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

Abstract

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 micromol/l) who were treated with oral cyclophosphamide (1.5-2.0 mg/kg/day for 12 months) and steroids (methylprednisolone pulses 3 x 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.

• Authors: Peggy W G du Buf-Vereijken, Amanda J W Branten, Jack F M Wetzels, Membranous Nephropathy Study Group
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 19 Issue 5 Pg. 1142-8 (May 2004) ISSN: 0931-0509 [Print] England
• PMID: 14993502 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Cyclophosphamide
• Creatinine
• Prednisone
• Methylprednisolone

Topics

• Adolescent
• Adult
• Aged
• Creatinine (blood)
• Cyclophosphamide (therapeutic use)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Glomerulonephritis, Membranous (complications, drug therapy)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Kidney Failure, Chronic (drug therapy, etiology)
• Male
• Methylprednisolone (therapeutic use)
• Middle Aged
• Prednisone (therapeutic use)
• Recurrence
• Survivors
• Time Factors
• Treatment Outcome