Renal vascular and thrombotic effects of cyclosporine

G. Remuzzi, T. Bertani

Research output: Contribution to journalArticlepeer-review


Cyclosporine A (CyA) given to prevent xenograft rejection induces renal function impairment. In the last few years many studies have been devoted to understanding the mechanism(s) of CyA-induced renal insufficiency. In humans, several specific findings - interstitial fibrosis, toxic tubulopathy, peritubular capillary congestion, arteriolopathy - have been associated with CyA administration. It is now recognized that CyA renal toxicity mainly manifests under three different syndromes: (1) acute reversible decrease in glomerular filtration rate (GFR), (2) acute microvascular disease with the pattern of thrombotic microangiopathy, and (3) chronic irreversible renal damage. This review analyzes the available evidence that the clinical syndromes of CyA nephrotoxicity are related to changes induced by CyA on renal vessels. Experimental studies have failed to document that the activation of renin-angiotensin axis or sympathetic nervous system plays a relevant role in the development of CyA-associated renal vasoconstriction, which is the main causal factor of acute reversible decrease in GFR, whereas it is possible that changes in arachidonic acid metabolites with vasoactive properties contribute to this CyA-induced phenomenon. In this context, findings of increased urinary TxB2 and protective effect of TxA2 receptors blocking are of particular interest. Since the introduction of CyA in clinical practice, a syndrome of thrombotic microangiopathy resembling hemolytic uremic syndrome/thrombotic thrombocytopenic purpura has been recognized in humans and reproduced in experimental animals. This is a rare form of vascular toxicity attributed to CyA which may have a poor prognosis and possibly results from a direct toxic effect of CyA on vascular endothelium. The syndrome of chronic progressive deterioration of renal function associated with CyA was first recognized in humans. Until recently the possibility of reproducing this syndrome in animals in order to better understand its nature was not addressed. As in humans, when animals are given CyA for >2 months they may develop chronic renal insufficiency with tubular arteriopathy and interstitial fibrosis. A peculiar form of tubulointerstitial damage has been recognized in association with CyA, and called striped interstitial fibrosis, that is probably due to tubular collapse induced by afferent vasoconstriction. This lesion may be improved by withdrawal of CyA, but renal function usually does not normalize. Recently, a few studies suggested that CyA chronic nephrotoxicity may have a progressive course, with a pattern of pathological changes which include arteriopathy, tubular atrophy, and interstitial fibrosis. Signs of chronic damage to the kidney have been detected in cardiac transplant patients given CyA for >12 months. Despite stable GFR, some glomeruli were sclerotic, probably as a result of ischemia, and the remaining were larger than normal. In conclusion, the administration of CyA is associated with a renal damage probably caused by a peculiar vascular toxicity. This risk should be considered carefully when the drug must be administered for a long time or for indications other than prevention of graft rejection.

Original languageEnglish
Pages (from-to)261-272
Number of pages12
JournalAmerican Journal of Kidney Diseases
Issue number4
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Nephrology


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