Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate.
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.
Department of Nephrology, University Medical Center St Radoud, Nijmegen, The Netherlands. P.duBuf@nier.umcn.nl
Peggy W G
PW
du Buf-Vereijken
Amanda J W
AJ
Branten
Jack F M
JF
Wetzels
D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D012008:Recurrence; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003404:Creatinine; D011241:Prednisone; D008775:Methylprednisolone