Background Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only (Pred group),40 received MMF and prednisone (MMF + Pred group),and 31 were treated with CTX and prednisone (CTX + Pred group).The median time of follow-up was 30 months (maximum:96 months).The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times (P=0.002),and the differences among the three groups were significant (P＜0.001).At 24 months of follow-up,the decline rates were 12.35％,32.95％,and 24.14％ in the Pred,MMF + Pred,and CTX + Pred groups respectively.For urine protein excretion,the decline rates were 49.12％ (Pred),73.67％ (MMF + Pred),and 63.53％ (CTX + Pred) respectively at 24 months of follow-up.The differences among the three groups were not significant (P=0.714).Renal survival (the primary endpoint) was significantly different (P=0.027); however,the sencondary endpoint was similar for all the three groups (P=0.100).Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combined MMF and orednisone treatment led to a better renal survival compared to that of prednisone with CTX.