Short- and long-term efficacy of oral cyclophosphamide and steroids in patients with membranous nephropathy and renal insufficiency. Study Group.
BACKGROUND
Up to half of the patients with idiopathic membranous nephropathy (iMN) will develop renal failure. Preferably, immunosuppressive treatment should be restricted to patients at risk for the development of end-stage renal disease. However, the evidence that immunosuppressive treatment is effective in patients with iMN and renal insufficiency is weak and based on few studies with short follow-up in a limited number of patients.


METHODS
We have analyzed the efficacy of immunosuppressive treatment in a large number of patients with membranous nephropathy and renal insufficiency. Since 1991, we have prospectively treated 39 patients (31 M, 8 F) with membranous nephropathy and evidence of deterioration of renal function. Treatment consisted of oral cyclophosphamide, 1.5-2.0 mg/kg body weight for 12 months, and corticosteroids for 6 months. At regular intervals blood pressure, serum creatinine, serum albumin, and proteinuria were measured. Adverse events were recorded.


RESULTS
Average follow-up is 32 months (range 6-104), 18 patients have been followed for more than 3 years. Mean age of the patients was 55 +/- 12 years. In the 6 months before start of therapy, serum creatinine increased from 150 +/- 74 to 226 +/- 108 micromol/l. After start of treatment renal function rapidly improved, serum creatinine at 12 months averaging 143 +/- 62 micromol/l. Proteinuria decreased from 10.3 +/- 4.9 g/10 mmol creatinine at baseline to 2.2 +/- 2.4 g/10 mmol creatinine at month 12. These initial favorable effects have persisted. Overall, 12 patients have developed a complete remission of proteinuria (persistent in 11), and an additional 19 have developed a partial remission of proteinuria (persistent in 15). Thus far, only one treated patient has developed end-stage renal disease. Side effects are a major drawback of the treatment, with 7 patients being admitted, mainly for the treatment of infectious complications.


CONCLUSIONS
Cyclophosphamide is effective in the treatment of patients with idiopathic membranous nephropathy and deterioration of renal function. The favorable effects are maintained well beyond the one-year treatment period. Therefore, we propose that in patients with iMN immunosuppressive therapy can be restricted to patients at high risk for end-stage renal disease.
Branten
A J
AJ
Department of Medicine, University Medical Center Nijmegen, The Netherlands. A.Branten@nefro.azn.nl
Wetzels
J F
JF
D000284:Administration, Oral; D000704:Analysis of Variance; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000517:prevention & control; D016896:Treatment Outcome
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011241:Prednisone; D008775:Methylprednisolone