Influence of genetic variants on renal uric acid handling in response to frusemide: an acute intervention study

Show simple item record Dalbeth, Nicola en Allan, J en Gamble, Gregory en Phipps-Green, A en Flynn, TJ en Mihov, Borislav en Horne, Anne en Doughty, Robert en Stamp, LK en Merriman, TR en 2017-07-21T04:47:40Z en 2017-06 en
dc.identifier.citation RMD Open 3(1):e000424 Jun 2017 en
dc.identifier.issn 2056-5933 en
dc.identifier.uri en
dc.description.abstract Abstract Objectives Genetic variation in the renal urate transporters SLC2A9 (GLUT9) and SLC22A11 (OAT4) has been reported to interact with diuretics to increase the risk of developing gout. The aim of this study was to determine whether variation in SLC2A9 or SLC22A11 influences acute renal handling of uric acid in response to frusemide. Methods Following an overnight fast, healthy participants (n=100) attended a study visit with oral intake of 40 mg frusemide. Blood and urine samples were obtained at baseline and 30, 60, 120 and 180 min after frusemide intake. The primary end point was change in fractional excretion of uric acid (FEUA). Results Following intake of frusemide, FEUA initially increased (mean (SD) change from baseline +1.9% (3.0%) at 60 min, p<0.001) and then decreased (mean (SD) change from baseline −1.5% (2.1%) at 180 min, p<0.001). A very small increase in serum urate was observed over the study period (mean (SD) change from baseline 0.007 (0.01) mmol/L at 180 min, p<0.001). The presence of the urate-lowering and gout-protective alleles for SLC2A9 (rs11942223 and rs13129697) and SLC22A11 (rs207826) did not significantly alter the FEUA following a frusemide load. At both 60 and 180 min, change in fractional excretion of sodium was independently associated with change in FEUA (standardised β≥0.40, p<0.001). Conclusions The tested variants in SLC2A9 and SLC22A11 do not influence acute changes in renal handling of uric acid in response to frusemide. en
dc.publisher BMJ Publishing Group en
dc.relation.ispartofseries RMD Open en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
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dc.title Influence of genetic variants on renal uric acid handling in response to frusemide: an acute intervention study en
dc.type Journal Article en
dc.identifier.doi 10.1136/rmdopen-2016-000424 en
pubs.issue 1 en
pubs.volume 3 en
dc.description.version VoR - Version of Record en
dc.rights.holder Copyright: The Authors en
dc.identifier.pmid 28951782 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 624450 en Medical and Health Sciences en School of Medicine en Medicine Department en
dc.identifier.eissn 2056-5933 en
pubs.number e000424 en
pubs.record-created-at-source-date 2017-07-21 en 2017-04-11 en
pubs.dimensions-id 28951782 en

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