Journal of the American Society of Nephrology Clinical Nephrology

Lower Progression Rate of End-Stage Renal Disease in Patients with Peripheral Arterial Disease Using Statins or Angiotensin-Converting Enzyme Inhibitors

2007-05-25

Patients with peripheral arterial disease (PAD) are at increased risk for ESRD and cardiovascular events. The primary objective was to assess the association between ankle-brachial index (ABI) values and renal outcome. The secondary objective was to evaluate whether statins and angiotensin-converting enzyme inhibitors (ACEI) are associated with improved renal and cardiovascular outcome in patients with PAD. In a prospective observational cohort study of 1940 consecutive patients with PAD, ABI was measured and chronic statin and ACEI therapy was noted at baseline. Serial creatinine concentrations were obtained at baseline, 6 mo, and every year after enrollment. End points were ESRD, all-cause mortality, and cardiac events during a median follow-up period of 8 yr. Baseline estimated GFR <60 ml/min per 1.73 m² was assessed in 27% of patients. ESRD, all-cause mortality, and cardiac events occurred in 10, 46, and 31% of patients, respectively. In multivariate analysis, a lower baseline ABI was significantly associated with a higher progression rate of ESRD (hazard ratio [HR] per 0.10 decrease 1.34; 95% confidence interval [CI] 1.21 to 1.49). Chronic use of statins and ACEI were significantly associated with lower ESRD (HR 0.41 [95% CI 0.28 to 0.63] and 0.74 [95% CI 0.54 to 0.98], respectively), mortality (HR 0.66; [95% CI 0.55 to 0.82] and 0.84 [95% CI 78 to 0.95], respectively), and cardiac events (HR 0.71 [95% CI 0.56 to 0.91] and 0.81 [95% CI 0.68 to 0.96], respectively). In patients with PAD, low ABI values independently predict the onset of ESRD. Less progression toward ESRD and improved cardiovascular outcome was observed among patients who were on long-term statins and ACEI.

IgACE: A Placebo-Controlled, Randomized Trial of Angiotensin-Converting Enzyme Inhibitors in Children and Young People with IgA Nephropathy and Moderate Proteinuria

2007-05-25

This European Community Biomedicine and Health Research–supported, multicenter, randomized, placebo-controlled, double-blind trial investigated the effect of an angiotensin-converting enzyme inhibitor (ACE-I) in children and young people with IgA nephropathy (IgAN), moderate proteinuria (>1 and <3.5 g/d per 1.73 m²) and creatinine clearance (CrCl) >50 ml/min per 1.73 m². Sixty-six patients who were 20.5 yr of age (range 9 to 35 yr), were randomly assigned to Benazepril 0.2 mg/kg per d (ACE-I) or placebo and were followed for a median of 38 mo. The primary outcome was the progression of kidney disease, defined as >30% decrease of CrCl; secondary outcomes were (1) a composite end point of >30% decrease of CrCl or worsening of proteinuria until ≥3.5 g/d per 1.73 m² and (2) proteinuria partial remission (<0.5 g/d per 1.73 m²) or total remission (<160 mg/d per 1.73 m²) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P = 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P = 0.033), with total remission in 12.5% of ACE-I–treated patients and in none in the placebo group (log-rank P = 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.

Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency

2007-05-25

The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.

A Randomized, Controlled Trial of Steroids and Cyclophosphamide in Adults with Nephrotic Syndrome Caused by Idiopathic Membranous Nephropathy

2007-05-25

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size, quality, and duration. This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, development of ESRD, and quality of life in a randomized, controlled trial. Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat basis. A total of 93 patients completed the study. Of the 47 patients who received the experimental protocol, 34 achieved remission (15 complete and 19 partial), compared with 16 (five complete, 11 partial) of 46 in the control group (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and the likelihood of survival without death, dialysis, and doubling of serum creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia, hyperlipidemia that required therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and better quality of life on follow-up. The incidence of infections was similar in the two groups. In conclusion, untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function. A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion, arrests progression of renal insufficiency, and improves quality of life.