Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity

Background. A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of immunosuppressive therapy is effective in such patients. Methods. We have prospectively studied and evaluated the clinical course in 15 patients (14 male, one female; age: 52 +/- 12 years) with iMN who have received a repeated course of immunosuppressive therapy because of deteriorating renal function associated with relapsing or persistent nephrotic syndrome. Results. The first course of immunosuppression was started 8 months (range: 0-143 months) after renal biopsy and consisted of chlorambucil (n = 8) or cyclophosphamide (n = 7); the second course consisted of cyclophosphamide in all patients. The interval between the first and second course was 40 months (range: 7-112 months). Total follow-up was 110 months (range: 46-289 months). Renal function and proteinuria improved at least temporarily in all patients after the second course. During follow-up, an additional course of therapy was given in four patients. Status at the end of follow-up was complete remission (n = 2), partial remission (n = 8), persistent proteinuria (n = 3), end-stage renal disease (n = 1) and death (n = 1, due to cardiovascular disease while nephrotic). Renal survival was 86% at 5 and 10 years of follow-up. The repeated courses of immunosuppression have resulted in a gain of dialysis-free survival time of greater than or equal to93 months (range: 43-192 months). Conclusions. Our results indicate that patients with iMN who do not respond well or relapse after a first course of immunosuppressive therapy and have renal insufficiency should be offered a second course of immunosuppression. Such a strategy maintains renal function in the majority of patients.