PRESERVING RENAL-FUNCTION IN PATIENTS WITH MEMBRANOUS NEPHROPATHY - DAILY ORAL CHLORAMBUCIL COMPARED WITH INTERMITTENT MONTHLY PULSES OF CYCLOPHOSPHAMIDE

Objective: To compare oral chlorambucil and intravenous cyclophosphami de-based drug regimens in the treatment of patients with membranous ne phropathy and deteriorating renal function. Design: Randomized study. Setting: University hospital and teaching hospitals. Patients: 18 pati ents with membranous nephropathy, a nephrotic syndrome, and deteriorat ing renal function. Intervention: Chlorambucil (0.15 mg/kg body weight per day orally in months 2, 4, and 6) and prednisone (three intraveno us pulses of 1 g of methylprednisolone followed by oral prednisone at 0.5 mg/kg per day in months 1, 3, and 5) or intravenous cyclophosphami de (750 mg/m(2) body surface area once every month for 6 months) and m ethylprednisolone (three intravenous 1-g pulses in months 1,3, and 5). Measurements: Serum creatinine, serum cholesterol, serum albumin, and urinary protein levels. Results: Before treatment, no statistical dif ferences were found between the treatment groups. Six months after tre atment was started, serum creatinine levels had decreased in the group treated with chlorambucil, methylprednisolone, and prednisone from a mean of 260 +/- 112 mu mol/L to 186 +/- 74 mu mol/L (P = 0.003) and ha d increased in the group treated with intravenous cyclophosphamide and methylprednisolone from 218 +/- 85 mu mol/L to 297 +/- 143 mu mol/L ( P = 0.02; difference between both groups, P < 0.001). Serum albumin le vels increased in both groups by 9 and 6 g/L, respectively, and the ur inary. protein/creatinine ratio decreased by 2.6 and 3.1 g/10 mmol, re spectively. At the end of follow-up (median, 15 months; range, 6 to 36 months), one patient in the chlorambucil group and four patients in t he cyclophosphamide group had reached end-stage renal failure after 36 , 12, 12, 18, and 18 months of therapy, respectively. One patient in t he intravenous cyclophosphamide group died after 6 months of therapy. Conclusions: Thus far, both oral chlorambucil and oral cyclophosphamid e have been shown to be effective in the treatment of patients with me mbranous nephropathy and deteriorating renal function. Our study shows that intermittent monthly pulses of low-dose cyclophosphamide are ine ffective in preserving renal function in such patients.