Immunosuppressant-induced nephropathy - Pathophysiology, incidence and management

Immunosuppressant-induced nephrotoxicity, in particular chronic progressive tubulointerstitial fibrosis/arteriopathy induced by the calcineurin inhibi tors cyclosporin and tacrolimus, has become the 'Achilles heel' of immunosu ppressive agents. The use of calcineurin inhibitors as primary immunosuppre ssants in hepatic and cardiac transplantation has led to end-stage renal di sease and dialysis, Calcineurin inhibitor-induced acute renal failure may occur as early as a f ew weeks or months after initiation of cyclosporin therapy. The clinical ma nifestations of acute renal dysfunction are caused by vasoconstriction of r enal arterioles, and include reduction in glomerular filtration rate, hyper tension, hyperkalaemia, tubular acidosis, increased reabsorption of sodium and oliguria, The acute adverse effects of calcineurin inhibitors on renal haemodynamics are thought to be directly related to the cyclosporin or tacr olimus dosage and blood concentration. However, new clinical data indicate that calcineurin inhibitor-induced chro nic nephropathy can occur independently of acute renal dysfunction, cyclosp orin dosage or blood concentration. Several strategies have been evaluated to attenuate cyclosporin-induced nephropathy, but their efficacy remains un known. Cytokine release syndrome associated with the use of muronomab-CD3 (OKT- 3) can also contribute to the pathogenesis of transient acute tubular necrosi s and renal dysfunction following renal transplantation. Continued research and clinical experience should provide information regar ding the aetiology of cyclosporin-induced chronic progressive tubulointerst itial fibrosis/arteriopathy and its potential treatment.