction of MELD has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplants performed. Thus, kidney dysfunction in this population is typically multifactorial and related to pre-existing conditions, pre-transplant renal injury, peri-operative events, and post-transplant nephrotoxic immunosuppressive therapies. The management of kidney disease following liver transplantation is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Also, immunological factors such as antibody-mediated rejection have become of greater interest given the rising liver-kidney transplant population. Therefore this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations. PMID:26932352

Emergency management of renal and genitourinary trauma: best practices update [digest].

PubMed

Bryant, Whitney K; Shewakramani, Sanjay; Zaurova, Milana

2017-08-22

In up to 10% of patients who experience abdominal trauma, renal and urogenital systems will be involved. In polytrauma patients with other potentially life-threatening injuries, renal and genitourinary trauma may be overlooked initially, but a delayed or missed diagnosis of these injuries may result in preventable complications. This review provides a best-practice approach to the diagnosis and management of renal and genitourinary injuries, with an emphasis on the systematic approach needed to identify subtle injuries and avoid long-term urinary sequelae such as hypertension, incontinence, erectile dysfunction, chronic kidney disease, and nephrectomy. [Points & Pearls is a digest of Emergency Medicine Practice.].

IgG4-related tubulointerstitial nephritis: A prospective analysis.

PubMed

Nada, Ritambhra; Ramachandran, Raja; Kumar, Ashwani; Rathi, Manish; Rawat, Amit; Joshi, Kusum; Kohli, Harbir Singh; Gupta, Krishan Lal

2016-07-01

Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease. IgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

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.

Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats.

PubMed

Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton

2013-11-01

Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.

Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice

PubMed Central

Billet, Sandrine; Bardin, Sabine; Verp, Sonia; Baudrie, Véronique; Michaud, Annie; Conchon, Sophie; Muffat-Joly, Martine; Escoubet, Brigitte; Souil, Evelyne; Hamard, Ghislaine; Bernstein, Kenneth E.; Gasc, Jean Marie; Elghozi, Jean-Luc; Corvol, Pierre; Clauser, Eric

2007-01-01

The role of the renin-angiotensin system has been investigated by overexpression or inactivation of its different genes in animals. However, there is no data concerning the effect of the constitutive activation of any component of the system. A knockin mouse model has been constructed with a gain-of-function mutant of the Ang II receptor, type 1A (AT1A), associating a constitutively activating mutation (N111S) with a C-terminal deletion, which impairs receptor internalization and desensitization. In vivo consequences of this mutant receptor expression in homozygous mice recapitulate its in vitro characteristics: the pressor response is more sensitive to Ang II and longer lasting. These mice present with a moderate (~20 mmHg) and stable increase in BP. They also develop early and progressive renal fibrosis and cardiac fibrosis and diastolic dysfunction. However, there was no overt cardiac hypertrophy. The hormonal parameters (low-renin and inappropriately normal aldosterone productions) mimic those of low-renin human hypertension. This new model reveals that a constitutive activation of AT1A leads to cardiac and renal fibrosis in spite of a modest effect on BP and will be useful for investigating the role of Ang II in target organs in a model similar to some forms of human hypertension. PMID:17607364

Impact of Reduced Renal Function on the Glucose-Lowering Effects of Luseogliflozin, a Selective SGLT2 Inhibitor, Assessed by Continuous Glucose Monitoring in Japanese Patients with Type 2 Diabetes Mellitus.

PubMed

Jinnouchi, Hideaki; Nozaki, Kazunari; Watase, Hirotaka; Omiya, Hirohisa; Sakai, Soichi; Samukawa, Yoshishige

2016-03-01

We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin. In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0-10.0%] and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m(2) were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m(2)): normal (≥90; n = 13; normal group), normal-to-mildly reduced renal function (≥75 to <90; n = 12; normal-mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild-moderate group). The mean [95% confidence interval (CI)] placebo-subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was -24.39 (-32.53, -16.26), -28.28 (-39.35, -17.22), and -11.53 (-23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was -26.9 (-46.9, -6.9), -38.1 (-59.6, -16.6), and 1.5 (-25.5, 28.4) in the normal, normal-mild, and mild-moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal-mild (121.0 vs. 97.9), and mild-moderate (104.0 vs. 91.1) groups. This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function. JapicCTI-142548. Taisho Pharmaceutical Co., Ltd.

[Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of duodenal ulcer perforation: a case report].

PubMed

Enokida, Kohei; Kikuyama, Masataka; Kurokami, Takafumi; Shirane, Naofumi; Aoyama, Haruna; Aoyama, Hiroyuki; Sato, Tatsunori; Taki, Yusuke

2015-10-01

A 75-year-old man with vomiting and right abdominal pain was admitted to the Department of Surgery in our hospital. With a diagnosis of perforated duodenal ulcer, he was treated conservatively. On the day 8 of hospitalization, his general condition worsened and he underwent surgery. During operation, the perforated duodenal ulcer and paraduodenal fluid collection was observed, and percutaneous drainage was accordingly established. After this procedure, renal dysfunction was exacerbated and he was transferred to our department for endoscopic treatment. On day 28 of hospitalization, nasobiliary and nasopancreatic drainage was administered. Renal dysfunction gradually improved, and healing of the perforated duodenal ulcer was recognized on day 93. On day 112, the patient was discharged.

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

Long-term outcomes and management of the heart transplant recipient.

PubMed

McCartney, Sharon L; Patel, Chetan; Del Rio, J Mauricio

2017-06-01

Cardiac transplantation remains the gold standard in the treatment of advanced heart failure. With advances in immunosuppression, long-term outcomes continue to improve despite older and higher risk recipients. The median survival of the adult after heart transplantation is currently 10.7 years. While early graft failure and multiorgan system dysfunction are the most important causes of early mortality, malignancy, rejection, infection, and cardiac allograft vasculopathy contribute to late mortality. Chronic renal dysfunction is common after heart transplantation and occurs in up to 68% of patients by year 10, with 6.2% of patients requiring dialysis and 3.7% undergoing renal transplant. Functional outcomes after heart transplantation remain an area for improvement, with only 26% of patients working at 1-year post-transplantation, and are likely related to the high incidence of depression after cardiac transplantation. Areas of future research include understanding and managing primary graft dysfunction and reducing immunosuppression-related complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neutrophil Gelatinase Associated Lipocalin (NGAL) - a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

PubMed

Firu, S G; Streba, C T; Firu, D; Tache, D E; Rogoveanu, I

2015-01-01

Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. We have searched through current literature and analyzed all significant full text articles on this topic. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

PubMed

Takada, Hideaki; Kobayashi, Takashi; Ogawa, Kohei; Miyata, Hitomi; Sawada, Atsuro; Akamatsu, Shusuke; Negoro, Hiromitsu; Saito, Ryoichi; Terada, Naoki; Yamasaki, Toshinari; Inoue, Takahiro; Teramoto, Yuki; Shibuya, Shinsuke; Haga, Hironori; Kaido, Toshimi; Uemoto, Shinji; Ogawa, Osamu

2017-08-01

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

PubMed Central

Atwa, Ahmed; Hegazy, Rehab; Mohsen, Rania; Yassin, Neamat; Kenawy, Sanaa

2017-01-01

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS). AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats. MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed. RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment. CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties. PMID:29362613

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

PubMed Central

Askari, Hassan; Seifi, Behjat; Kadkhodaee, Mehri; Sanadgol, Nima; Elshiekh, Mohammed; Ranjbaran, Mina; Ahghari, Parisa

2018-01-01

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney. PMID:29383015

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

PubMed

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

PubMed Central

Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

2014-01-01

Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. PMID:24651118

Role of transforming growth factor-β2 in, and apossible transforming growth factor-β2 gene polymorphism as a marker of, renal dysfunction in essential hypertension: A study in Turkish patients

PubMed Central

Bicik, Zerrin; Gönen, Sevim; Bahçebasi, Talat; Reis, Kadriye; Arinsoy, Turgay; Sindel, Sükrü

2005-01-01

Background: Many studies have shown that transforming growth factor(TGF)-β has a major role in renal scarring in many renal diseases and hypertension. Objectives: The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-β2 (a more sensitive isoform for glomeruli than TGF-β1), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-β2 levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-β2 gene polymorphism and essential hypertension. Methods: This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged ≥18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage lI hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-β2 and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-β2 primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-β2 kit. Results: Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-β2 levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-β2 level did not change significantly. Three patients, all of whom were found to have TGF-β2 gene mutations, had increased urinary TGF-β2 levels despite good blood pressure control. Conclusions: The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-β2 levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-β2 locus should be kept in mind. PMID:24672129

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida

PubMed Central

Routh, Jonathan C.; Cheng, Earl Y.; Austin, J. Christopher; Baum, Michelle A.; Gargollo, Patricio C.; Grady, Richard W.; Herron, Adrienne R.; Kim, Steven S.; King, Shelly J.; Koh, Chester J.; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S.; Smith, Kathryn A.; Tanaka, Stacy T.; Thibadeau, Judy K.; Walker, William O.; Wallis, M. Chad; Wiener, John S.; Joseph, David B.

2016-01-01

Purpose Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. Materials and Methods In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. Results An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. Conclusions The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. PMID:27475969

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PubMed

Routh, Jonathan C; Cheng, Earl Y; Austin, J Christopher; Baum, Michelle A; Gargollo, Patricio C; Grady, Richard W; Herron, Adrienne R; Kim, Steven S; King, Shelly J; Koh, Chester J; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S; Smith, Kathryn A; Tanaka, Stacy T; Thibadeau, Judy K; Walker, William O; Wallis, M Chad; Wiener, John S; Joseph, David B

2016-12-01

Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Atgl gene deletion predisposes to proximal tubule damage by impairing the fatty acid metabolism

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

Chen, Wen; Zhang, Qiong; Cheng, Shiwu

Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl{sup −/−} mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr). In vitro experiments indicated that inhibitionmore » of ATGL in proximal tubular cell line HK-2 promoted intracellular lipid deposition, reactive oxygen species (ROS) accumulation and cell apoptosis. Both in vitro and in vivo experiments showed that ATGL inhibition decreased the renal peroxisome proliferator-activated receptorα(PPARα) expression, which implied the suppressed lipid metabolism. The antioxidant N-acetylcysteine (NAC) could partially reverse the effect of ROS accumulation and cell apoptosis, but could not restore the PPARαdecrease. These data raise the possibility that ATGL deficiency could impair the renal fatty acid metabolism though inhibiting PPARαexpression, which may lead to lipid deposition and cell apoptosis of PCT, and finally contribute to the renal fibrosis and dysfunction. - Highlights: • Atgl{sup −/−} mice develop tubulointerstitial damage and renal dysfunction. • ATGL deficiency results in lipid accumulation and apoptosis of proximal tubular cells. • ROS scavenger alleviates the ATGL-knockdown mediated lipid accumulation and apoptosis. • PPARαdown-regulation is the reason of ROS elevating in ATGL-knockdown HK-2 cells.« less

How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study

PubMed Central

Isambert, Nicolas; Delord, Jean Pierre; Tourani, Jean Marc; Fumoleau, Pierre; Ravaud, Alain; Pinel, Marie Claire; Petain, Aurelie; Nguyen, Thierry; Nguyen, Laurent

2014-01-01

Aims Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL. Methods VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min−1) and were compared with a control cohort of patients (CLcr > 60 ml min−1). Results Thirty-three patients (46–86 years) were treated, 13 in group 1 (40 ml min−1 ≤ CLcr ≤ 60 ml min−1) and 20 in group 2 (20 ml min−1 ≤ CLcr < 40 ml min−1). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m−2 and 250 mg m−2 in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min−1. Conclusion In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m−2 when CLcr is between 40 and 60 ml min−1 and 250 mg m−2 when CLcr is between 20 and <40 ml min−1. PMID:24283925

Complications of transplantation. Part 1: renal transplants.

PubMed

Khaja, Minhaj S; Matsumoto, Alan H; Saad, Wael E

2014-10-01

Vascular complications after solid-organ transplantation are not uncommon and may lead to graft dysfunction and ultimately graft loss. A thorough understanding of the surgical anatomy, etiologies, and types of vascular complications, their presentation, and the options for management are important for managing these complex patients. This article reviews the basic surgical anatomy, vascular complications, and endovascular management options of vascular complications in patients with renal transplants.

Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.

PubMed

Bratoeva, Kameliya; Stoyanov, George S; Merdzhanova, Albena; Radanova, Mariya

2017-11-07

Introduction International studies show an increased incidence of chronic kidney disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the major components of MS - obesity, insulin resistance, dyslipidemia, and hypertension - are linked to renal damage through the systemic release of several pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and generalized oxidative stress. The aim of the present study was to investigate the extent of kidney impairment and manifestations of dysfunction in rats with fructose-induced MS. Methods We used a model of high-fructose diet in male Wistar rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16 weeks. The experimental animals were divided into two groups: control and high-fructose drinking (HFD). Serum samples were obtained from both groups for laboratory study, and the kidneys were extracted for observation via light microscopy examination. Results All HFD rats developed obesity, hyperglycemia, hypertriglyceridemia, increased levels of CRP and UA (when compared to the control group), and oxidative stress with high levels of malondialdehyde and low levels of reduced glutathione. The kidneys of the HFD group revealed a significant increase in kidney weight in the absence of evidence of renal dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and the walls of the large caliber blood vessels, early-stage atherosclerosis with visible ruptures and scarring, hydropic change (vacuolar degeneration) in the epithelial cells covering the proximal tubules, and increased eosinophilia in the distant tubules when compared to the control group. Conclusion Under the conditions of a fructose-induced metabolic syndrome, high serum UA and CRP correlate to the development of early renal disorders without a clinical manifestation of renal dysfunction. These phenomena are of particular importance for assessing the risk of developing future CKD.

Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.

PubMed

Lincevicius, Gisele S; Shimoura, Caroline G; Nishi, Erika E; Perry, Juliana C; Casarini, Dulce E; Gomes, Guiomar N; Bergamaschi, Cássia T; Campos, Ruy R

2015-09-01

Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood. The current study evaluated whether aldosterone contributes to cardiovascular and renal dysfunction in the 2 kidney-1 clip (2K1C) model. Mean arterial pressure (MAP) and baroreceptor reflex for control of the heart rate were evaluated in 2K1C treated or not treated with spironolactone (200mg/kg/day, 7 days). Tonic and reflex control of renal sympathetic nerve activity (rSNA) were assessed in urethane-anaesthetized rats. Plasma renin activity (PRA), kidney renin protein expression, renal injury, and central AT1 receptor protein expression were assessed. Spiro reduced MAP (198±4 vs. 170±9mm Hg; P < 0.05), normalized rSNA (147±9 vs. 96±10 pps; P < 0.05), and increased renal baroreceptor reflex sensitivity in the 2K1C rats. Spiro reduced α-smooth muscle actin expression in the nonclipped kidney in the 2K1C group (5±0.6 vs. 1.1±0.2%; P < 0.05). There was no change in PRA; however, a decrease in renin protein expression in the nonclipped kidney was found in the 2K1C treated group (217±30 vs. 160±19%; P < 0.05). Spiro treatment decreased AT1 receptor in the central nervous system (CNS) only in 2K1C rats (138±10 vs. 84±12%; P < 0.05). Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia.

PubMed

Young, S R; Stoelting, R K; Peterson, C; Madura, J A

1975-04-01

Anesthetic biotransformation and renal function were studied in obese adult patients (148 plus or minus 8 kg; mean plus or minus SE) anesthetized for three hours with 60 per cent nitrous oxide plus either methoxyflurane or halothane for elective jejunoileal small-bowel-bypass operations. There was no evidence of persistent renal dysfunction in any patient postoperatively, but serum osmolality was elevated 72 hours after methoxyflurane anesthesia. Urine concentrating ability was not determined. Peak serum ionic fluoride concentration was 55.8 plus or minus 5.8 muM/1 two hours after discontinuation of methoxyflurane. Urinary ionic fluoride and oxalate excretions increased postoperatively. Compared with previously reported data from nonobese patients, serum ionic fluoride concentrations in obese patients increased more rapidly during methoxyflurane anesthesia and peaked higher and sooner after discontinuation of methoxyflurane. The peak serum ionic fluoride concentration was 10.4 plus or minus 1.5 muM/1 at the conclusion of halothane anesthesia, significantly more than the corresponding value in nonobese patients. Intraoperative liver biopsies from 23 of 27 patients showed moderate to severe fatty metamorphosis. Fatty liver infiltration may have increased hepatic anesthetic uptake and exposed more methoxyflurane or halothane to hepatic microsomal enzymes. The more rapid elevation and higher peak levels of serum ionic fluoride following methoxyflurane, and to a lesser extent following halothane, may reflect increased anesthetic biotransformation in obese compared with nonobese patients. To avoid excessive serum ionic fluoride elevations the authors recommended limiting low-dose methoxyflurane anesthesia delivered to obese patients with potential fatty liver infiltration to no more than three hours.

