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  • Review Article
  • Published:

Improving cardiovascular and renal outcomes in gout: what should we target?

Nature Reviews Rheumatology volume 10, pages 654–661 (2014)Cite this article

Subjects

Key Points

  • Epidemiological studies have repeatedly shown that hyperuricaemia and gout are independent risk factors for cardiovascular disease

  • Longitudinal studies have shown that serum uric acid (SUA) level is an independent risk factor for the onset and progression of kidney disease

  • The mechanisms underlying these comorbidities probably involve low-grade systemic inflammation and xanthine oxidase activity, as well as the direct deleterious effect of hyperuricaemia

  • In some patients, lowering SUA levels might decrease blood pressure and ameliorate kidney function

  • Xanthine oxidase inhibition could ameliorate cardiovascular and renal comorbidities, through its dual roles in lowering SUA levels and scavenging free radicals during uric acid formation

  • Whether reducing the systemic inflammation associated with gout might improve cardiovascular or renal outcomes remains to be determined

Abstract

Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

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Figure 1: Comorbidities of hyperuricaemia and gout.
Figure 2: Uric acid formation.

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Acknowledgements

The authors wish to thank T. Kielstein and A. K. Tausche for helpful discussion. Editorial assistance for the preparation of this manuscript (copyediting for English language, prior to submission to the journal and before peer-review) was provided by L. Giacomelli (Content Ed Net).

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Authors and Affiliations

  1. Hôpital Lariboisière, Fédération de Rhumatologie, Centre Viggo Petersen 2, rue Ambroise Parè 75475 Cedex 10, Paris, France

    Pascal Richette & Thomas Bardin

  2. Servicio de Reumatología and BioCruces Health Research Institute, Cruces University Hospital, Plaza Cruces S/N, 48903, Barakaldo, Spain

    Fernando Perez-Ruiz

  3. Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital Nottingham, Hucknall Road, NG5 1PB, Nottingham, UK

    Michael Doherty

  4. Department of Rheumatology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, Netherlands

    Tim L. Jansen

  5. Department of Rheumatology, University of Edinburgh, Western General Hospital, Crewe Road South, EH4 2XU, Edinburgh, UK

    George Nuki

  6. Department of Medicine, Rheumatology Section, Alicante University and General Hospital, University Miguel Hernández, Av. Pintor Baeza 12, 03010, Alicante, Spain

    Eliseo Pascual

  7. Department of Rheumatology, Rheumatology Unit, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    Leonardo Punzi

  8. Service of Rheumatology, Centre Hospitalier Universitaire Vaudois, Avenue Pierre Decker 4, 1011, Lausanne, Switzerland

    Alexander K. So

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  1. Pascal Richette
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Contributions

All authors researched data for the article and made a substantial contribution to discussion of content and writing the article. P.R. and T.B. reviewed/edited the manuscript before submission.

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Correspondence to Pascal Richette.

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Competing interests

The authors declare they have received consultancy and/or speaker fees from Abbott (T.L.J.), Ardea Biosciences (F.P.-R., M.D., G.N., A.K.S., T.B.), Astra Zeneca (P.R.), Biocryst (G.N., T.B.), Ipsen (P.R., M.D., T.L.J., G.N., A.K.S., T.B.), Menarini (P.R., F.P.-R., M.D., T.L.J., G.N., E.P., A.K.S., T.B.), Metabolex (F.P.-R.), Novartis (P.R., F.P.-R., M.D., G.N., A.K.S., T.B.), Pfizer (F.P.-R.), Roche (T.L.J.), Sanofi (P.R.), Savient (P.R., F.P.-R. G.N., M.D., E.P., T.B.) and UCB (T.L.J.). F.P.-R. declares he has received grants from Ministerio de Sanidad, Gobierno de España and Asociación de Reumatólogos del Hospital de Cruces. P.R. declares he has received an educational grant from Menarini.

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Richette, P., Perez-Ruiz, F., Doherty, M. et al. Improving cardiovascular and renal outcomes in gout: what should we target?. Nat Rev Rheumatol 10, 654–661 (2014). https://doi.org/10.1038/nrrheum.2014.124

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