Predictors of worsening renal function in adult patients with congestive heart failure receiving recombinant human B-type brain natriuretic peptide (nesiritide).

BACKGROUND: A recent meta-analysis suggested that the use of nesiritide (NES), a new agent for the treatment of congestive heart failure (CHF), is associated with an increased risk of acute renal failure (ARF). METHODS: We examined this issue among 219 consecutive CHF patients, and determined the risk factors for development of ARF [defined as a rise in serum creatinine (SCr) >0.3 mg/dl]. The sole primary outcome was the development of ARF. RESULTS: Seventy one of 219 patients received NES. There was no difference in ARF between patients receiving vs not receiving NES (29 vs 20%, P = 0.17). Evaluation of the entire cohort employing forward stepwise regression analysis revealed the following independent predictors of ARF: admission blood urea nitrogen (BUN) [P = 0.0004, odds ratio (OR) = 1.026], and admission brain natiuretic peptide (P = 0.04, OR = 1.0003). We repeated the same analysis for the subgroups of patients receiving or not receiving NES. For patients not receiving NES (n = 148), ARF developed in 30 (20%), with lower estimated glomerular filtration rate and older age being independent predictors. For patients receiving NES (n = 71), ARF developed in 21 (29%), with hypertension, elevated BUN/SCr ratio, and lack of use of angiotensin inhibitors being independent predictors. CONCLUSION: Among all patients with CHF, the use of NES was not an independent risk factor for the development of ARF. However, risk factors for developing ARF differed among patients receiving vs not receiving NES. Comparison of these differing factors suggests that administering NES in the setting of diminished renal perfusion and/or altered renal autoregulation may confer an increased risk of ARF.     

The efficacy and safety of B-type natriuretic peptide (nesiritide) in patients with renal insufficiency and acutely decompensated congestive heart failure.

BACKGROUND: Nesiritide (B-type natriuretic peptide) reduces preload and afterload, and causes natriuresis, diuresis and suppression of norepinephrine, endothelin-1 and aldosterone. In this study, we sought to explore the safety and efficacy of nesiritide in patients with acute congestive heart failure (CHF) and renal insufficiency (RI). METHODS: We studied the effects of nesiritide in patients with RI in the VMAC trial database, a multi-centre, randomized controlled trial (n = 489) of patients with acute decompensated CHF. RESULTS: The mean serum creatinine (SCr) in nesiritide-treated patients with RI (SCr > or = 2.0 mg/dl, n = 60, range 2.0-11.1 mg/dl) and without RI (SCr < 2.0 mg/dl, n = 209) was 3.0+/-1.51 and 1.2+/-0.34 mg/dl, respectively. Pulmonary capillary wedge pressure (PCWP) was reduced significantly and similarly in both RI and no RI groups starting at 15 min into nesiritide infusion from a baseline of 29.9+/-8.1 and 26.6+/-6.0 mmHg, respectively. Addition of placebo to standard therapies yielded no further improvement in PCWP in patients with RI; in contrast, nesiritide significantly reduced PCWP at every time point during 24 h. The effects of nitroglycerin were less robust than those of nesiritide, and PCWP was not significantly reduced by nitroglycerin at the 3 h primary end-point. At 24 h, 83% of the RI patients and 91% of patients without RI treated with nesiritide reported improvements in dyspnoea. Nesiritide was well tolerated in patients with RI and no RI, and renal function was preserved in both groups. CONCLUSIONS: In patients with RI, nesiritide was safe and improved haemodynamics and dyspnoea.     

Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure

The present study was undertaken to verdy the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen pressure. Diastolic PBP were employed as plumonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m² (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased and improved arterial blood oxygen partial prissure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.     

