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Nephrol Dial Transplant. 2008 Apr;23(4):1179-85. Epub 2007 Nov 29.

Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.

Author information

1
Department of Nephrology, Instituto Nacional de Cardiologiá Ignacio Chavez, Juan Badiano 1, 14080-Mexico City, Mexico. lgsanchezlozada@hotmail.com

Abstract

BACKGROUND:

Experimentally-induced hyperuricaemia [due to inhibition of uricase with oxonic acid (OA)] in rats causes hypertension and renal alterations which can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an investigational, nonpurine and selective xanthine oxidase inhibitor, is a more effective UA-lowering agent than allopurinol. We therefore tested the hypothesis that Fx might be useful in treating hyperuricemia-induced hypertension and renal damage.

METHODS:

Four groups of male rats were studied: OA (750 mg/kg by daily gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n = 10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks after initiation of the study. Two groups of normal (N) rats were studied as controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting plasma UA were measured in all animals at baseline and at 4 and 8 weeks. Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks followed by histological evaluation of glomerular and afferent arteriole morphologies.

RESULTS:

In OA-induced hyperuricaemic rats, Fx lowered UA and ameliorated systemic and glomerular hypertension as well as mesangial matrix expansion and the development of preglomerular arteriolar disease as indicated by a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx tended to lower UA and had no effect on blood pressure, renal hemodynamics and afferent arteriole morphology.

CONCLUSION:

These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia.

PMID:
18048425
DOI:
10.1093/ndt/gfm783
[Indexed for MEDLINE]

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