RENAL ADVERSE EVENTS OF SANDIMMUN(R) (CYC LOSPORINE) IN PATIENTS WITHAUTOIMMUNE-DISEASES

Sandimmun(R) (SIM) leads to a preglomerular arteriolar vasoconstrictio n with reduction of GFR and increase in serum creatinine. The increase in serum creatinine is dose dependent, is apparent after 1-2 weeks of start of therapy, reaches a plateau after 1-2 months and remains stab le thereafter. The increase over baseline is on average 10% on 5 mg/kg /d. Increases in serum uric acid and potassium arc overproportional to the increase in serum creatinine, and indicate an additional effect o f SIM on tubular function. This is also the reason for reductions in s erum magnesium. After reduction of SIM dosage or stop of therapy, seru m creatinine drops within 1-2 weeks and usually reaches baseline value s within 2-3 months after stop Sandimmun(R)-nephropathy is characteriz ed by arteriolopathy, interstitial fibrosis and tubular atrophy. More than 400 renal biopsies in SIM-treated patients with autoimmune diseas es have been analysed. It appears that this complication can be avoide d. The most important risk factors are SIM-dosage and the extent of re nal dysfunction during SIM-therapy. If SIM-dosage is limited to max. 5 mg/kg/d, and is titrated to prevent increases of serum creatinine of more than 30% over baseline, then the risk of SIM-nephropathy is small even on longterm-therapy.