title: Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift.
abstract: End-stage renal disease (ESRD) comprises an enormous public health burden, with an increasing incidence and prevalence. Hypertension is a major risk factor for progressive renal disease. This escalating prevalence suggests that newer therapeutic interventions and strategies are needed to complement current antihypertensive approaches. Although much evidence demonstrates that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (i.e. remnant kidney). Whereas pharmacological blockade with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors reduces proteinuria and nephrosclerosis/ glomerulosclerosis, selective reinfusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 expression and consequent alterations of vascular fibrinolysis, by stimulation of transforming growth factor-beta 1, and by stimulation of reactive oxygen species. Based on this theoretical construct, randomized clinical studies will be initiated to delineate the potential renal-protective effects of antihypertensive therapy utilizing aldosterone receptor blockade.
authors.affiliation: Department of Medicine, University of Miami School of Medicine, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Epstein
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology; D051437:Renal Insufficiency / Q000209:etiology
chemical_list: D000450:Aldosterone