15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2006-01, Vol.21 (1), p.58-63
• Main Authors: Birck, Rainer, Newman, Mark, Braun, Claude, Neumann, Irmgard, Nemoto, Kyuichi, Yard, Benito, Waldherr, Rüdiger, van der Woude, Fokko J.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; animal model; Animals; Biological and medical sciences; Biopsy, Needle; Cyclophosphamide - pharmacology; Disease Models, Animal; Emergency and intensive care: renal failure. Dialysis management; Guanidines - pharmacology; gusperimus; Immunohistochemistry; immunosuppression; Immunosuppression - methods; Immunosuppressive Agents - pharmacology; Intensive care medicine; Medical sciences; Mice; Mice, Inbred Strains; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - pharmacology; Nephritis - drug therapy; Nephritis - immunology; Nephritis - mortality; Nephritis - pathology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Random Allocation; Renal failure; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; SCG/Kj mice; Sensitivity and Specificity; Survival Rate; systemic vasculitis; treatment
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfi070

Background. Here we compare the efficacy of cyclophosphamide (CYC) for treatment of crescentic nephritis (CGN) with the newer immunosuppressants 15-deoxyspergualin (DSG) and mycophenolate mofetil (MMF) in SCG/Kj mice, an inbred mouse strain that spontaneously develops CGN, systemic necrotizing vasculitis and antineutrophil cytoplasmic antibodies (ANCAs). Methods. Mice were randomly assigned to intraperitoneal treatment with either DSG (2 mg/kg/day), CYC (50 mg/kg/week), MMF (60 or 100 mg/kg/day) or vehicle (VEH, dextrose 5% 0.3 ml/day) beginning at the 10th week of life. ANCA, blood urea nitrogen (BUN) and proteinuria were determined in all animals regularly, and survival was calculated. Renal histology was obtained in the 18th week of life in the MMF- or VEH-treated groups and in the 24th week in DSG- or CYC-treated animals. Results. Mean survival in VEH-treated animals was 123 days. At that point, survival was 100% in the CYC- or DSG-treated animals (P