Randomized, Controlled Trial of Prednisone, Cyclophosphamide, and Cyclosporine in Lupus Membranous Nephropathy

• Published in: Journal of the American Society of Nephrology Vol. 20; no. 4; pp. 901 - 911
• Main Authors: AUSTIN, Howard A, ILLEI, Gabor G, BRAUN, Michelle J, BALOW, James E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.04.2009
• Subjects: Adolescent; Adult; Age of Onset; Biological and medical sciences; Clinical Research; Cyclophosphamide - therapeutic use; Cyclosporine - therapeutic use; Female; Hematocrit; Humans; Immunosuppressive Agents - therapeutic use; Kidneys; Lupus Nephritis - drug therapy; Lupus Nephritis - immunology; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Prednisone - therapeutic use; Prognosis; Proteinuria - drug therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Serum Albumin - drug effects; Serum Albumin - metabolism; Urinary system involvement in other diseases. Miscellaneous; Young Adult; Antineoplastic agent; Skin disease; Nephrology; Calcineurin inhibitor; Autoimmune disease; Lupus nephritis; Urology; Systemic disease; Lupus erythematosus; Ciclosporin; Membranous glomerulonephritis; Kidney disease; Corticosteroid; Immunopathology; Connective tissue disease; Urinary system disease; Antiinflammatory agent; Prednisone; Randomized controlled trial; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Nitrogen mustard; Adrenal hormone; Immunosuppressive agent
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2008060665

Patients with lupus membranous nephropathy (LMN) are at substantial long-term risk for morbidity and mortality associated with protracted nephrotic syndrome, including ESRD. The optimal treatment for this condition is controversial. Forty-two patients with LMN participated in a randomized, controlled trial to compare adjunctive immunosuppressive drugs with prednisone alone. Adjunctive regimens included either cyclosporine (CsA) for 11 mo or alternate-month intravenous pulse cyclophosphamide (IVCY) for six doses; the control group received alternate-day prednisone alone. Median proteinuria was 5.4 g/d (range 2.7 to 15.4 g/d). We assessed the primary outcome, time to remission of proteinuria during the 12-mo protocol, by univariate survival analysis. At 1 yr, the cumulative probability of remission was 27% with prednisone, 60% with IVCY, and 83% with CsA. Although both IVCY and CsA were more effective than prednisone in inducing remissions of proteinuria, relapse of nephrotic syndrome occurred significantly more often after completion of CsA than after IVCY. By multivariate survival analysis, treatment with prednisone and high-grade proteinuria (>5 g/d) but not race or ethnicity were independently associated with a decreased probability of remission. Adverse effects during the 12-mo protocol included insulin-requiring diabetes (one with prednisone and two with CsA), pneumonia (one with prednisone and two with CsA), and localized herpes zoster (two with IVCY). In conclusion, regimens containing CsA or IVCY are each more effective than prednisone alone in inducing remission of proteinuria among patients with LMN.