The Molecular Physiology of Uric Acid Homeostasis

Mandal, A. K.; Mount, David B.

doi:10.1146/annurev-physiol-021113-170343

Cited by 425 publications

(378 citation statements)

References 174 publications

(210 reference statements)

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“…The normal handling of Ua by the kidney includes filtration, reabsorption, and secretion taking place in the proximal tubule, although urate transporters exist farther down the nephron (36). Molecular mechanisms involved in the proximal tubule include the organic anion transporters URAT1 and OAT4, with the exact contribution of other transporters remaining uncertain (37).…”

Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Troyanov

Delmas-Frenette

Bollée

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives The urinary excretion of uromodulin is influenced by common variants in the UMOD gene, and it may be related to NaCl retention and hypertension. Levels of uromodulin are also dependent of the renal function, but other determinants remain unknown.Design, setting, participants, & measurements We tested associations between the urinary excretion of uromodulin; medical history and medication; serum and urinary levels of electrolytes, glucose, and uric acid; and the genotype at the UMOD/Protein Disulfide Isomerase-Like, Testis Expressed locus (rs4293393 and rs12446492); 943 participants from the CARTaGENE Cohort, a random sample from the Canadian population of 20,004 individuals, were analyzed. Participants with available genotyping were obtained from a substudy addressing associations between common variants and cardiovascular disease in paired participants with high and low Framingham risk scores and vascular rigidity indexes.Results The population studied was 5469 years old, with 51% women and eGFR of 9614 ml/min per 1.73 m 2 . Uromodulin excretion was 25 (11-42) mg/g creatinine. Using linear regression, it was independently higher among patients with higher eGFR, the TT genotype of rs4293393, and the TT genotype of rs12446492. The fractional excretions of urate and sodium showed a strong positive correlation with uromodulin, likely linked to the extracellular volume status. The presence of glycosuria and the use of uricosuric drugs, which both increased the fraction excretion of urate, were independently associated with a lower uromodulin excretion, suggesting novel interactions between uric acid and uromodulin excretion. ConclusionsIn this large cohort, the excretion of uromodulin correlates with clinical, genetic, and urinary factors. The strongest associations were between uric acid, sodium, and uromodulin excretions and are likely linked to the extracellular volume status.

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Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Troyanov

Delmas-Frenette

Bollée

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…Common variation in the SLC2A9 gene that encodes GLUT9 might explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan (Vitart et al 2008). Despite the everincreasing list of hyperuricaemic genes, variation in SLC2A9 remains the major single genetic determinant of serum uric acid, followed closely by the effects of variation in the ABCG2 gene (Mandal & Mount 2015). Mice with systemic knockout of Glut9 displayed moderate hyperuricaemia, massive hyperuricosuria and mild renal insufficiency (Preitner et al 2009).…”

Section: Glucose Transporter 9 (Glut9)mentioning

confidence: 99%

Uric acid transporters hiding in the intestine

Zhou

et al. 2016

Pharmaceutical Biology

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Context: Hyperuricaemia is known as an abnormally increased uric acid level in the blood. Although it was observed many years ago, since uric acid excretion via the intestine pathway accounted for approximately one-third of total elimination of uric acid, the molecular mechanism of 'extra-renal excretion' was poorly understood until the finding of uric acid transporters. Objective: The objective of this study was to gather all information related to uric acid transporters in the intestine and present this information as a comprehensive and systematic review article. Methods: A literature search was performed from various databases (e.g., Medline, Science Direct, Springer Link, etc.). The key terms included uric acid, transporter and intestine. The period for the search is from the 1950s to the present. The bibliographies of papers relating to the review subject were also searched for further relevant references. Results: The uric acid transporters identified in the intestine are discussed in this review. The solute carrier (SLC) transporters include GLUT9, MCT9, NPT4, NPT homolog (NPT5) and OAT10. The ATP binding cassette (ABC) transporters include ABCG2 (BCRP), MRP2 and MRP4. Bacterial transporter YgfU is a low-affinity and high-capacity transporter for uric acid. Conclusion: The present review may be helpful for further our understanding of hyperuricaemia and be of value in designing future studies on novel therapeutic pathways. ARTICLE HISTORY

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“…The kidneys are responsible for the excretion of a large part of uric acid daily. More than 90% of all cases of hyperuricemia are caused by disorders of uric acid excretion (21). Uric acid crystals have the ability to adhere to the surface of renal epithelial cells (22).…”

Section: Kidneys and Uric Acidmentioning

confidence: 99%

“…There are studies reporting elevated uric acid levels in people with diabetes; on the other hand, there are studies reporting that uric acid levels are lower in people with diabetes compared with healthy people (19,21,36). Uric acid levels have been found to be lower in diabetic people with normal blood pressure and without any problems in terms of renal function (19).…”

Section: Diabetes and Uric Acidmentioning

confidence: 99%

Analysis of Uric Acid Elevation

Ayyıldız¹

2016

JAREM

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Uric acid is a molecule that is produced following purine nucleotide metabolism. It is particularly synthesized in the liver and less often in other tissues. In normal concentrations, it is an antioxidant and a proinflammatory; however, if its serum concentration is over 7.0 mg/dL, it immediately crystalizes and precipitates, particularly in the vessel walls, soft tissues, joints, and renals. Several studies have demonstrated that there a positive relationship between hyperuricemia and diseases such as metabolic syndrome, stroke, preeclampsia, hypertension, kidney diseases, cardiovascular diseases, and diabetes mellitus. Identification of the elevated uric acid concentration and early treatment of hyperuricemia may help in early diagnosis and treatment of diseases that are positively related to hyperuricemia. Thus, serum uric acid concentrations should be well examined during biochemical analyses of patients visiting the hospital. In this review, uric acid and its elevated concentrations were re-checked and its importance in health was emphasized. (JAREM 2016; 6: 74-7)

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The Molecular Physiology of Uric Acid Homeostasis

Cited by 425 publications

References 174 publications

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Uric acid transporters hiding in the intestine

Analysis of Uric Acid Elevation

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