Martus Giedre, Siddhuraj Premkumar, Erjefält Jonas S, Kádár András, Lindström Martin, Bergling Karin, Öberg Carl M
Nephrology Division, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Perit Dial Int. 2024 Dec 5:8968608241299928. doi: 10.1177/08968608241299928.
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 results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved.
Here we sought to elucidate whether diffusion of radiolabeled F-deoxyglucose ([F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs.
GLUT inhibition using phloretin markedly reduced [F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate.
The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.