Uric acid--a uremic toxin?
Uric acid might often be regarded as a simple marker of renal disease. Although it is well known that hyperuricemia causes gout which is associated with renal insufficiency and cardiovascular disease, one might think that it could attribute to the intrarenal urate crystal, but not to uric acid per se. In order to clarify the role of uric acid in the kidney, we hypothesized that uric acid causes renal disease. To generate mild hyperuricemia without intrarenal crystal in rats, we used low doses of an uricase inhibitor (2% oxonic acid). Hyperuricemia induced systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis, and macrophage infiltration in normal rat kidney. In progressive renal disease, such as cyclosporine nephropathy and remnant kidney in rat, uric acid accelerated the progression of renal disease. Thus, we concluded that uric acid is not a simple marker, but a cause of renal disease.
Nakagawa
Takahiko
T
Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL 32610-0224, USA. nakagt@medicine.ufl.edu
Mazzali
Marilda
M
Kang
Duk-Hee
DH
Sánchez-Lozada
L Gabriela
LG
Herrera-Acosta
Jaime
J
Johnson
Richard J
RJ
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D033461:Hyperuricemia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010094:Oxonic Acid / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D014503:Urate Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D014527:Uric Acid; D010094:Oxonic Acid; D014503:Urate Oxidase