Oral cyclophosphamide versus chlorambucil in the treatment of patients with membranous nephropathy and renal insufficiency

We treated patients with idiopathic membranous nephropathy (iMGN) and renalinsufficiency, using: (i) (n = 15) monthly cycles of steroids (1 gmethyl-prednisolone i.v. on three consecutive days, followed by oralprednisone 0.5 mg/kg/day months 1, 3 and 5) and chlorambucil (0.15mg/kg/day months 2, 4 and 6); or (ii) (n = 17) oral cyclophosphamide(1.5-2.0 mg/kg/day for 1 year) and steroids in a comparable dose. Thegroups were comparable in age, renal function and levels of proteinuria.During the 6 months preceding treatment, serum creatinine levels increasedfrom 148 +/- 50 to 219 +/- 73 mumol/l in the chlorambucil group and from164 +/- 86 to 274 +/- 126 mumol/l in the cyclophosphamide group. Median(range) follow-ups were: chlorambucil 38 months (8-71); cyclophosphamide 26months (5-68) (NS). Renal function improved in both groups, but theimprovement was short-lived in the chlorambucil group; 12 months afterstarting treatment, mean serum creatinine was 6.3 mumol/l lower in thechlorambucil group and 121 mumol/l lower in the cyclophosphamide group (p< 0.01). Four chlorambucil-treated patients developed ESRD, and fiveneeded a second course of therapy, whereas only onecyclophosphamide-treated patient developed ESRD (p < 0.05). Remissionsof proteinuria occurred more frequently after cyclophosphamide treatment(15/17 vs. 5/15; p < 0.01). Side-effects necessitated interruption oftreatment in six patients on cyclophosphamide and in 11 on chlorambucil (p< 0.05). In our patients, oral cyclophosphamide was better toleratedthan oral chlorambucil. The suggested greater efficacy of the oralcyclophosphamide regimen needs to be ascertained by longer follow-up.