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01-12-2013 | Hot Topic

Uric Acid, Hypertension, and Cardiovascular and Renal Complications

Authors: Carmine Zoccali, Francesca Mallamaci

Published in: Current Hypertension Reports | Issue 6/2013

Abstract

Over the last decade, the biologic interference of uric acid with the cardiovascular (CV) system and the kidney has been intensively investigated, and several experimental studies in animal models and in vitro documented that hyperuricemia may trigger hypertension and incite endothelial dysfunction, vascular damage and renal disease. A substantial proportion of epidemiological studies are compatible with the hypothesis that hyperuricemia may be noxious to the CV system and the kidney as well. However, there are still no well-powered trials testing whether uric acid–lowering interventions may reduce BP or attenuate the risk for adverse CV and renal outcomes. Evidence still remains largely insufficient to recommend changes in the current policy of not prescribing uric acid–lowering drugs to individuals with asymptomatic hyperuricemia.

Feig DI. Hyperuricemia and hypertension. Adv Chronic Kidney Dis. 2012;19:377–85. A comprehensive review of the link between hyperuricemia and hypertension.PubMedCrossRef

Culleton BF, Larson MG, Kannel WB, Levy D. Serum uric acid and risk for CV disease and death: the Framingham Heart Study. Ann Intern Med. 1999;131:7–13.PubMedCrossRef

Moritz AR, Oldt MR. Arteriolar sclerosis in hypertensive and non-hypertensive individuals. Am J Pathol. 1937;13:679–728.PubMed

Walker MB, Boyd GW. The distribution of arteriolosclerosis along the arterioles in DOCA hypertensive rats. Clin Exp Pharmacol Physiol. 1983;10:319–23.PubMedCrossRef

Sumpio BE, Widmann MD, Ricotta J, et al. Increased ambient pressure stimulates proliferation and morphologic changes in cultured endothelial cells. J Cell Physiol. 1994;158:133–9.PubMedCrossRef

Hishikawa K, Nakaki T, Marumo T, et al. Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells. J Clin Invest. 1994;93:1975–80.PubMedCrossRef

Lombardi D, Gordon KL, Polinsky P, et al. Salt-sensitive hypertension develops after short-term exposure to Angiotensin II. Hypertension. 1999;33:1013–9.PubMedCrossRef

Quiroz Y, Pons H, Gordon KL, et al. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition. Am J Physiol Ren Physiol. 2001;281:F38–47.

Sanchez-Lozada LG, Tapia E, Jimenez A, et al. Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Ren Physiol. 2007;292:F423–9.CrossRef

10.

Aida Y, Shibata Y, Osaka D, et al. The relationship between serum uric acid and spirometric values in participants in a health check: the Takahata study. Int J Med Sci. 2011;8:470–8.PubMedCrossRef

11.

Nieto FJ, Iribarren C, Gross MD, et al. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis. 2000;148:131–9.PubMedCrossRef

12.

Corry DB, Eslami P, Yamamoto K, et al. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens. 2008;26:269–75.PubMedCrossRef

13.

Kanellis J, Watanabe S, Li JH, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension. 2003;41:1287–93.PubMedCrossRef

14.

Kang DH, Park SK, Lee IK, Johnson RJ. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005;16:3553–62.PubMedCrossRef

15.

Rao GN, Corson MA, Berk BC. Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem. 1991;266:8604–8.PubMed

16.

Kang DH, Joly AH, Oh SW, et al. Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J Am Soc Nephrol. 2001;12:1434–47.PubMed

17.

Sanchez-Lozada LG, Tapia E, Santamaria J, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005;67:237–47.PubMedCrossRef

18.

Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B. Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med. 2002;346:913–23.PubMedCrossRef

19.

Hsu CH, Patel SR, Young EW, Vanholder R. Effects of purine derivatives on calcitriol metabolism in rats. Am J Physiol. 1991;260:F596–601.PubMed

20.

Sigmund CD. Regulation of renin expression and blood pressure by vitamin D(3). J Clin Invest. 2002;110:155–6.PubMed

21.

Vanholder R, Patel S, Hsu CH. Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure. J Am Soc Nephrol. 1993;4:1035–8.PubMed

22.

Mazzali M, Kanellis J, Han L, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Ren Physiol. 2002;282:F991–7.

23.

Mori T, Cowley Jr AW. Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats. Hypertension. 2004;43:752–9.PubMedCrossRef

24.

