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Concept: Creatinine

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Background Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. Methods We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. Results Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P=0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was -0.04±0.53 mg per deciliter (-3.5±46.9 μmol per liter) in the pharmacologic-therapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P=0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P=0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03). Conclusions In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491 .).

Concepts: Clinical trial, Heart failure, Renal physiology, Blood urea nitrogen, Creatinine, Adverse event, Kilogram, Acute decompensated heart failure

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The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2blockers;n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m(2)and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.

Concepts: Kidney, Proportional hazards models, Renal physiology, Creatinine, Interstitial nephritis, Kidney diseases, Nephritis, H2 antagonist

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More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients' vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration.

Concepts: Hospital, Poverty, Blood pressure, Million, Renal physiology, Blood urea nitrogen, Creatinine, Vital signs

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BACKGROUND: Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment. METHODS: We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011. RESULTS: The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p = 0.024), nadir serum creatinine (p < 0.001), and last known serum creatinine level (p = 0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p = 0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation. CONCLUSIONS: Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Dialysis, Renal physiology, Creatinine, King Abdulaziz University

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Background: Experience with hydroxyethyl starch (HES) in children is limited. This study was conducted to observe the effects of HES or Ringer’s lactate (RL) usage as the priming solution on renal functions in children undergoing cardiac surgery. Methods: After ethical committee approval and parent informed consent, 24 patients were included in this prospective, randomized study. During cardiopulmonary bypass (CPB), Group I received RL and Group II received HES (130/0.4) as priming solution. Serum creatinine, blood urea nitrogen (BUN), β2-microglobulin, cystatin C, and urinary albumin and creatinine, serum, and urine electrolytes were analyzed after the induction (T1), before CPB (T2), during CPB (T3), after CPB (T4), at the end of the operation (T5), on 24th hour (T6), and on 48th hour postoperatively (T7). Fractional sodium excretion (FENa), urinary albumin/creatinine ratio, and creatinine clearance were calculated. Drainage, urine output, inotropes, diuretics, and blood requirements were recorded. Results: In both the groups, β2-microglobulin was decreased during CPB and cystatin C was decreased at T3,T4, and T5 periods (p < 0.05) and the levels remained within the normal range. Creatinine clearance did not differ in the HES group, but increased in the RL group (p < 0.05). Urine albumin/creatinine ratio was increased (p < 0.05) after CPB in the HES group, and it increased at T3, T4, and T5 in the RL group (p < 0.05). There were no differences in cystatin C, β2-microglobulin, FENa, urine albumin/creatinine ratio, creatinine clearance, total fluid amount, urine output, drainage, and inotropic and diuretic requirements between the groups. Conclusion: We conclude that usage of HES (130/0.4) did not have negative effects on renal function, and it can be used as a priming solution in pediatric patients undergoing cardiac surgery.

Concepts: Nephrology, Renal physiology, Renal function, Blood urea nitrogen, Creatinine, Electrolyte, Urea, Cystatin C

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Background  Although long-term cyclosporine administration may induce toxic effects, it may be the only option for the treatment of severe psoriasis. The objective of the present study was to retrospectively evaluate efficacy and safety of long-term cyclosporine treatment in a cohort of patients affected with moderate to severe psoriasis, recalcitrant or unresponsive to other treatments. Possible risk factors predicting an intolerance to cyclosporine were also investigated. Materials and methods  Data were collected on psoriatic patients treated with cyclosporine for at least six months at our Psoriasis Outpatient Unit between January 2005 and September 2010. The primary measure for clinical efficacy was the PASI 75 response. Cyclosporine safety was assessed through the review of both laboratory tests and the adverse events registered during the treatment. Results  Twenty patients affected with plaque or erythrodermic psoriasis were evaluated. At Week 16, the PASI 75 response was achieved by 85% of patients. Adverse events occurred in eight patients (40%): four experienced an increase in serum creatinine levels to more than 30% of their pre-treatment values and four developed hypertension. Among these patients, five discontinued cyclosporine. Side effects resolved after stopping treatment. Conclusions  Our findings suggest that long-term cyclosporine regimen can be justified in severe psoriasis not responsive to other treatments. When cyclosporine administration is required, obesity, pre-treatment controlled hypertension, increased age (>70 years), and metabolic syndrome should be taken into consideration, as a significant correlation with occurrence of cyclosporine-induced side effects has been found.

