Uromodulin in a Pathway Between Decreased Renal Urate Excretion and Albuminuria
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30551216
DOI
10.1093/ajh/hpy190
PII: 5245514
Knihovny.cz E-zdroje
- Klíčová slova
- SLC2A9 gene, albumin/creatinine ratio, blood pressure, hypertension, mediation analysis, renal solute excretion, sodium, urate transporter, uric acid, uromodulin,
- MeSH
- albuminurie genetika patofyziologie moč MeSH
- biologické markery moč MeSH
- dospělí MeSH
- eliminace ledvinami * MeSH
- genotyp MeSH
- hodnoty glomerulární filtrace fyziologie MeSH
- kyselina močová moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- proteiny usnadňující transport glukosy genetika metabolismus MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- uromodulin moč MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- kyselina močová MeSH
- proteiny usnadňující transport glukosy MeSH
- SLC2A9 protein, human MeSH Prohlížeč
- uromodulin MeSH
BACKGROUND: The mechanism explaining the inverse association between renal urate and albumin excretion remains unclear. First, we evaluated the impact of candidate variants in the main urate transporter genes (i.e., SLC2A9, SLC22A12, ABCG2) on the association between fractional excretion of uric acid (FEUA) and urinary albumin/creatinine ratio (uACR). Second, we examined uromodulin and sodium excretion as mediators of the association between FEUA and uACR. METHODS: We performed cross-sectional analysis of 737 French Canadians from the CARTaGENE cohort, a random sample of the Quebec population aged 40-69 years (a total of 20,004 individuals). Individuals with available genotyping and urinary data were obtained from a sub-study including gender-matched pairs with high and low Framingham Risk Score and vascular rigidity index. We further excluded individuals with an estimated glomerular filtration rate <60 ml/min/1.73 m2, glycosuria, and use of confounding medication. A spot urine sample was analyzed. Genotyping was performed using the Illumina Omni2.5-8 BeadChips. Genetic variants were analyzed using an additive model. RESULTS: Final analyses included 593 individuals (45.5% of men; mean age 54.3 ± 8.6). We observed an antagonistic interaction between rs13129697 variant of the SLC2A9 gene and FEUA tertiles on uACR (P = 0.002). Using the mediation analysis, uromodulin explained 32%, fractional excretion of sodium (FENa) 44%, and uromodulin together with FENa explained 70% of the inverse relationship between FEUA and uACR. Bootstrapping process confirmed the role of both mediators. CONCLUSIONS: Our data suggest that the association of albuminuria with decreased renal urate excretion may be modified by the transporter SLC2A9, and mediated by uromodulin and sodium handling.
Centre de recherche du CHUM Montréal Quebec Canada
Centre hospitalier universitaire Sainte Justine CHU Sainte Justine Montréal Quebec Canada
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