CYCLOSPORINE NEPHROTOXICITY IN HEART AND LUNG-TRANSPLANT PATIENTS

Twenty-two patients with heart, lung or heart and lung transplants mai ntained on cyclosporin for periods ranging from 3 months to 10 years d eveloped renal insufficiency which was investigated by renal biopsy. T he histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal se gmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a sp ectrum of pathology, some biopsies showing all three forms of glomerul ar injury. In all cases the glomerular changes were accompanied by art eriolar and arterial pathology, and we identified novel ultrastructura l changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence o f glomerular loss. Our findings are consistent with the nephrotoxic ef fects of cyclosporin being mediated chiefly via damage to preglomerula r vessels and glomerular capillary endothelium. From an analysis of th e clinical aspects of these cases, the effects of cyclosporin appear t o be to some extent idiosyncratic, and therefore not entirely preventa ble, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary prote in in addition to plasma creatinine may detect the onset of FSGS, as p roteinuria precedes creatinine elevation.