Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Could uric acid have a pathogenic role in pre-eclampsia?

Nature Reviews Nephrology volume 6, pages 744–748 (2010)Cite this article

Subjects

Abstract

Interest has been renewed over the role of uric acid in the pathogenesis of hypertension, endothelial dysfunction and renal dysfunction, which are all features of pre-eclampsia. Uric acid is not a consistent predictive factor for the development of pre-eclampsia but its levels generally increase once the disease manifests, and plasma levels of uric acid approximately correlate with disease severity. Hyperuricemia in pre-eclampsia was once thought to result solely from reduced renal clearance, but levels of uric acid are now also thought to increase through increased uric acid production caused by trophoblast breakdown, cytokine release and ischemia. Uric acid can promote endothelial dysfunction, damage and inflammation, which leads to oxidation. Pre-eclampsia, which is characterized by widespread endothelial dysfunction and inflammation, might be propagated by uric acid through these known in vitro activities. Of note, however, uric acid can also act as a scavenger of oxygen free radicals. Plasma urate measurements are currently used to support the diagnosis of pre-eclampsia during pregnancy. As further studies define the role of uric acid in the development of pre-eclampsia, monitoring levels of this factor may again become essential to the future treatment of pre-eclampsia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Uric acid synthesis via xanthine oxidase catalysis.

Similar content being viewed by others

Article 16 February 2023

Evdokia Dimitriadis, Daniel L. Rolnik, … Ellen Menkhorst

References

  1. Paula, L. G. et al. Does uric acid provide information about maternal condition and fetal outcome in pregnant women with hypertension? Hypertens. Pregnancy 27, 413–420 (2008).

    Article  CAS  Google Scholar 

  2. Sibai, B., Dekker, G. & Kupferminc, M. Pre-eclampsia. Lancet 365, 785–799 (2005).

    Article  Google Scholar 

  3. Roberts, J. M. & Redman, C. W. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 341, 1447–1451 (1993).

    Article  CAS  Google Scholar 

  4. Von Dadelzen, P., Magee, L. A. & Roberts, J. M. Subclassification of preeclampsia. Hypertens. Pregnancy 22, 143–148 (2003).

    Article  Google Scholar 

  5. Maynard, S. E., Epstein, F. H. & Karumanchi, S. A. Preeclampsia and angiogenic imbalance. Annu. Rev. Med. 59, 61–78 (2008).

    Article  CAS  Google Scholar 

  6. Maynard, S. E. et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. Clin. Invest. 111, 649–658 (2003).

    Article  CAS  Google Scholar 

  7. Maynard, S. E. & Thadhani, R. Pregnancy and the kidney. J. Am. Soc. Nephrol. 20, 14–22 (2009).

    Article  CAS  Google Scholar 

  8. LaMarca, B. D., Gilbert, J. & Granger, J. P. Recent progress toward the understanding of the pathophysiology of hypertension during preeclampsia. Hypertension 51, 982–988 (2008).

    Article  CAS  Google Scholar 

  9. Karumanchi, S. A. & Bdolah, Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology 145, 4835–4837 (2004).

    Article  CAS  Google Scholar 

  10. Levine, R. J. et al. Circulating angiogenic factors and the risk of pre-eclampsia. N. Engl. J. Med. 350, 672–683 (2004).

    Article  CAS  Google Scholar 

  11. Eremina, V. et al. VEGF inhibition and renal thrombotic microangiopathy. N. Engl. J. Med. 358, 1129–1136 (2008).

    Article  CAS  Google Scholar 

  12. Conde-Agudelo, A., Villar, J. & Lindheimer, M. World Health Organization systemic review of screening tests for pre-eclampsia. Obstet. Gynaecol. 104, 1367–1391 (2004).

    Article  Google Scholar 

  13. Carty, D. M., Delles, C. & Dominiczak, A. F. Novel biomarkers for predicting preeclampsia. Trends Cardiovasc. Med. 18, 186–194 (2008).

    Article  CAS  Google Scholar 

  14. Cnossen, J. S. et al. Are tests for prediction pre-eclampsia good enough to make screening viable? A review of reviews and critical appraisal. Acta Obstet. Gynecol. Scand. 88, 758–765 (2009).

    Article  Google Scholar 

  15. Sagen, N., Kjell, H. & Nilsen, S. Serum urate as a predictor of fetal outcome in severe preeclampsia. Acta Obstet. Gynecol. Scand. 63, 71–75 (1984).

    Article  CAS  Google Scholar 

  16. Lim, K. H., Friedman, S. A., Ecker, J. L., Kao, L. & Kilpatrick, S. J. The clinical utility of serum uric acid measurements in hypertensive diseases of pregnancy. Am. J. Obstet. Gynecol. 178, 167–171 (1998).

    Article  Google Scholar 

  17. Roberts, J. M. et al. Uric acid is as important as proteinuria in identifying fetal risk in women with gestational hypertension. Hypertension 46, 1263–1269 (2005).

    Article  CAS  Google Scholar 

  18. Watanabe, S. et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension 40, 355–360 (2002).

    Article  CAS  Google Scholar 

  19. Griebsch, A. & Zollner, N. Effects of ribonucleotides given orally on uric acid production in man. Adv. Exp. Med. Biol. 4, 4 (1974).

    Google Scholar 

  20. Anzai, N., Kanai, Y. & Endou, H. New insights into renal transport of urate. Curr. Opin. Rheumatol. 19, 151–157 (2007).

    Article  CAS  Google Scholar 

  21. Irani, R. A. & Xia, Y. The functional role of the renin-angiotensin system in pregnancy and preeclampsia. Placenta 29, 763–771 (2008).

