It is currently unknown whether therapeutic intervention will alter the course of membranous lupus nephropathy. In the present study, the efficacy and toxicity of three immunosuppressive drug regimens administered over a 12 month period will be evaluated in patients with membranous lupus nephropathy. Detailed tests of renal function (including radiolabelled compounds for glomerular filtration and renal plasma flow rates), glomerular permselectivity (using fractional clearance of graded dextrans) and kidney biopsy morphology will be performed at the beginning and end of treatment. Patients with systemic lupus erythematosus, nephrotic range proteinuria and biopsy documented membranous nephropathy will be randomized to receive: a) alternate day prednisone alone (control group), b) alternate day prednisone plus intravenous pulse cyclophosphamide up to 1.0 gram per square meter body surface area every other month for 6 total doses, or c) alternate day prednisone plus oral cyclosporin A up to 200 mg per square meter body surface area daily. Lupus disease activity, renal function tests and drug toxicities will be monitored closely. Analysis will include comparison of the numbers of favorable outcomes of glomerular filtration rate, renal plasma flow, permselectivity, glomerular pathology and drug-related toxicities appearing in each treatment group. To date, response rates have been higher in patients receiving cyclophosphamide or cyclosporin A than in those receiving corticosteroids alone.
