Titre
A model of uric acid transport in the rat proximal tubule.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Edwards, A.
Auteure/Auteur
Auberson, M.
Auteure/Auteur
Ramakrishnan, S.K.
Auteure/Auteur
Bonny, O.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1522-1466
Statut éditorial
Publié
Date de publication
2019-05-01
Volume
316
Numéro
5
Première page
F934
Dernière page/numéro d’article
F947
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
The objective of the present study was to theoretically investigate the mechanisms underlying uric acid transport in the proximal tubule (PT) of rat kidneys, and their modulation by factors, including Na <sup>+</sup> , parathyroid hormone, ANG II, and Na <sup>+</sup> -glucose cotransporter-2 inhibitors. To that end, we incorporated the transport of uric acid and its conjugate anion urate in our mathematical model of water and solute transport in the rat PT. The model accounts for parallel urate reabsorption and secretion pathways on apical and basolateral membranes and their coupling to lactate and α-ketoglutarate transport. Model results agree with experimental findings at the segment level. Net reabsorption of urate by the rat PT is predicted to be ~70% of the filtered load, with a rate of urate removal from the lumen that is 50% higher than the rate of urate secretion. The model suggests that apical URAT1 deletion significantly reduces net urate reabsorption across the PT, whereas ATP-binding cassette subfamily G member 2 dysfunction affects it only slightly. Inactivation of basolateral glucose transporter-9 raises fractional urate excretion above 100%, as observed in patients with renal familial hypouricemia. Furthermore, our results suggest that reducing Na <sup>+</sup> reabsorption across Na <sup>+</sup> /H <sup>+</sup> exchangers or Na <sup>+</sup> -glucose cotransporters augments net urate reabsorption. The model predicts that parathyroid hormone reduces urate excretion, whereas ANG II increases it. In conclusion, we have developed the first model of uric acid transport in the rat PT; this model provides a framework to gain greater insight into the numerous solutes and coupling mechanisms that affect the renal handing of uric acid.
PID Serval
serval:BIB_30D0BF2CABB3
PMID
Date de création
2019-03-25T18:10:32.032Z
Date de création dans IRIS
2025-05-20T16:31:39Z