AQP1 in peritoneal dialysate as predictive biomarker of integrity of the peritoneal barrier and ultrafiltration efficiency


The water channel Aquaporin 1 (AQP1) plays a pivotal role in the mechanism of free water ultrafiltration through the peritoneum during peritoneal dialysis (PD). In the proposed  three-pore model of peritoneal barrier, AQP1 molecules represent the so-called ultrasmall pores, responsible for the 50% of  water ultrafiltration in PD.  Wether or not is AQP1 exclusively expressed in peritoneal capillaries or also in the mesothelial cells (MC) is still debated.


It has been hypothesized that decreased expression or function of AQP1 may be responsible for some cases of ultrafiltration failure (UF). A non-invasive method to check changes in the abundance of AQP1 in the peritoneum of PD patients would help to predict the risk of UF.


Plasma membrane proteins are released in biological fluids through the exosome pathway to an extent proportional to their abundance at the plasma membrane. In this work we investigated the localization of AQP1 in human peritoneum and its presence in exosomes isolated from peritoneal dialysis effluent.


Proteomic analysis of peritoneal-derived exosomes showed a significant expression of AQP1. Interestingly, the same samples were devoid of the endothelial marker CD31 but were positive for the mesothelial marker mesothelin, thus suggesting a mesothelial, rather than endothelial origin for these vesicles. (Fig.1) In human omental biopsies, AQP1 was localized in peritoneal capillaries and at the plasma membrane of  MC, where it co-localized with mesothelin. (Fig.2)


In conclusion, our results suggest that AQP1 is expressed in MC and released in the peritoneal cavity through the exosome pathway. This evidence opens the debate on the role of MC in regulating the efficiency of PD and suggests that AQP1 released in the PD effluent may represent a potential non-invasive biomarker of integrity of the peritoneal barrier, predictive of the efficiency of ultrafiltration in PD patients.