Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment

Overview

End stage renal disease is annually diagnosed in about one thousand patients in Denmark, and one of the treatment modalities in renal replacement therapy is peritoneal dialysis with about 25 % of patients assigned to this treatment (Hommel2010). Peritoneal dialysis is based on the principle of filtering waste products to peritoneal fluid and by exchange of peritoneal fluid eliminate waste products from the body. In peritoneal dialysis commonly used fluids contain glucose. Exposure to high glucose levels in peritoneal fluid during peritoneal dialysis has several side effects. Primarily, as glucose passes over and into the peritoneal membrane it causes local inflammation which leads to fibrosis over time (Zhou2016). Fibrosis limits the capacity of the exchange of water and waste products over the peritoneal membrane. The decrease of peritoneal exchange capacity is most commonly the reason for termination of peritoneal dialysis. SGLT2-channels are identified in peritoneal mesothelial cells of rats (Debray-Carcia 2016), and most recently also in humans (Shentu2021). An in vitro model of human peritoneal mesothelial cells incubated with the SGLT2-inhibitor (empagliflozin) has shown significantly decrease in glucose uptake (Zhou2019). Exposure to intraperitoneal empagliflozin in rats, reduced the uptake of glucose over the peritoneal membrane significantly by 78 % and the ultrafiltration was increased (Zhou2019). Currently, to our knowledge, no clinical trials have been conducted in humans attending peritoneal dialysis with the aim of investigating either the effect or safety of SGLT2i, as it is indeed the first of its kind, with the aim of including participants in peritoneal dialysis.