Renal interstitial fibrosis and vascular changes. Occurrence in patients with autoimmune diseases treated with cyclosporine

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Abstract
Histologic examinations of kidney biopsy specimens from six patients with relapsing polychondritis (n = 1), Behcet''s syndrome (n = 3), and chronic uveitis (n = 2) were performed after four to 36 months of treatment with cyclosporine. Five of the patients had a variable degree of focal interstitial fibrosis and tubular atrophy, with and without minimal interstitial inflammation. Arteriolar hyalinization was noted in four and glomerular sclerosis in two patients. These renal lesions could not be attributed to underlying autoimmune disease or previous drug therapy but were similar to those recently reported in kidney and heart recipients receiving long-term cyclosporine. The initial cyclosporine doses were 15 mg/kg body weight in one patient and 10 mg/kg in the others. The maintenance cyclosporine doses ranged from 2.5 to 7.5 mg/kg with appropriate trough cyclosporine plasma levels (60 to 130 ng/mL). A rough correspondence between the extent of the histologic renal changes and the cumulative cyclosporine was seen, whereas serum creatinine increase or the development of hypertension during treatment did not predict the degree of interstitial fibrosis or the presence of arteriolar changes. Neither did a rapid fall in the serum creatinine level after withdrawal of cyclosporine exclude focal irreversible renal lesions. Since the histopathologic changes found in the kidneys are potentially progressive, we believe that, until more is known, long-term cyclosporine treatment should be reserved for situations where more established immunosuppression has failed to control an autoimmune process threatening the function of vital organs.