Selective Inhibition of Facilitative Glucose Transporter 1 Improves Ultrafiltration Efficiency in Experimental Peritoneal Dialysis

Abstract

Local and systemic side-effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent data indicated that some glucose is transferred via facilitative glucose channels. Here we used BAY-876, a potent and highly selective blocker of facilitative glucose channel 1 (GLUT1), in an experimental rat model of PD using either 1.5% or 2.3% glucose fluid in a 1-h dwell. We also sought to elucidate whether diffusion of radiolabeled [18F]-deoxyglucose in the opposite direction (plasma [->] dialysate) is also lowered by selective/non-selective GLUT inhibition. Results show that selective GLUT1 inhibition markedly improved UF and enhanced the sodium dip, but no alterations in glucose transport or [18F]-deoxyglucose diffusion could be detected. Non-selective GLUT-inhibition using phloretin showed similar improvements on water and sodium transport, but also markedly decreased diffusion capacity for [18F]-deoxyglucose. We conclude that selective GLUT1 inhibition improved the UF efficiency in terms of mL of water removed per gram glucose absorbed by almost 70% for 1.5% glucose, implicating a role for GLUT1 in glucose mediated osmotic water transport in PD. Selective inhibitors of facilitative glucose transporter 1 may be promising agents to improve UF efficacy in patients treated with PD. Translational StatementPeritoneal dialysis (PD) is limited by systemic and local glucose toxicity. Here we used a highly selective inhibitor of facilitative glucose channel 1 (GLUT1) in a rat model of PD, and show marked, direct improvements in osmotic water removal (UF) per gram glucose absorbed. Inhibitors of GLUT1 may provide marked improvements in UF in patients on PD.