Objective: To determine the effect of cyclophosphamide and prednisone on progressive renal failure and on nephrotic features in patients with membranous glomerulonephritis. Design: Prospective, nonrandomized time series. Setting: Outpatient clinic at a university medical center. Patients: Eleven consecutive patients with biopsy-proven membranous glomerulonephritis and rising plasma creatinine levels over at least 6 months. Intervention: Cyclophosphamide and prednisone in ten patients and cyclophosphamide alone in one patient. Measurements and Main Results: In ten patients treated with both agents, the median plasma creatinine rose 53-mu-mol/L (0.6 mg/dL) over the months before treatment from 141 to 194-mu-mol/L (1.6 to 2.2 mg/dL) (95% CI, 27 to 141-mu-mol/L; P = 0.002). After combined therapy for 6 months, the median plasma creatinine fell to 133-mu-mol/L (1.5 mg/dL) for a median decline of 62-mu-mol/L (0.7 mg/dL) (CI, 44 to 150-mu-mol/L; P = 0.006). Pretreatment plasma creatinine levels, which ranged from 159 to 371-mu-mol/L (1.8 to 4.2 mg/dL), decreased in the ten patients by 6 months and remained stable in seven of the eight patients followed 24 to 54 months after therapy was completed. The median urine protein excretion decreased by 9.6 g/d with 12 months of therapy in the ten patients from 11.9 to 2.3 g/d (CI, 6.0 to 15.1 g/d; P < 0.001). The median plasma albumin rose by 14 g/L from 24 to 38 g/L (CI, 11 to 19 g/L; P < 0.001). The median plasma cholesterol fell by 3.26-mu-mol/L (140 mg/dL) from 10.45 to 6.52-mu-mol/L (405 to 252 mg/dL) (CI, 1.42 to 7.16-mu-mol/L; P = 0.01). One patient who had a relapse 30 months after completing therapy responded to re-treatment with renal function and nephrotic variables returning toward normal. The eleventh patient received cyclophosphamide alone and had a course similar to that of the combined therapy group. Conclusion: Cyclophosphamide plus prednisone can promote prolonged remissions in membranous glomerulonephritis even when renal function is already declining.
