Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 12, 43-62
eCollection

Hyperuricemia and Hypertension: Links and Risks

Affiliations
Review

Hyperuricemia and Hypertension: Links and Risks

Douglas J Stewart et al. Integr Blood Press Control.

Abstract

Hyperuricemia has long been recognized to be associated with increased cardiovascular risk, including risk of developing hypertension. Epidemiological findings suggest that the link with hypertension is stronger in children and adolescents. Uric acid acts as a strong antioxidant compound in the extracellular environment but has pro-inflammatory effects within the intracellular setting. A chronic phase of microvascular injury is known to occur after prolonged periods of hyperuricemia. This is proposed to contribute to afferent arteriolopathy and elevation of blood pressure that may become unresponsive to uric acid-lowering therapies over time. Studies have struggled to infer direct causality of hyperuricemia due to a vast number of confounders including body mass index. The aim of this review is to present the available data and highlight the need for large scale prospective randomized controlled trials in this area. At present, there is limited evidence to support a role for uric acid-lowering therapies in helping mitigate the risk of hypertension.

Keywords: cardiovascular; chronic kidney disease; hypertension; hyperuricemia; urate.

Conflict of interest statement

The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Urate production pathways. De novo synthesis of urate starts with the generation of phosphoribosyl pyrophosphate (PRPP) from ribose 5-phosphate (ribose 5-P) and adenosine triphosphate (ATP), leading to the formation of the purine mononucleotide inosine monophosphate (IMP). IMP is indirectly converted to hypoxanthine, a purine base. Adenosine monophosphate (AMP) and guanosine monophosphate (GMP) are involved in the production of the other purine bases adenine and guanine respectively. Enzymatic salvage pathways exist that allow for further generation of AMP, IMP and GMP from these purine bases. The conversion of fructose to fructose 1-phosphate by fructokinase generates AMP. Under conditions of ischemia, the conversion of hypoxanthine to xanthine, and subsequently to the urate anion, generates superoxide (O₂⁻) and thus stimulates the release of ROS. Allopurinol and febuxostat act as xanthine oxidase (XO) inhibitors to block the formation of urate. Rasburicase and pegloticase are recombinant versions of uricase that promote the breakdown of uric acid (UA) into allantoin. Abbreviations: ADP, adenosine diphosphate; GTP, guanosine triphosphate; 5’NT, 5’nucleotidase; APRT, adenine phosphoribosyl transferase; HPRT, hypoxanthine-guanine phosphoribosyl transferase; PNP, purine nucleotide phosphorylase; XDH, xanthine dehydrogenase; NAD⁺, nicotinamide adenine dinucleotide (oxidized form); NADP, nicotinamide adenine dinucleotide (reduced form).
Figure 2
Figure 2
Renal urate transporters. Urate reabsorption is mediated by the proximal tubular apical transporters URAT 1 and OAT4, and the basolateral transporter GLUT 9. Urate secretion is mediated by the apical transporters ABCG2, NPT1, NPT4, and the basolateral transporters OAT1 and OAT3. Benzbromarone and probenecid act as inhibitors of URAT 1, OAT1, OAT 3 and GLUT9. Lesinurad and sulfinpyrazone inhibit URAT 1 and OAT4.

Similar articles

See all similar articles

References

    1. Stevens G. Global health risks: mortality and burden of disease attributable to selected major risks. Bull World Health Organ. 2009.
    1. Mahomed FA. On chronic Bright’s disease, and its essential symptoms. Lancet. 1879;1:389–404.
    1. Griebsch A, Zöllner N. Effect of ribomononucleotides given orally on uric acid production in man. Adv Exp Med Biol. 1974;41:443–449. doi:10.1007/978-1-4757-1433-3_9 - DOI - PubMed
    1. Roch-Ramel F, Guisan B. Renal transport of urate in humans. News Physiol Sci. 1999;Apr(14):80–84. - PubMed
    1. Bobulescu IA, Moe OW. Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis. 2012;19(6):358–371. doi:10.1053/j.ackd.2012.07.009 - DOI - PMC - PubMed

LinkOut - more resources

Feedback