Hypothyroidism presenting as reversible renal impairment: an interesting case report.

PubMed

Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

2013-10-01

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

[The role of percutaneous renal biopsy in kidney transplant].

PubMed

Manfro, R C; Lee, J Y; Lewgoy, J; Edelweiss, M I; Gonçalves, L F; Prompt, C A

1994-01-01

Percutaneous renal biopsy (PRB) is an useful tool for diagnostic and therapeutic orientation in renal transplantation. PURPOSE--To evaluate the current role of PRB in post-transplant acute renal dysfunction (ARD) of renal allografts. METHODS--Sixty-five renal transplant patients were submitted to 95 valid renal biopsies with no major complications. RESULTS--There was disagreement between the clinical and the pathological diagnosis in 28 occasions (29.5%). In 36 cases (37.9%) the results of the pathological examination led to a modification in patient's management. These modifications were most commonly the avoidance or witholding of a steroid pulse (8 cases); nephrectomy of the renal allograft (8 cases); witholding or decrease of cyclosporine dosage (6 cases); giving a steroid pulse (5 cases) and giving antibiotics to treat acute pyelonephritis in 4 cases. The use of kidneys from cadaveric donors was significantly associated with an increased number of biopsies (p < 0.05). CONCLUSION--These results demonstrate that even though several less invasive procedures are currently employed, renal biopsy is still an indispensable method to the management of ARD in renal transplant patients.

Family Functioning and Dysfunctional Eating Among Italian Adolescents: The Moderating Role of Gender.

PubMed

Laghi, Fiorenzo; McPhie, Meghan L; Baumgartner, Emma; Rawana, Jennine S; Pompili, Sara; Baiocco, Roberto

2016-02-01

The first aim of this study was to examine the association between different dimensions of family functioning and dysfunctional eating in a sample of Italian adolescent boys and girls. The second aim was to investigate whether gender moderates the relationship between family functioning and dysfunctional eating. Seven hundred and twenty seven adolescents (500 boys and 227 girls) with ages ranging from 15 to 18 years completed a survey of self-report measures. Findings from hierarchical multiple regression analysis suggested that aspects of family functioning such as flexibility, cohesion, disengagement, enmeshment, rigidity and chaotic were related to dysfunctional eating in adolescents. Additionally the results indicated differences between boys and girls, in particular dysfunctional eating in adolescent boys seemed to be more affected by dimensions of enmeshment and disengagement than dysfunctional eating in girls. This research highlights the important role of various aspects of family functioning in relation to dysfunctional eating in adolescents.

Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

PubMed Central

Mulenga, Lloyd B.; Kruse, Gina; Lakhi, Shabir; Cantrell, Ronald A.; Reid, Stewart E.; Zulu, Isaac; Stringer, Elizabeth M.; Krishnasami, Zipporah; Mwinga, Alwyn; Saag, Michael S.; Stringer, Jeffrey S. A.; Chi, Benjamin H.

2009-01-01

Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment. PMID:18753939

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

PubMed

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

2016-10-01

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

Dengue fever in renal transplant patients: a systematic review of literature.

PubMed

Weerakkody, Ranga Migara; Patrick, Jean Ansbel; Sheriff, Mohammed Hussain Rezvi

2017-01-13

Dengue fever in renal transplanted patients has not been studied well, and we review all the literature about episodes dengue fever in renal transplant patients. The aim was to describe clinico-pathological characteristics, immunosuppressive protocols, need renal outcome and mortality. PubMed, LILACS, Google Scholar and Research Gate were searched for "Dengue" and "Renal/Kidney Transplantation" with no date limits. Hits were analyzed by two researchers separately. Fever, myalgia, arthralgia and headache was significantly lower than normal population, while pleural effusions and ascites were observed more. Incidence of severe dengue is significantly higher among transplant patients in this review, as well as they had a significantly higher mortality (8.9% vs 3.7%, p = 0.031). Age, period after transplantation and immunosuppressive profile had no effect on disease severity, mortality or graft out come. Presence of new bleeding complications and ascites was associated with more severe disease (p < 0.001 and p = 0.005), death (p = 0.033) or graft loss (p = 0.035). Use of tacrolimus was associated with new bleeding complications (p = 0.027), and with ascites (p = 0.021), but not with thrombocytopenia. 25% of patients with primary disease fail to mount an IgG response by 15 weeks of the illness. 58.9% had graft dysfunction during illness. Postoperative transplanted patients were at risk of severe disease and unfavorable outcome. The physical and laboratory findings in dengue fever in renal transplanted patients differ from the general population. Some degree of graft dysfunction is common during the illness, but only a minority develops graft failure.

Optimal conditions of LDR to protect the kidney from diabetes

PubMed Central

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-01-01

Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

Novel Renal Biomarkers to Assess Cardiorenal Syndrome

PubMed Central

Brisco, Meredith A.; Testani, Jeffrey M.

2014-01-01

Renal dysfunction (RD) in heart failure portends adverse outcomes and often limits aggressive medical and decongestive therapies. Despite the high prevalence in this population, not all forms of RD are prognostically or mechanistically equivalent: RD can result from irreversible nephron loss secondary to diabetic or hypertensive kidney disease or it can develop secondary to the HF itself, i.e. the cardiorenal syndrome. Furthermore, filtration is only one aspect of renal performance such that significant renal impairment secondary to cardiorenal syndrome can exist despite a normal glomerular filtration rate. Renal biomarkers have the potential to inform some of the intricacies involved in accurately assessing cardiorenal interactions. This article discusses novel biomarkers for cardiorenal syndrome and their utility in prognosis, diagnosis, and targeted treatment of heart failure-induced RD. PMID:25239434

[Cardio-renal axis: pathophysiological evidences and clinical implications].

PubMed

Di Lullo, Luca; Ronco, Claudio

2017-03-01

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS acute cardio - renal syndrome is characterized by acute worsening of cardiac function leading to AKI in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury, while type 4 represent cardiovascular involvement in chronic kidney disese patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Assessment of endothelial dysfunction: the role of symmetrical dimethylarginine and proinflammatory markers in chronic kidney disease and renal transplant recipients.

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Bogavac-Stanojevic, Natasa; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-01-01

The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙-) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙- to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙- had better screening performance than SDMA alone. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.

Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis.

PubMed

Kwok, Chun Shing; Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M; Phillips, Martin G; Gelson, William

2013-01-01

Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I² statistic. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08-0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25-0.86) and renal impairment (OR 0.34 95%, CI 0.15-0.75) when albumin was used. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis.

Albumin Reduces Paracentesis-Induced Circulatory Dysfunction and Reduces Death and Renal Impairment among Patients with Cirrhosis and Infection: A Systematic Review and Meta-Analysis

PubMed Central

Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M.; Phillips, Martin G.

2013-01-01

Background. Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. Methods. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I2 statistic. Results. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08–0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25–0.86) and renal impairment (OR 0.34 95%, CI 0.15–0.75) when albumin was used. Conclusion. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis. PMID:24222902

Bcl-2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis.

PubMed

Suzuki, Chigure; Isaka, Yoshitaka; Shimizu, Shigeomi; Tsujimoto, Yoshihide; Takabatake, Yoshitsugu; Ito, Takahito; Takahara, Shiro; Imai, Enyu

2008-01-01

Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucidated; however, cellular stress may induce apoptosis during the first hours and days after transplantation, which might play a crucial role in early graft dysfunction. Bcl-2 is known to inhibit apoptosis induced by the etiological factors promoting ischemia and reperfusion injury. Accordingly, we hypothesized that an augmentation of the antiapoptotic factor Bcl-2 may thus protect tubular epithelial cells by inhibiting apoptosis, thereby ameliorating the subsequent tubulointerstitial injury. We examined the effects of Bcl-2 overexpression on ischemia-reperfusion (I/R) injury using Bcl-2 transgenic mice (Bcl-2 TG) and their wild-type littermates (WT). To investigate the effects of I/R injury, the left renal artery and vein were clamped for 45 min, followed by reperfusion for 0-96 h. Bcl-2 TG exhibited decreased active caspase protein in the tubular cells, which led to a reduction in TUNEL-positive apoptotic cells. Consequently, interstitial fibrosis and phenotypic changes were ameliorated in Bcl-2 TG. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R, and subsequent interstitial injury by inhibiting tubular apoptosis.

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury

PubMed Central

Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik

2018-01-01

Background. Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Methods. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Results. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H2O2. Conclusions. Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney. PMID:29326403

Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

PubMed

Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

2017-04-01

To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Benefits and Safety of Long-Term Fenofibrate Therapy in People With Type 2 Diabetes and Renal Impairment

PubMed Central

Ting, Ru-Dee; Keech, Anthony C.; Drury, Paul L.; Donoghoe, Mark W.; Hedley, John; Jenkins, Alicia J.; Davis, Timothy M.E.; Lehto, Seppo; Celermajer, David; Simes, R. John; Rajamani, Kushwin; Stanton, Kim

2012-01-01

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive. PMID:22210576

Nationwide survey of Arima syndrome: revised diagnostic criteria from epidemiological analysis.

PubMed

Itoh, Masayuki; Iwasaki, Yuji; Ohno, Kohsaku; Inoue, Takehiko; Hayashi, Masaharu; Ito, Shuichi; Matsuzaka, Tetsuo; Ide, Shuhei; Arima, Masataka

2014-05-01

We have never known any epidemiological study of Arima syndrome since it was first described in 1971. To investigate the number of Arima syndrome patients and clarify the clinical differences between Arima syndrome and Joubert syndrome, we performed the first nationwide survey of Arima syndrome, and herein report its results. Furthermore, we revised the diagnostic criteria for Arima syndrome. As a primary survey, we sent out self-administered questionnaires to most of the Japanese hospitals with a pediatric clinic, and facilities for persons with severe motor and intellectual disabilities, inquiring as to the number of patients having symptoms of Arima syndrome, including severe psychomotor delay, agenesis or hypoplasia of cerebellar vermis, renal dysfunction, visual dysfunction and with or without ptosis-like appearance. Next, as the second survey, we sent out detailed clinical questionnaires to the institutes having patients with two or more typical symptoms. The response rate of the primary survey was 72.7% of hospitals with pediatric clinic, 63.5% of national hospitals and 66.7% of municipal and private facilities. The number of patients with 5 typical symptoms was 13 and that with 2-4 symptoms was 32. The response rate of the secondary survey was 52% (23 patients). After reviewing clinical features of 23 patients, we identified 7 Arima syndrome patients and 16 Joubert syndrome patients. Progressive renal dysfunction was noticed in all Arima syndrome patients, but in 33% of those with Joubert syndrome. It is sometimes difficult to distinguish Arima syndrome from Joubert syndrome. Some clinicians described a patient with Joubert syndrome and its complications of visual dysfunction and renal dysfunction, whose current diagnosis was Arima syndrome. Thus, the diagnosis of the two syndromes may be confused. Here, we revised the diagnostic criteria for Arima syndrome. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

PubMed Central

Papista, Christina; Berthelot, Laureline; Monteiro, Renato C

2011-01-01

Immunoglobulin A (Iga)-isotype antibodies play an important role in immunity owing to their structure, glycosylation, localization and receptor interactions. Dysfunctions in this system can lead to multiple types of pathology. This review describes the characteristics of Iga and discusses the involvement of abnormalities in the Iga system on the development of celiac disease and Iga nephropathy. PMID:21278767

Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.

PubMed

Yanes, Licy L; Romero, Damian G; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D; Zhang, Huimin; Lockhart, Rachel; Racusen, Lorraine C; Reckelhoff, Jane F

2011-04-01

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Reversible preoperative renal dysfunction does not add to the risk of postoperative acute kidney injury after cardiac valve surgery

PubMed Central

Xu, Jia-Rui; Zhuang, Ya-Min; Liu, Lan; Shen, Bo; Wang, Yi-Mei; Luo, Zhe; Teng, Jie; Wang, Chun-Sheng; Ding, Xiao-Qiang

2017-01-01

Objective To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. Method Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function – preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. Results Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. Conclusion For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI. PMID:29184415

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

Historical perspectives on cadmium toxicology

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

Nordberg, Gunnar F.

2009-08-01

The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects weremore » studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.« less

The basic data for residents aged 16 years or older who received a comprehensive health check examinations in 2011-2012 as a part of the Fukushima Health Management Survey after the great East Japan earthquake.

PubMed

Kawasaki, Yukihiko; Hosoya, Mitsuaki; Yasumura, Seiji; Ohira, Tetsuya; Satoh, Hiroaki; Suzuki, Hitoshi; Sakai, Akira; Ohtsuru, Akira; Takahashi, Atsushi; Ozasa, Kotaro; Kobashi, Gen; Kamiya, Kenji; Yamashita, Shunichi; Abe, Masafumi

2014-01-01

To assist in the long-term health management of residents and evaluate health impacts after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident in Fukushima Prefecture, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey. This report describes the results for residents aged 16 years or older who received the health check examinations and evaluates the data obtained from 2011 and 2012. The target group consisted of residents aged 16 years or older who had lived in the evacuation zone. The health check examinations were performed on receipt of an application for a health check examination from any of the residents. The examinations, including measurements of height, weight, abdominal circumference/body mass index (BMI), blood pressure, biochemical laboratory findings, and peripheral blood findings, were performed as required. 1) A total of 56,399 (30.9%) and 47,009 (25.4%) residents aged 16 years or older received health checks in 2011 and 2012, respectively. 2) In both years, a number of male and female residents in the 16-39 year age group were found to suffer obesity, hyperlipidemia, hyperuricemia, or liver dysfunction, and the prevalence of obesity and hyperlipidemia among residents increased with age. Furthermore, the proportion of residents with hypertension, glucose metabolic abnormalities or renal dysfunction was higher in those aged 40 years or older. 3) The frequencies of obesity, hypertension and hyperlipidemia among residents in 2012 were lower than those in 2011. However, the prevalence of liver dysfunction, hyperuricemia, glucose metabolic abnormalities and renal dysfunction among residents was higher in 2012 than in 2011. These results suggested the number of residents who had lived in the evacuation zone with obesity, hyperlipidemia, hyperuricemia, liver dysfunction, hypertension, glucose metabolic abnormalities, or renal dysfunction increased with age in all age groups. Therefore, we think that it is necessary to continue with health check examinations for these residents in order to ameliorate lifestyle-related disease.

The macro- and microcirculation of the kidney.

PubMed

Guerci, Philippe; Ergin, Bulent; Ince, Can

2017-09-01

Acute kidney injury (AKI) remains one of the main causes of morbidity and mortality in the intensive care medicine today. Its pathophysiology and progress to chronic kidney disease is still under investigation. In addition, the lack of techniques to adequately monitor renal function and microcirculation at the bedside makes its therapeutic resolution challenging. In this article, we review current concepts related to renal hemodynamics compromise as being the event underlying AKI. In doing so, we discuss the physiology of the renal circulation and the effects of alterations in systemic hemodynamics that lead to renal injury specifically in the context of reperfusion injury and sepsis. The ultimate key culprit of AKI leading to failure is the dysfunction of the renal microcirculation. The cellular and subcellular components of the renal microcirculation are discussed and how their injury contributes to AKI is described. Copyright © 2017. Published by Elsevier Ltd.

[Renal dysfunction in patients with myocardial infarction concurrent with type 2 diabetes mellitus].

