N-acetylcysteine attenuates NSAID-induced rat renal failure by restoring intrarenal prostaglandin synthesis.

BACKGROUND: Renal failure is a threatening side-effect of NSAID administration, consequent to NSAID-mediated abrogation of prostaglandin synthesis and resultant renal ischaemia. N-acetylcysteine (NAC) has renoprotective properties. We examined effects of NAC in a rat model of NSAID-induced renal failure. METHODS: Renal failure was generated in 80 rats by 6-day water deprivation and 3-day 15 mg/kg/day diclofenac injection. The rats were concomitantly treated, or not, by NAC, 40 mg/kg/day. Renal function was evaluated by cystatin C, creatinine and urea. Intrarenal blood flow was measured by laser Doppler. The kidneys were subjected to pathological examination or evaluation of intrarenal NO, H2O2 and PGE2. RESULTS: NAC significantly attenuated deterioration of renal function in diclofenac-treated rats: cystatin C dropped from 2.8+/-0.35 to 2.2+/-0.67 mg/l, P=0.016; creatinine from 1.2+/-0.97 to 0.96+/-0.19 mg/dl, P=0.02; urea from 208.4+/-57.9 to 157.6+/-33.7 mg/dl, P=0.028. Diclofenac-inflicted hystopathological damage was significantly reduced following NAC treatment. Intrarenal medullar blood flow dropped by 51+/-12.4% in diclofenac-treated rats, but only by 14+/-3.39% in those receiving NAC after diclofenac injection (P<0.001). H2O2 was elevated in renal tissues of diclofenac-receiving rats, while decreased in NAC-treated animals. PGE2 release by diclofenac-treated rats dropped significantly, but was restored after NAC administration both in renal cortices (144.7+/-10.4 vs 19.7+/-1.5 pmol/ml, P<0.001) and medullae (148.5+/-7.3 vs 66.6+/-7.3 pmol/ml, P<0.001). CONCLUSIONS: In this model of renal failure induced by NSAID administration combined with water deprivation, NAC treatment successfully attenuated the deterioration of renal function by inducing renal vasodilatation, decreasing oxidative stress via inhibition of intrarenal ROS content and restoration of intrarenal PGE2 release back to the basal levels.     

Determinants of survival and recovery in acute renal failure patients dialyzed in intensive-care units

The survival rate of critically ill patients who develop acute renal failure is extremely low, in spite of the sophisticated support systems, including dialysis. Therefore, it would be advantageous to identify, early in the disease course, those few survivors. We reviewed the clinical course of 43 consecutive critically ill patients who developed acute renal failure and were first dialyzed in an intensive-care unit setting to define comorbid conditions, present at the time of first dialysis, that were predictive of outcome. Mortality rate was 88%. Adult respiratory distress syndrome (p less than 0.05), requirement for antibiotics (p less than 0.01) and ventilatory failure (p less than 0.01) impacted negatively on recovery of renal function. The most powerful predictor of mortality was the need for ventilatory support (p less than 0.001). The presence of ventilatory failure at the initiation of dialysis predicted a 100% mortality (89-100%; 95% confidence limits). The initiation of dialysis in intensive-care unit patients with acute renal failure requiring ventilatory support did not alter the uniformly fatal outcome.     

Risk factors of acute renal failure after liver transplantation

The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child-Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II-IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.     

重症急性胰腺炎急性肾功能衰竭临床危险因素及其预防

目的研究重症急性胰腺炎(severe acute pancreatitis，SAP)病人急性肾功能衰竭(acute renal failure，ARF)发生的易患因素，估价ARF与SAP病人预后的相关性，探讨预防ARF发生的措施。方法回顾性分析我院1990年以来收治的SAP病人246例，对病人年龄、性别、病因、Ranson评分、APACHEⅡ评分、低氧血症、腹腔室隔综合征、感染、血淀粉酶水平、尿淀粉酶水平、急诊手术、禁食天数、是否应用生长抑素等因素，进行多因素Logistic回归分析。结果246例SAP病人31例发生ARF，ARF的发病率为12．6％。ARF组APACHEⅡ评分明显高于无ARF组，两组比较有显著性差异。腹腔室隔综合征、低氧血症和急诊手术在两组之间比较有显著性差异。结论在SAP发病过程中，APACHEⅡ评分增高、低氧血症和腹腔室隔综合征可能是导致ARF发生的危险因素。维持病人全身状态稳定、防止肾脏低灌注损害、预防低氧血症的发生以及手术引流腹腔减压可能有预防ARF发生的作用。     

Risk factors of acute renal injury in patients with acute left heart failure

Objectives To investigate the risk factors of acute renal injury (acute kidney injury) in patients with acute left heart failure. Methods Clinical data of 188 patients with acute left heart failure who were admitted to our hospital were retrospectively analyzed. Logistic regression analysis was used to assess the risk factors for AKI. Results Among 188 patients with acute left heart failure, incidence of acute kidney injury was 33.51%. Univariate and Multivariable logistic regression analyses showed that the independent predictors of acute kidney injury were lower baseline eGFR (OR=4.294, P＜0.001) and anemia (OR=3.573, P=0.006). Conclusions The incidence of acute left heart failure complicated with AKI was high. Basic state of renal function and anemia were the independent risk factors for AKI.     

Candidaemia in patients with dialysis-dependent acute renal failure: aetiology, predisposing and prognostic factors.

