The rationale for the need to study sodium-glucose co-transport 2 inhibitor usage in peritoneal dialysis patients

Abstract

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.

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

“…There is growing evidence of SGLT2 inhibitor's role in the prevention of cardiovascular mortality and kidney function deterioration which may be of particular benefit in patients on dialysis. 9 Reports suggest that mechanisms other than simple paracellular diffusion are involved in glucose leakage during PD, namely SGLTs and glucose transporters (GLUTs) responsible for transcellular transport via mesothelial cells. 10,11 Schroppel et al found that SGLT1 is located on the apical surface of peritoneal mesothelial cells, while GLUTs -on the basolateral surface of these cells.…”

“…There is growing evidence of SGLT2 inhibitor’s role in the prevention of cardiovascular mortality and kidney function deterioration which may be of particular benefit in patients on dialysis. 9…”

SGLT2 inhibition, glucose transport and peritoneal dialysis: Finding the sweet spot

“…[11][12][13] Borkum et al subsequently discuss the importance of studying SGLT2 inhibition as a therapy to preserve RKF. 14…”

Extending SGLT2 Inhibitor Use for People Undergoing Dialysis?

“…Evaluation of SGLT2is in patients with residual kidney function receiving peritoneal dialysis warrants close attention because this population may derive cardiovascular benefits and longer preservation of residual kidney function. 10 The sampling procedure and pharmacokinetic analysis also warrant consideration. A noncompartmental analysis was employed using blood samples from every 30 minutes for the first 4 hours, then at hours 24 and 48.…”

“…Evaluation of SGLT2is in patients with residual kidney function receiving peritoneal dialysis warrants close attention because this population may derive cardiovascular benefits and longer preservation of residual kidney function. 10…”