Abstract
The water channel Aquaporin 1 (AQP1) plays a fundamental role in water ultrafiltration during peritoneal dialysis (PD) and its reduced expression or function may be responsible for ultrafiltration failure (UFF). In humans, AQP1 is expressed in the endothelium of the peritoneal capillaries but its expression in mesothelial cells (MC) and its functional role in PD is still being debated. Here, we studied a cohort of 30 patients using PD in order to determine the presence of AQP1 in peritoneal biopsies, AQP1 release in the PD effluent through exosomes and the correlation of AQP1 abundance with the efficiency of peritoneal ultrafiltration. The experiments using immunofluorescence showed a strong expression of AQP1 in MCs. Immunoblotting analysis on vesicles isolated from PD effluents showed a consistent presence of AQP1, mesothelin and Alix and the absence of the CD31. Thus, this suggests that they have an exclusive mesothelial origin. The immunoTEM analysis showed a homogeneous population of nanovesicles and confirmed the immunoblotting results. Interestingly, the quantitative analysis by ELISA showed a positive correlation between AQP1 in the PD effluent and ultrafiltration (UF), free water transport (FWT) and Na-sieving. This evidence opens the discussion on the functional role of mesothelial AQP1 during PD and suggests that it may represent a potential non-invasive biomarker of peritoneal barrier integrity, with predictive potential of UFF in PD patients.
Highlights
Peritoneal dialysis (PD) was introduced more than three decades ago as a renal replacement therapy to restore fluid homeostasis in dialysis patients with end-stage renal disease (ESRD).peritoneal dialysis (PD) is a simple therapy in which a hypertonic solution containing glucose as its osmotic agent is instilled in the patient’s peritoneal cavity and is exchanged four times a day
We confirm that the water channel Aquaporin 1 (AQP1) [9] is expressed in the plasma membrane of human mesothelial cells and we demonstrate that the mesothelial AQP1 is released in the PD effluent through exosomes
The samples of parietal and visceral human peritoneum were analyzed by immunofluorescence with antibodies against AQP1 and the surface marker of mesothelial cells [19]
Summary
Peritoneal dialysis (PD) was introduced more than three decades ago as a renal replacement therapy to restore fluid homeostasis in dialysis patients with end-stage renal disease (ESRD). PD is a simple therapy in which a hypertonic solution containing glucose as its osmotic agent is instilled in the patient’s peritoneal cavity and is exchanged four times a day. The peritoneum is a continuous membrane that lines the peritoneal cavity. It is composed of a monolayer of mesothelial cells sitting on a basement membrane and a sub-mesothelium characterized by several bundles of collagen fibers, scattered fibroblasts and blood vessels. The continuous exposure of the peritoneum to non-physiological hypertonic PD solutions and occasional peritonitis causes inflammation of the peritoneal membrane, which progressively undergoes fibrosis, angiogenesis and ultrafiltration failure (UFF)
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