A METAANALYSIS AND MORPHOLOGICAL REVIEW OF CYCLOSPORINE-INDUCED NEPHROTOXICITY IN AUTOIMMUNE-DISEASES

Background. The risk-benefit ratio of cyclosporine A (CsA) is much mor e critical in some auto-immune diseases in comparison to transplantati on medicine, due to its renal toxic potential. The present meta-analys is is based on an a priori defined methodology, and is linked with a r eview of CsA-induced morphological lesions, in order to draw relevant conclusions with regard to CsA-induced nephrotoxicity in auto-immune d iseases. Methods. Only controlled, randomized trials with a treatment period of two months or more, published from January 1979 to August 19 96, were selected for the evaluation of functional renal impairment du e to CsA treatment. To assess the risk of developing nephrotoxicity du ring CsA therapy, individual peak rises in serum creatinine level were compared between the CsA-treated group and the control group. Nephrot oxicity was defined as an increase in serum creatinine level of 50% or more above baseline at least once during the study period. Papers rep orting CsA-induced renal morphological lesions were reviewed. Results. A risk difference of 20.9% for developing nephrotoxicity, between a t herapy with CsA and an alternative therapy, was found. Already after a treatment period of 12 months with low dose CsA (less than or equal t o 5 mg/kg/day), de novo nonspecific morphological damage could be indu ced in patients with auto-immune diseases. Conclusions. From this anal ysis of the literature, it is obvious that a therapy with CsA in patie nts affected by auto-immune diseases is not without risk. A rigorous e valuation of the risk-benefit ratio is strongly recommended for each p atient, with strict monitoring of serum creatinine and CsA trough leve ls during treatment. Renal biopsies during treatment must be seriously taken into consideration in patients who develop even a slight renal functional impairment, particularly when prolonged therapy of longer t han one year, even with low dose CsA (less than or equal to 5 mg/kg/da y), is given.