PubMed

Evseeva, M V; Karetnikova, V N; Barbarash, O L

2015-01-01

Carbohydrate metabolic disturbances are an independent risk factor for not only the development, but also poor course of cardiovascular diseases, particularly those concurrent with renal dysfunction (RD). This factor acquires particular relevance due to the fact that the incidence of type 2 diabetes mellitus significantly continues to rise worldwide. The review considers the main mechanisms and common components of the pathogenesis of RD, as well as the constituents forming its basis in the presence of carbohydrate metabolic disturbances. Moreover, it highlights the timely detection of RD, a search for new biomarkers of prognostic value for cardiovascular events, and the early diagnosis of RD. The review unveils the present view of optimal diagnostic and management tactics for patients with myocardial infarction concurrent with background diseases.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

"Macho" Beliefs Moderate the Association Between Negative Sexual Episodes and Activation of Incompetence Schemas in Sexual Context, in Gay and Heterosexual Men.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-04-01

Despite the existence of conceptual models of sexual dysfunction based on cognitive theory, few studies have tested the role of vulnerability factors such as sexual beliefs as moderators of the activation of cognitive schemas in response to negative sexual events. To test the moderator role of dysfunctional sexual beliefs in the association between the frequency of negative sexual episodes and the activation of incompetence schemas in gay and heterosexual men. Five-hundred seventy-five men (287 gay, 288 heterosexual) who completed an online survey on cognitive-affective dimensions and sexual functioning were selected from a larger database. Hierarchical regression analyses were conducted to test the hypothesis that dysfunctional sexual beliefs moderate the association between the frequency of unsuccessful sexual episodes and the activation of incompetence schemas. Participants completed the Sexual Dysfunctional Beliefs Questionnaire and the Questionnaire of Cognitive Schemas Activated in Sexual Context. Findings indicated that men's ability for always being ready for sex, to satisfy the partner, and to maintain an erection until ending sexual activity constitute "macho" beliefs that moderate the activation of incompetence schemas when unsuccessful sexual events occur in gay and heterosexual men. In addition, activation of incompetence schemas in response to negative sexual events in gay men was moderated by the endorsement of conservative attitudes toward moderate sexuality. The main findings suggested that psychological interventions targeting dysfunctional sexual beliefs could help de-catastrophize the consequences of negative sexual events and facilitate sexual functioning. Despite being a web-based study, it represents the first attempt to test the moderator role of dysfunctional sexual beliefs in the association between the frequency of unsuccessful sexual episodes and the activation of incompetence schemas in gay and heterosexual men. Overall, findings support the role of sexual beliefs as facilitators of the activation of incompetence schemas in the face of negative sexual events in gay and heterosexual men, emphasizing the need to develop treatment and prevention strategies aimed at challenging common male beliefs about sexuality. Peixoto MM, Nobre P. "Macho" Beliefs Moderate the Association Between Negative Sexual Episodes and Activation of Incompetence Schemas in Sexual Context, in Gay and Heterosexual Men. J Sex Med 2017;14:518-525. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

PubMed Central

Bakajsova, Diana; Samarel, Allen M.

2011-01-01

PKC-ε activation mediates protection from ischemia-reperfusion injury in the myocardium. Mitochondria are a subcellular target of these protective mechanisms of PKC-ε. Previously, we have shown that PKC-ε activation is involved in mitochondrial dysfunction in oxidant-injured renal proximal tubular cells (RPTC; Nowak G, Bakajsova D, Clifton GL Am J Physiol Renal Physiol 286: F307–F316, 2004). The goal of this study was to examine the role of PKC-ε activation in mitochondrial dysfunction and to identify mitochondrial targets of PKC-ε in RPTC. The constitutively active and inactive mutants of PKC-ε were overexpressed in primary cultures of RPTC using the adenoviral technique. Increases in active PKC-ε levels were accompanied by PKC-ε translocation to mitochondria. Sustained PKC-ε activation resulted in decreases in state 3 respiration, electron transport rate, ATP production, ATP content, and activities of complexes I and IV and F0F1-ATPase. Furthermore, PKC-ε activation increased mitochondrial membrane potential and oxidant production and induced mitochondrial fragmentation and RPTC death. Accumulation of the dynamin-related protein in mitochondria preceded mitochondrial fragmentation. Antioxidants blocked PKC-ε-induced increases in the oxidant production but did not prevent mitochondrial fragmentation and cell death. The inactive PKC-ε mutant had no effect on mitochondrial functions, morphology, oxidant production, and RPTC viability. We conclude that active PKC-ε targets complexes I and IV and F0F1-ATPase in RPTC. PKC-ε activation mediates mitochondrial dysfunction, hyperpolarization, and fragmentation. It also induces oxidant generation and cell death, but oxidative stress is not the mechanism of RPTC death. These results show that in contrast to protective effects of PKC-ε activation in cardiomyocytes, sustained PKC-ε activation is detrimental to mitochondrial function and viability in RPTC. PMID:21289057

Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus.

PubMed

Gómez-Guzmán, Manuel; Jiménez, Rosario; Romero, Miguel; Sánchez, Manuel; Zarzuelo, María José; Gómez-Morales, Mercedes; O'Valle, Francisco; López-Farré, Antonio José; Algieri, Francesca; Gálvez, Julio; Pérez-Vizcaino, Francisco; Sabio, José Mario; Duarte, Juan

2014-08-01

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. © 2014 American Heart Association, Inc.

Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi Syndrome

PubMed Central

Luciani, Alessandro; Sirac, Christophe; Terryn, Sara; Javaugue, Vincent; Prange, Jenny Ann; Bender, Sébastien; Bonaud, Amélie; Cogné, Michel; Aucouturier, Pierre; Ronco, Pierre

2016-01-01

Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS. PMID:26614382

Albumin Overload and PINK1/Parkin Signaling-Related Mitophagy in Renal Tubular Epithelial Cells.

PubMed

Tan, Jin; Xie, Qi; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-03-01

BACKGROUND Albumin, as a major urinary protein component, is a risk factor for chronic kidney disease progression. Mitochondrial dysfunction is one of the main causes of albumin-induced proximal tubule cells injury. Mitophagy is considered as a pivotal protective mechanism for the elimination of dysfunctional mitochondria. The objective of this research was to determine whether albumin overload-induced mitochondrial dysfunction can activate PINK1/Parkin-mediated mitophagy in renal tubular epithelial cells (TECs). MATERIAL AND METHODS Immunofluorescence assay and Western blot assay were used to detect the effects of albumin overload on autophagy marker protein LC3. Transmission electron microscopy and Western blot assay were used to investigate the role of albumin in mitochondrial injury. Western blot assay and co-localization of acidic lysosomes and mitochondria assay were employed to detect the activation of mitophagy induced by albumin. Finally, we explored the role of PINK1/Parkin signaling in albumin-induced mitophagy by inhibiting mitophagy by knockdown of PARK2 (Parkin) level. RESULTS Immunofluorescence and Western blot results showed that the expression level of LC3-II increased, and the maximum increase point was observed after 8 h of albumin treatment. Transmission electron microscopy results demonstrated that albumin overload-induced mitochondrial injury and quantity of autophagosomes increased. Additionally, expression of PINK1 and cytosolic cytochrome C increased and mitochondria cytochrome C decreased in the albumin group. The co-localization of acidic lysosomes and mitochondria demonstrated that the number of albumin overload-induced mitophagy-positive dots increased. The transient transfection of PARK2 siRNA result showed knockdown of the expression level of PARK2 can inhibit mitophagy induced by albumin. CONCLUSIONS In conclusion, our study suggests that mitochondrial dysfunction activates the PINK1/Parkin signaling and mitophagy in renal tubular epithelial cells under albumin overload condition.

Mutations in HPSE2 cause urofacial syndrome.

PubMed

Daly, Sarah B; Urquhart, Jill E; Hilton, Emma; McKenzie, Edward A; Kammerer, Richard A; Lewis, Malcolm; Kerr, Bronwyn; Stuart, Helen; Donnai, Dian; Long, David A; Burgu, Berk; Aydogdu, Ozgu; Derbent, Murat; Garcia-Minaur, Sixto; Reardon, Willie; Gener, Blanca; Shalev, Stavit; Smith, Rupert; Woolf, Adrian S; Black, Graeme C; Newman, William G

2010-06-11

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.

Mutations in HPSE2 Cause Urofacial Syndrome

PubMed Central

Daly, Sarah B.; Urquhart, Jill E.; Hilton, Emma; McKenzie, Edward A.; Kammerer, Richard A.; Lewis, Malcolm; Kerr, Bronwyn; Stuart, Helen; Donnai, Dian; Long, David A.; Burgu, Berk; Aydogdu, Ozgu; Derbent, Murat; Garcia-Minaur, Sixto; Reardon, Willie; Gener, Blanca; Shalev, Stavit; Smith, Rupert; Woolf, Adrian S.; Black, Graeme C.; Newman, William G.

2010-01-01

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction. PMID:20560210

Association between left ventricular dysfunction, anemia, and chronic renal failure. Analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) cohort.

PubMed

Kepez, A; Mutlu, B; Degertekin, M; Erol, C

2015-06-01

Anemia and chronic renal failure (CRF) are frequent comorbidities in patients with heart failure (HF), and they have been reported to be associated with increased mortality and hospitalization rates. HF, anemia, and CRF have been reported to interact with each other forming a vicious cycle termed cardio-renal-anemia syndrome. The aim of the present study was to evaluate the association of HF, anemia, and CRF using data from the large-scale"Heart Failure Prevalence and Predictors in Turkey (HAPPY)" study. Among the HAPPY cohort, 3,369 subjects who had either left ventricular dysfunction (LVD) or normal left ventricular function on echocardiography or normal serum NT-proBNP levels were included in this analysis. The prevalence of anemia and CRF was significantly higher in patients with LVD compared with subjects with normal ventricular function (20.7 % vs. 4.0 % and 19.0 % vs. 3.7 %, respectively; p < 0.001 for each). Binary logistic regression analyses for the presence of LVD, anemia, and CRF demonstrated that each one was an independent predictor for the presence of the others. These findings point to the presence of cardio-renal-anemia syndrome and the necessity of treating these comorbidities in patients with HF.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

PubMed

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

PubMed Central

Yu, Jun-Feng; Feng, Yan-Yan

2017-01-01

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment. PMID:28867961

Recent analytical approaches to detect exhaled breath ammonia with special reference to renal patients.

PubMed

Krishnan, Sanduru Thamarai; Devadhasan, Jasmine Pramila; Kim, Sanghyo

2017-01-01

The ammonia odor from the exhaled breath of renal patients is associated with high levels of blood urea nitrogen. Typically, in the liver, ammonia and ammonium ions are converted into urea through the urea cycle. In the case of renal dysfunction, urea is unable to be removed and that causes a buildup of excessive ammonia. As small molecules, ammonia and ammonium ions can be forced into the blood-lung barrier and occur in exhaled breath. Therefore, people with renal failure have an ammonia (fishy) odor in their exhaled breath. Thus, exhaled breath ammonia can be a potential biomarker for monitoring renal diseases during hemodialyis. In this review, we have summarized the source of ammonia in the breath of end-stage renal disease patient, cause of renal disorders, exhaled breath condensate, and breath sampling. Further, various biosensor approaches to detect exhaled ammonia from renal patients and other ammonia systems are also discussed. We conclude with future perspectives, namely colorimetric-based real-time breathing diagnosis of renal failure, which might be useful for prospective studies.

Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

PubMed

Núñez, Julio; Miñana, Gema; Santas, Enrique; Bertomeu-González, Vicente

2015-05-01

Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney. Worsening renal function that occurs in patients with acute heart failure has been classified as cardiorenal syndrome type 1. In this setting, worsening renal function is a common finding and is due to complex, multifactorial, and not fully understood processes involving hemodynamic (renal arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors. Traditionally, worsening renal function has been associated with worse outcomes, but recent findings have revealed mixed and heterogeneous results, perhaps suggesting that the same phenotype represents a diversity of pathophysiological and clinical situations. Interpreting the magnitude and chronology of renal changes together with baseline renal function, fluid overload status, and clinical response to therapy might help clinicians to unravel the clinical meaning of renal function changes that occur during an episode of heart failure decompensation. In this article, we critically review the contemporary evidence on the pathophysiology and clinical aspects of worsening renal function in acute heart failure. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Contribution of the amiloride-sensitive component and the Na+/H+ exchanger to renal responsiveness to vasoconstrictors.

PubMed

Vargas, Pablo; Wangensteen, Rosemary; Rodríguez-Gómez, Isabel; Perez-Abud, Rocío; Osuna, Antonio; Quesada, Andrés; Vargas, Félix

2011-01-01

This study analyzed the role of the amiloride-sensitive component and the participation of the Na(+)/H(+) exchanger in renal responsiveness to vasoconstrictors in the isolated perfused rat kidney. The renal responses to vasoconstrictors (angiotensin II, phenylephrine, vasopressin and KCl) were studied under baseline conditions and after the administration of amiloride (10 and 100 μmol/l) or the specific Na(+)/H(+) exchange inhibitor ethylisopropylamiloride (EIPA, 10 μmol/l). The effects of amiloride and EIPA on renal responsiveness to vasoconstrictors were also analyzed in endothelium-denuded preparations. Amiloride reduced renal responsiveness to all vasoconstrictors in a dose-related manner, whereas EIPA did not affect the renal pressor response to KCl. The inhibitory effects of amiloride and EIPA on renal responsiveness to vasoconstrictors persisted after endothelium removal. These results indicate that the amiloride-sensitive component and the Na(+)/H(+) exchanger play an important role in responsiveness to the main endogenous vasoconstrictors in the renal vasculature. These results also suggest that amiloride might be useful as an inhibitor of renal vasoconstriction, even in diseases with endothelial dysfunction. Copyright © 2011 S. Karger AG, Basel.

Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Kopp, U C

1999-01-01

This study tested the hypothesis that decreased responsiveness of renal mechanosensitive neurons constitutes an intermediate phenotype in spontaneously hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would contribute to increased renal sympathetic nerve activity and sodium retention, characteristic findings in hypertension. A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40 mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure and afferent renal nerve activity were determined. Mean arterial pressure ranged from 110 to 212 mm Hg and was inversely correlated with the magnitude of the increase in afferent renal nerve activity during increased ureteral pressure. Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated with hypertension in this backcross population. This aspect of the complex quantitative trait of altered renal sympathetic neural control of renal function, ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate phenotype in SHR.

Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model.

PubMed

Ohkawa, Sakae; Yanagida, Momoko; Uchikawa, Tsuyoshi; Yoshida, Takuya; Ikegaya, Naoki; Kumagai, Hiromichi

2013-09-01

The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model. © 2013.

Epidemiology and outcome of tuberculosis in immunocompromised patients.

PubMed

Metry, Abdul Massiah; Al Salmi, Issa; Al-Abri, Seif; Al Ismaili, Faisal; Al Mahrouqi, Yaqoub; Hola, Alan; Shaheen, Faissal A M

2017-01-01

The United States Renal Data System showed 1.2% and 1.6% incidences of tuberculosis (TB) in patients on peritoneal dialysis and hemodialysis (HD), respectively. Kidney transplant (KTX) patients have higher rates. We studied the epidemiology and outcome of TB in patients with kidney dysfunction in a tertiary care hospital in the past decade. We examined data of patients with TB with and without kidney dysfunction from 2006 to 2015 through an electronic system. Statistical analysis was completed using Stata software, Chicago, IL, USA. We found 581 patients with active TB of whom 37 had renal dysfunction including chronic kidney disease, HD, and KTX. No difference was found in the prevalence, age, or gender predilection. The age ranged from 1 to 95 with a mean (standard deviation) of 38.6 (21.1) years. The incidence of TB is 3 per 100,000. The number of patients per year with active TB ranges from 52 to 128 and 3 to 4 in the general population and kidney dysfunction group, respectively. Sixty-five percent of patients with kidney dysfunction had pulmonary TB, 5% had pleurisy, and 30% had extrapulmonary TB. Eighty-four percent of patients with kidney dysfunction completed the course of treatment with 16% treatment failure and 0.4% developed multidrug-resistant TB; 8% were lost to follow-up and 8% died during the treatment period. This study showed no gender predilection for TB in the general population and immunocompromised. Duration of symptoms before diagnosis of TB was shorter in kidney dysfunction patients in comparison to the general population. TB cultures were the most positive tests whereas bronchoalveolar lavage and skin test were the least positive for detecting TB in the kidney dysfunction group. Improvement in registries and screening is required to enhance the capturing rate and detection among this group, as well as providing accurate data to health authorities and the public about the magnitude, future trends, treatments, and outcomes regarding TB in kidney dysfunction.

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Nitrooleic acid protects against cisplatin nephropathy: role of COX-2/mPGES-1/PGE2 cascade.

PubMed

Wang, Haiping; Jia, Zhanjun; Sun, Jing; Xu, Liang; Zhao, Bing; Yu, Kezhou; Yang, Meng; Yang, Tianxin; Wang, Rong

2015-01-01

Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2 for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2 pretreatment group. In summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2 cascade.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

Pituitary and/or hypothalamic dysfunction following moderate to severe traumatic brain injury: Current perspectives

PubMed Central

Javed, Zeeshan; Qamar, Unaiza; Sathyapalan, Thozhukat

2015-01-01

There is an increasing deliberation regarding hypopituitarism following traumatic brain injury (TBI) and recent data have suggested that pituitary dysfunction is very common among survivors of patients having moderate-severe TBI which may evolve or resolve over time. Due to high prevalence of pituitary dysfunction after moderate-severe TBI and its association with increased morbidity and poor recovery and the fact that it can be easily treated with hormone replacement, it has been suggested that early detection and treatment is necessary to prevent long-term neurological consequences. The cause of pituitary dysfunction after TBI is still not well understood, but evidence suggests few possible primary and secondary causes. Results of recent studies focusing on the incidence of hypopituitarism in the acute and chronic phases after TBI are varied in terms of severity and time of occurrence. Although the literature available does not show consistent values and there is difference in study parameters and diagnostic tests used, it is clear that pituitary dysfunction is very common after moderate to severe TBI and patients should be carefully monitored. The exact timing of development cannot be predicted but has suggested regular assessment of pituitary function up to 1 year after TBI. In this narrative review, we aim to explore the current evidence available regarding the incidence of pituitary dysfunction in acute and chronic phase post-TBI and recommendations for screening and follow-up in these patients. We will also focus light over areas in this field worthy of further investigation. PMID:26693424

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

PubMed

Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

2015-07-01

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

PubMed

Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

2017-03-07

Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury

PubMed Central

Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A.

