scholarly journals AQP1-Containing Exosomes in Peritoneal Dialysis Effluent As Biomarker of Dialysis Efficiency

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 330 ◽  
Author(s):  
Simone Corciulo ◽  
Maria Celeste Nicoletti ◽  
Lisa Mastrofrancesco ◽  
Serena Milano ◽  
Maria Mastrodonato ◽  
...  

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.

2003 ◽  
Vol 23 (2_suppl) ◽  
pp. 20-25 ◽  
Author(s):  
Kar Neng Lai ◽  
Man Fai Lam ◽  
Joseph C. Leung

The aquaporins (AQPs) constitute a large family of water channels that play a part in transcellular water movement in many tissues. They are particularly abundant and important in the kidney and the lung. Derangement of AQP structure or function leads to a variety of water-balance disorders. Aquaporin-1 (AQP1) is constitutively expressed in the endothelial cells of the capillaries and venules that provide the ultrasmall pores predicted by the three-pore model of water movement during peritoneal dialysis. The ultrasmall pores are critical for ultrafiltration. In addition, AQP1 and AQP3 are constitutively expressed in peritoneal mesothelial cells. The expression of those AQPs is upregulated by hyperosmolality. Reduced expression or function of AQP1 may be responsible for some cases of ultrafiltration failure, but further evidence is required to establish that link.


2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 144-149
Author(s):  
Raymond T. Krediet ◽  
Annemieke M. Coester ◽  
Alena Parikova ◽  
Watske Smit ◽  
Dirk G. Struijk

A review is given on the mechanisms of free water transport, the various methodologies for its measurement, its dependency on the osmotic gradient, and the assessment of osmotic conductance in individual patients. The importance of impaired free water transport in long-term ultra-filtration failure is discussed, relative to peritoneal solute transport status. Furthermore, the relationship of free water transport with locally released potassium is considered, together with a potential role of impaired K+ channel function with peritoneal alterations. Finally, the role of impaired osmotic conductance to glucose and its effects on free water transport in long-term patients with ultrafiltration failure is reviewed.


2014 ◽  
Vol 34 (6) ◽  
pp. 582-593 ◽  
Author(s):  
Erika De Sousa–Amorim ◽  
Gloria Del Peso ◽  
M. Auxiliadora Bajo ◽  
Laura Alvarez ◽  
Marta Ossorio ◽  
...  

BackgroundEncapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS (“EPS-prone”) and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit.MethodsFor a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure).ResultsOf 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 – 102.7 months) and a median follow-up of 30.91 months (range: 4.6 – 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 – 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%).ConclusionsBeing a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.


PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117398 ◽  
Author(s):  
Donatienne Tyteca ◽  
Tomoya Nishino ◽  
Huguette Debaix ◽  
Patrick Van Der Smissen ◽  
Francisca N'Kuli ◽  
...  

2015 ◽  
Vol 39 (1-3) ◽  
pp. 70-73 ◽  
Author(s):  
Isaac Teitelbaum

Background: Ultrafiltration failure is a significant cause of technique failure for peritoneal dialysis and subsequent transfer to hemodialysis. Summary: Ultrafiltration failure is defined as failure to achieve at least 400 ml of net ultrafiltration during a 4 h dwell using 4.25% dextrose. Four major causes of ultrafiltration failure have been described. A highly effective peritoneal surface area is characterized by transition to a very rapid transport state with D/P creatinine >0.81. Low osmotic conductance to glucose is characterized by attenuation of sodium sieving and decreased peritoneal free water clearance to <26% of total ultrafiltration in the first hour of a dwell. Low effective peritoneal surface area manifests with decreases in the transport of both solute and water. A high total peritoneal fluid loss rate is the most difficult to diagnose clinically; failure to achieve ultrafiltration with an 8-10 h icodextrin dwell may provide a clue to diagnosis. Key Messages: Knowledge of the specific pathophysiology of the various causes of ultrafiltration failure will aid in the diagnosis thereof.


2021 ◽  
Vol 22 (22) ◽  
pp. 12535
Author(s):  
Francesca Piccapane ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
Serena Milano ◽  
Arduino Arduini ◽  
...  

We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.


