Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

Uetake, Daijiro; Ohno, Iwao; Ichida, Kimiyoshi; Yamaguchi, Yoshihiro; Saikawa, Hajime; Endou, Hitoshi; Hosoya, Tatsuo

doi:10.2169/internalmedicine.49.2597

Cited by 67 publications

(45 citation statements)

References 17 publications

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“…Glycosuria may also inhibit the activity of the TAL and consequently, lower uromodulin excretion (44). The uricosuric drugs losartan and fenofibrate both inhibit URAT1 (24,45). Because the FE-Ua showed the strongest association of uromodulin excretion in our cohort, we could have expected a positive association with uromodulin excretion.…”

Section: Discussionmentioning

confidence: 87%

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: 87%

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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“…Three days' administration of fenofibrate 450 mg increased fractional clearance of uric acid, compared to baseline value, while the plasma concentration decreased in normal subjects [63]. Mechanism by which fenofibrate decreases serum uric acid levels by increasing its urinary excretion is considered to be through the inhibition of URAT1 by fenofibric acid, major metabolite of fenofibrate [64]. An in vitro study using HEK 293 cells expressing URAT1 showed IC 50 of fenofibric acid is reported to be 35.68 ± 3.94 mM (benzbromarone, 0.13 ± 0.01 mM) [64].…”

Section: Fenofibratementioning

confidence: 99%

“…Mechanism by which fenofibrate decreases serum uric acid levels by increasing its urinary excretion is considered to be through the inhibition of URAT1 by fenofibric acid, major metabolite of fenofibrate [64]. An in vitro study using HEK 293 cells expressing URAT1 showed IC 50 of fenofibric acid is reported to be 35.68 ± 3.94 mM (benzbromarone, 0.13 ± 0.01 mM) [64].…”

Section: Fenofibratementioning

confidence: 99%

Effects on Uric Acid Metabolism of the Drugs except the Antihyperuricemics

Moriwaki

2014

J Bioequiv Availab

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“…74 Several other OAT are most likely also involved and may be related to some of the age, gender, disease, and genetic differences known to occur in serum uric acid. [75][76][77][78][79][80] Interestingly, some angiotensin II receptor blockers trans-stimulate the uptake of uric acid by URAT1 whereas others cis-inhibit such transport by URAT1 and other OAT. 77 Similarly competition from other organic anions for OAT may explain the hyperuricemia known to occur in lactic acidosis, ketoacidosis, and alcohol ingestion 78 and even by drugs Figure 3.…”

Section: Uric Acidmentioning

confidence: 99%

“…79 More difficult to explain is the hyperuricemia associated with hyperinsulinemia and salt absorption. Enhanced activity of OAT is noted after 24 h of water restriction regardless of changes in effective renal plasma flow; 81 however, the effect is not related to urine output or concentration, 82 which may explain why vasopressin (ADH) has such conflicting effects, being associated with hyperuricemia with appropriate ADH and hypouricemia with inappropriate ADH (SIADH).…”

Section: Uric Acidmentioning

confidence: 99%

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

et al. 2010

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While the fractional excretion of solutes have long been considered excellent research tools to investigate tubular physiology, their clinical use has become common over the last 40 years in the diagnoses of many disorders; however, none have reached the clinical utility of the fractional excretion of sodium in the ability to distinguish pre-renal azotemia from acute tubular necrosis. Nevertheless, there are many drugs and medical conditions that interfere with that utility and recently other solutes, including urea, uric acid and lithium, have been recently investigated to improve the diagnostic ability in clinical situations where the fractional excretion of sodium is known to be unreliable. We review the tubular physiology of these solutes and show how the differences in tubular physiology might be exploited to develop a strategy for their optimal clinical use.

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Effect of Fenofibrate on Uric Acid Metabolism and Urate Transporter 1

Cited by 67 publications

References 17 publications

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Effects on Uric Acid Metabolism of the Drugs except the Antihyperuricemics

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

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