PMID: 8937936Nov 1, 1996Paper

Insights into chronic cyclosporine nephrotoxicity

International Journal of Clinical Pharmacology and Therapeutics
William M Bennett

Abstract

Cyclosporine has proven to be an invaluable immunosuppressive agent in solid organ transplantation. However, its major side effect is dose-related acute and chronic nephrotoxicity. The acute effects of cyclosporine are predominantly hemodynamic and mediated by a variety of vasoactive compounds, including endothelin, thromboxane A2, and/or inhibition of nitric oxide synthase. The chronic lesion of cyclosporine nephropathy which consists of afferent arteriolopathy combined with striped tubulointerstitial fibrosis and glomerulosclerosis has been much more difficult to understand. An experimental model using the salt-depleted rat has been developed which reproduces the structural and functional changes of chronic cyclosporine nephropathy. Furthermore, it has been shown in this animal model that the renin angiotensin system within the kidney is activated and is important in the pathogenesis of this lesion. Inhibition of the renin angiotensin system with angiotensin II receptor blockade or ACE inhibition markedly reduces the tubulointerstitial fibrosis and arteriolopathy while leaving the glomerular and hemodynamic effects of the drug unchanged. Thus, in the chronic animal model, the vascular and tubulointerstitial effect of cyclospo...Continue Reading

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