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


CONCLUSIONS
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.
Sánchez-Lozada
Laura G
LG
Department of Nephrology, INC Ignacio Chavez, Mexico City, Mexico. lgsanchezlozada@hotmail.com
Tapia
Edilia
E
Soto
Virgilia
V
Avila-Casado
Carmen
C
Franco
Martha
M
Wessale
Jerry L
JL
Zhao
Lin
L
Johnson
Richard J
RJ
D000818:Animals; D004195:Disease Models, Animal; D000069465:Febuxostat; D033461:Hyperuricemia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology* / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000503:physiopathology; D009392:Nephrectomy; D010094:Oxonic Acid; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
D013844:Thiazoles; D000069465:Febuxostat; D010094:Oxonic Acid