Khosla UM, Zharikov S, Finch JL, et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 2005;67:1739–42.PubMedCrossRef

25.

Waring WS, Adwani SH, Breukels O, et al. Hyperuricaemia does not impair CV function in healthy adults. Heart. 2004;90:155–9.PubMedCrossRef

26.

Zoccali C, Maio R, Mallamaci F, et al. Uric acid and endothelial dysfunction in essential hypertension. J Am Soc Nephrol. 2006;17:1466–71.PubMedCrossRef

27.

Perticone F, Maio R, Tripepi G, Zoccali C. Endothelial dysfunction and mild renal insufficiency in essential hypertension. Circulation. 2004;110:821–5.PubMedCrossRef

28.

Johnson RJ, Rodriguez-Iturbe B, Kang DH, et al. A unifying pathway for essential hypertension. Am J Hypertens. 2005;18:431–40.PubMedCrossRef

29.

Kahn HA, Medalie JH, Neufeld HN, et al. The incidence of hypertension and associated factors: the Israel ischemic heart disease study. Am Heart J. 1972;84:171–82.PubMedCrossRef

30.

Dyer AR, Liu K, Walsh M, et al. Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary artery risk development in (Young) adults. J Hum Hypertens. 1999;13:13–21.PubMedCrossRef

31.

Taniguchi Y, Hayashi T, Tsumura K, et al. Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: the Osaka health survey. J Hypertens. 2001;19:1209–15.PubMedCrossRef

32.

Imazu M, Yamamoto H, Toyofuku M, et al. Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima study. Hypertens Res. 2001;24:531–6.PubMedCrossRef

33.

Masuo K, Kawaguchi H, Mikami H, et al. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003;42:474–80.PubMedCrossRef

34.

Nakanishi N, Okamoto M, Yoshida H, et al. Serum uric acid and risk for development of hypertension and impaired fasting glucose or Type II diabetes in Japanese male office workers. Eur J Epidemiol. 2003;18:523–30.PubMedCrossRef

35.

Nagahama K, Inoue T, Iseki K, et al. Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res. 2004;27:835–41.PubMedCrossRef

36.

Rovda I, Kazakova LM, Plaksina EA. Parameters of uric acid metabolism in healthy children and in patients with arterial hypertension. Pediatriia. 1990;8:19–22.

37.

Torok E, Gyarfas I, Csukas M. Factors associated with stable high blood pressure in adolescents. J Hypertens Suppl. 1985;3:S389–90.PubMed

38.

Goldstein HS, Manowitz P. Relation between serum uric acid and blood pressure in adolescents. Ann Hum Biol. 1993;20:423–31.PubMedCrossRef

39.

Nefzger MD, Acheson RM, Heyman A. Mortality from stroke among U.S. veterans in Georgia and 5 western states. I. Study plan and death rates. J Chronic Dis. 1973;26:393–404.PubMedCrossRef

40.

Saito I, Folsom AR, Brancati FL, et al. Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Ann Intern Med. 2000;133:81–91.PubMedCrossRef

41.

Staessen J. The determinants and prognostic significance of serum uric acid in elderly patients of the European Working Party on High Blood Pressure in the Elderly trial. Am J Med. 1991;90:50S–4S.PubMedCrossRef

42.

Moriarity JT, Folsom AR, Iribarren C, et al. Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) study. Ann Epidemiol. 2000;10:136–43.PubMedCrossRef

43.

Alper Jr AB, Chen W, Yau L, et al. Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension. 2005;45:34–8.PubMedCrossRef

44.

Sundstrom J, Sullivan L, D'Agostino RB, et al. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension. 2005;45:28–33.PubMedCrossRef

45.

Feig DI, Kang DH, Johnson RJ. Uric acid and CV risk. N Engl J Med. 2008;359:1811–21.PubMedCrossRef

46.

Schretlen DJ, Inscore AB, Vannorsdall TD, et al. Serum uric acid and brain ischemia in normal elderly adults. Neurology. 2007;69:1418–23.

47.

Niskanen LK, Laaksonen DE, Nyyssonen K, et al. Uric acid level as a risk factor for CV and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med. 2004;164:1546–51.PubMedCrossRef

48.

Wannamethee SG, Shaper AG, Whincup PH. Serum urate and the risk of major coronary heart disease events. Heart. 1997;78:147–53.PubMed

49.

