title: Hemodynamics of hyperuricemia.
abstract: Prolonged hyperuricemia is associated with the development of hypertension, renal arteriolosclerosis, glomerulosclerosis, and tubulointerstitial injury. It confers a greater risk than proteinuria for developing chronic renal disease and is associated with the development of hypertension. Mild chronic hyperuricemia without intrarenal crystal deposition was induced in rats by inhibiting uricase with oxonic acid. Hyperuricemic rats developed hypertension, afferent arteriolar thickening, and mild renal interstitial fibrosis. Additionally, hyperuricemia accelerated renal damage and vascular disease in rats undergoing renal ablation. To better understand the role of hyperuricemia in the kidney, micropuncture studies were performed. Hyperuricemia resulted in renal cortical vasoconstriction (single nephron glomerular filtration rate (SNGFR) 35%, P < .05) and glomerular hypertension (P < .05). The possibility that hyperuricemia could modify renal hemodynamic disturbances during progression of renal disease was tested in rats with 5/6 nephrectomy. Hyperuricemia accentuated the renal vascular damage and caused cortical vasoconstriction (SNGFR 40%, P < .05) and persistent glomerular hypertension. In conclusion, hyperuricemia impairs the autoregulatory response of preglomerular vessels, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening results in severe vasoconstriction. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis as well as arterial hypertension.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Ignacio Chávez, 14080 Mexico City, Mexico.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodríguez-Iturbe
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002908:Chronic Disease; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D033461:Hyperuricemia / Q000150:complications / Q000503:physiopathology*; D007672:Kidney Cortex / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology*