188宝金博页面版

HOT TOPICUric Acid, Hypertension, and Cardiovascularand Renal ComplicationsCarmine Zoccali & Francesca MallamaciPublished online: 27 September 2013# Springer Science+Business Media New York 2013Abstract Over the last decade, the biologic interference ofuric acid with the cardiovascular (CV) system and the kidneyhas been intensively investigated, and several experimentalstudies in animal models and in vitro documented that hyper-uricemia may trigger hypertension and incite endothelial dys-function, vascular damage and renal disease. A substantialproportion of epidemiological studies are compatible withthe hypothesis that hyperuricemia may be noxious to the CVsystem and the kidney as well. However, there are still nowell-powered trials testing whether uric acid–lowering inter-ventions may reduce BP or attenuate the risk for adverse CVandrenal outcomes.Evidencestillremains largelyinsufficienttorecommend changes inthe current policyofnot prescribinguric acid–lowering drugs to individuals with asymptomatichyperuricemia.Keywords Uricacid . Hypertension . Chronickidneydisease . CKD . End-stagerenaldisease . ESRD .Cardiovascularrisk . Endothelialdysfunction . Inflammation .Atherosclerosis . Arteriolosclerosis . NephrosclerosisIntroductionUricacidisperhaps one ofthe firstfactors tobesuspectedasapossible cause of hypertension. Mahomed, a prominent nine-teenth century British physician, hypothesized that hyperten-sion could be incited by circulating toxins damaging the heartand kidneys via an increase in blood pressure. Among severalfactors, he singled out uric acid as a main causative factor ofhigh BP and documented hypertension with sphymographtracings in a patient with gout (quoted by Feig DI [1]). Afterthis seminal observation, interest on uric acid as a noxiousfactor for the cardiovascular (CV) system waxed and waned.In the nineties it was prevailing view that uric acid is a meresurrogate of other, more important, risk factors such diabetes,overweightandobesityandrenaldisease[2].Themainreasonwhy the role of uric acid was dismissed as a pro-hypertensivefactor and as a CV risk factor rested on the fact that therewas no plausible biological hypothesis to explain its pro-hypertensive effect, and that the association between uric acidand blood pressure and CV complications registered in obser-vational studies is confounded by diabetes and other majorrisk factors. Over the last two decades, groundbreaking ex-perimental work in animal and in vitro models and epidemi-ological studies have given new impetus to research on thehealthrisks ofuricacid. Hereinwewillreview(1) experimen-tal studies showing that hyperuricemia disturbs endothelialfunction and integrity and incites arterial damage, (2) epide-miologicalstudieslookingattheassociationbetweenuricacidand hypertension. Additionally, in this section we will expandupon the relationship between hyperuricemia and CV renaldisease and (3) clinical trials testing the effect of uric acid-lowering interventions on major clinical end-points includinghypertension, the risk of CV complications and progressivechronic kidney disease (CKD).C. Zoccali : F. MallamaciCNR National Research Council (Italy) Clinical Epidemiology andPhysiopathology of Renal Disease and Hypertension Unit andNephrology, Hypertension and Renal Transplantation unit, OspedaliRiuniti, Reggio Calabria 89124, ItalyF. Mallamacie-mail: francesca.mallamaci@libero.itC. Zoccali : F. MallamaciRenal and Transplantation Unit Ospedali Riuniti, ReggioCalabria 89124, ItalyC. Zoccali (*)Nefrologia e CNR, Ospedali Riuniti, Reggio Calabria 89124, Italye-mail: carmine.zoccali@tin.itCurr Hypertens Rep (2013) 15:531–537DOI 10.1007/s11906-013-0391-y