A meta-analysis and morphological review of cyclosporine-induced nephrotoxicity in auto-immune diseases

Abstract

The risk-benefit ratio of cyclosporine A (CsA) is much more critical in some auto-immune diseases in comparison to transplantation medicine, due to its renal toxic potential. The present meta-analysis is based on an a priori defined methodology, and is linked with a review of CsA-induced morphological lesions, in order to draw relevant conclusions with regard to CsA-induced nephrotoxicity in auto-immune diseases. Only controlled, randomized trials with a treatment period of two months or more, published from January 1979 to August 1996, were selected for the evaluation of functional renal impairment due to CsA treatment. To assess the risk of developing nephrotoxicity during CsA therapy, individual peak rises in serum creatinine level were compared between the CsA-treated group and the control group. Nephrotoxicity was defined as an increase in serum creatinine level of 50% or more above baseline at least once during the study period. Papers reporting CsA-induced renal morphological lesions were reviewed. A risk difference of 20.9% for developing nephrotoxicity, between a therapy with CsA and an alternative therapy, was found. Already after a treatment period of 12 months with low dose CsA (< or = 5 mg/kg/day), de novo nonspecific morphological damage could be induced in patients with auto-immune diseases. From this analysis of the literature, it is obvious that a therapy with CsA in patients affected by auto-immune diseases is not without risk. A rigorous evaluation of the risk-benefit ratio is strongly recommended for each patient, with strict monitoring of serum creatinine and CsA trough levels 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 than one year, even with low dose CsA (< or = 5 mg/kg/day), is given.