Uric acid transport and disease

So, Alexander; Thorens, Bernard

doi:10.1172/jci42344

Cited by 669 publications

(554 citation statements)

References 105 publications

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“…Therefore, other contributing factors such as endothelial dysfunction and oxidative stress are also involved in the pathophysiological mechanisms leading to elevated SUA levels and the incidences of hypertension and MetS. [16][17][18] UA potently decreases endothelial nitric oxide bioavailability and induces endothelial dysfunction. 33 Elevated SUA levels were also associated with the increased generation of free radicals 34 and oxidative stress, which could abolish endothelium-dependent vasodilatation, leading to hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…Confirming the involvement of elevated SUA levels in the pathogenesis of hypertension has been difficult, because MetS can confound the relationship between elevated SUA levels and hypertension and because these conditions share common pathophysiological features, such as insulin resistance, endothelial dysfunction, oxidative stressand inflammation. [16][17][18] For these reasons, controlling for MetS is important in clinical studies that examine the association between elevated SUA levels and the incidence of hypertension.…”

Section: Introductionmentioning

confidence: 99%

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Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

et al. 2014

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The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

et al. 2014

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“…[44][45][46] Studies in rodents and other molecular observations indicate an important role for SLC2A9 in proximal tubular urate absorption. 47,48 Genome-wide (GWAS) and candidate association studies have found strong association of SLC2A9 SNPs with SUA levels. [14][15][16][17][18][19] These studies were mainly conducted in Caucasian, African American and Asian populations.…”

Section: Discussionmentioning

confidence: 99%

Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians

et al. 2013

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Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal and cardiovascular diseases, is caused by either increased production or decreased excretion of uric acid or a mix of both. The solute carrier protein 2 family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux across the renal proximal tubule. Genome-wide association studies have consistently shown the association of single-nucleotide polymorphisms in this gene with SUA in majority populations. American Indian participants of the Strong Heart Family Study, belonging to multigenerational families, have high prevalence of hyperuricemia. We conducted measured genotype analyses, based on variance components decomposition method and accounting for family relationships, to assess whether the association between SUA and SLC2A9 gene polymorphisms generalized to American Indians (n ¼ 3604) of this study. Seven polymorphisms were selected for genotyping based on their association with SUA levels in other populations. A strong association was found between SLC2A9 gene polymorphisms and SUA in all centers combined (P-values: 1.3 Â 10 À31 -5.1 Â 10 À23 ) and also when stratified by recruitment center; P-values: 1.2 Â 10 À14 -1.0 Â 10 À5 . These polymorphisms were also associated with the estimated glomerular filtration rate and serum creatinine but not albumin-creatinine ratio. In summary, the association of polymorphisms in the uric acid transporter gene with SUA levels extends to a new population of American Indians.

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“…34,35 The reabsorption of urate by URAT1 and GLUT9 is inhibited by uricosuric agents such as probenecid and benbromarone, and drugs such as losartan, which have a uricosuric effect. 34,36 An understanding of the physiological effects of urate transporters has led to the development of several drugs that inhibit URAT1. One of them, Lesinurad, is currently in phase 3 clinical trials.…”

Section: Epidemiology Of Goutmentioning

confidence: 99%

Update on hyperuricaemia and gout with evidence based management guidelines

Mody

2015

South African Family Practice

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Gout is now the leading cause of inflammatory arthritis, affecting 1-2% of the population. The metabolic syndrome, cardiovascular risk factors, cardiovascular events and mortality are more common with gout. However, the role of uric acid as an independent risk factor is inconclusive. The identification of urate transporters has improved our understanding of urate homeostasis and identified targets for the development of newer drugs. Experience with ultrasound and dual energy computed tomography led to the detection of urate crystals in patients with asymptomatic hyperuricaemia. Several evidence-based management guidelines are now available. The dietary and lifestyle recommendations focus on general health and management of comorbidities. A low dose colchicine regimen is effective and better tolerated than the traditional use of higher doses in acute gout. Alternative measures for acute gout include non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. Allopurinol is the most widely used initial therapy; treatment is started with 100 mg or less per day, and titrated upwards to achieve a target level of 0.36 mmol/l (in patients with tophi, a lower target of 0.30 mmol/l is recommended). A new non-purine more potent xanthine oxidase inhibitor, febuxostat, is available (currently not registered in South Africa). Probenecid is the most widely used uricosuric agent. Prophylactic therapy with colchicine, NSAIDs or corticosteroids is used when urate lowering therapy is initiated. Although the cause of gout is known and effective treatment is available, gout is poorly managed worldwide with failure to achieve the target urate level.

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Uric acid transport and disease

Cited by 669 publications

References 105 publications

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians

Update on hyperuricaemia and gout with evidence based management guidelines

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