Evaluation of cyclosporine-induced nephrotoxicity by immunoperoxidase analysis of renal allograft biopsies

Renal allograft biopsies are frequently performed in order to distinguish rejection from cyclosporine nephrotoxicity (CsA-NT). Histopathologic evaluation alone or in conjunction with clinical information, however, has not been shown to be effective in diagnosing CsA-NT. The critical differences in treatment required for CsA-NT (decreased CsA dosage) v rejection (increased immunosuppression) make the accurate identification of CsA-NT an important clinical problem in renal transplantation. Recently, we have reported an association between cellular rejection and interstitial infiltrates of predominantly Leu 2 (CD8) positive (T cytotoxic-suppressor, T(c-s)) cells, which may be helpful in distinguishing rejection from CsA-NT. von Willebrand and Hayry have reported that deposits of CsA could be identified by CsA antibody labeling of tubular epithelial cells (fine-needle aspiration cytology specimens) from cases of presumed CsA-NT. In this study, we have performed immunoperoxidase labeling with polyclonal antibody to CsA in a series of renal allograft biopsies obtained from patients treated with CsA in order to characterize the specificity and pattern of CsA deposition within renal allograft tissue.