Internal and Emergency Medicine

, Volume 7, Issue 1, pp 5–8 | Cite as

Uric acid: a starring role in the intricate scenario of metabolic syndrome with cardio-renal damage?

  • Davide Stellato
  • Luigi Francesco Morrone
  • Chiara Di Giorgio
  • Loreto Gesualdo


Elevated uric acid levels are a common finding in patients with metabolic syndrome and in those with cardiovascular and renal disease, but the meaning of this elevation is still unclear. In patients with chronic kidney diseases, it could merely reflect the reduction in glomerular filtration rate: but uric acid levels are known to be elevated in people, also in younger ones, prior to the development of hypertension or renal disease, independently of several risk factors. Multiple potential mechanisms suggest a causative role for uric acid in vascular disease. Uric acid has been shown to be involved in metabolic pathways that lead to oxidative stress, endothelial disfunction, and to a vascular and systemic inflammatory response. Moreover, the elevation in uric acid levels observed after fructose ingestion, with a consequent reduction in nitric oxide, may lead to a reduced glucose uptake in the skeletal muscle, hyperinsulinemia, and insulin resistance. Besides these bench research data, also clinical studies showed the beneficial effects of lowering uric acid therapies on several markers of cardiovascular and renal disease. To date, however, there is no evidence indicating that such therapies, that are not free of risk, may reduce cardiovascular events; so that to manage our prescriptions, we need larger, prospective, interventional data.


