Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy

Abstract

Recent studies have shown that steroids improve renal survival and reduce proteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein excretion and normal renal function. However, this effect seems to diminish over time. Moreover, it has been demonstrated that long-term use of ramipril reduces the risk of end-stage renal disease in proteinuric diabetic and non-diabetic chronic nephropathies. We have planned a long-term unblinded, prospective, centrally randomized, controlled, multicentric trial to assess whether combined treatment of steroids and ramipril is superior to ramipril alone in patients with progressive IgAN disease. A minimum of 134 patients with biopsy-proven IgAN, grade G3 or G4, daily proteinuria > 1.0 g and creatinine clearance > 50 mL/min will be enrolled during a 2-year recruitment period. The patients will be allocated randomly to receive a six-month course of oral prednisone (1.0 mg/Kg/day for 2 months, tapered by 0.2 mg/Kg/day every month) plus ramipril (2.5 mg/day for one month, increased by 1.25 mg/day every month to achieve and maintain a blood pressure less than 120-80 mm Hg and/or to reduce daily proteinuria to 1.0 g or less or by at least 50%) in the experimental group or ramipril alone in the control group. Ramipril will be administered during the whole 5-year follow-up period in both groups. The primary endpoint will be renal survival estimated by 50% increase in baseline serum creatinine; the secondary endpoints will be urinary protein and cytokine excretion and side-effects. Analyses will be done by intention to treat. A p <0.05 will be taken as significant.