Short- and long-term efficacy of oral cyclophosphamide and steroids in patients with membranous nephropathy and renal insufficiency

Background: Up to half of the patients with idiopathic membranous nephropat hy (iMN) will develop renal failure. Preferably, immunosuppressive treatmen t should be restricted to patients at risk for the development of end-stage renal disease. However, the evidence that immunosuppressive treatment is e ffective 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 num ber 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 con sisted of oral cyclophosphamide, 1.5 - 2.0 mg/kg body weight for 12 months, and corticosteroids for 6 months. At regular intervals blood pressure, ser um 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 patient s was 55 +/- 12 years. In the 6 months before start of therapy, serum creat inine increased from 150 +/- 74 to 226 +/- 108 mu mol/l. After start of tre atment renal function rapidly improved, serum creatinine at 12 months avera ging 143 +/- 62 mu mol/l. Proteinuria decreased from 10.3 4.9 g/10 mmol cre atinine at baseline to 2.2 +/- 2.4 g/10 mmol creatinine at month 12. These initial favorable effects have persisted. Overall, 12 patients have develop ed a complete remission of proteinuria (persistent in 11), and an additiona l 19 have developed a partial remission of proteinuria (persistent in 15). Thus far, only one treated patient has developed end-stage renal disease. S ide effects are a major drawback of the treatment, with 7 patients being ad mitted, 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 e ffects are maintained well beyond the one-year treatment period. Therefore, we propose that in patients with iMN immunosuppressive therapy can be rest ricted to patients at high risk for end-stage renal disease.