TY - JOUR T1 - Influence of genetic variants on renal uric acid handling in response to frusemide: an acute intervention study JF - RMD Open JO - RMD Open DO - 10.1136/rmdopen-2016-000424 VL - 3 IS - 1 SP - e000424 AU - Nicola Dalbeth AU - Jordyn Allan AU - Gregory D Gamble AU - Amanda Phipps-Green AU - Tanya J Flynn AU - Borislav Mihov AU - Anne Horne AU - Robert Doughty AU - Lisa K Stamp AU - Tony R Merriman Y1 - 2017/04/01 UR - http://rmdopen.bmj.com/content/3/1/e000424.abstract N2 - 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.Trial registration number ACTRN12614000871640; Results. ER -