How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)

Abstract

Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling—and their metabolic sequelae—on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.

Aging of the Peritoneal Dialysis Membrane

“…This was well tolerated and had no effect on peritoneal clearances and residual kidney function. A randomized multicenter clinical trial is currently in progress ( Bonomini et al, 2021 ). It should be appreciated however that although ref ( Bonomini et al, 2021 ; Masola et al, 2021 ; Rago et al, 2021 ) were published in different journals, all were part of MCPI, a publisher of many on-line journals that has been criticized in the past for the quality of its peer review.…”

The Peritoneal Membrane—A Potential Mediator of Fibrosis and Inflammation among Heart Failure Patients on Peritoneal Dialysis

“…Both solutions demonstrated efficiency in sodium and water removal and have the potential for glucose sparing when used as part of the PD prescription [ 50 ]. A new peritoneal dialysis solution containing L-carnitine and xylitol was recently reported (reviewed in [ 51 ]). These two molecules have molecular weights similar to that of glucose, high water solubility, chemical stability in aqueous solutions, and osmotic properties, which render them suitable for use in PD fluids [ 51 ].…”

“…A new peritoneal dialysis solution containing L-carnitine and xylitol was recently reported (reviewed in [ 51 ]). These two molecules have molecular weights similar to that of glucose, high water solubility, chemical stability in aqueous solutions, and osmotic properties, which render them suitable for use in PD fluids [ 51 ]. Studies on the biocompatibility of a PD solution containing carnitine or xylitol have shown a better profile than glucose-based solutions.…”

Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

“…Finally, promising results may come from the new PD solutions containing L-carnitine and xylitol as osmotic agents [ 43 , 44 , 45 , 46 , 47 ]. Indeed, the use of more biocompatible crystalloid agents [ 43 , 44 , 45 , 46 ] might enable compensated low-sodium PD solutions to be formulated.…”

“…Finally, promising results may come from the new PD solutions containing L-carnitine and xylitol as osmotic agents [ 43 , 44 , 45 , 46 , 47 ]. Indeed, the use of more biocompatible crystalloid agents [ 43 , 44 , 45 , 46 ] might enable compensated low-sodium PD solutions to be formulated. The initial clinical experience using L-carnitine and xylitol solutions in ten CAPD patients over four consecutive weeks proved safe and well tolerated [ 47 ]; however, larger trials designed ad hoc are needed to verify the efficacy and safety of these new strategies in ESKD patients treated by PD.…”