PMID: 8587288Dec 1, 1995Paper

Cyclosporine-induced renal dysfunction in experimental animals and humans

Kidney International. Supplement
G Remuzzi, N Perico

Abstract

Cyclosporine (CsA) has improved one-year allograft survival in renal, liver, heart and pancreas transplantation, and has now also been advocated as a promising treatment for some autoimmune diseases. However, the use of CsA is associated with major nephrotoxicity, very likely a consequence of its toxic effect on vascular endothelium as consistently documented in experimental animals and humans. Evidence is now available that in kidney transplant recipients each oral dose of CsA is followed by a transient reduction in renal plasma flow and glomerular filtration rate that results from a form of acute reversible renal hypoperfusion. The repeated daily episodes of acute renal hypoperfusion might explain the structural alterations of pre-glomerular vessels and glomerular obsolescence well documented in transplant recipients on chronic CsA for more than two years. In heart transplant recipients CsA measurements of renovascular pressures and flows and analysis of transglomerular sieving of dextrans showed that renal vascular resistance was elevated more than twofold, due largely to an increase in pre-glomerular resistance. Three-dimensional reconstruction of individual glomeruli showed a distribution of capillary tuft volume shifted t...Continue Reading

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