Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia.

Abstract

BACKGROUND/AIMS:

The effect of febuxostat (Fx), a non-purine and selective xanthine oxidase inhibitor, on glomerular microcirculatory changes in 5/6 nephrectomy (5/6 Nx) Wistar rats with and without oxonic acid (OA)-induced hyperuricemia was evaluated.

METHODS:

Four groups were studied: 5/6 Nx+vehicle (V)+placebo (P) (n = 7); 5/6 Nx+V+Fx (n = 8); 5/6 Nx+OA+P (n = 6) and 5/6 Nx+OA+Fx (n = 10). OA (750 mg/kg/day, oral gavage) and Fx (3-4 mg/kg/day, drinking water) were administered for 4 weeks. Systolic blood pressure, proteinuria and plasma uric acid were measured at baseline and at the end of 4 weeks. Measurement of glomerular hemodynamics and evaluation of histology were performed at the end of 4 weeks.

RESULTS:

5/6 Nx+OA+P rats developed hyperuricemia, renal vasoconstriction and glomerular hypertension in association with further aggravation of afferent arteriolopathy compared to 5/6 Nx+V+P. Fx prevented hyperuricemia in 5/6 Nx+OA+Fx rats and ameliorated proteinuria, preserved renal function and prevented glomerular hypertension in both 5/6 Nx+V+Fx and 5/6 Nx+OA+Fx groups. Functional improvement was accompanied by preservation of afferent arteriolar morphology and reduced tubulointerstitial fibrosis.

CONCLUSION:

Fx prevented renal injury in 5/6 Nx rats with and without coexisting hyperuricemia. Because Fx helped to preserve preglomerular vessel morphology, normal glomerular pressure was maintained even in the presence of systemic hypertension.

• Authors: Laura G Sánchez-Lozada, Edilia Tapia, Virgilia Soto, Carmen Avila-Casado, Martha Franco, Jerry L Wessale, Lin Zhao, Richard J Johnson
• Journal: Nephron. Physiology (Nephron Physiol) Vol. 108 Issue 4 Pg. p69-78 ( 2008) ISSN: 1660-2137 [Electronic] Switzerland
• PMID: 18434753 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2008 S. Karger AG, Basel.

Chemical References

• Thiazoles
• Febuxostat
• Oxonic Acid

Topics

• Animals
• Disease Models, Animal
• Febuxostat
• Hyperuricemia (chemically induced, diagnosis, physiopathology, prevention & control)
• Kidney (blood supply, drug effects, physiopathology)
• Kidney Failure, Chronic (diagnosis, physiopathology, prevention & control)
• Male
• Microcirculation (drug effects, physiopathology)
• Nephrectomy
• Oxonic Acid
• Rats
• Rats, Wistar
• Recovery of Function (drug effects)
• Thiazoles (administration & dosage)
• Treatment Outcome