Effect of Cyclophosphamide and Glucocorticoid Therapy in IgA Nephropathy: A Single-Center Retrospective Analysis

Key Points Immunosuppressive therapy with cyclophosphamide combined with glucocorticoids improves kidney function, proteinuria, and hematuria. Immunosuppressive therapy with cyclophosphamide combined with glucocorticoids is safe for infectious complications. Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis in adults, which causes ESKD in ≤45% of patients in the long term. The optimal therapeutic approach remains undetermined. In this study, we report the results of a single-center retrospective analysis of patients with IgAN. Methods We retrospectively evaluated the therapeutic approach and outcome of all patients at our center with biopsy-proven IgAN between 2000 and 2020, focusing on the effect of intravenous cyclophosphamide therapy combined with glucocorticoids (“immunosuppressive therapy group”). The control group received standard supportive care. Results Patients in the immunosuppressive therapy group had worse kidney function before the initiation of therapy, as indicated by higher serum creatinine, more proteinuria, and a higher degree of hematuria than the control group; they also displayed a higher body mass index. The Oxford classification of IgA nephropathy (MEST-C score) suggested more inflammatory activity in the immunosuppressive therapy group, including more crescents and endocapillary hypercellularity. During the follow-up, proteinuria and hematuria decreased in both groups, and to a significantly greater extent in the immunosuppressive therapy group. Cyclophosphamide treatment significantly improved kidney function as determined by the fold-change of eGFR during the observation period. The number of infections and hospitalizations did not differ, but the incidence of diabetes was increased in the immunosuppressive therapy group. Conclusions This study suggests immunosuppressive therapy with cyclophosphamide combined with glucocorticoids improves kidney function, proteinuria, and hematuria. The therapy was safe for infectious complications, but was associated with an increased incidence of diabetes, which might be attributable in part to the use of steroids in patients with a higher body mass index at baseline. Although immunosuppressive therapy in IgAN remains controversial, our findings suggest that at least some patients benefit from more aggressive therapy.