Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2004-05, Vol.19 (5), p.1142-1148
• Main Authors: du Buf-Vereijken, Peggy W. G., Branten, Amanda J. W., Wetzels, Jack F. M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Creatinine - blood; cyclophosphamide; Cyclophosphamide - therapeutic use; Drug Therapy, Combination; Emergency and intensive care: renal failure. Dialysis management; Female; Follow-Up Studies; Glomerulonephritis, Membranous - complications; Glomerulonephritis, Membranous - drug therapy; Humans; Immunosuppressive Agents - therapeutic use; immunosuppressive therapy; Intensive care medicine; kidney failure; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - etiology; Male; Medical sciences; membranous nephropathy; Methylprednisolone - therapeutic use; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nephrotic syndrome; prednisone; Prednisone - therapeutic use; proteinuria; Recurrence; Renal failure; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Survivors; Time Factors; Treatment Outcome
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh036

Background. Patients with idiopathic membranous nephropathy (iMN) and renal insufficiency have a high risk for progression to end-stage renal disease (ESRD). In the short term, treatment with oral cyclophosphamide and steroids attenuates the deterioration of renal function in these patients; however, the long-term efficacy is unknown. Methods. We have studied prospectively 65 patients with iMN and renal insufficiency (serum creatinine >135 µmol/l) who were treated with oral cyclophosphamide (1.5–2.0 mg/kg/day for 12 months) and steroids (methylprednisolone pulses 3 × 1 g, i.v. at months 1, 3 and 5, and oral prednisone 0.5 mg/kg/48 h for 6 months). Results. Follow-up was 51 (5–132) months. Renal function temporarily improved or stabilized in all patients. A partial remission (PR) occurred in 56 patients followed by a complete remission (CR) in 17. During follow-up, 11 patients had relapsed (28% relapse rate after 5 years), of whom nine were re-treated because of renal function deterioration. At the end of follow-up, 16 patients were in CR, 31 in PR, eight had a persistent nephrotic syndrome, one had mild proteinuria, four had progressed to ESRD and five had died. Overall renal survival was 86% after 5 years and 74% after 7 years, compared with 32% after 5 and 7 years in a historical control group. Treatment-related complications occurred in two-thirds of patients, mainly consisting of bone marrow depression and infections. One patient has developed bladder cancer, another patient prostate cancer. Conclusions. Renal survival is good if patients with iMN and renal insufficiency are treated with oral cyclophosphamide. However, side effects occur frequently and relapse rate is high during longer follow-up.