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

Recent studies have shown that steroids improve renal survival and reduce p roteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein excretion and normal renal function. However, this effect seems to diminis h over time. Moreover, it has been demonstrated that long-term use of ramip ril 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, c ontrolled, multicentric trial to assess whether combined treatment of stero ids 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 alloca ted randomly to receive a six-month course of oral prednisone (1.0 mg/Kg/da y 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 mai ntain a blood pressure less than 120-80 nim Hg and/or to reduce daily prote inuria to 1.0 g or less or by at least 50%) in the experimental group or ra mipril 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 ba seline serum creatinine; the secondary endpoints will be urinary protein an d cytokine excretion and side-effects. Analyses will be done by intention t o treat. A p <0.05,will be taken as significant.