    Article  CAS  Google Scholar 

  22. Gersch, C. et al. Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. Nucleosides Nucleotides Nucleic Acids 28, 119–149 (2009).

    Article  Google Scholar 

  23. Bainbridge, S. A. & Roberts, J. M. Uric acid as a pathogenic factor in preeclampsia. Placenta 29 (Suppl. A), S67–S72 (2008).

    Article  Google Scholar 

  24. Kang, D. H. et al. Uric acid, endothelial dysfunction and pre-eclampsia: searching for a pathogenetic link. J. Hypertens. 22, 229–235 (2004).

    Article  CAS  Google Scholar 

  25. Mazzali, M. et al. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38, 1101–1106 (2001).

    Article  CAS  Google Scholar 

  26. Fieg, D. I. et al. Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney Int. 66, 281–287 (2004).

    Article  Google Scholar 

  27. Jossa, F. et al. Serum uric acid and hypertension: the Olivetti heart study. J. Hum. Hypertens. 8, 677–681 (1994).

    CAS  PubMed  Google Scholar 

  28. Anker, S. D. et al. Uric acid and survival in chronic heart failure: Validation and application in metabolic, functional and haemodynamic staging. Circulation 107, 1991–1997 (2003).

    Article  Google Scholar 

  29. Kannel, W. B. Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study. Am. Heart J. 114, 413–418 (1987).

    Article  CAS  Google Scholar 

  30. Ohno, I. et al. Serum uric acid and renal prognosis in patients with IgA nephropathy. Nephron 87, 333–339 (2001).

    Article  CAS  Google Scholar 

  31. Waring, W. S., Webb, D. J. & Maxwell, S. R. J. Effect of local hyperuricemia on endothelial dysfunction in the human forearm vascular bed. Br. J. Clin. Pharmacol. 49, 511 (2000).

    Google Scholar 

  32. Doehner, W. et al. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricaemic patients with chronic heart failure. Circulation 105, 2619–2624 (2002).

    Article  CAS  Google Scholar 

  33. Khosla, U. M. et al. Hyperuricemia induces endothelial dysfunction. Kidney Int. 67, 1739–1742 (2005).

    Article  Google Scholar 

  34. Granger, J. P. et al. Pathophysiology of preeclampsia: linking placental ischaemia/hypoxia with microvascular dysfunction. Microcirculation 9, 147–160 (2002).

    Article  CAS  Google Scholar 

  35. Mustard, J. F., Murphy, E. A., Ogryzlo, M. A. & Smythe, H. A. Blood coagulation and platelet economy in subjects with primary gout. Can. Med. Assoc. J. 89, 1207–1211 (1963).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mene, P. & Punzo, G. Uric acid: bystander or culprit in hypertension and progressive renal disease? J. Hypertens. 26, 2085–2092 (2008).

    Article  CAS  Google Scholar 

  37. Johnson, R. J. et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41, 1183–1190 (2003).

    Article  CAS  Google Scholar 

  38. Kang, D. H., Park, S. K., Lee, I. K. & Johnson, R. J. Uric acid-induced CRP expression: implication on cell proliferation and nitric oxide production of human vascular cells. J. Am. Soc. Nephrol. 16, 3553–3562 (2005).

    Article  CAS  Google Scholar 

  39. Tsukimori, K., Yoshitomi, T., Morokuma, S., Fukushima, K. & Wake, N. Serum uric acid levels correlate with plasma hydrogen peroxide and protein carbonyl levels in preeclampsia. Am. J. Hypertens. 21, 1343–1346 (2008).

    Article  CAS  Google Scholar 

  40. Gulmezoglu, A. M., Hofmeyr, G. J. & Oosthuisen, M. M. J. Antioxidants in the treatment of severe pre-eclampsia: an exploratory randomized controlled trial. Br. J. Obstet. Gynaecol. 104, 689–696 (1997).

    Article  CAS  Google Scholar 

  41. Schackis, R. C. Hyperuricemia and preeclampsia: is there a pathogenic link? Med. Hypotheses 63, 239–244 (2004).

    Article  CAS  Google Scholar 

  42. Lam, C., Lim, K. H., Kang, D. H. & Karumanchi, S. A. Uric acid and preeclampsia. Semin. Nephrol. 25, 56–60 (2005).

    Article  CAS  Google Scholar 

  43. Homer, C. S. E. et al. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension. J. Hypertens. 26, 295–302 (2008).

    Article  CAS  Google Scholar 

  44. Koopmans, C. M. et al. Accuracy of serum uric acid as a predictive test for maternal complications in preeclampsia: Bi-variate meta-analysis and decision analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. 146, 8–14 (2009).

    Article  CAS  Google Scholar 

  45. Many, A., Hubel, C. A., Fisher, S. J., Roberts, J. M. & Zhou, Y. Invasive cytotrophoblasts manifest evidence of oxidative stress in preeclampsia. Am. J. Pathol. 156, 321–331 (2000).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Renal Medicine & Medicine, St. George Hospital, University of New South Wales, Grey Street, Kogarah, Sydney, NSW 2217, Australia

    Annabel C. Martin & Mark A. Brown

Authors
  1. Annabel C. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark A. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A. C. Martin and M. A. Brown contributed equally to researching data, discussing content, writing the article, and reviewing/editing the manuscript before submission.

Corresponding author

Correspondence to Mark A. Brown.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, A., Brown, M. Could uric acid have a pathogenic role in pre-eclampsia?. Nat Rev Nephrol 6, 744–748 (2010). https://doi.org/10.1038/nrneph.2010.125

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2010.125

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing