objective：To investigate the effect and safety of immunosuppressant therapy using prednisone， mycophenolate mofetil and cyclosporine in IgA nephropathy with severe proteinuria (>3.5 g/24 h）. Methods：Forty-two patients with IgA nephropathy proved by biopsy were enrolled and randomly assigned into standard dose prednisone therapy group(control group, 20 cases) and combined immunosuppressant therapy group(trial group, 22 cases). The body mass index, systolic blood pressure, diastolic blood pressure, serum creatinine urine protein and glomerular filtration rate (GFR) were regularly measured. The data of two groups were compared in the 3rd month and 6th month. Adverse effects were recorded. Results：After immunosuppressant treatment of 6 months，urine protein were significantly reduced compared with baseline in both groups. The urine protein of trial group decreased from（4.1±0.6）g/24 h to（0.8±0.1）g/24 h（P < 0.01），and that of control group decreased from(4.0±0.5）g/24 h to（1.8±0.1）g/24 h(P< 0.01.="" the="" urine="" protein="" in="" trial="" group="" was="" lower="" than="" that="" of="" control="" group.serum="" creatinine="" and="" gfr="" were="" unchanged="" in="" both="" groups="" during="" the="" treatmentp="">0.05). Upper respiratory tract infections (one patient in control group, one patient in trial group) and the herpes zoster (one patient in trial group) were observed and cured through antiviral therapy and antibiotic therapy. The temporary transaminase rise (one patient in trial group) was observed and cured through liver-protecting therapy. No patient withdrew from the study due to adverse effects. Conclusions：Combined therapy with prednisone， mycophenolate mofetil， and cyclosporine appears to be more effective, tolerated and safe than standard dose prednisone therapy in reducing proteinuria in IgA nephropathy patients with severe proteinuria.