Uric acid  Oxidative stress  Endothelial disfunction  Inflammatory response 


Conflict of interest



  1. 1.
    World Health Organization (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Diabet Med 15(7): 539–553. (Available at
  2. 2.
    National Cholesterol Education Program (2002) Third report of the national cholesterol education program (NCEP) on detection and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106:3143–3421Google Scholar
  3. 3.
    Alberti KGM, Zimmet P, Shaw J (2006) Metabolic syndrome: a new world-wide definition. A consensus statement from the International diabetes federation. Diabet Med 23:469–480PubMedCrossRefGoogle Scholar
  4. 4.
    Chen J, Muntner P, Hamm L et al (2004) The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med 140:167–174PubMedGoogle Scholar
  5. 5.
    Wahba IM, Mak RH (2007) Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2:550–562PubMedCrossRefGoogle Scholar
  6. 6.
    Ramirez SP, McClellan W, Port FK et al (2002) Risk factors for proteinuria in a large, multiracial, Southeast Asian population. J Am Soc Nephrol 13:1907–1917PubMedCrossRefGoogle Scholar
  7. 7.
    Tozawa M, Iseki K, Iseki C et al (2002) Influence of smoking and obesity on the development of proteinuria. Kidney Int 62:956–962PubMedCrossRefGoogle Scholar
  8. 8.
    Trayhurn P (2005) Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184:285–293PubMedCrossRefGoogle Scholar
  9. 9.
    Thatcher S, Yiannikouris F, Gupte M et al (2009) The adipose renin-angiotensin system: role in cardiovascular disease. Mol Cell Endocrinol 302:111–117PubMedCrossRefGoogle Scholar
  10. 10.
    Iseki K (2008) Metabolic syndrome and chronic kidney disease: a Japanese perspective on a worldwide problem. J Nephrol 21:305–312PubMedGoogle Scholar
  11. 11.
    Gertler MM, Garn SM, Levine SA (1951) Serum uric acid in relation to age and physique in health and in coronary heart disease. Ann Intern Med 34:1421–1431PubMedGoogle Scholar
  12. 12.
    Cannon PJ, Stason WB, Demartini FE et al (1966) Hyperuricemia in primary and renal hypertension. N Engl J Med 275:457–464PubMedCrossRefGoogle Scholar
  13. 13.
    Bos MJ, Koudstaal PJ, Hofman A et al (2006) Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam Study. Stroke 37:1503–1507PubMedCrossRefGoogle Scholar
  14. 14.
    Feig DI, Kang DH, Nakagawa T et al (2006) Uric acid and hypertension. Curr Hypertens Rep 8:111–115PubMedCrossRefGoogle Scholar
  15. 15.
    Obermayr RP, Temml C, Knechtelsdorfer M et al (2008) Predictors of new-onset decline in kidney function in a general middle-european population. Nephrol Dial Transplant 23:1265–1273PubMedCrossRefGoogle Scholar
  16. 16.
    Weiner DE, Tighiouart H, Elsayed EF et al (2008) Uric acid and incident kidney disease in the community. J Am Soc Nephrol 19:1204–1211PubMedCrossRefGoogle Scholar
  17. 17.
    K/DOQI (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(S1):S1–S266Google Scholar
  18. 18.
    Feig DI, Kang DH, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821PubMedCrossRefGoogle Scholar
  19. 19.
    Feig DI, Johnson RJ (2003) Hyperuricemia in childhood primary hypertension. Hypertension 42:247–252PubMedCrossRefGoogle Scholar
  20. 20.
    Feig DI, Mazzali M, Kang D-H et al (2006) Serum uric acid: a risk factor and a target for treatment? J Am Soc Nephrol 17:S69–S73PubMedCrossRefGoogle Scholar
  21. 21.
    Gertzberg N, Neumann P, Rizzo V et al (2004) NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-alpha. Am J Physiol Lung Cell Mol Physiol 286:L37–L48PubMedCrossRefGoogle Scholar
  22. 22.
    Sautin YY, Nakagawa T, Zharikov S et al (2007) Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 293:C584–C596PubMedCrossRefGoogle Scholar
  23. 23.
    Mazzali M, Hughes J, Kim YG et al (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106PubMedCrossRefGoogle Scholar
  24. 24.
    Sarafidis PA, Bakris GL (2007) Insulin and endothelin: an interplay contributing to hypertension development? J Clin Endocrinol Metab 92:379–385PubMedCrossRefGoogle Scholar
  25. 25.
    TerMaaten JC, Voorburg A, Heine RJ et al (1997) Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects. Clin Sci (Lond) 92:51–58Google Scholar
  26. 26.
    Heinig M, Johnson RJ (2006) Role of uric acid in hypertension, renal disease, and metabolic syndrome. Cleve Clin J Med 73:1059–1064PubMedCrossRefGoogle Scholar
  27. 27.
    Hallfrisch J (1990) Metabolic effects of dietary fructose. FASEB J 4:2652–2660PubMedGoogle Scholar
  28. 28.
    Viazzi F, Leoncini G, Vercelli M et al (2011) Serum uric acid levels predict new-onset type 2 diabetes in hospitalized patiants with primary hypertension: the MAGIC study. Diabetes Care 34:126–128PubMedCrossRefGoogle Scholar
  29. 29.
    Nakagawa T, Cirillo P, Sato W et al (2009) The conundrum of hyperuricemia, metabolic syndrome, and renal disease. Intern Emerg Med 3:313–318CrossRefGoogle Scholar
  30. 30.
    Mazzali M, Kanellis J, Han L et al (2002) Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol 282:F991–F997PubMedGoogle Scholar
  31. 31.
    Ames BN, Cathcart R, Schwiers E et al (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 78:6858–6862PubMedCrossRefGoogle Scholar
  32. 32.
    Sautin YY, Johnson RJ (2008) Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 27:608–619PubMedCrossRefGoogle Scholar
  33. 33.
    So A, Thorens B (2010) Uric acid transport and disease. J Clin Invest 120:1791–1799PubMedCrossRefGoogle Scholar
  34. 34.
    Higgins P, Dawson J, Walters M (2009) The potential for xanthine oxidase inhibition in the prevention and treatment of cardiovascular and cerebrovascular disease. Cardiovasc Psychiatry Neurol 2009:282059PubMedGoogle Scholar
  35. 35.
    Noman A, Ang DSC, Ogston S et al (2010) Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet 9732:2161–2167CrossRefGoogle Scholar
  36. 36.
    Goicoechea M, Vinuesa SG, Verdalles U et al (2010) Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 5(8):1388–1393PubMedCrossRefGoogle Scholar

Copyright information

© SIMI 2011

Authors and Affiliations

  • Davide Stellato
    • 1
  • Luigi Francesco Morrone
    • 1
  • Chiara Di Giorgio
    • 2
  • Loreto Gesualdo
    • 2
  1. 1.Struttura Complessa di Nefrologia e DialisiAzienda Ospedaliera RummoBeneventoItaly
  2. 2.Struttura Complessa di Nefrologia, Dialisi e TrapiantoAzienda Ospedaliero-Universitaria “OO.RR.”FoggiaItaly

Personalised recommendations