Morphology of cyclosporine nephrotoxicity and acute rejection in patients immunosuppressed with cyclosporine and prednisone

Abstract

Cyclosporine nephrotoxicity is a common and usually reversible cause of renal insufficiency in the renal allograft recipient. We examined 132 renal biopsy specimens of 54 patients with elevated serum creatinine concentrations in the posttransplant period in an attempt to characterize histologic features that would identify patients with cyclosporine nephrotoxicity as opposed to those with acute rejection. Nine histologic parameters were examined--vasculitis, interstitial edema, distribution and intensity of mononuclear cell interstitial infiltrate, mononuclear cell exudation within glomerular capillaries ("glomerulitis"), tubular ectasia, tubular necrosis, exudation of mononuclear cells within tubular epithelial cells ("tubulitis"), and the ratio of mononuclear cells in interstitial tissues and in the peritubular capillaries (I/C ratio). A clinical response to an increased dose of steroids or a reduced dose of cyclosporine was correlated with the histologic picture. Tubulo-interstitial nephritis was identified in all but one patient with cyclosporine nephrotoxicity and only the finding of vasculitis allowed the identification of rejection with any certainly. However, the linear logistic regression method identified four histologic parameters--vasculitis, edema, glomerulitis, and I/C ratio, which were useful in differentiating the nephritis of cyclosporine nephrotoxicity from that of acute rejection in 94% of the biopsies. Although it is possible to precisely predict clinical response to antirejection therapy or reduction in cyclosporine dose based on histologic criteria, it is possible that cyclosporine toxicity, alone or in combination with rejection, may lead to chronic interstitial fibrosis responsible for late graft loss.