title: Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link?
abstract: Hypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.
authors.affiliation: University of Florida, Division of Nephrology, Hypertension, and Transplantation, 1600 SW Archer Road, Gainesville, FL 32610, USA. johnsrj@medicine.ufl.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
authors.forename: Titte
authors.initials: T
authors.lastname: Srinivas
authors.forename: Ahsan
authors.initials: A
authors.lastname: Ejaz
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.forename: Carlos
authors.initials: C
authors.lastname: Roncal
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: Michael
authors.initials: M
authors.lastname: Gersch
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.forename: Jaime Herrera
authors.initials: JH
authors.lastname: Acosta
mesh_terms: D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D033461:Hyperuricemia / Q000209:etiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology; D014527:Uric Acid / Q000378:metabolism
chemical_list: D014527:Uric Acid