Author(s):  
N. Stepanova ◽  
O. Burdeyna ◽  
V. Driyanska ◽  
V. Savchenko ◽  
M. Kolesnyk

Peritonealfibrosis (PF) is a common morphological change in peritoneal dialysis (PD) patients. With the progression of PF, peritoneal membrane function is impaired, which leads to ultrafiltration failure. Results of studies in recent years show the crucial role of high production monocytic chemoattractant protein -1 (MCP-1) of peritoneal fibrosis in PD-patients. The aim was to determine intraperitoneally production ofIL-10 and MCP-1 and its relationship with clinical and laboratory parameters of adequacy of dialysis. Patients and methods. A prospective observational study involved 18patients with CKD stage Vwith non-diabetic nephropathy, were treated with continuous ambulatory peritoneal dialysis (PAPD). The limits of the normal range (reference range) were obtained from the survey results of 10 conditionally healthy individuals. ELISA method in serum and peritoneal dialysis effluent (PDE) investigated levels ofIL-10 and MSP-1. PAPD adequacy indicators evaluated by determining the concentration of urea and creatinine in plasma, urine and dialysate, calculated weekly creatinine clearance (CrCl), dialysis (Ш/ Vd), renal (Ш / Vr) and шА weekly urea clearance (Kt/ V). [email protected]  Results. In all of the PD-patients compared to healthy donors conventionally, there was a significant increase in concentration of the cytokines. We determined the positive regression relationship between the concentration of MCP-1 and IL-10 in PDE and the level of total weekly (Kt / V) and renal (Kt / Vr). Conclusions. We determined the regression dependence, which allowed to identify clinical parameters that are most closely (statistically significant) related to intraperitoneal production of MCP-1 and IL-10.


2016 ◽  
Vol 36 (4) ◽  
pp. 442-447 ◽  
Author(s):  
Daniela Machado Lopes ◽  
Ana Rodríguez-Carmona ◽  
Teresa García Falcón ◽  
Andrés López Muñiz ◽  
Tamara Ferreiro Hermida ◽  
...  

BackgroundUltrafiltration failure (UFF) diagnosed at the initiation of peritoneal dialysis (PD) has been insufficiently characterized. In particular, few longitudinal studies have analyzed the time course of water transport in patients with this complication.ObjectiveTo investigate the time course of peritoneal water transport during the first year on PD in patients presenting UFF since the initiation of this therapy (study group).MethodProspective, observational, single-center design. We analyzed, at baseline and after 1 year of follow-up, peritoneal water transport in 19 patients incident on PD with UFF. We used incident patients without UFF as a control group. Water transport was characterized with the help of 3.86/4.25% dextrose-based peritoneal equilibration tests (PETs) with complete drainage at 60 minutes.ResultsThe study group revealed a disorder of water transport affecting both small-pore ultrafiltration (SPUF) ( p = 0.054 vs incident without UFF) and free water transport (FW T) ( p = 0.001). After 1 year of follow-up, FWT displayed a general increasing trend in the study group (mean variation 48.9 mL, 95% confidence interval [CI] 15.5, 82.2, p = 0.012), while the behavior of SPUF was less predictable (-4.8 mL, 95% CI -61.4, 71.1, p = 0.85). These changes were not observed in incident patients without UFF. Neither initial clinical characteristics, baseline PET-derived parameters, or suffering peritoneal infections during the first year predicted the time course of the capacity of UF in the study group. Recovery from incident UFF was apparently linked to improvement of SPUF.ConclusionsPatients with UFF at the start of PD suffer a disorder of peritoneal water transport affecting both FWT and SPUF. Free water transport increases systematically in these patients after 1 year of follow-up. The evolution of SPUF is less predictable, and improvement of this parameter marks reversibility of this complication.


2021 ◽  
pp. ASN.2021010080
Author(s):  
Raymond Krediet

Ultrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency preferably called ultrafiltration failure—an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD+ ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, as well as the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality long-term PD.


2009 ◽  
Vol 29 (6) ◽  
pp. 664-669 ◽  
Author(s):  
Jacek Waniewski ◽  
Malgorzata Debowska ◽  
Bengt Lindholm

Free water transport, an estimate of aquaporin function, was evaluated in 7 continuous ambulatory peritoneal dialysis (CAPD) patients with permanent ultrafiltration failure. In 3 patients, peritoneal transport was studied also before the onset of ultrafiltration failure. Transcapillary ultrafiltration and fluid absorption rates were assessed using radiolabeled albumin, and free water transport by kinetics of sodium concentration in dialysis fluid. Diffusive and convective transport rates of small solutes were estimated using the modified Babb–Randerson–Farrell model. Increased diffusive transport of small solutes was found in 5 patients and increased peritoneal fluid absorption in 2 patients. The 3-pore model was fitted to these data. Overall, hydraulic conductivity and the fractional contributions of aquaporins to hydraulic conductivity were either decreased or normal. We conclude that the quantitative role of aquaporins in overall fluid transport may vary substantially in normal patients as well in patients with ultrafiltration failure.


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