Combined renin angiotensin blockade in childhood steroid-resistant nephrotic syndrome

Reduced proteinuria results in delayed deterioration of renal function and remission of proteinuria predicts a good long-term prognosis in steroid-resistant nephrotic syndrome (SRNS). The aim of this study was to analyze the effects of the combined angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker in reducing proteinuria in SRNS.

A prospective study of eight patients with SRNS was conducted at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University from September 2003 to December 2007. Enalapril was given at 0.1 mg/kg/day and was increased by 0.1 mg/kg/day every 4 weeks up to 0.6 mg/kg/day (maximum 40 mg/day) and 1 mg/kg/day of losartan was added for 4 weeks and stepped up to 2 mg/kg/day (maximum 100 mg/day) for another 4 weeks.

There were five boys (62.5%) and three girls (37.5%). The mean age at diagnosis was 8.3 ± 4.1 years (range 2.05-13 years) and age at enrollment was 11.7 ± 3.8 years (range 6-16 years). Renal histology revealed seven focal segmental glomerulosclerosis and one immunoglobulin M nephropathy. The results showed significant reduction on mean spot urine protein : creatinine ratio from 9.6 ± 2.3 to 3.6 ± 1.6 (P < 0.05) and 24-h urine protein from 182.8 ± 59.6 to 28.7 ± 8.2 mg/m(2) /h (P < 0.05). Urine protein reduction ratio at the end of the study was 50% (P= 0.08). Serum cholesterol, albumin, potassium, blood pressure and renal function had no significant change. No clinical and laboratory side-effects were reported.

Combined high-dose angiotensin II receptor blocker to high-dose angiotensin-converting enzyme inhibitor therapy is safe and effective in reducing proteinuria in childhood SRNS. However a large-scale study should be conducted to validate this result.