Pentosan polysulfate treatment reduces cyclosporine-induced nephropathy insalt-depleted rats

Background. Long-term cyclosporine (CsA) treatment leads to a decreased glo merular filtration rate, hyalinosis of afferent arterioles, and striped cor tical tubulo-interstitial fibrosis. We showed previously that pentosan poly sulfate (SP54) prevented the development of microvascular and interstitial lesions in mouse models of progressive glomerulosclerosis. In this study, w e examined the effect of pentosan polysulfate on the development of CsA nep hropathy. Methods. Pair-fed Sprague-Dawley rats were fed a low-sodium (0.03%) diet an d received CsA (15 mg/kg, subcutaneously, in olive oil)/5% glucose, pentosa n polysulfate (10 mg/kg, subcutaneously in 5% glucose) plus CsA, olive oil/ pentosan polysulfate, or olive oil/5% glucose for 30 days. Creatinine clear ance (CrCl) was determined at three time points. Afferent arteriolar lesion s, glomerular volume, and tubulo-interstitial lesions were quantitated. RNA was extracted from cortex. Results. Severe lesions were found in the CsA group. A reduction in the num ber of affected arterioles (32%) and the degree of chronic tubulo-interstit ial lesions (44%) was found in pentosan polysulfate/CsA-treated rats. A 20% decrease in glomerular volume was found in CsA rats, but not in pentosan p olysulfate/CsA-treated rats. Pentosan polysulfate treatment did not prevent the CsA-induced decrease in CrCl (similar to 30%) at 4 weeks. CsA did not affect cortical endothelial or neuronal nitric-oxide synthase or mRNA level s, but there was small increase in neuronal nitric-oxide synthase mRNA leve ls in the pentosan polysulfate/CsA-treated group. Conclusions. Pentosan polysulfate reduced structural renal lesions in CsA-t reated, salt-depleted Sprague-Dawley rats.