Wheeler JG, Juzwishin KD, Eiriksdottir G, et al. Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis. PLoS Med. 2005 Mar;2(3):e76.

50.

Bos MJ, Koudstaal PJ, Hofman A, et al. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke. 2006;37:1503–7.PubMedCrossRef

51.

Baker JF, Krishnan E, Chen L, Schumacher HR. Serum uric acid and CV disease: recent developments, and where do they leave us? Am J Med. 2005;118:816–26.PubMedCrossRef

52.

Iseki K, Oshiro S, Tozawa M, et al. Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res. 2001;24:691–7.PubMedCrossRef

53.

Jalal DI, Rivard CJ, Johnson RJ, et al. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010;25:1865–9.PubMedCrossRef

54.

Ficociello LH, Rosolowsky ET, Niewczas MA, et al. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care. 2010;33:1337–43.PubMedCrossRef

55.

Weiner DE, Tighiouart H, Elsayed EF, et al. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19:1204–11.PubMedCrossRef

56.

Obermayr RP, Temml C, Knechtelsdorfer M, et al. Predictors of new-onset decline in kidney function in a general middle-european population. Nephrol Dial Transplant. 2008;23:1265–73.PubMedCrossRef

57.

Bellomo G, Venanzi S, Verdura C, et al. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56:264–72.PubMedCrossRef

58.

Madero M, Sarnak MJ, Wang X, et al. Uric acid and long-term outcomes in CKD. Am J Kidney Dis. 2009;53:796–803.PubMedCrossRef

59.

Sturm G, Kollerits B, Neyer U, et al. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study. Exp Gerontol. 2008;43:347–52.PubMedCrossRef

60.

Syrjanen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant. 2000;15:34–42.PubMedCrossRef

61.

• Le W, Liang S, Hu Y, et al. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2012;27:1479–85. A large observational study linking uric acid levels and progression to end stage renal diseae in IgA nephropathy.PubMedCrossRef

62.

• Helal I, McFann K, Reed B, et al. Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease. Nephrol Dial Transplant. 2013;28:380–5. A study suggesting that high serum uric acid may be involved in renal function loss in ADPPKD.PubMedCrossRef

63.

Kolz M, Johnson T, Sanna S, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009 Jun;5(6):e1000504.

64.

Testa A, Leonardis D, Catalano F, et al. The SLC2A9 polymorphism, the major genetic determinant of serum uric acid levels, predicts progression to kidney failure in CKD patients. (Abstract SAP014). Presented at the 49th ERA-EDTA Congress, Paris, France; May 24-27, 2012.

65.

Feig DI, Nakagawa T, Karumanchi SA, et al. Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int. 2004;66:281–7.PubMedCrossRef

66.

Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924–32.PubMedCrossRef

67.

Kanbay M, Ozkara A, Selcoki Y, et al. Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol. 2007;39:1227–33.PubMedCrossRef

68.

Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47:51–9.PubMedCrossRef

69.

Goicoechea M, de Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and CV risk. Clin J Am Soc Nephrol. 2010;5:1388–93.PubMedCrossRef

70.

Dahlof B, Devereux RB, Kjeldsen SE, et al. CV morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995–1003.PubMedCrossRef

71.

Kao MP, Ang DS, Gandy SJ, et al. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol. 2011;22:1382–9.PubMedCrossRef

72.

•• Rekhraj S, Gandy SJ, Szwejkowski BR, et al. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol. 2013;61:926–32. A randomized double-blinded, placebo controlled trial (RCT) showing that allopurinol at the dose of 800 mg/d reduces left ventricular hypertrophy and arterial stiffness in patients with coronary heart disease. This trial fully confirms findings in a previous RCT in CKD patients (Ref.71).PubMedCrossRef

73.

Okin PM, Devereux RB, Jern S, et al. Relation of echocardiographic left ventricular mass and hypertrophy to persistent electrocardiographic left ventricular hypertrophy in hypertensive patients: the LIFE Study. Am J Hypertens. 2001;14:775–82.PubMedCrossRef

Title: Uric Acid, Hypertension, and Cardiovascular and Renal Complications
Authors: Carmine Zoccali
Francesca Mallamaci
Publication date: 01-12-2013
Publisher: Springer US
Published in: Current Hypertension Reports / Issue 6/2013
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI: https://doi.org/10.1007/s11906-013-0391-y

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