2014-01-01

Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI. PMID:24346647

Acceptance and effects of a therapeutic renal food in pet cats with chronic kidney disease

PubMed Central

Fritsch, Dale A; Jewell, Dennis E

2015-01-01

Introduction Renal foods are used to manage chronic kidney disease (CKD) in dogs and cats, but their effectiveness may be limited by the ability to transition animals to them. Material and Methods In a prospective study, pet cats with previously undiagnosed kidney disease (20 International Renal Interest Society (IRIS) 1, 61 IRIS 2, 14 IRIS 3/4, 33 at risk for CKD) were transitioned to a renal food. Markers of renal function were measured and owners answered questionnaires about their pet over one year. Results All but eight cats (120/128; 94 per cent) successfully transitioned to the renal food. Most of the time, cats moderately or extremely liked the food (89 per cent), ate at least half (73 per cent) and were moderately or extremely enthusiastic while eating (68 per cent). Cats rarely disliked the food (2 per cent) or refused to eat it (1 per cent). Markers of renal function were unchanged in IRIS 1 and 2 cats and changed little in IRIS 3/4 cats. In all groups, owner-assessed quality of life improved initially and then remained stable. Mean bodyweight did not change in cats with CKD. Conclusions Most cats with CKD successfully transitioned to the renal food. The results also support previous studies that the renal food can help stabilise cats with CKD. PMID:26587240

Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

PubMed

Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

2016-06-19

In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR < 60) were estimated with logistic regression model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

HPLC determination of plasma dimethylarginines: method validation and preliminary clinical application.

PubMed

Ivanova, Mariela; Artusi, Carlo; Boffa, Giovanni Maria; Zaninotto, Martina; Plebani, Mario

2010-11-11

Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. The intra- and inter-assay CVs (<5.2%), the absolute and relative recoveries (96-106%) were highly satisfactory. ADMA levels were significantly elevated in all groups of patients compared with controls (p<0.001) with the exception of samples from patients with type II diabetes. SDMA levels were significantly elevated both in the patients with chronic kidney disease and in the patients with type II diabetes complicated by renal insufficiency, the values being closely correlated with both eGFR (R=0.740) and plasmatic creatinine (R=0.700). The findings made in the present study shows that ADMA levels are significantly increased in patients with diseases associated with endothelial dysfunction This molecule might, therefore, be used as a biochemical marker for the evaluation of endothelial function. Furthermore, the preliminary results reported suggest that SDMA might be a reliable marker of renal function, especially in peadiatric populations, for which the use of eGFR is not recommended. 2010 Elsevier B.V. All rights reserved.

Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance.

PubMed

Rosner, Mitchell H; Edeani, Amaka; Yanagita, Motoko; Glezerman, Ilya G; Leung, Nelson

2016-12-07

Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders. Copyright © 2016 by the American Society of Nephrology.

Nonsteroidal Anti-Inflammatory Drugs and the Kidney

PubMed Central

Hörl, Walter H.

2010-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

Management of bladder dysfunction in Wolfram syndrome with Mitrofanoff appendicovesicostomy: long-term follow-up.

PubMed

Mozafarpour, Sarah; Kajbafzadeh, Abdol-Mohammad; Mojtahed, Ali; Mojtahed, Mohammad; Mahboubi, Hossein; Shalileh, Keivan

2015-07-01

To present the long-term outcomes of appendicovesicostomy using the Mitrofanoff principle for end-stage Wolfram bladder dysfunction as an alternative to clean intermittent self-catheterization (CIC) per urethra mainly following blindness. Twelve Wolfram patients presenting with bilateral hydroureteronephrosis and advanced bladder dysfunction were included in this study. All patients were managed initially by CIC per urethra. All of these patients became blind during follow-up and were unable to perform urethral CIC independently. Out of these patients, six patients agreed to proceed to appendicovesicostomy. Appendicovesicostomy urinary diversion using the Mitrofanoff principle was performed in these six blind patients. The rest of the patients stopped CIC or performed CIC irregularly. Severe hydroureteronephrosis and large bladders were found in all patients prior to intervention. All patients were able to conduct CIC independently through the stoma and maintained overnight bladder free drainage. In all patients with urinary diversion and CIC, the hydroureteronephrosis was reduced and renal function returned to normal. However, the non-intervention group ended with different degrees of progressive renal failure with three mortalities during the follow-up. We suggest appendicovesicostomy as a safe and lifesaving procedure for long-term management of bladder dysfunction in Wolfram syndrome particularly after progression to blindness. Copyright © 2015 Elsevier Inc. All rights reserved.

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.

PubMed Central

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI. PMID:2765391

The Association Between Inflammatory Markers and Hypertension. A Call for Anti-Inflammatory Strategies?

PubMed Central

García, Néstor H.; Juncos, Luis I.

2006-01-01

The most important goal of antihypertensive therapy is to prevent the complications associated with hypertension (stroke, myocardial infarction, end-stage renal disease, etc). For this, secondary targets such as left ventricular hypertrophy, proteinuria, dementia, and other signs of hypertension-induced organ damage help the physician to assess risks and monitor treatment efficacy. New treatment targets may be arising, however. One such target may be endothelial dysfunction. In effect, endothelial dysfunction not only may precede the elevation of blood pressure, but may also pave the way to conditions often associated with hypertension, such as diabetes, arteriosclerosis, microalbuminuria, congestive heart failure, and tissue hypertrophy. Because inflammation often accompanies endothelial dysfunction, approaches to counteract inflammation are now being evaluated. For this, antagonists of the renin-angiotensin-aldosterone system, statins, and beta blockers are all being tested. All of these agents seem to prevent or delay the induction of proinflammatory molecules aside from, and in addition to, their specific effects on blood pressure. The focus of this review is to update some of the animal and human research showing that hypertension sets off an inflammatory state and also to consider some of the anti-inflammatory approaches that may prevent the development of endothelial dysfunction, and the subsequent renal and cardiovascular damage.

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

PubMed

Winnett, Georgia; Cranfield, Lesley; Almond, Michael

2011-02-01

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

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

[Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

PubMed

García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

2009-02-01

Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

[Primary vesicoureteral reflux with renal failure in adults].

PubMed

Hagen, R H; Klevmark, B

1991-05-30

The present article describes the case of two men, 18 and 30 years respectively, in whom renal insufficiency was discovered incidently. In the two cases renography showed 46 and 30% of expected function given two healthy kidneys. They had neither experienced clinical symptoms of urinary tract disorder, been operated upon, nor endoscopically examined. Micturition was normal without any sign of vesicourethral dysfunction. Micturition cystography revealed severe vesicoureteral reflux in both patients. They were treated by bilateral ureterovesical reimplantation. The cases presented here show that primary vesicoureteral reflux complicated by impaired renal function can be revealed in adults who have had no symptoms of urinary tract disorder. In these cases the probable cause of renal damage is the mechanical effect of reflux ("water-hammer effect") alone.

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation.

PubMed

McHugh, Kirk M

2014-04-01

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.

Hemolytic anemia after ingestion of the natural hair dye Lawsonia inermis (henna) in a dog.

PubMed

Jardes, Daniel J; Ross, Linda A; Markovich, Jessica E

2013-01-01

To describe the clinical presentation and case management of a dog that developed hemolytic anemia and evidence of renal tubular dysfunction after ingestion of a natural hair dye containing Lawsonia inermis (henna). To review cases of henna toxicity reported in the human literature. An 8-year-old female spayed Border Collie was presented 5 days after ingestion of a box of natural hair dye. The dog was showing signs of lethargy, vomiting, diarrhea, and weakness. A serum biochemistry profile, complete blood count, and urinalysis demonstrated evidence of renal tubular dysfunction and a regenerative anemia without spherocytosis. The dog was treated with a transfusion of packed RBCs and IV fluids, resulting in significant clinical improvement. Repeat diagnostics showed resolution of the anemia and no lasting evidence of tubular dysfunction. To the authors' knowledge, this is the first reported case in the veterinary literature of toxicity following ingestion of Lawsonia inermis (henna). Henna ingestion was associated with the development of hemolytic anemia and acute kidney injury. © Veterinary Emergency and Critical Care Society 2013.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice

PubMed Central

Chang, Wen-Wei; Liu, Jau-Jin; Liu, Chi-Fan; Liu, Wen-Sheng; Lim, Yun-Ping; Cheng, Yu-Jung; Lee, Che-Hsin

2013-01-01

Cisplatin is used as a treatment for various types of solid tumors. Renal injury severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found that an extract of Rhodobacter sphaeroides (Lycogen™) inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect of Lycogen™, a potent anti-inflammatory agent, in mice with cisplatin-induced renal injury. We found that attenuated renal injury correlated with decreased apoptosis due to a reduction in caspase-3 expression in renal cells. Oral administration of Lycogen™ significantly reduced the expression of tumor necrosis factor-α and interleukin-1β in mice with renal injury. Lycogen™ reduces renal dysfunction in mice with cisplatin-induced renal injury. The protective effects of the treatment included blockage of the cisplatin-induced elevation in serum urea nitrogen and creatinine. Meanwhile, Lycogen™ attenuated body weight loss and significantly prolonged the survival of mice with renal injury. We propose that Lycogen™ exerts anti-inflammatory activities that represent a promising strategy for the treatment of cisplatin-induced renal injury. PMID:24335753

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PubMed

Whiting, Penny; Birnie, Kate; Sterne, Jonathan A C; Jameson, Catherine; Skinner, Rod; Phillips, Bob

2018-05-01

We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m 2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m 2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

Congenital renal anomalies in cloacal exstrophy: Is there a difference?

PubMed

Suson, K D; Inouye, B; Carl, A; Gearhart, J P

2016-08-01

Cloacal exstrophy (CE) is the most severe manifestation of the epispadias-exstrophy spectrum. Previous studies have indicated an increased rate of renal anomalies in children with classic bladder exstrophy (CBE). Given the increased severity of the CE defect, it was hypothesized that there would be an even greater incidence among these children. The primary objective was to characterize renal anatomy in CE patients. Two secondary objectives were to compare these renal anatomic findings in male and female patients, and female patients with and without Müllerian anomalies. An Institutional Review Board-approved retrospective review of 75 patients from an institutional exstrophy database. Data points included: age at analysis, sex, and renal and Müllerian anatomy. Abnormal renal anatomy was defined as a solitary kidney, malrotation, renal ectopia, congenital cysts, duplication, and/or proven obstruction. Abnormal Müllerian anatomy was defined as uterine or vaginal duplication, obstruction, and/or absence. The Summary Table presents demographic data and renal anomalies. Males were more likely to have renal anomalies. Müllerian anomalies were present in 65.7% of female patients. Girls with abnormal Müllerian anatomy were 10 times more likely to have renal anomalies than those with normal Müllerian anatomy (95% CI 1.1-91.4, P = 0.027). Patients with CE had a much higher rate of renal anomalies than that reported for CBE. Males and females with Müllerian anomalies were at greater risk than females with normal uterine structures. Mesonephric and Müllerian duct interaction is required for uterine structures to develop normally. It has been proposed that women with both Müllerian and renal anomalies be classified separately from other uterine malformations on an embryonic basis. In these patients, an absent or dysfunctional mesonephric duct has been implicated as potentially causal. This provided an embryonic explanation for uterine anomalies in female CE patients. There were also clinical implications. Women with renal agenesis and uterine anomalies were more likely to have endometriosis than those with isolated uterine anomalies, but were also more likely to have successful pregnancies. Males may have had an analogous condition with renal agenesis and seminal vesicle cysts. Future research into long-term kidney function in this population, uterine function, and possible male sexual duct malformation is warranted. Congenital renal anomalies occurred frequently in children with CE. They were more common in boys than in girls. Girls with abnormal Müllerian anatomy were more likely to have anomalous renal development. Mesonephric duct dysfunction may be embyologically responsible for both renal and Müllerian maldevelopment. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase.

PubMed

Tripatara, Pinpat; Patel, Nimesh S A; Webb, Andrew; Rathod, Krishnaraj; Lecomte, Florence M J; Mazzon, Emanuela; Cuzzocrea, Salvatore; Yaqoob, Mohammed M; Ahluwalia, Amrita; Thiemermann, Christoph

2007-02-01

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.

Renal function in hepatosplenic schistosomiasis--an assessment of renal tubular disorders.

PubMed

Duarte, Daniella Bezerra; Vanderlei, Lucas Alexandre; Bispo, Raianne Kívia de Azevêdo; Pinheiro, Maria Eliete; da Silva, Geraldo Bezerra; Martins, Alice Maria Costa; Meneses, Gdayllon Cavalcante; Daher, Elizabeth De Francesco

2014-01-01

Renal involvement in Schistosoma mansoni infection is not well studied. The aim of this study is to investigate the occurrence of renal abnormalities in patients with hepatosplenic schistosomiasis (HSS), especially renal tubular disorders. This is a cross-sectional study with 20 consecutive patients with HSS followed in a medical center in Maceió, Alagoas, Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2) after a 12-h period of water and food deprivation. The biomarker monocyte chemoattractant protein 1 (MCP-1) was quantified in urine. Fractional excretion of sodium (FENa+), transtubular potassium gradient (TTKG) and solute-free water reabsorption (TcH2O) were calculated. The HSS group was compared to a group of 17 healthy volunteers. Patients' mean age and gender were similar to controls. Urinary acidification deficit was found in 45% of HSS patients. Urinary osmolality was significantly lower in HSS patients (588 ± 112 vs. 764 ± 165 mOsm/kg, p = 0,001) after a 12-h period of water deprivation. TcH2O was lower in HSS patients (0.72 ± 0.5 vs. 1.1 ± 0.3, p = 0.04). Urinary concentration deficit was found in 85% of HSS patients. The values of MCP-1 were higher in HSS group than in control group (122 ± 134 vs. 40 ± 28 pg/mg-Cr, p = 0.01) and positively correlated with the values of microalbuminuria and proteinuria. HSS is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating ability and incomplete distal acidification defect, demonstrating the occurrence of tubular dysfunction. There was also an increase in urinary MCP-1, which appears to be a more sensitive marker of renal damage than urinary albumin excretion rate.

Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes.

PubMed

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-05-08

We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study. Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice. Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Management of Bladder Cancer After Renal Transplantation.

PubMed

Demirdag, C; Citgez, S; Talat, Z; Onal, B

2017-03-01

In renal transplant recipients, the risk of developing bladder cancer and rate of diagnosis of advanced staged bladder cancer are generally higher than the general population. Also, it is more challenging to treat renal transplant recipients than the regular patient population. We aimed to evaluate the efficacy and safety of radical cystectomy (RC) and urinary diversion with ileal conduit in renal transplant recipients. We identified 2 patients with prior history of renal transplantation who underwent RC and ileal conduit urinary diversion for bladder cancer. Preoperative clinical and demographic data were presented and outcomes were assessed. The RC and ileal conduit urinary diversion were performed in the first patient 56 months after renal transplantation and in the second patient 64 months after renal transplantation. Clinical staging was high-grade T2 transitional cell cancer of the bladder for patient 1 and T2 with pure squamous cell cancer of the bladder for patient 2. No perioperative or postoperative complication and no graft dysfunction occurred in either patient. Our experience demonstrated that RC with ileal conduit reconstruction in renal transplant recipients is safe and feasible. Copyright © 2016 Elsevier Inc. All rights reserved.

Clevidipine for severe hypertension in patients with renal dysfunction: A VELOCITY trial analysis

PubMed Central

PEACOCK, W FRANK; VARON, JOSEPH; EBRAHIMI, RAMIN; DUNBAR, LALA; POLLACK, CHARLES V

2011-01-01

Introduction. Acute and severe hypertension is common, especially in patients with renal dysfunction (RD). Clevidipine is a rapidly acting (t½∼1 min) intravenous (IV) dihydropyridine calcium-channel blocker metabolized by blood and tissue esterases and may be useful in patients with RD. The purpose of this analysis was to assess the safety and efficacy of clevidipine in patients with RD. Methods. VELOCITY, a multicenter open-label study of severe hypertension, enrolled 126 patients with persistent systolic blood pressure (SBP) >180 mmHg. Investigators pre-specified a SBP initial target range (ITR) for each patient to be achieved within 30 min. Blood pressure monitoring was by cuff. Clevidipine was infused via peripheral IV at 2 mg/h for at least 3 min, then doubled every 3 min as needed to a maximum of 32 mg/h (non-weightbased treat-to-target protocol). Per protocol, clevidipine was continued for at least 18 h (96 h maximum). RD was diagnosed and reported as an end-organ injury by the investigator and was defined as requiring dialysis or an initial creatinine >2.0 mg/dl. Primary endpoints were the percentage of patients within the ITR by 30 min and the percentage below the ITR after 3 min of clevidipine infusion. Results. Of the 24 patients with moderate to severe RD, most (13/24) were dialysis dependent. Forty-six percent were male, with mean age 51 >14 years; 63% were black and 96% had a hypertension history. Median time to achieve the ITR was 8.5 min. Almost 90% of patients reached the ITR in 30 min without evidence of overshoot and were maintained on clevidipine through 18 h. Most patients (88%) transitioned to oral antihypertensive therapy within 6 h of clevidipine termination. Conclusions. This report is the first demonstrating that clevidipine is safe and effective in RD complicated by severe hypertension. Prolonged infusion maintained blood pressure within a target range and allowed successful transition to oral therapy. PMID:21091269

Evaluation of a protocol for vancomycin administration in critically patients with and without kidney dysfunction.

