Blockade of sodium–glucose co-transporters improves peritoneal ultrafiltration in uraemic rodent models

Autor: Marina Vorobiov, Boris Rogachev, Reut Riff, Cidio Chaimowitz, Endre Z Neulander, Anna Basok, Alla Shnaider, Amos Douvdevani, Yosef-Shmuel Haviv
Rok vydání: 2023
Předmět:
Zdroj: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis. :089686082311658
ISSN: 1718-4304
0896-8608
Popis: Background: The most used PD fluids contain glucose as a primary osmotic agent. Glucose peritoneal absorption during dwell decreases the osmotic gradient of peritoneal fluids and causes undesirable metabolic consequences. Inhibitors of sodium–glucose co-transporter (SGLT) type 2 are wildly used for the treatment of diabetes, heart and kidney failure. Previous attempts to use SGLT2 blockers in experimental peritoneal dialysis yielded contrasting results. We studied whether peritoneal SGLTs blockade may improve ultrafiltration (UF) via partial inhibition of glucose uptake from dialysis fluids. Methods: Kidney failure was induced in mice and rats by bilateral ureteral ligation, and dwell was performed by injection of glucose-containing dialysis fluids. The effect of SGLT inhibitors on glucose absorption during fluid dwell and UF was measured in vivo. Results: Diffusion of glucose from dialysis fluid into the blood appeared to be sodium-dependent, and blockade of SGLTs by phlorizin and sotagliflozin attenuated blood glucose increment thereby decreasing fluid absorption. Specific SGLT2 inhibitors failed to reduce glucose and fluid absorption from the peritoneal cavity in a rodent kidney failure model. Conclusions: Our study suggests that peritoneal non-type 2 SGLTs facilitate glucose diffusion from dialysis solutions, and we propose that limiting glucose reabsorption by specific SGLT inhibitors may emerge as a novel strategy in PD treatment to enhance UF and mitigate the deleterious effects of hyperglycaemia.
Databáze: OpenAIRE
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