Concepts: Clinical trial, Hypertension, Obesity, Creatinine, Metabolic syndrome, Psoriasis, Nephrotoxicity, Psoriatic erythroderma

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BACKGROUND: Proteinuria is associated with poorer outcomes in renal transplant recipients. Fractional excretion of total protein (FEPR) may better reflect kidney damage than urine protein-to-creatinine ratio (PCR). METHODS: We assessed FEPR (FEPR = [serum creatinine × urine protein] / [serum protein × urine creatinine], %) and PCR ([urinary protein/urinary creatinine] × 1000, mg/mM) 1 year after first renal transplantation as predictors of transplant failure. The primary endpoints were transplant failure and death. The use of the tests was analyzed by constructing receiver operator characteristic curves and comparing the area under the curve. Using receiver operator characteristic analysis, patients were stratified into high- and low-risk groups. RESULTS: Two hundred nineteen recipients were followed up for a median of 4.9 years. At a median of 2.7 years, 11.4% (n=25) of the transplants failed. Eight percent (n=17) of the patients died. The area under the curve was higher for FEPR than PCR (0.92 vs. 0.84). Patients with an FEPR of 0.019% or higher had a 3.4-fold (P=0.003) increased risk of transplant failure and a 2.3-fold (P=0.02) increased risk of death compared with those with an FEPR of less than 0.019%. Patients with a PCR of 97 mg/mM or greater had a 2.1-fold (P=0.04) increased risk of transplant failure and a 1.6-fold (P=0.04) increased risk of death compared with those with a PCR of less than 97 mg/mM (P=0.04). In multivariate analysis with time to transplant failure as the dependent variable, FEPR and PCR were independent predictors of transplant failure (hazards ratio, 1.07 [P=0.013] and 1.03 [P=0.03], respectively). CONCLUSIONS: FEPR and PCR at 1 year are independent predictors of transplant failure, but FEPR may be superior.

Concepts: Chronic kidney disease, Kidney, Nephrology, Creatinine, Ureter, Organ transplant, Kidney transplantation, Serum total protein

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BACKGROUND: Chronic drug interactions that exist between symptomatic congestive heart failure (CHF) therapy and pharmacologic agents used for hyperuricemia and gout are a challenging problem in clinical practice. Recent observational studies showed that prednisone can induce a potent diuresis and lower serum uric acid concentration (SUA) in CHF. We therefore designed a randomized study to compare the effect of prednisone with allopurinol on SUA in symptomatic CHF patients with hyperuricemia. METHODS: Thirty-four symptomatic CHF participants with hyperuricemia (≥ 565 μmol/L) were randomized to receive prednisone (1 mg/kg/d, orally) or allopurinol (100 mg, thrice daily, orally) for 4 weeks. The primary outcome measure was change from baseline in SUA. The secondary outcome measures were change from baseline in serum creatinine levels, estimated glomerular filtration rate, daily urine output, body weight, N-terminal pro-B-type natriuretic peptide levels, physician-assessed global clinical status, and New York Heart Association functional class. RESULTS: Both prednisone and allopurinol greatly lowered SUA rapidly. The overall SUA-lowering effect did not differ between treatment groups during the study period (P = 0.48, 2-way repeated measures analysis of variance). However, prednisone increased estimated glomerular filtration rate and daily urine output, and lowered body weights and N-terminal pro-B-type natriuretic peptide. Consequently, participants treated with prednisone had an improvement in clinical status. CONCLUSIONS: The study showed that the SUA-lowering effect of prednisone and allopurinol is similar in symptomatic CHF patients. Prednisone might be useful for short-term SUA-lowering in CHF patients with hyperuricemia.

Concepts: Heart failure, Blood urea nitrogen, Creatinine, Gout, Urea, Uric acid, Hyperuricemia, Hyperuricosuria

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Renal ischemia/reperfusion(I/R) is an important injury part of ischemic acute renal failure, and it is also the main factor that affects the early functional recovery and the long-term survival of transplanted kidney in renal transplantation. In this study, we cloned and expressed truncated Na+/K+-ATPase β(tNKAβ) and demonstrated that tNKAβ could activate NKA α subunit and induce protective effect on human kidney-2(HK-2) cells via PKCε signal pathway. The half maximum effective concentrations (EC50) of tNKAβ were 0.24 µM. Furthermore, the application of EAVSLKPT (PKCε inhibitor) could abolish the protective effect of tNKAβ in HK-2 cells subjected to ischemia/reperfusion. To identify the protective effect of tNKAβ against the I/R injury in the kidney, Sprague-Dawley rats were treated with tNKAβ (75 mg/kg) for 2 h before ischemia. The tNKAβ-treated group demonstrated a significant improvement in renal function with a lower serum creatinine and blood urea nitrogen (BUN) levels on postoperative days 1-6. Renal sections obtained from rats of the I/R group showed serious renal injury which included degeneration of tubular structure, tubular dilation, swelling and necrosis, luminal congestion, and muddy brown casts formed by sloughing of severely damaged tubular epithelial cells. However, sections of rats that were administered with tNKAβ 2 h before reperfusion showed marked reduction of the histological features of renal injury compared with kidneys that were subjected to I/R only. In conclusion, the protective effects of tNKAβ against renal I/R injury have been evaluated for the first time, and these protective effects may occur via stimulation of PKCε pathways.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Renal physiology, Blood urea nitrogen, Creatinine, BUN-to-creatinine ratio