Predictors of mortality in elderly patients with acute renal failure in a developing country

This prospective study was undertaken to systematically analyze the predictors of mortality in the elderly in a developing country. All elderly patients with ARF hospitalized at this tertiary care centre over 1 year were studied. Various predictors analyzed were hospital-acquired ARF, causative factors of ARF, preexisting hypertension and diabetes mellitus, severity of renal failure (initial and peak serum creatinine, need for dialysis), and complications of ARF: infection during the course of illness; serum albumin levels and critical illness defined as presence of two or more organ system failures excluding renal failure. Of 33,301 patients admitted, 4,255 (12.7%) were elderly. Of these 69 (1.6%) had ARF. On analysis of the whole group, both young and elderly, age >60 years had an independent predictor of mortality (odds ratio 5.6, P = 0.001). Forty-two of the 69 (60.9%) elderly ARF patients died. The mortality was significantly increased in those elderly with hospital-acquired ARF (79.2%, P = 0.027), those with sepsis as a cause of ARF (71.2%, P = 0.004), those who required dialysis (72.5%, P = 0.022), those developing an infection during the course of ARF (87.9%, P = 0.000) and in those with a critical illness (90.0%, P = 0.00). On logistic regression analysis of those variables that were significant on univariate analysis, only critical illness (odds ratio 9.97) and infection during course (odds ratio 9.72) were the independent predictors of mortality. To conclude, ARF complicates only 1.6% of hospitalized elderly patients but is associated with a high mortality rate of 61%. Infection during the course of illness and critical illness were the independent predictors of mortality.     

Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.     

Renal effects of human urotensin-II in rats with experimental congestive heart failure.

BACKGROUND: Urotensin II (U-II) and its receptor GPR-14 are expressed in the kidney and the cardiovascular system of various mammalian species. Recent studies suggested that the U-II/GPR-14 system is upregulated in patients with congestive heart failure (CHF). However, the involvement of the peptide in the alterations of renal function in CHF remains unknown. METHODS: The effects of incremental doses (1.0-100.0 nmol/kg) of human U-II (hU-II) on renal haemodynamic and clearance parameters were assessed in rats with an aorto-caval fistula, an experimental model of CHF, and sham controls. Additionally, the effects of pre-treatment with the nitric oxide (NO) synthase blocker, nitro-L-arginine methyl ester (L-NAME), and the cyclooxygenase inhibitor, indomethacin, on the renal haemodynamic response to hU-II were studied in CHF rats. RESULTS: hU-II caused a decrease in mean arterial pressure in control and CHF rats. In controls, hU-II did not alter renal blood flow (RBF), and caused a minimal decrease (-12.5%) in renal vascular resistance (RVR). However, in CHF rats, the peptide induced a marked increase in RBF (+28%) and a decrease in RVR (-21.5%). These effects were attenuated by L-NAME, but not by indomethacin. Furthermore, hU-II caused a significant increase (+29%) in glomerular filtration rate (GFR) in CHF rats, whereas GFR tended to decrease in controls. Sodium excretion was not altered in control or in CHF rats in response to hU-II. CONCLUSIONS: hU-II exerts an NO-dependent renal vasodilatation that is more pronounced in rats with CHF. The data further suggest that the U-II/GPR-14 system may be involved in the regulation of renal haemodynamics in CHF.     

Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.

Combined simultaneous organ transplantation has become more common as selection criteria for transplantation have broadened. Broadening selection criteria is secondary to improved immunosuppression and surgical techniques. The kidney is the most common extrathoracic organ to be simultaneously transplanted with the heart. A series of 13 patients suffering from both end-stage heart and renal failure underwent 14 simultaneous heart and kidney transplantations at Temple University Hospital between 1990 and 1999. This is the largest series reported from a single center. Three patients died during the initial hospitalization for an in-hospital mortality of 21%. Of 10 patients who left the hospital, 1-year survival was 100% and 2-year survival 75%. One patient required retransplant for rejection within the first year. Overall mortality at 1 and 2 years was 25 and 41%, respectively. Four out of nine (44%) patients greater than 5 years post-transplant were alive. Of the 10 patients who left the hospital, 66% were alive at 5 years. One patient succumbed to primary nonfunction of the cardiac allograft, while the four other deaths were secondary to bacterial or fungal sepsis. The patient's racial backgrounds were equally divided between African-American and white. These results are similar to those reported in a United Network of Organ Sharing Database (UNOS) registry analysis of 84 simultaneous heart and kidney transplants that found 1- and 2-year survival to be 76 and 67%, respectively. Simultaneous heart and kidney transplantation continues to be a viable option for patients suffering from failure of these two organ systems, although the results do not match those of heart transplant alone.     

