The kidney in cyclosporin A-treated diabetic patients: a long-term clinicopathological study

Abstract

This was an analysis of the renal investigations performed in 248 cyclosporin A (CyA)-treated patients who had recent-onset type I insulin-dependent diabetes mellitus (IDDM) to assess the clinicopathological relationships, risk factors and predictive indices of CyA nephrotoxicity, and renal function observed with different CyA treatment regimens. There were four different protocols, using initial CyA dosages ranging from 7.5 to 10 mg/kg/day, with dose modification according to serum creatinine concentration, which was measured regularly in some patients for up to 9 years after starting treatment. Kidney biopsies were obtained from 125 patients (74 adults and 51 children) who had received only CyA for an average duration of 13 months before biopsy and had no other sources of renal injury at this stage of IDDM. Of these patients, 58% showed normal or minimal changes on biopsy, 26% showed slight abnormalities, and 16% showed medium-grade (grade III nephropathy) abnormalities. Lesion severity was related to the degree of interstitial fibrosis and tubular atrophy which, in turn, was related to the use of high maximum CyA dosages. Patients' age, and excessive CyA dose and blood trough levels were the main risk factors, and serum creatinine increase was the best predictive factor of CyA-induced nephropathy. However, CyA-induced renal dysfunction was essentially reversible on dosage reduction, and morphological changes were not followed by progressive renal insufficiency when CyA doses were low and adjusted according to serum creatinine levels. We conclude that, at present, it is recommended that low-dose CyA in combination with other non-nephrotoxic immunosuppressive strategies be used in patients with IDDM.