PubMed

Spadaro, Savino; Berselli, Angela; Fogagnolo, Alberto; Capuzzo, Maurizia; Ragazzi, Riccardo; Marangoni, Elisabetta; Bertacchini, Sara; Volta, Carlo Alberto

2015-06-27

Administration of vancomycin in critically ill patients needs close regulation. While subtherapeutical vancomycin serum concentration (VSC) is associated with increased mortality, accumulation is responsible for nephrotoxicity. Our study aimed to estimate the efficacy of a vancomycin-dosing protocol in reaching appropriate serum concentration in patients with and without kidney dysfunction. This was a retrospective study in critically ill patients treated with continuous infusion of vancomycin. Patients with creatinine clearance > 50 ml/min (Group A) were compared to those with creatinine clearance ≤ 50 ml/min (Group B). 348 patients were enrolled (210 in Group A, 138 in Group B). At first determination, patients with kidney dysfunction (Group B) had a statistically higher percentage of vancomycin in target range, while the percentage of patients with a VSC under the range was almost equal. These percentages differed at the subsequent measurements. The number of patients with low vancomycin concentration progressively decreased, except in those with augmented renal clearance; the percentage of patients with VSC over 30 mg/L was about 28 %, irrespective of the presence or absence of kidney dysfunction. Patients who reached a subtherapeutic level at the first VSC measurement had a significant correlation with in-hospital mortality. Our protocol seems to allow a rapid achievement of a target VSC particularly in patients with kidney dysfunction. In order to avoid subtherapeutical VSC, our algorithm should be implemented by the estimation of the presence of an augmented renal clearance.

Assessment of Endothelial Dysfunction: The Role of Symmetrical Dimethylarginine and Proinflammatory Markers in Chronic Kidney Disease and Renal Transplant Recipients

PubMed Central

Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana

2013-01-01

Objectives. The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙−) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. Materials and Methods. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Results. Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙− to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙− had better screening performance than SDMA alone. Conclusions. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies. PMID:24167363

[Retinal vasculopathy with cerebral leukoencephalopathy carrying TREX1 mutation diagnosed by the intracranial calcification: a case report].

PubMed

Komaki, Ryouhei; Ueda, Takehiro; Tsuji, Yukio; Miyawaki, Toko; Kusuhara, Sentaro; Hara, Shigeo; Toda, Tatsushi

2018-02-28

A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.

Pathophysiologic Implications of Reduced Podocyte Number in a Rat Model of Progressive Glomerular Injury

PubMed Central

Macconi, Daniela; Bonomelli, Maria; Benigni, Ariela; Plati, Tiziana; Sangalli, Fabio; Longaretti, Lorena; Conti, Sara; Kawachi, Hiroshi; Hill, Prue; Remuzzi, Giuseppe; Remuzzi, Andrea

2006-01-01

Changes in podocyte number or density have been suggested to play an important role in renal disease progression. Here, we investigated the temporal relationship between glomerular podocyte number and development of proteinuria and glomerulosclerosis in the male Munich Wistar Fromter (MWF) rat. We also assessed whether changes in podocyte number affect podocyte function and focused specifically on the slit diaphragm-associated protein nephrin. Age-matched Wistar rats were used as controls. Estimation of podocyte number per glomerulus was determined by digital morphometry of WT1-positive cells. MWF rats developed moderate hypertension, massive proteinuria, and glomerulosclerosis with age. Glomerular hypertrophy was already observed at 10 weeks of age and progressively increased thereafter. By contrast, mean podocyte number per glomerulus was lower than normal in young animals and further decreased with time. As a consequence, the capillary tuft volume per podocyte was more than threefold increased in older rats. Electron microscopy showed important changes in podocyte structure of MWF rats, with expansion of podocyte bodies surrounding glomerular filtration membrane. Glomerular nephrin expression was markedly altered in MWF rats and inversely correlated with both podocyte loss and proteinuria. Our findings suggest that reduction in podocyte number is an important determinant of podocyte dysfunction and progressive impairment of the glomerular permselectivity that lead to the development of massive proteinuria and ultimately to renal scarring. PMID:16400008

Association of N-Terminal Pro-B-Type Natriuretic Peptide with Left Ventricular Structure and Function in Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC])

PubMed Central

Mishra, Rakesh K.; Li, Yongmei; Ricardo, Ana C.; Yang, Wei; Keane, Martin; Cuevas, Magdalena; Christenson, Robert; DeFilippi, Christopher; Chen, Jing; He, Jiang; Kallem, Radhakrishna R.; Raj, Dominic S.; Schelling, Jeffrey R.; Wright, Jackson; Go, Alan S.; Shlipak, Michael G.

2017-01-01

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without clinical heart failure (HF), the Chronic Renal Insufficiency Cohort (n=3,232). Associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated by multivariable logistic and linear regression models. Reclassification of participants’ predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement (NRI) index that compared a clinical model with and without NT-proBNP. The median (interquartile range) NT-proBNP was 126.6 pg/ml (55.5–303.7). The highest quartile of NT-proBNP was associated with nearly three-fold odds of LVH (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.8–4.0) and LV systolic dysfunction (2.7, 1.7–4.5) and two-fold odds of diastolic dysfunction (2.0, 1.3–2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve, AUC 0.66) and LV systolic dysfunction (AUC 0.62), and poorly for the detection of diastolic dysfunction (AUC 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants’ likelihood of having LVH (NRI 0.14, 95% CI 0.13–0.15; p<0.001) and LV systolic dysfunction (0.28, 0.27–0.30; p<0.001), but not diastolic dysfunction (0.10, 0.10–0.11; p=0.07). In conclusion, in this large CKD cohort without HF, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. PMID:23178053

Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients.

PubMed

Campbell, Lucy J; Dew, Tracy; Salota, Rashim; Cheserem, Emily; Hamzah, Lisa; Ibrahim, Fowzia; Sarafidis, Pantelis A; Moniz, Caje F; Hendry, Bruce M; Poulton, Mary; Sherwood, Roy A; Post, Frank A

2012-08-10

Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI). Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR. In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.

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.

Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study.

PubMed

Wiebe, Sabrina; Schnell, David; Külzer, Raimund; Gansser, Dietmar; Weber, Anne; Wallenstein, Gudrun; Halabi, Atef; Conrad, Anja; Wind, Sven

2017-06-01

Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30-59 mL/min/1.73 m 2 and 15-29 mL/min/1.73 m 2 , respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC last ) and maximum plasma concentration (C max ) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUC last and C max , was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUC last for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3-213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28-39 % for moderate impairment, 34-42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

Early audit of renal complications in a new cardiac surgery service in Australia.

PubMed

Bolsin, Stephen N; Stow, Peter; Bucknell, Sarah

2004-09-01

To assess the incidence of renal failure in a cardiac surgery service commencing in Australia. Prospective data collection and retrospective database analysis. A tertiary referral, university teaching hospital in the state of Victoria, Australia. The first 502 patients undergoing cardiac surgery in this institution from commencement of the service. The overall rate of renal failure was low in comparison to other studies at 0.2% (95% CI 0.04-1.3%). The rate of postoperative renal dysfunction was also low at 4.2% (95% CI 2.7-6.5%). The safety of the new service with respect to this complication of cardiac surgery was good when compared with published data. However the lack of uniform definitions of renal failure following cardiac surgery make comparisons between studies difficult. Uniform reporting of this complication would facilitate comparisons between units and quality assurance activities in this field.

Serum cystatin C is independently associated with renal impairment and high sensitivity C-reactive protein in systemic lupus erythematosus.

PubMed

Chew, Christine; Pemberton, Philip W; Husain, Awal Al-M; Haque, Sahena; Bruce, Ian N

2013-01-01

In systemic lupus erythematosus (SLE) patients, glomerular filtration rate (GFR) is usually estimated using the modified Cockcroft-Gault (mCG) and Modification of Diet in Renal Disease (MDRD) equations. We aimed to study cystatin C (sCysC) in SLE to assess its agreement with standard renal indices and investigate factors affecting sCysC in SLE. SLE patients (≥4 ACR criteria) and healthy women from Greater Manchester were recruited and clinical assessments were undertaken. SCysC was measured using R & D Systems' ELISA. Agreement between renal measures was assessed using Deming plots and factors associated with sCysC in SLE were examined by multiple linear regression analyses. 178 patients and 68 controls had median (IQR) ages of 53 (46-61) and 50 (39-60) years, respectively. In an age-adjusted analysis, SLE patients had higher sCysC (1.16 [0.98-1.36] vs. 0.950 [0.73-1.13] mg/l; p<0.0001) and within SLE those with a history of lupus nephritis had higher sCysC (1.31 [1.10-1.66] vs. 1.11 [0.95-1.29] mg/l; p<0.005). SCysC correlated positively with serum creatinine, and inversely to renal measures (r=-0.530; p<0.0001 [mCG], and r=-0.620; p<0.0001 [MDRD]). There was closer agreement between the two eGFR measures than between either eGFR measures and sCysC. In addition to age and serum creatinine, a multivariate analysis (β, p) found that high-sensitivity C-reactive protein (hs-CRP) (0.03, 0.026) was also independently associated with sCysC in SLE. In SLE, sCysC may be influenced by low grade inflammation as well as by renal dysfunction. Therefore, SCysC should not supplant current assessment of renal dysfunction in SLE.

Renal outcomes of simultaneous liver-kidney transplantation compared to liver transplant alone for candidates with renal dysfunction.

PubMed

Brennan, Todd V; Lunsford, Keri E; Vagefi, Parsia A; Bostrom, Alan; Ma, Michael; Feng, Sandy

2015-01-01

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD-LTA; n = 103) or simultaneous liver-kidney transplant (RD-SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)-glomerular filtration rate (GFR) <25 mL/min/1.73 m(2) . RD-LTAs had worse one-yr post-transplant survival compared to RD-SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD-LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD-LTA recipients died in the first post-transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD-LTA recipients might have derived survival benefit from RD-SLKT. Overall, 87% of RD-LTA patients recovered renal function within one month of transplant. One yr after RD-LTA or RD-SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD-SLKT would have yielded substantial short-term survival benefit to RD-LTA recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

PubMed

Shin, Dong Ho; Lee, Young-Ki; Oh, Jieun; Yoon, Jong-Woo; Rhee, So Yon; Kim, Eun-Jung; Ryu, Jiwon; Cho, Ajin; Jeon, Hee Jung; Choi, Myung-Jin; Noh, Jung-Woo

2017-01-01

Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis. This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment. The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08). Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

[Diagnosis and treatment of symptomatic hydronephrosis in pregnancy].

PubMed

Simonsen, Jane Angel; Graumann, Ole; Toft, Anja; Henriques, Carsten Ulrik; Walter, Steen

2015-09-14

Hydronephrosis in pregnancy is common in the second and third trimester. Only a few cases are symptomatic, caused by a ureteric stone or by the pregnancy itself. The clinical dilemma is when to treat and when not to treat. We propose a multidisciplinary management based on renal ultrasonography to verify hydronephrosis and renography to diagnose obstructive hydronephrosis. Obstruction with a high intra-renal pressure must be treated to avoid kidney dysfunction. Patients with pyonephrosis need immediate treatment.

The effect of methoxyflurane analgesia on renal function in burned patients: an investigation

PubMed Central

Laird, S. M.; Chrystal, Kathleen M. R.

1972-01-01

This paper reports an investigation into evidence of renal dysfunction following methoxyflurane analgesia for burns dressings. Twelve patients were studied and small increases in serum uric acid were observed in all of them. This increase may have been dose-related. Four patients had small but consistent increases in blood urea nitrogen and serum creatinine on the third post-dressing day. No definite conclusions can be adduced and further research is needed. PMID:5024150

The International Scoring System (ISS) for multiple myeloma remains a robust prognostic tool independently of patients' renal function.

PubMed

Dimopoulos, M A; Kastritis, E; Michalis, E; Tsatalas, C; Michael, M; Pouli, A; Kartasis, Z; Delimpasi, S; Gika, D; Zomas, A; Roussou, M; Konstantopoulos, K; Parcharidou, A; Zervas, K; Terpos, E

2012-03-01

The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction.

A Canola Oil-Supplemented Diet Prevents Type I Diabetes-Caused Lipotoxicity and Renal Dysfunction in a Rat Model.

PubMed

Cano-Europa, Edgar; Ortiz-Butron, Rocio; Camargo, Estela Melendez; Esteves-Carmona, María Miriam; Oliart-Ros, Rosa Maria; Blas-Valdivia, Vanessa; Franco-Colin, Margarita

2016-11-01

We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated. The mesenteric, retroperitoneal, and epididymal fat pads were dissected and weighed. The kidneys were used for lipid peroxidation (LP) and reactive oxygen species (ROS) quantifications. Diabetic rats fed with a canola oil-supplemented diet had higher body weights, were less hyperphagic, and their mesenteric, retroperitoneal, and epididymal fat pads weighed more than diabetic rats on an unsupplemented diet. The canola oil-supplemented diet decreased plasmatic concentrations of free fatty acids, triglycerides, and cholesterol; showed improved osmolarity, water clearances, and creatinine depuration; and had decreased LP and ROS. A canola oil-supplemented diet decreases hyperphagia and prevents lipotoxicity and renal dysfunction in a type I diabetes mellitus model.

Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

2018-01-01

The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice*

PubMed Central

Villar, Van Anthony M.; Jones, John Edward; Armando, Ines; Asico, Laureano D.; Escano, Crisanto S.; Lee, Hewang; Wang, Xiaoyan; Yang, Yu; Pascua-Crusan, Annabelle M.; Palmes-Saloma, Cynthia P.; Felder, Robin A.; Jose, Pedro A.

2013-01-01

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that SNX1 depletion results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension. PMID:23152498

Mortality predictors in renal transplant recipients with severe sepsis and septic shock.

PubMed

de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

2014-01-01

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51 ± 13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16-23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6-2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤ 1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥ 2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2-2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8-102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0-22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2-9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9-16.6; p = 0.002). Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

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

Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov; Ho, Wen-Chao; Caffrey, James L.

Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214more » had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues. • Nutritional status is important in the assessment of cadmium nephrotoxicity.« less

Detection of relationships between SUDOSCAN with estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes.

PubMed

Mao, Fei; Zhu, Xiaoming; Lu, Bin; Li, Yiming

2018-04-01

SUDOSCAN (Impeto Medical, Paris, France) has been proved to be a new and non-invasive method in detecting renal dysfunction in type 2 diabetes mellitus (T2DM) patients. In this study, we sought to compare the result of diabetic kidney dysfunction score (DKD-score) of SUDOSCAN with estimated glomerular filtration rate (eGFR) by using quantile regression analysis, which was completely different from previous studies. A total number of 223 Chinese T2DM patients were enrolled in the study. SUDOSCAN, renal function test (including blood urea nitrogen, creatinine and uric acid) and 99 mTc-diethylenetriamine pentaacetic acid ( 99 mTc-DTPA) renal dynamic imaging were performed in all T2DM patients. DKD-score of SUDOSCAN was compared with eGFR detected by 99 mTc-DTPA renal dynamic imaging through quantile regression analysis. Its validation and utility was further determined through bias and precision test. The quantile regression analysis demonstrated the relationship with eGFR was inverse and significant for almost all percentiles of DKD-score. The coefficients decreased as the percentile of DKD-score increased. And in validation data set, both the bias and precision were increased with the eGFR (median difference, -21.2 ml/min/1.73 m 2 for all individuals vs. -4.6 ml/min/1.73 m 2 for eGFR between 0 and 59 ml/min/1.73 m 2 ; interquartile range [IQR] for the difference, -25.4 ml/min/1.73 m 2 vs. -14.7 ml/min/1.73 m 2 ). The eGFR category misclassification rate were 10% in eGFR 0-59 ml/min/1.73 m 2 group, 57.3% in 60-90 group, and 87.2% in eGFR > 90 ml/min/1.73 m 2 group. DKD-score of SUDOSCAN could be used to detect renal dysfunction in T2DM patients. A higher prognostic value of DKD-score was detected when eGFR level was lower. Copyright © 2018 Elsevier B.V. All rights reserved.