Poor prognosis of heart transplant patients with end-stage renal failure.

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal failure (ESRF) are major complications after a heart transplant. The aim of this study is to compare survival in heart transplant (HT) vs non-heart transplant (non-HT) patients starting dialysis. METHODS: Survival was studied among the 539 newly dialysed patients between 1 January 1995 and 31 December 2005 in our Department. All patients were prospectively followed from the date of first dialysis up to death or 31 December 2005. Multivariate survival analysis adjusted on baseline characteristics was performed with the Cox model. RESULTS: There were 21 HT patients and they were younger than non-HT patients at first dialysis: 58.6+/-11.6 vs 63.0+/-16.2 years (P=0.09). Calcineurin inhibitor nephrotoxicity was the main cause of ESRF in HT patients (47.6%). Crude 1, 3 and 5-year survival rates in HT and in non-HT patients were as follows: 76.2%, 57.1%, 28.6% and 79.1%, 58.7%, 46.7% (P=0.2). The adjusted hazard ratio of death in HT vs non-HT patients was 2.27 [1.33-3.87], P=0.003. Sudden death was the main cause of death in HT patients, in 33.3% vs 10.4% in non-HT patients (P=0.01). Five HT patients benefited from renal transplant. They were all alive at the end of the study period, while one patient among the 16 remaining on dialysis survived. CONCLUSION: HT patients with CKD who reached ESRF have a poor outcome after starting dialysis in comparison with other ESRF patients. Improvement in renal function management in the case of CKD is needed in these patients and non-nephrotoxic immunosuppressive regimens have to be evaluated. Renal transplant should be the ESRF treatment of choice in HT patients.     

Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Olmesartan associated with acute renal failure in a patient with bilateral renal artery stenosis

In patients with renal artery stenosis (RAS), the inhibition of renin-angiotensin-aldosterone system can cause deterioration of renal function. Here we present a 75-year-old man who developed acute renal failure after olmesartan treatment. Following discontinuation of olmesartan, his renal functions normalized. His renal Doppler ultrasonography and renal angiography showed findings consistent with bilateral RAS. In this case, unlike those previously reported, renal failure developed with olmesartan for the first time and after only a single dose, which is thought to be a new, safe, and tolerable antihypertensive agent. This is a well-defined effect of angiotensin-converting enzyme inhibitors, in patients with RAS. Also with the increasing use of angiotensin II receptor blockers (ARBs), renal failure associated with ARBs in patients with RAS is rising. The use of olmesartan also requires caution and close follow-up of renal functions for patients who have risk factors.     

Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure

BACKGROUND: Short-term infusion of atrial natriuretic peptide (ANP) increases renal blood flow (RBF) and glomerular filtration rate (GFR) in patients with acute renal dysfunction. In the present study we evaluated the effects of long-term infusion (>48 h) of ANP on (RBF) and (GFR) in 11 postcardiac surgical patients requiring pharmacological circulatory support and with acute renal impairment. METHODS: Urinary clearance of Cr-EDTA and PAH as well as central hemodynamic measurements were performed for 2-3 consecutive 30-min periods during ANP infusion (50 ng. kg-1. min-1), one hour after abrupt discontinuation of ANP and again immediately after reinstitution of ANP infusion. RESULTS: During ANP infusion, urine flow (UF), GFR, RBF and renal vascular resistance (RVR) were 6.4+/-1.1 ml. min-1, 19.9+/-3.1 ml. min-1, 408+/-108 ml. min-1 and 0.286+/-0.054 mmHg. min. ml-1, respectively. UF, GFR and RBF decreased significantly by 28% (P<0.001), 32% (P<0.01) and 31% (P<0.05), respectively when ANP infusion was discontinued. RVR increased by 93% (P<0.05) while there was no change in filtration fraction. After reinstitution of ANP infusion, all measured renal variables returned to baseline. There was no significant correlation between the number of ANP treatment days and the percentage decrease in GFR (r=0.18) or RBF (r=0.22) during ANP withdrawal. Central hemodynamic variables were not affected by ANP withdrawal. CONCLUSIONS: ANP infusion improves RBF and GFR in patients with acute renal impairment after cardiac surgery. This renal vasodilatory effect is maintained during a long-term infusion and seems to be hemodynamically safe.     

