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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Use of Uric Acid-Lowering Agents Limits Experimental Cyclosporine Nephropathy

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Author(s):
Mazali, Fernanda Cristina ; Johnson, Richard J. [1] ; Mazzali, Marilda [2]
Total Authors: 3
Affiliation:
[1] Univ Colorado, Dept Med, Div Renal Dis & Hypertens, Denver, CO - USA
[2] Univ Estadual Campinas, DCM, Sch Med Sci, Dept Med, Div Nephrol, Nephrol Lab 1, FCM, UNICAMP, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: NEPHRON EXPERIMENTAL NEPHROLOGY; v. 120, n. 1, p. E12-E19, 2012.
Web of Science Citations: 17
Abstract

Background: Hyperuricemia frequently complicates cyclosporine (CsA) therapy. Previous studies have shown that hyperuricemia exacerbates interstitial and vascular lesions in the cyclosporine model. We tested the hypothesis that normalization of uric acid could prevent the development of cyclosporine toxicity. Methods: CsA nephropathy was induced by administering CsA (15 mg/kg/day) for 7 weeks to rats on a low salt diet (CsA group). The effect of preventing hyperuricemia was determined by concomitant treatment with a xanthine oxidase inhibitor, allopurinol (CsAALP), or with a uricosuric, benzbromarone (CsABENZ), in drinking water. Control groups included vehicle-treated rats. Results: CsA-treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, increased cell proliferation and decreased VEGF expression. Treatment with allopurinol or benzbromarone limited renal disease, with reduced interstitial fibrosis, cell proliferation, macrophage infiltration, osteopontin expression and arteriolar hyalinosis, in association with restoration of VEGF expression. Both drugs provided comparable protection. Conclusions: An increase in uric acid exacerbates CsA nephropathy in the rat. Concomitant treatment with allopurinol or benzbromarone reduced the severity of renal disease. The similar protection observed with both drugs suggests that the effect is associated more with lowering uric acid levels than the antioxidant effect of allopurinol. Copyright (C) 2011 S. Karger AG, Basel (AU)