AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis

2021 ◽  
Vol 385 (17) ◽  
pp. 1570-1580
Author(s):  
Johann Morelle ◽  
Céline Marechal ◽  
Zanzhe Yu ◽  
Huguette Debaix ◽  
Tanguy Corre ◽  
...  
2008 ◽  
Vol 28 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Michael F. Flessner

Recent advances in the study of the microcirculation have demonstrated the critical role of the endothelial glycocalyx in transcapillary transport from the plasma to the tissue interstitium. Since the capillary wall represents the initial resistance to solute transfer from the plasma through the tissue to the dialysate, the glycocalyx is potentially of major importance to peritoneal dialysis. Inadvertently removed in early histological studies, this thin, delicate layer of glycosaminoglycans and proteoglycans is now recognized as a primary barrier in transendothelial solute and water transport. Subperitoneal endothelia are exposed to inflammation, angiogenesis, and hyperglycemia, which have been shown to affect the layer by increasing permeability. This entity permits new hypotheses concerning the factors that influence the transport characteristics of peritoneal dialysis patients and provides new avenues of basic research into the fundamental mechanisms of alteration of the peritoneal barrier.


2001 ◽  
Vol 21 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Simon J. Davies

Objective Peritoneal membrane function influences dialysis prescription and clinical outcome and may change with time on treatment. Increasingly sophisticated tools, ranging from the peritoneal equilibration test (PET) to the standard permeability analysis (SPA) and personal dialysis capacity (PDC) test, are available to the clinician and clinical researcher. These tests allow assessment of a number of aspects of membrane function, including solute transport rates, ultrafiltration capacity, effective reabsorption, transcellular water transport, and permeability to macromolecules. In considering which tests are of greatest value in monitoring long-term membrane function, two criteria were set: those that result in clinically relevant interpatient differences in achieved ultrafiltration or solute clearances, and those that change with time in treatment. Study Selection Clinical validation studies of the PET, SPA, and PDC tests. Studies reporting membrane function using these methods in either long-term (5 years) peritoneal dialysis patients or longitudinal observations (> 2 years). Data Extraction Directly from published data. Additional, previously unpublished analysis of data from the Stoke PD Study. Results Solute transport is the most important parameter. In addition to predicting patient and technique survival at baseline, there is strong evidence that it can increase with time on treatment. Whereas patients with initially high solute transport drop out early from treatment, those with low transport remain longer on treatment, although, over 5 years, a proportion develop increasing transport rates. Ultrafiltration capacity, while being a composite measure of membrane function, is a useful guide for the clinician. Using the PET (2.27% glucose), a net ultrafiltration capacity of < 200 mL is associated with a 50% chance of achieving less than 1 L daily ultrafiltration at the expense of 1.8 hypertonic (3.86%) exchanges in anuric patients. Using a SPA (3.86% glucose), a net ultrafiltration capacity of < 400 mL indicates ultrafiltration failure. While there is circumstantial evidence that, with time on peritoneal dialysis, loss of transcellular water transport might contribute to ultrafiltration failure, none of the current tests is able to demonstrate this unequivocally. Of the other membrane parameters, evidence that interpatient differences are clinically relevant (permeability to macro-molecules), or that they change significantly with time on treatment (effective reabsorption), is lacking. Conclusion A strong case can be made for the regular assessment by clinicians of solute transport and ultrafiltration capacity, a task made simple to achieve using any of the three tools available.


1996 ◽  
Vol 271 (6) ◽  
pp. H2254-H2262 ◽  
Author(s):  
O. Carlsson ◽  
S. Nielsen ◽  
el-R. Zakaria ◽  
B. Rippe

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.


2007 ◽  
Vol 22 (12) ◽  
pp. 3593-3600 ◽  
Author(s):  
A. M. Coester ◽  
D. G. Struijk ◽  
W. Smit ◽  
D. R. de Waart ◽  
R. T. Krediet

2017 ◽  
Vol 46 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Ana Fernandes ◽  
Roi Ribera-Sanchez ◽  
Ana Rodríguez-Carmona ◽  
Antía López-Iglesias ◽  
Natacha Leite-Costa ◽  
...  

Background: Volume overload is frequent in diabetics undergoing peritoneal dialysis (PD), and may play a significant role in the excess mortality observed in these patients. The characteristics of peritoneal water transport in this population have not been studied sufficiently. Method: Following a prospective, single-center design we made cross-sectional and longitudinal comparisons of peritoneal water transport in 2 relatively large samples of diabetic and nondiabetic PD patients. We used 3.86/4.25% glucose-based peritoneal equilibration tests (PET) with complete drainage at 60 min, for these purposes. Main Results: We scrutinized 59 diabetic and 120 nondiabetic PD patients. Both samples showed relatively similar characteristics, although diabetics were significantly more overhydrated than nondiabetics. The baseline PET disclosed lower ultrafiltration (mean 439 mL diabetics vs. 532 mL nondiabetics, p = 0.033) and sodium removal (41 vs. 53 mM, p = 0.014) rates in diabetics. One hundred and nine patients (36 diabetics) underwent a second PET after 12 months, and 45 (14 diabetics) underwent a third one after 24 months. Longitudinal analyses disclosed an essential stability of water transport in both groups, although nondiabetic patients showed a trend where an increase in free water transport (p = 0.033) was observed, which was not the case in diabetics. Conclusions: Diabetic patients undergoing PD present lower capacities of ultrafiltration and sodium removal than their nondiabetic counterparts. Longitudinal analyses disclose an essential stability of water transport capacities, both in diabetics and nondiabetics. The clinical significance of these differences deserves further analysis.


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.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Francesca Piccapane ◽  
Rosa Caroppo ◽  
Arduino Arduini ◽  
Roberto Corciulo ◽  
Roberto Russo ◽  
...  

Abstract Background and Aims The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD). We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD. We previously demonstrated that the water channel AQP1 is expressed in vivo by mesothelial cells. Here, we characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 in mediating water transport during PD and also to test the biocompatibility of glucose-sparing PD solutions (Xylocore), containing xylitol and L-carnitine as the main osmotic agents. Method Cells were grown onto porous cell culture inserts to achieve polarization. Polarization was demonstrated by expression of the tight junction markers Zo-1 and occludin. Transepithelial water transport was measured by TEA+-sensitive microelectrodes. HMC cell monolayers were exposed to PD solutions at the apical side for 8 hours. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT-test, measurement of transepithelial electrical resistance (TEER) and production of pro-inflammatory cytokines by by Luminex xMAP technology. Results HMC cells showed polarized expression of Na+/K+-ATPase and tight junctions markers but no endogenous expression of AQP1. HMC showed a low TEER (40Ω/cm2) compared to renal cells not expressing AQP1(1000Ω/cm2). However, the transepithelial water transport was comparable between the two cell types. Experiments in HMCs transfected with AQP1 cDNA, suggested that the water permeability of HMC was increased by two-fold in the presence of AQP1. Biocompatibility assays indicated that in conventional dialysis solutions glucose concentration decreased cell viability in a dose-dependent manner. Glucose concentration also strongly decreased the TEER, suggesting reduction of the barrier integrity, and increased pro-inflammatory cytokines production. Interestingly, substitution of part of the glucose with xylitol and L-carnitine minimized these effects. Conclusion These results suggest that the mesothelium may represent an additional selective barrier regulating water transport through the water channel AQP1 in PD. Importantly, we also demonstrate that the formulation of glucose-sparing PD solutions containing xylitol and L-carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.


2019 ◽  
Vol 39 (4) ◽  
pp. 323-329
Author(s):  
Lilian Bolte ◽  
Maria Jose Ibacache ◽  
Iris Delgado ◽  
Francisco Cano

BackgroundVolume overload is one of the most important factors associated with left ventricular hypertrophy (LVH) and cardiovascular disease in chronic peritoneal dialysis (PD) patients. MiniPET is a reliable tool to evaluate free water transport (FWT). In a clinical setting, the significance of FWT has not been evaluated in terms of outcome in children on PD. The objective was to define a FWT value of clinical significance in children on PD, fixing its relationship to left ventricular mass index (LVMI) as a well-known outcome parameter.MethodsMiniPET was performed with 3.86% glucose, 1-h long, to measure FWT in PD patients > 6 years old. An echocardiogram (ECG) was performed within 2 months of the MiniPET. Left ventricular hypertrophy was defined as LVMI ≥ 38.6 g/height2.7(95th percentile). Receiver operating characteristic curve (ROC) analysis was used to determine the cut-off value of FWT searching the highest sensitivity and specificity to differentiate patients with normal/abnormal LVMI. A p < 0.05 was considered significant.ResultsForty-six studies were performed on 32 patients, 16 males; mean age 11.59 ± 3.07 years. Mean normalized FWT (nFWT) was 144.4 ± 84.8 mL/m2, corresponding to 46.7% of total ultrafiltration. Mean LVMI was 42 ± 11.3 g/m2.7with a negative correlation to nFWT ( p < 0.01). Eighteen out of 32 patients had LVH. The ROC analysis (nFWT vs LVMI) showed an area under the curve of 0.71 (95% confidence interval [CI], 0.53 – 0.89; p = 0.04), allowing a cut-off nFWT value of 110 mL/m2to be defined, dividing the population into 2 groups of patients according to the LVMI cut-off value of 38,6 g/m2.7.ConclusionsThe nFWT showed an inverse correlation to LVMI. A nFWT value < 110 mL/m2was significantly associated with LVH. The negative relationship observed between nFWT and LVMI, and the cut-off level for nFWT according to the 95th percentile of LVMI, suggest that the regular evaluation of nFWT could become a useful tool in assessing the capacity of PD treatment to keep patients’ volume status under control, avoiding cardiovascular impairment.


Sign in / Sign up

Export Citation Format

Share Document