Outcomes after heart transplantation in patients with and without pretransplant renal dysfunction

Abstract

Objective. To compare long-term survival and incidence of ESRD between patients with and without preoperative renal dysfunction following heart transplantation. Design. Fifty consecutive patients with preoperative estimated GFR ≤ than 50 ml/min were compared with 50 age-matched patients with estimated GFR ≥ than 80 ml/min who underwent heart transplantation between 1994 and 1998. We investigated two primary outcomes: death and development of ESRD. We also analyzed risk factors. Results. Eight patients (16%) developed ESRD and 19 (38%) died in the control group whereas 10 patients (20%) developed ESRD and 26 (52%) died in the renal failure group during a mean follow-up period of 6.74 ± 3.31 years. Survival and time to ESRD were not significantly different. In univariate and multivariate analysis, waiting time was the only risk factor found to predict mortality but not ESRD. High cyclosporine levels were only found to be associated with lower estimated GFR (p < 0.009). Among the control group, mortality was significantly higher in the subgroup of patients that developed ≥ 50% reduction of estimated GFR at the end of the first post transplant year (p < 0.05). Conclusions. This study suggests that low pre-transplant estimated GFR may not accurately predict long-term development of ESRD.     

Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure.

BACKGROUND: Congestive heart failure (CHF) is an independent risk factor for mortality in the end-stage renal disease (ESRD) population. Nocturnal haemodialysis (NHD), a novel mode of renal replacement therapy, may be more effective than conventional haemodialysis in reducing intravascular volume or in removing uraemic toxins with vasoconstrictor or myocardial depressant actions, and may, therefore, improve the left ventricular (LV) systolic function of patients with coexisting cardiac and renal failure. METHODS: To test this hypothesis, we determined, in six patients (mean age+/-SD: 49.5+/-9 years), blood pressure (BP), ejection fraction (EF: radionucleotide angiography), left ventricular mass index (LVMI: echocardiography), LV fractional shortening (FS), and extracellular fluid volume (ECFV: bioelectrical impedance): before and after a mean of 3.2+/-2.1 years following conversion from conventional dialysis (3 days/week x 4 h) to NHD (6 nights/week x 8-10 h). RESULTS: There were significant reductions in systolic and mean arterial BP (138+/-10 to 120+/-9 mmHg, P=0.04; 99+/-6 to 86+/-7 mmHg, P=0.01). There was a significant increase in EF (28+/-12 to 41+/-18%, P=0.01) and a trend to greater LV FS (20+/-10 to 38+/-17%, P=0.06). Post-dialysis ECFV was not affected by dialysis mode (18.5+/-5.1 vs 18.2+/-3.5 l, P=0.76). The number of prescribed cardiovascular medications was reduced (2.2-0.7, P=0.02). CONCLUSIONS: In ESRD patients with systolic dysfunction, NHD leads to a sustained increase of EF and a reduction in the requirement for vasoactive medications in the absence of any reduction in post-dialysis ECFV.     