BACKGROUND: Infections remain the major cause of death among patients with acute renal failure (ARF), especially in severe ARF necessitating dialysis therapy (ARF(d)). Although the clinical features and outcomes of candidaemia in various patient populations have been described, data concerning candidaemic episodes among patients with ARF(d) are scarce. This study investigated the aetiology, predisposing, and prognostic factors for candidaemia in the ARF(d) patient population. Three patient groups were investigated in this study. METHODS: During an 8-year study period from January 1992 to December 1999, 37 candidaemic episodes that developed among 653 ARF(d) patients were assigned to ARF(d) candidaemic group, and 170 candidaemic episodes developing in patients without ARF(d) or chronic uraemia as the non-ARF(d) candidaemic group, and 28 matched ARF(d) patients without candidaemia were assigned to the ARF(d) control group. Among these groups, clinical characteristics in ARF(d) candidaemia patients, predisposing factors, and outcomes were compared. Four management strategies including central catheter removal, anti-fungal therapy, both, or neither were applied. The prognostic factors for attributable death were evaluated by univariate analysis followed by the multivariate logistic regression analysis. RESULTS: The proportion of ARF(d) patients with candidaemia was significantly higher than in patients who had no ARF(d) or chronic uraemia (5.7% vs 0.15%, P<0.001). Compared with the non-ARF(d) candidaemic group, systemic lupus erythematosus (SLE), administration of corticosteroid, and central venous catheter-associated candidaemia were more common in the ARF(d) candidaemic group (P<0.05). In matched case-control study, multiple antibiotic usage was shown to be a predisposing factor for developing candidaemia in patients with ARF(d), and corticosteroid therapy has a marginal significance (P=0.059). The occurrence of candidaemia increased the mortality rate of ARF(d) (71% vs 39.2% in ARF(d) control group, P<0.05). By multivariate logistic analysis, the variables associated with attributable death in ARF(d) candidaemic group were identified to be an APACHE II score of >or=18, and anti-fungal therapy for >48 h. Central venous catheters were removed in 32 (86.5%) of the 37 ARF(d) candidaemic patients, among whom the 18 patients who had received anti-fungal therapy for >48 h had a lower attributable death rate than those patients who had not (27.8% vs 64.3%, P<0.05). Of the remaining five patients who did not have their catheter removed, three patients subsequently died and two patients improved only after catheter removal. CONCLUSIONS: The higher prevalence of candidaemia in ARF(d) patients is due to their underlying illnesses and multiplicity of predisposing factors, rather than ARF and dialysis therapy per se. Predisposing factors include SLE, indwelling central venous catheter, multiple antibiotic usage, and corticosteroid therapy. Prompt anti-fungal therapy and catheter removal should be mandatory for ARF(d) patients with candidaemia.     

Beneficial effect of intrarenal verapamil in human acute renal failure

Cellular Ca2+ influx during the reperfusion period after an ischemic insult has been proposed to be a crucial pathogenetic factor in the development of experimental acute renal failure (ARF). The present study, therefore, examined the potential beneficial effect of intrarenal verapamil, a calcium entry blocking agent, on ARF in patients. Twelve patients were enrolled in the study. Six ARF patients (experimental group)--ARF caused by malaria (4 patients) and leptospirosis (2 patients)--had a catheter placed in their renal artery; verapamil was infused at 100 micrograms/min for 3 h and intravenous furosemide, 0.8 mg/kg/h x 24 h was also administered. Another six ARF patients (control group)--ARF caused by malaria (5 patients) and leptospirosis (1 patient)--were treated with intravenous furosemide alone. Baseline renal function was comparable in both groups; GFR (3.16 +/- 3.24 vs 0.7 +/- 1.5 mL/min, NS), serum creatinine (Scr), (9.1 +/- 2.1 vs 11.3 +/- 2.2 mg/dL, NS), and urine volume (V) (41.79 +/- 4.77 vs 34.54 +/- 13.52 mL/h, NS), were comparable in the experimental and control groups. Twenty-four hours posttreatment, the increment of GFR (9.66 +/- 4.25 vs 1.32 +/- 0.50 mL/min, P less than .02) and V (181.8 +/- 61.7 vs 79 +/- 18 mL/h, P less than .04), were significantly greater in the experimental group as compared to the control group. The course of ARF was also shorter in the experimental group (6.5 +/- 2.1 vs 13 +/- 1.1 days, P less than .05), who also required less dialysis. Thus, combination of a renal arterial infusion of verapamil and intravenous furosemide significantly improves the renal function in tropical ARF as compared to intravenous furosemide alone.     

Clinical profile and factors affecting mortality in acute renal failure.

The records of 110 patients with acute renal failure (ARF) admitted to the Department of Medicine of the Philippine General Hospital during a 5-year period (1983-1988) were reviewed. The objectives were to evaluate the clinical profile of ARF patients and to determine what factors influenced mortality. Infection significantly influenced the causation and prognosis of ARF. Fifteen patients died, for an overall mortality rate of 14%. Forty-six clinical variables were analyzed in order to identify factors correlated with mortality. Four variables significantly increased the risk of death from ARF: older age, hyperkalemia, oliguria, and presence of sepsis on admission. These characteristics define a subset of patients for whom more aggressive treatment of ARF is warranted.     

Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease

BACKGROUND: Acute renal failure (ARF) occurs in 5-50% of patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT. METHODS: We studied all OLT recipients between 9/1/1988 through 12/31/2000. RESULTS: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1-12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1-8 yr). Multivariate logistic regression analysis revealed creatinine levels > 1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005). CONCLUSIONS: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher 10-yr survival rates when compared with patients maintained on dialysis.     

Ethambutol-induced acute renal failure.

Sir, Ethambutol can cause ocular toxicity and hyperuricaemia, butethambutol-associated acute renal failure during treatment ofpulmonary tuberculosis is extremely rare [1,2]. Here we reportthe case of a man who manifested with oliguric acute renal failureand jaundice associated with ethambutol. Case.