Drug Therapy in Lupus Nephropathy

INCLUSION CRITERIA - All patients admitted to the study must satisfy each of the following criteria: Ability to provide informed consent to all aspects of the study after full information is provided. SLE as defined by the presence of at least 4 criteria established by the American Rheumatism Association. Age 12 years or older. Membranous lupus nephropathy manifested by 2 or more grams per day of proteinuria in the absence of infection or recognized non-lupus renal disease. A renal biopsy must reveal typical membranous lupus nephropathy by light microscopy. Immune deposits must be predominately sub-epithelial and/or intramembranous in location by electron microscopy. EXCLUSION CRITERIA - Patients with any one of the following conditions will be excluded: Medication history of: cytotoxic drugs or cyclosporin A for more than 2 weeks during the 10 week period prior to study entry. cytotoxic drug therapy or cyclosporin A for more than 10 weeks at anytime in the past. cytotoxic drug therapy or cyclosporin A during the 30 day period prior to study entry. requirement of corticosteroids in doses greater than 20 mg/m(2)/day of prednisone (or equivalent) for control of extrarenal disease at the time of study entry. Active acute or chronic infection requiring antimicrobial therapy, or serious viral infection (eg. hepatitis, herpes zoster). Pregnant females, nursing mothers, or females not practicing birth control. Patients with a single functioning kidney. Pre-existent malignancy. Insulin-treated diabetes mellitus. GFR less than 25 ml/min/1.73m(2) BSA. Known toxicity to cyclophosphamide. Positive tests for HIV infection. Furthermore, patients with any one of the following conditions (related to the use of cyclosporin A) will be excluded from randomization within renal function group 2 (Glomerular filtration rate greater than 66 ml/min/1.73m(2)): Renal biopsy revealing global sclerosis of greater than 50 percent of glomeruli, severe tubular atrophy, or severe interstitial fibrosis. Persistently abnormal and unexplained liver function abnormalities (defined as elevated transaminases, bilirubin, or alkaline phosphatase twice the upper limit of normal for at least 1 month) or evidence of active viral hepatitis. Hypertension difficult to control or uncontrollable with conventional anti-hypertensive regimens. Documented coronary artery disease. Convulsive disorders.