The long-term course of cyclosporine-associated chronic nephropathy

Abstract

We evaluated a chronic renal injury in 37 cardiac transplant recipients treated for 12 to 24 months with cyclosporine (CsA). Twenty-four cardiac transplant recipients treated with azathioprine for more than 24 months served as controls. Despite equivalent cardiac performance, GFR in those treated with CsA was depressed, 47 +/- 3 versus 94 +/- 4 ml/min/1.73 m2 (P less than 0.001). CsA therapy was also associated with significant elevation of renal vascular resistance (RVR), proteinuria, arterial hypertension, and impaired intrarenal conversion of inactive prorenin to active renin. Histopathological changes associated with CsA included an obliterative arteriolopathy with deposition of proteinaceous material in necrotic arteriolar walls, and associated tubulointerstitial damage. A minority of glomeruli exhibited either ischemic collapse or sclerosis. Area perimeter analysis revealed enlargement of the remaining glomeruli with significant expansion of the mesangium. Longitudinal examination over a 48 month period (N = 15) during which CsA was reduced in dosage or withdrawn revealed persistent hypofiltration, increasingly elevated RVR and heavier proteinuria. Further histopathological deterioration was observed when renal tissue was sampled a second time in six patients, and three members of the experimental group developed end-stage renal disease. We conclude that continuous CsA therapy for more than 12 months causes a chronic injury to renal microvessels that is rarely reversible and potentially progressive.