血清脑钠肽及氨基末端脑钠肽前体在评价慢性肾衰竭患者心功能中的价值

目的探讨血清脑钠肽(B-type natriuretic peptide,BNP)及氨基末端脑钠肽前体(Nterminal pro-B type natriuretic peptide,NT-pmBNP)在评价慢性肾衰竭患者心功能状态的临床应用价值。方法选择住院的慢性肾衰竭患者120例,测定患者血清肌酐、BNP、NT-proBNP浓度,按照我国改良的肾脏病膳食改善试验(modification of diet in renal disease,MDRD)公式计算肾小球滤过率,依据2003版肾脏病预后质量倡议(Kidney Disease Outcomes Quality Initiative,K/DOQI)指南标准将120例患者分为慢性肾脏病(chronic kidney disease,CKD)3、4、5(未透析)期三组进行比较;按照美国纽约心脏病学会(NYHA)制定的心功能分级将患者分为NYHAⅠ、Ⅱ、Ⅲ、Ⅳ四组进行比较。比较同一肾功能水平下不同心功能水平患者BNP及NT-proBNP的浓度差异,同一心功能水平下不同肾功能水平患者BNP及NT-proBNP的浓度差异。结果同一肾功能分期血BNP及NT-proBNP浓度随着NYHA分级升高逐渐升高,各级之间差异均有统计学意义(均P0.01)。同一NYHA分级、不同CKD分期BNP浓度比较,差异无统计学意义(P0.05)。同一NYHA分级,NYHAⅠ、Ⅱ、Ⅲ级时CKD 4期与CKD 3期的NT-proBNP浓度差异无统计学意义(P0.05),CKD 5期与CKD 4期、CKD 3期比较NT-proBNP浓度显著升高(P0.05)NYHAⅣ级时,NT-proBNP浓度在CKD 3期、4期、5期的浓度分别为(2 5540.00±4 537.30)μg/L、(25 820.00±3 636.18)μg/L、(26 208.00±3 920.68)μg/L,差异无统计学意义(P0.05)。结论 BNP可作为CKD 3、CKD 4及CKD 5(未透析)期患者判断心功能不全的诊断指标。NT-proBNP受肾功能影响较大,对CKD 3及CKD 4期患者在考虑肾功能的前提下可评价心功能状态,但对于CKD 5期患者不建议使用。     

妊娠合并急性肾衰竭的临床分析

目的探讨妊娠合并急性肾衰竭ARF）诊治。方法回顾性分析24例妊娠并急性肾衰竭患者的临床资料。结果24例患者中22例患者治愈或好转出院，2例患者死亡。结论早期诊断、积极治疗妊娠合并急性肾衰竭，可以挽救母婴生命。治疗措施包括：适时终止妊娠、早期透析、积极治疗原发病、防治感染。     

Acute renal failure in patients with pre-existing renal dysfunction following coronary artery bypass grafting

BACKGROUND: Pre-existing renal dysfunction predisposes to acute renal failure (ARF) in patients undergoing coronary artery bypass grafting. We assessed the incidence and impact of the development of ARF in this patient population in our unit. METHODS: One-hundred and six patients had a preoperative serum creatinine of >or=0.13 mmol/L and underwent coronary artery bypass grafting in the year 2000. The incidence of ARF (as defined by a >or=50% rise in postoperative serum creatinine), hospitalization days, dialysis requirement, in-hospital and 1-year mortality, and potential risk factors for ARF were recorded. RESULTS: Of the patients recorded, 43/104 (41.35%) developed ARF following coronary artery bypass grafting. Patients with ARF stayed in hospital longer (P < 0.02). Ten out of forty-three patients required some form of dialysis and the in-hospital mortality of the renal failure group was 23% compared to 3.1% in the other group (P < 0.002). One year postoperatively, the group with renal failure had significantly worse survival (71.8% vs 98%P < 0.0001). CONCLUSION: For patients undergoing coronary artery bypass grafting, pre-existing renal dysfunction predisposes to the development of ARF, this is associated with prolonged hospitalization and increased mortality.     

Cause of death in acute renal failure.

The cause of 636 deaths during acute renal failure (ARF) occurring between 1956 and 1989 were analysed. Deaths due to haemorrhage and to non-recovery of renal function have declined but cardiovascular deaths and withdrawal of active treatment have increased. The causes of death varied with the clinical situation in which ARF arose. The most important factor contributing to death was the underlying cause of ARF. 67% deaths due to sepsis resulted from infection present at the time of development of ARF. Deaths due to secondary complications have declined, indicating that the precipitating causes of ARF are the main determinant of overall mortality.