THE KIDNEY IN CYCLOSPORINE A-TREATED DIABETIC-PATIENTS - A LONG-TERM CLINICOPATHOLOGICAL STUDY

This was an analysis of the renal investigations performed in 248 cycl osporin A (CyA)treated patients who had recent-onset type I insulin-de pendent diabetes mellitus (IDDM) to assess the clinicopathological rel ationships, risk factors and predictive indices of CyA nephrotoxicity, and renal function observed with different CyA treatment regimens. Th ere were four different protocols, using initial CyA dosages ranging f rom 7.5 to 10 mg/kg/day, with dose modification according to serum cre atinine concentration, which was measured regularly in some patients f or up to 9 years after starting treatment. Kidney biopsies were obtain ed 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 oth er sources of renal injury at this stage of IDDM. Of these patients, 5 8% showed normal or minimal changes on biopsy, 26% showed slight abnor malities, and 16% showed medium-grade (grade III nephropathy) abnormal ities. Lesion severity was related to the degree of interstitial fibro sis 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 increas e was the best predictive factor of CyA-induced nephropathy. However, CyA-induced renal dysfunction was essentially reversible on dosage red uction, and morphological changes were not followed by progressive ren al insufficiency when CyA doses were low and adjusted according to ser um creatinine levels. We conclude that, at present, it is recommended that low-dose CyA in combination with other non-nephrotoxic immunosupp ressive strategies be used in patients with IDDM.