Fibrosis chronic cyclosporine nephrotox

Extensive expression of KlM-1 has been found in proximal tubule cells in biopsies from patients with acute tubular necrosis [302]. KlM-1 is also expressed in other conditions where proximal tubules are dedifferentiated, including renal cell carcinoma [303, 304], chronic cyclosporine nephrotoxicity [305], a protein-overload model of tubulointerstitial disease [306], polycystic kidney disease [307], and contrast nephropathy. In several chronic conditions, KlM-1 has been found primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis and inflammation. Independent of the specific disease, renal KIM-1 correlated positively with the extent of renal damage and negatively with renal function. In these patients, urinary levels of KIM-1 were and correlated positively with tissue KIM-1 and negatively with renal function. Thus, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. Urinary KIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1. 

Kon V, Flunley TE, Fogo A. Combined antagonism of endothelin A/B receptors links endothelin to vasoconstriction whereas angiotensin II effects fibrosis. Studies in chronic cyclosporine nephrotoxicity in rats.Transplantation 1995 60 89-95. 

Shihab FS, Bennett WM,Yi FI, AndohTF. Pirfenidone treatment decreases transforming growth factor-beta and matrix proteins and ameliorates fibrosis in chronic cyclosporine nephrotoxicity. Am J Transplant 2002 2 111-119. 

Nephrotoxicity is a common toxicity and significant problem associated with the use of cyclosporine in humans. Three types of nephrotoxicity have been observed in patients receiving cyclosporine (1) an acute, reversible renal failure (2) acute vasculopathy or thrombotic microangiopathy and (3) chronic renal failure with interstitial fibrosis that may not be reversible. 

The immunosuppressive drug cyclosporine A (CSA) has revolutionized transplant medicine. However, CSA induced-nephrotoxicity still represents a major therapeutic challenge. Chronic CSA nephropathy is characterized by a decrease in glomerular filtration rate (GFR), tubular atrophy, interstitial fibrosis and progressive renal dysfunction. It is difficult to delineate the mechanisms of CSA toxicity from clinical data since the majority of clinical experiences with CSA have been in renal transplant recipients. Animal models of CSA nephropathy have brought some insights, how-... 

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