The Peritoneal Membrane and Its Role in Peritoneal Dialysis

Abstract

A healthy and functional peritoneal membrane is key to achieving sufficient ultrafiltration and restoring fluid balance, a major component of high-quality prescription in patients treated with peritoneal dialysis (PD). Variability in membrane function at the start of PD or changes over time on treatment influence dialysis prescription and outcomes, and dysfunction of the peritoneal membrane contributes to fluid overload and associated complications. In this review, we summarize the current knowledge about the structure, function, and pathophysiology of the peritoneal membrane with a focus on clinical implications for patient-centered care. We also discuss the molecular and genetic mechanisms of solute and water transport across the peritoneal membrane, including the role of aquaporin water channels in crystalloid versus colloid osmosis; why and how to assess membrane function using peritoneal equilibration tests; the etiologies of membrane dysfunction and their specific management; and the effect of genetic variation on membrane function and outcomes in patients treated with PD. This review also identifies the gaps in current knowledge and perspectives for future research to improve our understanding of the peritoneal membrane and, ultimately, the care of patients treated with PD.

Trial registration: ClinicalTrials.gov NCT01944852.

Figure 1

The peritoneal membrane, water channels AQP1, and mechanisms of osmosis. (A) At a structural level, the peritoneal membrane is composed of a single layer of mesothelial cells, an interstitium, and a dense microvascular network. (B) Peritoneal transport can be explained by a three-pore model, in which pores of different sizes (large, small, and ultrasmall) contribute to the diffusion of small solutes (i.e., removal of urea and creatinine and absorption of glucose via the small pores) and osmotic water transport (i.e., solute-coupled water transport across small pores and free-water transport via the ultrasmall pores). (C) AQP1 water channels facilitate the movement of water molecules across biological membranes, following an osmotic gradient. Water channels are expressed in endothelial cells lining the microvessels of the peritoneal membrane, as illustrated on these immunohistochemistry (brown) and immunogold electron microscopy (black dots corresponding to AQP1). (D) In a mouse model of PD with hypertonic glucose, the genetic deletion of the Aqp1 gene resulted in reduced IPV increase, lower net UF (in µl/g of BW), and abolition of the sodium sieving in Aqp1^−/− mice (blue) compared with their wild-type Aqp1^+/+ littermates (red). (E) Osmosis refers to the movement of water across biological membranes, in response to the presence of an osmotic agent, such as glucose or icodextrin, in PD solutions. The fundamental mechanisms and pathways differ between osmotic water transport driven by glucose (AQP1-mediated, crystalloid osmosis) versus icodextrin (AQP1-independent, colloid osmosis). Created using BioRender.com and adapted from refs. – with permission. AQP1, aquaporin-1; BW, body weight; IPV, intraperitoneal volume; PD, peritoneal dialysis; UF, ultrafiltration.

Figure 2

AQP1 gene variant, UF, and outcomes in PD. (A) The significant interindividual variability in peritoneal net UF at the start of PD (here shown at the end of the baseline 4-hour PET using 4.25% glucose) along with the role of AQP1 water channels in osmotic water transport suggested that genetic variation may contribute to this variability. (B and C) The common AQP1 promoter variant rs2075574 is associated with peritoneal UF, and patients with a TT genotype (14% of the cohort, red) had lower daily net UF than those with the CC genotype (gray), despite similar PSTR estimated from the D/Pcreat. (D) Patients with the TT genotype (red) showed a higher risk of a composite of death and technique failure compared with those with the CC genotype (gray), while patients with the CT genotype (blue) had intermediate outcomes. (E) The rs2075574 variant, which influences the transcriptional activity of the AQP1 promoter, is associated with lower expression of AQP1 water channels in the peritoneal microvasculature of patients with the TT genotype (red) versus those with the CC genotype (gray). Figure adapted from ref. with permission. **P ≤ 0.01; ***P ≤ 0.001. CI, confidence interval; DAPI, 4',6-diamidino-2-phénylindole; D/Pcreat, dialysate-over-plasma creatinine ratio; M.F.I., mean fluorescence intensity; PET, peritoneal equilibration test; PSTR, peritoneal solute transfer rate; sHR, subdistribution hazard ratio; vWF, von Willebrand Factor.