LOW-DOSE PREDNISOLONE CHLORAMBUCIL THERAPY IN PATIENTS WITH SEVERE MEMBRANOUS GLOMERULONEPHRITIS

Because of the high rate of spontaneous remission, treatment of membra nous nephropathy with prednisolone and chlorambucil is still controver sial. The aim of this study was to give this therapy only to those pat ients at risk of developing renal insufficiency and to test the effica cy of a low-dose therapeutic regimen. Seventeen patients with more tha n 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Se rum total protein, serum lipids, proteinuria, serum creatinine, and bl ood pressure were measured, along with the diuretic and antihypertensi ve medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methy lprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Ch lorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kg BW daily. At the end of treatment proteinuria had significantly decrea sed (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six month s after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia h ad improved; diuretic and antihypertensive medication were reduced. El evated serum creatinine decreased in 7 of 9 patients (pretreatment, 22 7 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with re spect to serum creatinine responded with respect to proteinuria. Regar ding adverse effects, two patients complained of dyspepsia while takin g steroids; during chlorambucil treatment two patients experienced nau sea and lack of appetite, and one developed leukopenia (1600/mul). Chl orambucil was stopped and cell counts normalized 2 weeks later. We con clude that low-dose prednisolone/chlorambucil is both safe and efficie nt in the majority of patients with severe membranous nephropathy.