Skip to main content

Advertisement

SpringerLink
Log in

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

  • IM - REVIEW
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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 http://whqlibdoc.who.int/hq/1999/who_ncd_ncs_99.2.pdf)

  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 106:3143–3421

    Google Scholar 

  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 23:469–480

    Article  PubMed  CAS  Google Scholar 

  4. Chen J, Muntner P, Hamm L et al (2004) The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med 140:167–174

    PubMed  Google Scholar 

  5. Wahba IM, Mak RH (2007) Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2:550–562

    Article  PubMed  CAS  Google Scholar 

  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 13:1907–1917

    Article  PubMed  Google Scholar 

  7. Tozawa M, Iseki K, Iseki C et al (2002) Influence of smoking and obesity on the development of proteinuria. Kidney Int 62:956–962

    Article  PubMed  Google Scholar 

  8. Trayhurn P (2005) Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184:285–293

    Article  PubMed  CAS  Google Scholar 

  9. Thatcher S, Yiannikouris F, Gupte M et al (2009) The adipose renin-angiotensin system: role in cardiovascular disease. Mol Cell Endocrinol 302:111–117

    Article  PubMed  CAS  Google Scholar 

  10. Iseki K (2008) Metabolic syndrome and chronic kidney disease: a Japanese perspective on a worldwide problem. J Nephrol 21:305–312

    PubMed  Google Scholar 

  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 34:1421–1431

    PubMed  CAS  Google Scholar 

  12. Cannon PJ, Stason WB, Demartini FE et al (1966) Hyperuricemia in primary and renal hypertension. N Engl J Med 275:457–464

    Article  PubMed  CAS  Google Scholar 

  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 37:1503–1507

    Article  PubMed  CAS  Google Scholar 

  14. Feig DI, Kang DH, Nakagawa T et al (2006) Uric acid and hypertension. Curr Hypertens Rep 8:111–115

    Article  PubMed  CAS  Google Scholar 

  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 23:1265–1273

    Article  PubMed  Google Scholar 

  16. Weiner DE, Tighiouart H, Elsayed EF et al (2008) Uric acid and incident kidney disease in the community. J Am Soc Nephrol 19:1204–1211

    Article  PubMed  CAS  Google Scholar 

  17. K/DOQI (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(S1):S1–S266

    Google Scholar 

  18. Feig DI, Kang DH, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821

    Article  PubMed  CAS  Google Scholar 

  19. Feig DI, Johnson RJ (2003) Hyperuricemia in childhood primary hypertension. Hypertension 42:247–252

    Article  PubMed  CAS  Google Scholar 

  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–S73

    Article  PubMed  CAS  Google Scholar 

  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–L48

    Article  PubMed  CAS  Google Scholar 

  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–C596

    Article  PubMed  CAS  Google Scholar 

  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 38:1101–1106

    Article  PubMed  CAS  Google Scholar 

  24. Sarafidis PA, Bakris GL (2007) Insulin and endothelin: an interplay contributing to hypertension development? J Clin Endocrinol Metab 92:379–385

    Article  PubMed  CAS  Google Scholar 

  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) 92:51–58

    CAS  Google Scholar 

  26. Heinig M, Johnson RJ (2006) Role of uric acid in hypertension, renal disease, and metabolic syndrome. Cleve Clin J Med 73:1059–1064

    Article  PubMed  Google Scholar 

  27. Hallfrisch J (1990) Metabolic effects of dietary fructose. FASEB J 4:2652–2660

    PubMed  CAS  Google Scholar 

  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 34:126–128

    Article  PubMed  Google Scholar 

  29. Nakagawa T, Cirillo P, Sato W et al (2009) The conundrum of hyperuricemia, metabolic syndrome, and renal disease. Intern Emerg Med 3:313–318

    Article  Google Scholar 

  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–F997

    PubMed  CAS  Google Scholar 

  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 78:6858–6862

    Article  PubMed  CAS  Google Scholar 

  32. Sautin YY, Johnson RJ (2008) Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 27:608–619

    Article  PubMed  CAS  Google Scholar 

  33. So A, Thorens B (2010) Uric acid transport and disease. J Clin Invest 120:1791–1799

    Article  PubMed  CAS  Google Scholar 

  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 2009:282059

    PubMed  Google Scholar 

  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 9732:2161–2167

    Article  Google Scholar 

  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):1388–1393

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Struttura Complessa di Nefrologia e Dialisi, Azienda Ospedaliera Rummo, Benevento, Italy

    Davide Stellato & Luigi Francesco Morrone

  2. Struttura Complessa di Nefrologia, Dialisi e Trapianto, Azienda Ospedaliero-Universitaria “OO.RR.”, Foggia, Italy

    Chiara Di Giorgio & Loreto Gesualdo

Authors
  1. Davide Stellato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luigi Francesco Morrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara Di Giorgio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Loreto Gesualdo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Loreto Gesualdo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stellato, D., Morrone, L.F., Di Giorgio, C. et al. Uric acid: a starring role in the intricate scenario of metabolic syndrome with cardio-renal damage?. Intern Emerg Med 7, 5–8 (2012). https://doi.org/10.1007/s11739-011-0642-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-011-0642-3

Keywords

Search

Navigation