Dose-Response Relationship of Phloretin Therapy on Water and Glucose Transport during Experimental Peritoneal Dialysis.

KEY POINTS

Water retention and metabolic complications due to glucose absorption remain a challenge in patients treated with peritoneal dialysis (PD). We determined the dose-response relationship for glucose transporter blocker phloretin—previously shown to reduce glucose absorption in PD. Glucose transporter blockers like phloretin seem to be promising agents to improve ultrafiltration and reduce glucose absorption in patients on PD.

BACKGROUND

Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis (PD). Phloretin, a nonselective inhibitor of facilitative glucose transporter channels, has shown to improve water transport and lower glucose absorption in experimental PD. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intraperitoneal phloretin therapy.

METHODS

Experimental PD was performed in 50 healthy Sprague-Dawley rats, using glucose-based dialysis fluid containing five different concentrations of phloretin. We used radiolabeled F-deoxyglucose to determine the plasma-to-dialysate transport. The data were then analyzed to determine the dose-response relationship of phloretin according to the Hill model equation.

RESULTS

Intraperitoneal phloretin therapy followed a dose-response relationship where higher concentrations of phloretin lowered the diffusion capacity of F-deoxyglucose and conventional glucose while enhancing ultrafiltration. Phloretin showed high potency for water removal and diffusion outcomes, requiring low concentrations to achieve substantial effects.

CONCLUSIONS

Intraperitoneal phloretin therapy followed a distinct dose-response relationship, showing high potency in improving ultrafiltration and reducing glucose absorption in experimental PD. These findings support the therapeutic potential of glucose transporter inhibitors like phloretin and support future clinical studies to evaluate efficacy and optimal dosing in patients undergoing PD.