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial.

PubMed

Davies, Melanie J; Bain, Stephen C; Atkin, Stephen L; Rossing, Peter; Scott, David; Shamkhalova, Minara S; Bosch-Traberg, Heidrun; Syrén, Annika; Umpierrez, Guillermo E

2016-02-01

Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment. In this 26-week, double-blind trial, 279 patients with HbA1c 7-10%, BMI 20-45 kg/m(2), and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2); MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139). The estimated treatment difference in HbA1c from baseline to week 26 was -0.66% (-7.25 mmol/mol) (95% CI -0.90 to -0.43 [-9.82 to -4.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (-1.22 mmol/L [-22.0 mg/dL]) than with placebo (-0.57 mmol/L [-10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (-2.41 kg) than with placebo (-1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: -1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P < 0.0001). Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A two-hit mechanism for sepsis-induced impairment of renal tubule function

PubMed Central

Watts, Bruns A.; George, Thampi; Sherwood, Edward R.

2013-01-01

Renal insufficiency is a common and severe complication of sepsis, and the development of kidney dysfunction increases morbidity and mortality in septic patients. Sepsis is associated with a variety of defects in renal tubule function, but the underlying mechanisms are incompletely understood. We used a cecal ligation and puncture (CLP) model to examine mechanisms by which sepsis influences the transport function of the medullary thick ascending limb (MTAL). MTALs from sham and CLP mice were studied in vitro 18 h after surgery. The results show that sepsis impairs the ability of the MTAL to absorb HCO3− through two distinct mechanisms. First, sepsis induces an adaptive decrease in the intrinsic capacity of the tubules to absorb HCO3−. This effect is associated with an increase in ERK phosphorylation in MTAL cells and is prevented by pretreatment of CLP mice with a MEK/ERK inhibitor. The CLP-induced reduction in intrinsic HCO3− absorption rate appears to involve loss of function of basolateral Na+/H+ exchange. Second, sepsis enhances the ability of LPS to inhibit HCO3− absorption, mediated through upregulation of Toll-like receptor 4 (TLR4)-ERK signaling in the basolateral membrane. The two inhibitory mechanisms are additive and thus can function in a two-hit capacity to impair renal tubule function in sepsis. Both effects depend on ERK and are eliminated by interventions that prevent ERK activation. Thus the TLR4 and ERK signaling pathways represent potential therapeutic targets to treat or prevent sepsis-induced renal tubule dysfunction. PMID:23324175

The Zhongshan score: a novel and simple anatomic classification system to predict perioperative outcomes of nephron-sparing surgery.

PubMed

Zhou, Lin; Guo, Jianming; Wang, Hang; Wang, Guomin

2015-02-01

In the zero ischemia era of nephron-sparing surgery (NSS), a new anatomic classification system (ACS) is needed to adjust to these new surgical techniques. We devised a novel and simple ACS, and compared it with the RENAL and PADUA scores to predict the risk of NSS outcomes. We retrospectively evaluated 789 patients who underwent NSS with available imaging between January 2007 and July 2014. Demographic and clinical data were assessed. The Zhongshan (ZS) score consisted of three parameters. RENAL, PADUA, and ZS scores are divided into three groups, that is, high, moderate, and low scores. For operative time (OT), significant differences were seen between any two groups of ZS score and PADUA score (all P < 0.05). For ZS score, patients with moderate and high scores had longer warm ischemia time (WIT) and greater increase in SCr compared with low score (all P < 0.05). What is more, the differences between moderate and high scores classified by ZS score were borderline but trending toward significance in WIT (P = 0.064) and increase in SCr (P = 0.052). Interestingly, RENAL showed no significant difference between moderate and high complexity in OT, WIT, estimated blood loss, and increase in SCr. Compared with patients with a low score of ZS, those with a high or moderate score had 8.1-fold or 3.3-fold higher risk of surgical complications, respectively (all P < 0.05). As for RENAL score, patients with a high or moderate score had 5.7-fold or 1.9-fold higher risk of surgical complications, respectively (all P < 0.05). Patients with a high or moderate score of PADUA had 2.3-fold or 2.8-fold higher risk of surgical complications, respectively (all P < 0.05). In the ROC curve analysis, ZS score had the greatest AUC for surgical complications (AUC = 0.632) and the conversion to radical nephrectomy (AUC = 0.845) (all P < 0.05). In conclusion, the ability of ZS score to predict the surgical complexity and surgical complications of NSS is better than RENAL and PADUA scores. ZS score could be used to reflect the surgical complexity and predict the risk of surgical complications in patients undergoing NSS.

The Zhongshan Score

PubMed Central

Zhou, Lin; Guo, Jianming; Wang, Hang; Wang, Guomin

2015-01-01

Abstract In the zero ischemia era of nephron-sparing surgery (NSS), a new anatomic classification system (ACS) is needed to adjust to these new surgical techniques. We devised a novel and simple ACS, and compared it with the RENAL and PADUA scores to predict the risk of NSS outcomes. We retrospectively evaluated 789 patients who underwent NSS with available imaging between January 2007 and July 2014. Demographic and clinical data were assessed. The Zhongshan (ZS) score consisted of three parameters. RENAL, PADUA, and ZS scores are divided into three groups, that is, high, moderate, and low scores. For operative time (OT), significant differences were seen between any two groups of ZS score and PADUA score (all P < 0.05). For ZS score, patients with moderate and high scores had longer warm ischemia time (WIT) and greater increase in SCr compared with low score (all P < 0.05). What is more, the differences between moderate and high scores classified by ZS score were borderline but trending toward significance in WIT (P = 0.064) and increase in SCr (P = 0.052). Interestingly, RENAL showed no significant difference between moderate and high complexity in OT, WIT, estimated blood loss, and increase in SCr. Compared with patients with a low score of ZS, those with a high or moderate score had 8.1-fold or 3.3-fold higher risk of surgical complications, respectively (all P < 0.05). As for RENAL score, patients with a high or moderate score had 5.7-fold or 1.9-fold higher risk of surgical complications, respectively (all P < 0.05). Patients with a high or moderate score of PADUA had 2.3-fold or 2.8-fold higher risk of surgical complications, respectively (all P < 0.05). In the ROC curve analysis, ZS score had the greatest AUC for surgical complications (AUC = 0.632) and the conversion to radical nephrectomy (AUC = 0.845) (all P < 0.05). In conclusion, the ability of ZS score to predict the surgical complexity and surgical complications of NSS is better than RENAL and PADUA scores. ZS score could be used to reflect the surgical complexity and predict the risk of surgical complications in patients undergoing NSS. PMID:25654399

Endothelial dysfunction, platelet activation, thrombogenesis and fibrinolysis in patients with hypertensive crisis.

PubMed

van den Born, Bert-Jan H; Löwenberg, Ester C; van der Hoeven, Niels V; de Laat, Bas; Meijers, Joost C M; Levi, Marcel; van Montfrans, Gert A

2011-05-01

Hypertensive crisis is an extreme phenotype of hypertension and hypertension-related thrombotic complications. This is most evident in patients with hypertensive crisis having advanced retinopathy and thrombotic microangiopathy (TMA). We examined whether hypertensive crisis complicated by advanced retinopathy is associated with endothelial dysfunction, platelet activation, thrombin generation and decreased fibrinolytic activity. In addition, we tested the association between these procoagulant changes and the development of TMA and end-organ dysfunction. Several key mediators of coagulation were assessed in 40 patients with hypertensive crisis with and without retinopathy and compared with 20 age, sex and ethnicity-matched normotensive controls. In patients with hypertensive crisis, associations with markers of TMA and renal dysfunction were assessed by regression analysis. Soluble P-selectin levels were higher in patients with hypertensive crisis compared with controls regardless of the presence or absence of retinopathy (P<0.01). Levels of von Willebrand factor (VWF), VWF propeptide, prothrombin fragment 1+2 (F1+2) and plasmin-antiplasmin (PAP) complexes were significantly higher in hypertensive crisis with retinopathy compared with normotensive controls (P-values<0.01), whereas in patients without retinopathy only VWF propeptide was higher (P=0.04). VWF, VWF propeptide, soluble tissue factor, F1+2 and PAP were positively associated with markers of TMA and renal dysfunction (P≤0.05). Hypertensive crisis with retinopathy confers a prothrombotic state characterized by endothelial dysfunction, platelet activation and increased thrombin generation, whereas fibrinolytic activity is enhanced. The observed changes in prothrombotic and antithrombotic pathways may contribute to the increased risk of ischaemic and haemorrhagic complications in this extreme hypertension phenotype. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

PubMed

Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

2014-01-01

A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction

PubMed Central

Leung, Angela M.; Braverman, Lewis E.; Brent, Gregory A.; Pearce, Elizabeth N.

2015-01-01

Context: Thyroid hormone production is dependent on adequate iodine intake. Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in susceptible individuals after excess iodine exposure. Radiological iodinated contrast media represent an increasingly common source of excess iodine. Objective: This review will discuss the thyroidal response after acute exposure to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine-induced thyroid dysfunction in vulnerable populations, such as the fetus, neonate, and patients with impaired renal function; and recommendations for the assessment and treatment of contrast iodine-induced thyroid dysfunction. Methods: Data for this review were identified by searching PubMed, Google Scholar, and references from relevant articles from 1948 to 2014. Conclusions: With the increase in the use of computed tomography scans in the United States, there is increasing risk of contrast-induced thyroid dysfunction. Patients at risk of developing iodine-induced thyroid dysfunction should be closely monitored after receiving iodinated contrast media and should be treated as needed. PMID:25375985

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Protective role of curcumin on renal ischemia reperfusion injury via attenuating the inflammatory mediators and Caspase-3.

PubMed

Liu, F-H; Ni, W-J; Wang, G-K; Zhang, J-J

2016-09-30

Renal ischemia/reperfusion (I/R) damage may arise due to nephron sparing surgery in patient with a solitary kidney of restricted renal parenchymas. Apoptosis, inflammation and oxidative stress play a significant role in the expansion of renal dysfunction following renal I/R. The aim of the current investigation was to particularize the potential effect of curcumin against hypoxia induced renal injury. The albino Wistar rats divided into groups and each group contains six rats. They groups are normal control; disease control; curcumin (5 mg/kg per day) and another group orally treated with curcumin (10 mg/kg per day) for two weeks before induction of renal I/R. The renal and serum samples were collected and used for the biochemical estimation. The renal tissue was further used for the histopathological estimation. The result of the current investigation demonstrated that the curcumin significantly (P<0.01) attenuated I/R induced renal injury in a dose-dependent way. It also causes significant (P<0.01) reduction in the serum creatinine, blood urea nitrogen level and also suppressed the kidney injury molecules-1. Additionally, it also causes significant inhibition of the malonaldehyde, caspase-3, myeloperoxide, lactose dehydrogenase and interferon-gamma together with enhanced interlukin-10 content.

Sickle cell disease: renal manifestations and mechanisms

PubMed Central

Nath, Karl A.; Hebbel, Robert P.

2015-01-01

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

Renal function monitoring in heart failure – what is the optimal frequency? A narrative review

PubMed Central

Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2017-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication‐based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. PMID:28901643

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction.

PubMed

Gosselin, H; Qi, X; Rouleau, J L

1998-01-01

Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly overestimate the degree of ventricular dysfunction. In moderate infarctions, the remaining viable myocardium of the ventricular wall has preserved contractility while papillary muscle function is depressed. In this relatively early postinfarction phase, ventricular remodelling appears to help maintain left ventricular function in both moderate and large infarctions.

Cirrhotic cardiomyopathy

PubMed Central

Ruiz-del-Árbol, Luis; Serradilla, Regina

2015-01-01

During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice

PubMed Central

Liu, Mi; Sun, Ying; Zhang, Aihua; Yang, Tianxin

2016-01-01

Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response. PMID:27340345

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature

PubMed Central

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

2017-01-01

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

PubMed

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Ketorolac as an analgesic agent for infants and children after cardiac surgery: safety profile and appropriate patient selection.

PubMed

Jalkut, Meredith K

2014-01-01

Ketorolac has been used safely as an analgesic agent for children following cardiac surgery in selected populations. Controversy exists among institutions about the risks involved with this medication in this patient group. This article reviews the current literature regarding the safety of ketorolac for postoperative pain management in children after cardiac surgery. Specifically, concerns about renal dysfunction and increased bleeding risk are addressed. Additionally, the article details pharmacokinetics and potential benefits of ketorolac, such as its opioid-sparing effect. The literature reflects that the use of this medication is not well studied in certain pediatric cardiac patients such as neonates and those with single-ventricle physiology, and the safety of this medication in regards to these special populations is reviewed. In conclusion, ketorolac can be used in specific pediatric patients after cardiac surgery with minimal risk of bleeding or renal dysfunction with appropriate dosing and duration of use.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

PubMed Central

Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae

2016-01-01

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

[Change of creatinine clearance rate in accordance with aging in Japanese patients with head and neck cancer].

PubMed

Nishimura, Goshi; Horiuchi, Choichi; Yoshida, Takafumi; Kawakami, Mariko; Yabuki, Kenichiro; Taguchi, Takahide; Nagao, Junichi; Kondo, Norio; Masuda, Yoko; Matsuda, Hideki; Mikami, Yasukazu; Tsukuda, Mamoru

2006-04-01

Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5-fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate pre and post-hydration or combined administration of neutralizing agents is performed during CDDP injection. Before the CDDP administration, we have to evaluate renal function of the patients using creatinine clearance rate (Ccr). In Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over 65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the discrepancy is based on the poor renal function of Japanese. We calculated Ccrs of 107 head and neck cancer patients since January, 2004 to August, 2005, and evaluated renal function before any treatment. Ccr was decreased in proportion to aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65 ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the United States, the average glomerular filtration rate of over 70 year-old healthy people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient kidney function for the administration of CDDP at the dose of 70-100 mg/ m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the United States than in Japan. The incident rate of diabetes, which is the main cause of renal dysfunction, is almost the same in both countries. Though the reason is unclear, it is the fact that the renal function of Japanese decreases quickly in accordance with aging.

Prenatal and early postnatal intoxication by inorganic mercury resulting from the maternal use of mercury containing soap.

PubMed

Lauwerys, R; Bonnier, C; Evrard, P; Gennart, J P; Bernard, A

1987-05-01

A case of slight renal tubular dysfunction associated with cataract and anaemia was diagnosed in a 3-month-old black boy in whom high levels of mercury were found in blood and urine. Several arguments suggest that the renal, ocular and haematological defects may have resulted from exposure to mercury during foetal life and the 1-month lactation period due to the extensive use of inorganic mercury containing cosmetics by the mother.

Memantine-associated hyperkalaemia in a patient with Alzheimer's disease.

PubMed

Tsukamoto, Tatsuo; Yamada, Hidetaka; Uchimura, Naohisa

2013-09-01

Memantine is an N-methyl-D-aspartate glutamate receptor antagonist that may improve cognitive functions in patients with Alzheimer's disease. It is predominantly excreted unchanged via the kidneys, and patients with decreased creatinine clearance must be treated with lower doses of memantine. However, it is unclear whether memantine itself can lead to renal dysfunction and/or hyperkalaemia. We report a patient with renal impairment and hyperkalaemia possibly associated with memantine administration. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

Acute renal failure related to rhabdomyolysis: pathophysiology, diagnosis, and collaborative management.

PubMed

Russell, T A

2000-12-01

Acute renal failure related to exertional rhabdomyolysis is a medical condition that, if not diagnosed correctly and treated aggressively, can lead to serious dysfunction and may result in death. Although the history is invaluable in diagnosing this condition, it must be confirmed by laboratory testing. The sometimes subtle manifestations of exertional (non-traumatic) rhabdomyolysis make it mandatory that the health care team is able to recognize the signs and symptoms and understand the pathophysiology for prompt treatment and referral.

Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

PubMed Central

Oniki, Kentaro; Saruwatari, Junji; Izuka, Tomoko; Kajiwara, Ayami; Morita, Kazunori; Sakata, Misaki; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

2015-01-01

In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11–8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction. PMID:26200108

Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction

PubMed Central

Ito, Sadayoshi; Satoh, Minoru; Tamaki, Yuko; Gotou, Hiromi; Charney, Alan; Okino, Naoko; Akahori, Mizuki; Zhang, Jack

2015-01-01

This 8-week, multi-center, open-label study assessed the safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Patients (n=32) with mean sitting systolic blood pressure (msSBP) ⩾140 mm Hg (after a 2–5-week washout of previous antihypertensive medications) and estimated glomerular filtration rate (eGFR) ⩾15 and <60 ml min−1 1.73 m−2 received LCZ696 100 mg with an optional titration to 200 and 400 mg in a sequential manner starting from Week 2 in patients with inadequate BP control (msSBP ⩾130 mm Hg and mean sitting diastolic blood pressure (msDBP) ⩾80 mm Hg) and without safety concerns. Safety was assessed by monitoring and recording all adverse events (AEs) and change in potassium and creatinine. Efficacy was assessed as change from baseline in msSBP/msDBP. The mean baseline BP was 151.6/86.9 mm Hg, urinary albumin/creatinine ratio (UACR) geometric mean was 7.3 mg mmol−1 and eGFR was ⩾30 and <60 in 25 (78.1%) patients and was ⩾15 and <30 in 7 (21.9%) patients. Fourteen (43.8%) patients reported at least one AE, which were mild in severity. No severe AEs or deaths were reported. There were no clinically meaningful changes in creatinine, potassium, blood urea nitrogen and eGFR. The geometric mean reduction in UACR was 15.1%, and the mean reduction in msSBP and msDBP was 20.5±11.3 and 8.3±6.3 mm Hg, respectively, from baseline to Week 8 end point. LCZ696 was generally safe and well tolerated and showed effective BP reduction in Japanese patients with hypertension and renal dysfunction without a decline in renal function. PMID:25693859

The relationship between the Activities-specific Balance Confidence Scale and the Dynamic Gait Index in peripheral vestibular dysfunction.

PubMed

Legters, Kristine; Whitney, Susan L; Porter, Rebecca; Buczek, Frank

2005-01-01

People with vestibular dysfunction experience dizziness, vertigo and postural instability. The persistence of these symptoms may result in decreased balance confidence. The purpose of the present study was to examine the relationship between decreased balance confidence and gait dysfunction in patients with unilateral peripheral vestibular dysfunction. A retrospective review of 137 charts with the Activities-specific Balance Confidence (ABC) Scale and the Dynamic Gait Index (DGI) scores was completed. Spearman rank-order correlation analysis was performed of the total sample, by age group and by degree of vestibular weakness. A moderate correlation of r = 0.58 (p < 0.001) was found between the ABC Scale score and the DGI score in the total sample. Those with mild or moderate vestibular weakness had a correlation of r = 0.72 (p < 0.001) between the ABC Scale score and the DGI score, compared with a correlation of r = 0.48 in those with severe or total vestibular weakness. Decreased balance confidence and increased fall risk are critical issues for people with vestibular dysfunction. The effects of aging did not have a significant impact on the relationship. The correlation between balance confidence and gait dysfunction was stronger in those with mild or moderate vestibular weakness, although those with severe or total weakness were more disabled by their vestibular symptoms.

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

PubMed Central

Mimoz, O; Jacolot, A; Padoin, C; Quillard, J; Tod, M; Louchahi, K; Samii, K; Petitjean, O

1996-01-01

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy. PMID:8851623

Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

PubMed

Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

2011-08-01

Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

The association between changes in lifestyle behaviors and the incidence of chronic kidney disease (CKD) in middle-aged and older men.

PubMed

Michishita, Ryoma; Matsuda, Takuro; Kawakami, Shotaro; Tanaka, Satoshi; Kiyonaga, Akira; Tanaka, Hiroaki; Morito, Natsumi; Higaki, Yasuki

2017-08-01

This study was designed to evaluate whether changes in lifestyle behaviors are correlated with the incidence of chronic kidney disease (CKD). The subjects consisted of 316 men without a history of cardiovascular disease, stroke, or renal dysfunction or dialysis treatment. The following lifestyle behaviors were evaluated using a standardized self-administered questionnaire: habitual moderate exercise, daily physical activity, walking speed, eating speed, late-night dinner, bedtime snacking, skipping breakfast, and drinking and smoking habits. The subjects were divided into four categories according to the change in each lifestyle behavior from baseline to the end of follow-up (healthy-healthy, unhealthy-healthy, healthy-unhealthy and unhealthy-unhealthy). A multivariate analysis showed that, with respect to habitual moderate exercise and late-night dinner, maintaining an unhealthy lifestyle resulted in a significantly higher odds ratio (OR) for the incidence of CKD than maintaining a lifestyle (OR 8.94; 95% confidence interval [CI], 1.10-15.40 for habitual moderate exercise and OR 4.00; 95% CI, 1.38-11.57 for late-night dinner). In addition, with respect to bedtime snacking, the change from a healthy to an unhealthy lifestyle and maintaining an unhealthy lifestyle resulted in significantly higher OR for incidence of CKD than maintaining a healthy lifestyle (OR 4.44; 95% CI, 1.05-13.93 for healthy-unhealthy group and OR 11.02; 95% CI, 2.83-26.69 for unhealthy-unhealthy group). The results of the present study suggest that the lack of habitual moderate exercise, late-night dinner, and bedtime snacking may increase the risk of CKD. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

[Differential diagnosis of hypercalcemia--a retrospective study of 46 dogs].

PubMed

Uehlinger, P; Glaus, T; Hauser, B; Reusch, C

1998-01-01

The case records of 46 dogs with hypercalcemia were studied retrospectively. The most common cause of hypercalcemia was malignancy, of which the majority were diagnosed as having lymphosarcoma (LSA, n = 23). Interestingly only 15 had palpable lymphadenopathy. Other neoplasia were apocrine adenocarcinoma of the anal sac (n = 4), mammary adenocarcinoma (n = 2), anaplastic carcinoma (n = 1), and malignant histiocytosis (n = 1). Non-neoplastic reasons for hypercalcemia were hypoadrenocorticism (n = 5), acute renal failure (n = 2), chronic renal failure (n = 2), hypervitaminosis D (n = 1), and primary hyperparathyroidism (n = 1). In 4 cases no definitive diagnosis could be obtained. Moderate to marked hyperphosphatemia and azotemia was found in all dogs with primary renal failure and in 4 of 5 dogs with hypoadrenocorticism. In contrast only 4 of 31 dogs with neoplasia showed (mild) hyperphosphatemia and 20 showed mild to moderate azotemia. Elevated PTH levels were found in dogs with primary chronic renal failure and with primary hyperparathyroidism, but also in one dog with neoplasia. Low PTH concentrations were measured in the dog with hypervitaminosis D and in 8 cases with neoplasia. Additional three cases with neoplasia had values in the reference range. 1. The most common cause of hypercalcemia is LSA. Absence of palpable lymphadenopathy does not exclude LSA and further diagnostic steps may be necessary 2. The combination of moderate to marked hyperphosphatemia suggests primary renal failure or hypoadrenocorticism. 3. An elevated PTH level is consistent with primary hyperparathyroidism, but does not exclude other causes of hypercalcemia.

The pharmacokinetics of peginterferon lambda-1a following single dose administration to subjects with impaired renal function.

PubMed

Hruska, Matthew W; Adamczyk, Robert; Colston, Elizabeth; Hesney, Michael; Stonier, Michele; Myler, Heather; Bertz, Richard

2015-09-01

This open label study was conducted to assess the effect of renal impairment (RI) on the pharmacokinetics (PK) of peginterferon lambda-1a (Lambda). Subjects (age 18-75 years, BMI 18-35 kg m(-2) ) were enrolled into one of five renal function groups: normal (n = 12), mild RI (n = 8), moderate RI (n = 8), severe RI (n = 7), end-stage renal disease (ESRD, n = 8) based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Subjects received a single dose of Lambda (180 µg) subcutaneously on day 1 followed by PK serum sample collections through day 29. Safety, tolerability and immunogenicity data were collected through day 43. PK parameters were estimated and summarized by group. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated between normal and RI groups. With decreasing eGFR, Lambda exposure (Cmax , AUC) increased while apparent clearance (CL/F) and apparent volume of distribution (V/F) decreased. Relative to subjects with normal renal function (geometric mean AUC = 99.5 ng ml(-1) h), Lambda exposure estimates (AUC) were slightly increased in the mild RI group (geometric mean [90% CI]: 1.20 [0.82, 1.77]) and greater in the moderate (1.95 [1.35, 2.83]), severe RI (1.95 [1.30, 2.93]) and ESRD (1.88 [1.30, 2.73]) groups. Lambda was generally well tolerated. The results demonstrated that RI reduces the clearance of Lambda and suggests that dose modifications may not be required in patients with mild RI but may be required in patients with moderate to severe RI or ESRD. © 2015 The British Pharmacological Society.

Pharmacokinetics of brotizolam in renal failure

PubMed Central

Evers, J.; Renner, E.; Bechtel, W. D.

1983-01-01

1 Kinetics of brotizolam (0.25 mg) were studied in patients with different degrees of renal failure after single and repeated oral ingestion. Serum levels were analysed by radio-immunoassay. 2 Patients were divided into three groups according to their renal function, i.e. creatinine clearance values of 45-80, 15-45, or less than 15 ml/min. 3 The mean elimination half-life was 6.9-8.15 h, with a considerable variation of the peak concentration and elimination half-life in slight to moderate renal failure. There was no delay in elimination in severe renal failure and there was no drug accumulation. 4 No dose adjustment is necessary for brotizolam in renal failure. PMID:6661376

Epidemiologic characteristics and risk factors for renal cell cancer

PubMed Central

Lipworth, Loren; Tarone, Robert E; Lund, Lars; McLaughlin, Joseph K

2009-01-01

Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches, including evaluation of gene–environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer. PMID:20865085

Preventing Contrast-induced Renal Failure: A Guide.

PubMed

Faggioni, Michela; Mehran, Roxana

2016-10-01

Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid deterioration of renal function within a few days of parenteral administration of contrast media (CM) in the absence of alternative causes. CI-AKI is the most common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 % in patients undergoing percutaneous coronary intervention. Although usually self-resolving, in patients with pre-existing chronic kidney disease (CKD) or concomitant risk factors for renal damage, CI-AKI is associated with increased short-and long-term morbidity and mortality. Therefore, risk stratification based on clinical and peri-procedural characteristics is crucial in selecting patients at risk of CI-AKI who would benefit the most from implementation of preventive measures.

Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway.

PubMed

Osumi, Tomoo; Awazu, Midori; Fujimura, Eriko; Yamazaki, Fumito; Hashiguchi, Akinori; Shimada, Hiroyuki

2013-06-01

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.

A case of denosumab-induced hypocalcaemia in a patient with non-metastatic prostate cancer and renal impairment.

PubMed

Blackley, S; Anderson, K; Berg, J

2015-01-01

Denosumab is an emerging new treatment for osteoporosis in postmenopausal women and men with non-metastatic prostate cancer. It is largely used by specialists as an alternative treatment in patients with contraindications to traditional, more commonly used drugs such as bisphosphonates. One important side effect is hypocalcaemia, which may be life threatening. The risk of this is increased in renal impairment, mainly if eGFR < 30 ml/min/1.73m(2), and is exacerbated by vitamin D insufficiency. This is a case study of prolonged symptomatic hypocalcaemia after a single dose of denosumab in a patient with non-metastatic prostate cancer and moderate renal impairment (eGFR 40 ml/min/1.73m(2)). The patient presented with acute confusion, muscle cramps and myoclonic jerks 5 weeks after treatment. This case demonstrates the need to be aware of adverse effects of denosumab in mild-moderate renal impairment and the need to monitor calcium levels pre- and post-treatment.

Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research.

PubMed

Allen, Mark S; Walter, Emma E

2018-04-01

Sexual dysfunction is a common problem among men and women and is associated with negative individual functioning, relationship difficulties, and lower quality of life. To determine the magnitude of associations between 6 health-related lifestyle factors (cigarette smoking, alcohol intake, physical activity, diet, caffeine, and cannabis use) and 3 common sexual dysfunctions (erectile dysfunction, premature ejaculation, and female sexual dysfunction). A comprehensive literature search of 10 electronic databases identified 89 studies that met the inclusion criteria (452 effect sizes; N = 348,865). Pooled mean effects (for univariate, age-adjusted, and multivariable-adjusted estimates) were computed using inverse-variance weighted random-effects meta-analysis and moderation by study and population characteristics were tested using random-effects meta-regression. Mean effect sizes from 92 separate meta-analyses provided evidence that health-related lifestyle factors are important for sexual dysfunction. Cigarette smoking (past and current), alcohol intake, and physical activity had dose-dependent associations with erectile dysfunction. Risk of erectile dysfunction increased with greater cigarette smoking and decreased with greater physical activity. Alcohol had a curvilinear association such that moderate intake was associated with a lower risk of erectile dysfunction. Participation in physical activity was associated with a lower risk of female sexual dysfunction. There was some evidence that a healthy diet was related to a lower risk of erectile dysfunction and female sexual dysfunction, and caffeine intake was unrelated to erectile dysfunction. Publication bias appeared minimal and findings were similar for clinical and non-clinical samples. Modification of lifestyle factors would appear to be a useful low-risk approach to decreasing the risk of erectile dysfunction and female sexual dysfunction. Strengths include the testing of age-adjusted and multivariable-adjusted models and tests of potential moderators using meta-regression. Limitations include low statistical power in models testing diet, caffeine, and cannabis use as risk factors. Results provide compelling evidence that cigarette smoking, alcohol, and physical activity are important for sexual dysfunction. Insufficient research was available to draw conclusions regarding risk factors for premature ejaculation or for cannabis use as a risk factor. These findings should be of interest to clinicians treating men and women with complaints relating to symptoms of sexual dysfunction. Allen MS, Walter EE. Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research. J Sex Med 2018;15:458-475. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin

PubMed Central

do Carmo, Jussara M.; Hosler, Jonathan P.; Hall, John E.

2015-01-01

We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R−/−), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R−/− mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R−/− mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R−/− mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin. PMID:26290368

Epidemiologic Study and Genotyping of BK Virus in Renal Transplant Recipients.

PubMed

Cobos, M; Aquilia, L; Garay, E; Ochiuzzi, S; Alvarez, S; Flores, D; Raimondi, C

2018-03-01

BK virus (BKV) infection occurs during childhood and remains latent in the urinary tract. The virus is reactivated in immunosuppressed patients, particularly in those with cellular immunity deficiency, allowing its detection in urine and blood. Nephropathy caused by the virus in renal transplantation recipients may lead to graft failure. The purpose of this study is to know the prevalence of BKV variables in renal transplantation recipients and to evaluate their clinical evolution through molecular methods of "in house" development. Urine and peripheral blood samples from 66 renal transplantation recipients from the province of Buenos Aires, Argentina, were systematically analyzed every 3 months as well as when there was graft dysfunction. Renal biopsies, which were included in the BKV detection study, were performed on those patients with graft dysfunction. Genotyping of 24 BKVs was performed, and the following distribution was found: 21 (87.5%) belonged to subtype I, 3 (12.5%) to subtype II. BKV belonging to subtypes III or IV were not found. As regards subtype I subgroups, the following were identified: 1 (4.76%) from Ia, 10 (47.61%) from Ib1 and 10 (47.61%) from Ib2. Presence of subgroup Ic was not shown. Viremia presented in 33.33% of cases, whereas 75% corresponded to subgroup Ib 1. Genotype Ib1 is prevailing in Southeast Asia, while Ib2 is prominent in Europe. Although an important proportion of the inhabitants of the province of Buenos Aires are European descendants, the prevailing genotype is Ib1, the Asian type. Genotyping might be related to the evolution of the disease in the recipient. Copyright © 2017 Elsevier Inc. All rights reserved.

Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology.

PubMed

Yang, Chih-Wei

2018-01-01

Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy. Proximal tubule dysfunction and hypokalemia are observed in adult male workers with leptospirosis, a characteristic similarity to CKD unknown etiology (CKDu). CKDu is a form of CKD that is not attributable to traditional risk factors clustering in agricultural communities affecting young male farmers. Kidney pathology shows a chronic tubulointerstitial disease. CKDu is being reported as an endemic nephropathy across the globe. Recent surveys suggest that asymptomatic leptospira renal colonization is an overlooked risk for renal fibrosis and CKDu. Population with anti-leptospira seropositivity is associated with lower estimated glomerular filtration rate in endemic regions and carrier may progress to CKD. Leptospirosis has been considered as a risk factor for CKDu in Sri Lanka and in Mesoamerican area. Sugarcane workers in Nicaragua showed increased anti-leptospira seropositivity and higher urinary biomarkers for kidney injury. Emerging evidence with signs of infection were reported in these endemic population, indicating that leptospira exposure could play a role in CKDu as a cause of primary kidney disease or a susceptible factor when secondary injury such as heat stress or dehydration aggravates kidney disease. Therefore, leptospirosis as an emerging culprit of CKDu deserves further in-depth investigation. © 2017 S. Karger AG, Basel.

G Protein-Coupled Receptor-G-Protein βγ-Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure.

