Enalapril dosage in steroid-resistant nephrotic syndrome

Abstract

We have examined, in a randomized crossover trial, the antiproteinuric effect of treatment with low- (0.2 mg/kg daily) and high-dose (0.6 mg/kg daily) enalapril in 25 consecutive patients with steroid-resistant nephrotic syndrome (SRNS). Patients in group A ( n=11) received enalapril at low doses for 8 weeks, followed by 2 weeks of washout and then at high doses for 8 weeks. Those in group B ( n=14) initially received enalapril at high and then low doses. Patients continued to receive treatment with tapering doses of prednisolone; none received concomitant therapy with daily oral or intravenous steroids, alkylating agents, cyclosporine, non-steroidal anti-inflammatory drugs, and other antihypertensive medications. The urine albumin-to-creatinine (Ua/Uc) ratio and the percentage reduction were determined for each phase of therapy. Baseline clinical, biochemical, and histological features were comparable in the two groups. In the first phase, treatment with low-dose enalapril (group A) resulted in median 34.8% Ua/Uc reduction compared with 62.9% with high doses (group B) ( P<0.01). High-dose enalapril was associated with a significant reduction in Ua/Uc ratio in both groups. The combined median Ua/Uc (95% confidence interval) reduction in the low-dose phase was 33% (-10.3% to 72.4%) and in the high-dose 52% (15.4%-70.4%) ( P<0.05). The median Ua/Uc ratio at the end of 20 weeks was 1.1 and 1.8 in groups A and B, respectively ( P>0.05). Systolic and diastolic blood pressure reductions were similar in both groups. No period or carry-over effect was found. Prolonged treatment with enalapril thus resulted in a dose-related reduction in nephrotic-range proteinuria. Titration of the dose of enalapril may be a useful strategy for achieving substantial reduction of proteinuria in children with SRNS.

The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review

“…In total, 1815 references were identified and, of these, two systematic reviews 40,42 and 11 trials met the inclusion criteria for the review. Six were parallel RCTs, 22,32,[43][44][45][46] three were randomised cross-over trials, 38,41,47 one was a CCT 48 and one was a prospective cohort study with concurrent controls. 34 The following interventions were evaluated:…”

“…The method of randomisation was adequate in just four trials, 22,41,45,46 with concealment of allocation being adequately reported in only one of these. 22 There is the possibility therefore of selection bias within the trials included in this review.…”

“…44,47 None of the trials reported whether the outcome assessor was blinded; however, this is less of a problem when the outcomes are objective, such as proteinuria. The study by Ponticelli and colleagues 45 Six trials 32,38,41,44,46,47 adequately reported the point estimates and measures of variability; however, only Ponticelli and colleagues 45 included an intention-to-treat (ITT) analysis.…”

“…32 The three randomised cross-over trials had study sample sizes ranging from only five patients 38 to 25 patients. 41 Four trials reported a higher proportion of male patients than female patients, 38,41,44,47 with Chongviriyaphan and colleagues having only male patients in their small study sample. 38 Two of the ISKDC studies 22,43 included only patients aged 12-16 years.…”

Clinical Profile and Outcome of Steroid Resistant Nephrotic Syndrome in Children: An Eastern Indian Single Centre Study

“…MMF is a promising therapeutic alternative without nephrotoxicity [20]. But there is no single consensus regarding the indications of renal biopsy and treatment protocols in children with SRNS [13,14,15,16]. Optimal combinations of these agents with the least toxicity remain to be determined [12].…”