Abstract

Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145-178) in sham animals and 157 mg 95% CI (137-172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425-494) and 472 mg 95% CI (420-506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.

Highlights

  • Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients

  • Glucose remains the prototypic osmotic agent in peritoneal dialysis (PD), but its use leads to considerable glucose absorption during the treatment, accounting for 20% of total daily energy intake1 in PD patients

  • Glucose is impermeable across cell membranes, and the entry of glucose into cells occurs via a family of hexose transporters: sodium and glucose co-transporters (SGLT)-1 and 2, allowing secondary active glucose transport, and facultative glucose transporters (GLUTs), allowing facilitated diffusion

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Summary

Introduction

Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may occur via intracellular or trans-cellular pathways. Glucose remains the prototypic osmotic agent in peritoneal dialysis (PD), but its use leads to considerable glucose absorption during the treatment, accounting for 20% of total daily energy intake in PD patients. Recent results by Xue et al indicate that about half of the PD patients develop a glucose disorder, which may significantly increase mortality.. SGLT1 transporters account for almost all sodium-dependent glucose uptake in the small intestine (1 Naþ : 1 glucose) but play only a minor role in renal glucose handling

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