PubMed

Kamal, Fadia A; Travers, Joshua G; Schafer, Allison E; Ma, Qing; Devarajan, Prasad; Blaxall, Burns C

2017-01-01

Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein-coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G-protein βγ-subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR-Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR-Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor-Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI. Copyright © 2016 by the American Society of Nephrology.

THE PATTERN OF LONGITUDINAL CHANGE IN SERUM CREATININE AND NINETY-DAY MORTALITY AFTER MAJOR SURGERY

PubMed Central

Hobson, Charles E; Pardalos, Panos

2016-01-01

Objective Calculate mortality risk that accounts for both severity and recovery of postoperative kidney dysfunction using the pattern of longitudinal change in creatinine. Summary Background Data Although the importance of renal recovery after acute kidney injury (AKI) is increasingly recognized, the complex association that accounts for longitudinal creatinine changes and mortality is not fully described. Methods We used routinely collected clinical information for 46,299 adult patients undergoing major surgery to develop a multivariable probabilistic model optimized for non-linearity of serum creatinine time series that calculates the risk function for ninety-day mortality. We performed a 70/30 cross validation analysis to assess the accuracy of the model. Results All creatinine time series exhibited nonlinear risk function in relation to ninety-day mortality and their addition to other clinical factors improved the model discrimination. For any given severity of AKI, patients with complete renal recovery, as manifested by the return of the discharge creatinine to the baseline value, experienced a significant decrease in the odds of dying within ninety days of admission compared to patients with partial recovery. Yet, for any severity of AKI even complete renal recovery did not entirely mitigate the increased odds of dying as patients with mild AKI and complete renal recovery still had significantly increased odds for dying compared to patients without AKI (odds ratio 1,48 (95% confidence interval 1.30-1.68). Conclusions We demonstrate the nonlinear relationship between both severity and recovery of renal dysfunction and ninety-day mortality after major surgery. We have developed an easily applicable computer algorithm that calculates this complex relationship. PMID:26181482

Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension.

PubMed

Hashimoto, Junichiro; Ito, Sadayoshi

2015-07-01

Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function. © 2015 American Heart Association, Inc.

Low thyroid function is not associated with an accelerated deterioration in renal function.

PubMed

Meuwese, Christiaan L; van Diepen, Merel; Cappola, Anne R; Sarnak, Mark J; Shlipak, Michael G; Bauer, Douglas C; Fried, Linda P; Iacoviello, Massimo; Vaes, Bert; Degryse, Jean; Khaw, Kay-Tee; Luben, Robert N; Åsvold, Bjørn O; Bjøro, Trine; Vatten, Lars J; de Craen, Anton J M; Trompet, Stella; Iervasi, Giorgio; Molinaro, Sabrina; Ceresini, Graziano; Ferrucci, Luigi; Dullaart, Robin P F; Bakker, Stephan J L; Jukema, J Wouter; Kearney, Patricia M; Stott, David J; Peeters, Robin P; Franco, Oscar H; Völzke, Henry; Walsh, John P; Bremner, Alexandra; Sgarbi, José A; Maciel, Rui M B; Imaizumi, Misa; Ohishi, Waka; Dekker, Friedo W; Rodondi, Nicolas; Gussekloo, Jacobijn; den Elzen, Wendy P J

2018-04-18

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

Association of Chronic Kidney Disease With Small Vessel Disease in Patients With Hypertensive Intracerebral Hemorrhage.

PubMed

Tsai, Yuan-Hsiung; Lee, Meng; Lin, Leng-Chieh; Chang, Sheng-Wei; Weng, Hsu-Huei; Yang, Jen-Tsung; Huang, Yen-Chu; Lee, Ming-Hsueh

2018-01-01

Chronic kidney disease (CKD) has been closely associated with hypertension and stroke. Although studies have reported the relationship between CKD and cerebral small vessel disease (SVD), the link between CKD, hypertension, and SVD is uncertain. The aim of this study was to investigate the association between CKD and SVD in patients with strictly hypertensive intracerebral hemorrhage (ICH). 142 patients with acute hypertensive ICH were enrolled in this study. Magnetic resonance imaging was performed to assess imaging markers for SVD. Patients were categorized into three CKD groups based on the degree of kidney dysfunction [glomerular filtration rate (GFR) in milliliters per minute per 1.73 m 2 ]: normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60). The prevalence rate of mild and moderate to severe CKD was 50 and 14.8%, respectively. The stage of CKD was associated with history of chronic hypertension ( p  = 0.046) as well as the prevalence rate of overall and deep cerebral microbleed (CMB) ( p  = 0.001 and p  = 0.002, respectively). The stage of CKD was a significant risk factor for deep white matter hyperintensity (WMH) (OR 1.848; 95% CI 1.022-3.343, p  = 0.042), overall CMB (OR 2.628; 95% CI 1.462-4.724, p  = 0.001), lobar CMB (OR 2.106; 95% CI 1.119-3.963, p  = 0.021), and deep CMB (OR 2.237; 95% CI 1.263-3.960, p  = 0.006), even after adjustment for confounders. In patients with hypertensive ICH, the prevalence of CKD is high even at the early stage of renal function impairment and is associated with the prevalence of CMB and deep WMH. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and cerebral SVD.

Metabolic syndrome, insulin resistance, and chronic allograft dysfunction.

PubMed

Porrini, Esteban; Delgado, Patricia; Torres, Armando

2010-12-01

Metabolic syndrome (MS) is a cluster of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and glucose homeostasis alterations), and insulin resistance (IR) is suggested to be a common pathogenic background. In the general population, MS and IR have been proven to be risk factors for diabetes, CV disease, and chronic kidney disease. In the renal transplant setting, few studies have analyzed the relevance of MS and IR. According to the few data available, the prevalence of MS in renal transplant patients has been described as 22.6% at 12 months, 37.7% at 36 months, and 64% at 6 years after transplantation. Importantly, MS has been shown to be an independent risk factor for chronic allograft dysfunction (CAD), graft failure, new-onset diabetes, and CV disease. Also, persistent hyperinsulinemia during the first posttransplant year has been related to an increase in glomerular filtration rate, probably reflecting glomerular hyperfiltration as observed in prediabetes and early type 2 diabetes. Importantly, prediabetes (impaired fasting glucose and impaired glucose tolerance), a state hallmarked by IR, proved to be highly frequent among stable renal transplant recipients (30%), which is nearly three times its incidence in the general population. Posttransplant IR has been associated with subclinical atheromatosis as assessed by carotid intima-media thickness, and with chronic subclinical inflammation. In conclusion, MS and IR are important modifiable risk factors in renal transplant recipients, and prompt interventions to avoid its deleterious effects at the metabolic, CV, and graft function levels are needed.

[Andrologic consequences of chronic renal failure: State of the art for the yearly scientific report of the French National Association of Urology].

PubMed

Neuzillet, Y; Thuret, R; Kleinclauss, F; Timsit, M-O

2016-11-01

To describe the state of the art of current knowledge regarding gonadal consequences of end-stage chronic kidney disease (CKD) and renal transplantation. A systematic review of the literature search was performed from the databases Medline (NLM, Pubmed) and Embase, focused on the following keywords: "chronic kidney disease"; "chronic renal failure"; "hypogonadism"; "kidney transplantation"; "testicular dysfunction"; "testosterone". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 383 articles. After reading titles and abstracts, 51 were included in the text, based on their relevance. The prevalence of hypogonadism in CKD is reported between 24 % and 66 %, and decreases partially after renal transplantation. This is a hypogonadotropic hypogonadism whose pathophysiology is multifactorial, involving mainly a primitive testicular deficit, a hypothalamic-pituitary dysregulation, and an hyperprolactinemia. The consequences of this hypogonadism are not only sexual but also contribute to anemia, sarcopenia, atherosclerosis, and potentially in the progression of CKD. Hypogonadism is an independent risk factor for mortality in CKD patients. CKD is frequently associated with an hypogonadism whose correction is validated only in the setting of erectile dysfunction treatment. The other benefits of the correction of hypogonadism in the CKD patients, including overall survival, needs to be evaluated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue.

PubMed

Uchiyama, Tsuyoshi; Okajima, Fumikazu; Mogi, Chihiro; Tobo, Ayaka; Tomono, Shoichi; Sato, Koichi

2017-01-01

Obesity is associated with an increased risk of diabetes mellitus, hypertension, and renal dysfunction. Angiotensin 1-7 and alamandine are heptameric renin angiotensin system peptide hormones. Further, alamandine levels increase with renal dysfunction. In the cardiovascular system, angiotensin 1-7 and alamandine produce similar improvements and counterbalance angiotensin II in regulating vascular function. We aimed to determine whether the effect of alamandine on leptin expression and secretion in adipocytes was similar to that of angiotensin 1-7. We studied isolated peri-renal visceral adipose tissue and peri-renal isolated visceral adipocytes from male Wistar rats. Angiotensin II from 0.01 to 10nM had no effect on leptin expression. Angiotensin 1-7 (1 nM) increased leptin secretion and expression, whereas alamandine (1 nM) decreased leptin secretion and expression in adipose tissue and isolated adipocytes and reduced blood leptin levels in vivo. These effects were mediated by Gq, c-Src, p38 mitogen-activated protein, and IκB activation. Additionally, alamandine induced nitric oxide expression via inducible nitric oxidase synthase and plasminogen activator inhibitor 1 expression in adipose tissue and isolated adipocytes. Angiotensin 1-7 and alamandine produced opposing effects on leptin expression and secretion in adipose tissue. This result suggests that the action of Mas (angiotensin 1-7 receptor) and Mas-related G-protein coupled receptor D in adipocytes exhibited opposing actions similar to angiotensin II type 1 and type 2 receptors.

RISK ASSESSMENT AND MANAGEMENT OF ENVIRONMENTAL CADMIUM

EPA Science Inventory

Cadmium consumed in foods grown on soils contaminated by industrial Cd+Zn discharge has caused renal tubular dysfunction in
exposed humans in discrete situations. However, lack of understanding about environmental Cd has caused wide concern that general
populations may...

The RenTg mice: a powerful tool to study renin-dependent chronic kidney disease.

PubMed

Huby, Anne-Cecile; Kavvadas, Panagiotis; Alfieri, Carlo; Abed, Ahmed; Toubas, Julie; Rastaldi, Maria-Pia; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E

2012-01-01

Several studies have shown that activation of the renin-angiotensin system may lead to hypertension, a major risk factor for the development of chronic kidney disease (CKD). The existing hypertension-induced CDK mouse models are quite fast and consequently away from the human pathology. Thus, there is an urgent need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. The objective of this study was dual: to investigate whether mice overexpressing renin could mimic the kinetics and the physiopathological characteristics of hypertension-induced renal disease and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. We used a novel transgenic strain, the RenTg mice harboring a genetically clamped renin transgene. At 3 months, heterozygous mice are hypertensive and slightly albuminuric. The expression of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are increased in the renal vasculature indicating initiation of endothelial dysfunction. At 5 months, perivascular and periglomerular infiltrations of macrophages are observed. These early renal vascular events are followed at 8 months by leukocyte invasion, decreased expression of nephrin, increased expression of KIM-1, a typical protein of tubular cell stress, and of several pro-fibrotic agents of the TGFβ family. At 12 months, mice display characteristic structural alterations of hypertensive renal disease such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion and tubular dilation. The RenTg strain develops CKD progressively. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide new insights into the mechanisms of chronic renal failure and help to identify new targets for arresting and/or reversing the development of the disease.

STAT3 inhibition attenuates the progressive phenotypes of Alport syndrome mouse model.

PubMed

Yokota, Tsubasa; Omachi, Kohei; Suico, Mary Ann; Kamura, Misato; Kojima, Haruka; Fukuda, Ryosuke; Motomura, Keishi; Teramoto, Keisuke; Kaseda, Shota; Kuwazuru, Jun; Takeo, Toru; Nakagata, Naomi; Shuto, Tsuyoshi; Kai, Hirofumi

2018-02-01

Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model (Col4a5 G5X mutant). To determine the effect of blocking STAT3 signaling, we treated AS mice with the STAT3 inhibitor stattic (10 mg/kg i.p., three times per week for 10 weeks; n = 10). We assessed the renal function [proteinuria, blood urea nitrogen (BUN), serum creatinine] and analyzed the glomerular injury score, fibrosis and inflammatory cell invasion by histological staining. Moreover, we analyzed the gene expression of nephritis-associated molecules. Phosphorylated STAT3 was upregulated in AS kidneys and glomeruli. Treatment with stattic ameliorated the progressive renal dysfunction, such as increased levels of proteinuria, BUN and serum creatinine. Stattic also significantly suppressed the gene expression levels of renal injury markers (Lcn2, Kim-1), pro-inflammatory cytokines (Il-6, KC), pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) and Mmp9. Stattic treatment decreased the renal fibrosis congruently with the decrease of transforming growth factor beta (TGF-β) protein and increase of antifibrosis-associated markers p-Smad1, 5 and 8, which are negative regulators of TGF-β signaling. STAT3 inhibition significantly ameliorated the renal dysfunction in AS mice. Our finding identifies STAT3 as an important regulator in AS progression and provides a promising therapeutic target for AS. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-κB signaling pathways in diabetic nephropathy.

PubMed

Zhang, Mingyan; Yan, Zhibin; Bu, Lili; An, Chunmei; Wang, Dan; Liu, Xin; Zhang, Jianfeng; Yang, Wenle; Deng, Bochuan; Xie, Junqiu; Zhang, Bangzhi

2018-01-01

Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-κB pathways.

Renal function assessment in atrial fibrillation: Usefulness of chronic kidney disease epidemiology collaboration vs re-expressed 4 variable modification of diet in renal disease.

PubMed

Abumuaileq, Rami Riziq-Yousef; Abu-Assi, Emad; López-López, Andrea; Raposeiras-Roubin, Sergio; Rodríguez-Mañero, Moisés; Martínez-Sande, Luis; García-Seara, Francisco Javier; Fernandez-López, Xesus Alberte; González-Juanatey, Jose Ramón

2015-10-26

To compare the performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation. We studied 911 consecutive patients with non-valvular atrial fibrillation on vitamin-K antagonist. The performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation with respect to either a composite endpoint of major bleeding, thromboembolic events and all-cause mortality or each individual component of the composite endpoint was assessed using continuous and categorical ≥ 60, 59-30, and < 30 mL/min per 1.73 m(2) estimated glomerular filtration rate. During 10 ± 3 mo, the composite endpoint occurred in 98 (10.8%) patients: 30 patients developed major bleeding, 18 had thromboembolic events, and 60 died. The new equation provided lower prevalence of renal dysfunction < 60 mL/min per 1.73 m(2) (32.9%), compared with the re-expressed equation (34.1%). Estimated glomerular filtration rate from both equations was independent predictor of composite endpoint (HR = 0.98 and 0.97 for the re-expressed and the new equation, respectively; P < 0.0001) and all-cause mortality (HR = 0.98 for both equations, P < 0.01). Strong association with thromboembolic events was observed only when estimated glomerular filtration rate was < 30 mL/min per 1.73 m(2): HR is 5.1 for the re-expressed equation, and HR = 5.0 for the new equation. No significant association with major bleeding was observed for both equations. The new equation reduced the prevalence of renal dysfunction. Both equations performed similarly in predicting major adverse outcomes.

Alga Ecklonia bicyclis, Tribulus terrestris, and Glucosamine Oligosaccharide Improve Erectile Function, Sexual Quality of Life, and Ejaculation Function in Patients with Moderate Mild-Moderate Erectile Dysfunction: A Prospective, Randomized, Placebo-Controlled, Single-Blinded Study

PubMed Central

Sansalone, Salvatore; Leonardi, Rosario; Antonini, Gabriele; Vitarelli, Antonio; Vespasiani, Giuseppe

2014-01-01

We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in patients with erectile dysfunction (ED) at 3 months of follow-up. From January 2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF < 26) were enrolled in this multicenter, single-blinded, placebo-controlled study and randomized in Group A (Tradamix, n = 87) and Group B (placebo, n = 90). Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life (SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group A (mean difference: 11.54; P < 0.05) at 3 months versus Group B (P < 0.05). PSV (P < 0.05), IIEF-intercourse satisfaction (P < 0.05), IIEF-orgasmic function (mean P < 0.05), IIEF-sexual desire (P < 0.05), IIEF-overall satisfaction (P < 0.05), MSHQ-EjD (mean difference: 1.21; P < 0.05), and SQoL-M (mean difference: 10.2; P < 0.05) were significantly changed in Group A versus baseline and Group B. Patients with moderate arterial dysfunction showed significant increase of PSV (P < 0.05), IIEF-EF (P < 0.05), MSHQ-EjD (P < 0.05), and SQoL-M (P < 0.05) in Group A. Therapy with Tradamix improves erectile and ejaculation function and sexual quality of life in patients with mild-moderate ED and in particular for those with moderate arterial dysfunction. PMID:25136552