Cyclosporin nephrotoxicity in heart and lung transplant patients

Twenty-two patients with heart, lung or heart and lung transplantsmaintained on cyclosporin for periods ranging from 3 months to 10 yearsdeveloped renal insufficiency which was investigated by renal biopsy. Thehistopathological changes were: (i) severe vascular and glomerular damagedue to thrombotic microangiopathy (TM); (ii) a form of focal segmentalglomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than beingseparate entities, these changes appeared to represent a spectrum ofpathology, some biopsies showing all three forms of glomerular injury. Inall cases the glomerular changes were accompanied by arteriolar andarterial pathology, and we identified novel ultrastructural changes in thearteriolar endothelial basal lamina. Tubular atrophy was a consistentfeature, the severity of which reflected the severity of the glomerularsclerosis, and which appeared to be a consequence of glomerular loss. Ourfindings are consistent with the nephrotoxic effects of cyclosporin beingmediated chiefly via damage to preglomerular vessels and glomerularcapillary endothelium. From an analysis of the clinical aspects of thesecases, the effects of cyclosporin appear to be to some extentidiosyncratic, and therefore not entirely preventable, but strictmonitoring of blood cyclosporin levels is essential to minimize the risk ofpermanent renal damage. Monitoring urinary protein in addition to plasmacreatinine may detect the onset of FSGS, as proteinuria precedes creatinineelevation.