Peritoneal Function: The Role of Aquaporins

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.

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.


2000 ◽  
Vol 20 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Rafael Selgas ◽  
M.-Auxiliadora Bajo ◽  
M.-José Castro ◽  
Gloria Del Peso ◽  
Abelardo Aguilera ◽  
...  

Objective To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). Design Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. Setting A tertiary-care public university hospital. Patients Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. Main Outcome Measures Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). Results None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 ± 0.5% in the LUFF group, but as high as 25.5 ± 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group ( p = 0.016). Conclusions Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms.


2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 123-127
Author(s):  
Tadashi Tomo

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has bio-compatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.


2002 ◽  
Vol 22 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Tomoko Ota ◽  
Michio Kuwahara ◽  
Shuling Fan ◽  
Yoshio Terada ◽  
Takashi Akiba ◽  
...  

Objective The purpose of this study was to determine the localization of the aquaporin-1 (AQP1) water channel in peritoneal tissues and the effect of hyperosmolality on the peritoneal expression and function of AQP1. Methods Immunohistochemical localization of AQP1 was identified in rat peritoneal tissues. Cultured rat peritoneal mesothelial cells (RPMCs) were exposed to hyperosmolality by adding 4% glucose to the culture medium. After 1 hour, 4 hours, 24 hours, and 48 hours, AQP1 was identified by semiquantitative immunoblot and immunocytochemistry. Osmotic water permeability was measured using a light-scattering method. Results Immunohistochemistry of rat peritoneal tissues showed the presence of AQP1 in mesothelial cells, venular endothelial cells, and capillary endothelial cells, but not in arteriole and interstitial cells. Semiquantitative immunoblot revealed that exposure to hyperosmolality significantly increased AQP1 expression after 24 hours in whole RPMC lysates (3.3-fold at 24 hours and 3.9-fold at 48 hours). Consistent with the immunoblot, osmotic water permeability of RPMC was augmented 1.7-fold and 2.7-fold after 1 hour and 24 hours, respectively, in a hyperosmotic environment. In RPMC membrane fractions, AQP1 expression was significantly increased after 1 hour of exposure to hyperosmolality (3.9-fold at 1 hour, 7.1-fold at 4 hours, and 8.7-fold at 24 hours). Immunocytochemistry of RPMCs showed that AQP1 was gradually redistributed from the perinuclear area to the peripheral cytoplasm, and then to the plasma membrane after a 1-hour hyperosmotic challenge, suggesting hyperosmolality-induced translocation of AQP1. Upregulation of AQP1 was also observed in the omentum of rats loaded intraperitoneally with hyperosmotic dialysate every day for 10 weeks. Conclusion AQP1 is widely distributed in the peritoneal cavity and may provide the major aqueous pathway across the peritoneal barrier. In addition, our findings suggested that hyperosmolality increases AQP1-dependent water permeability in peritoneal tissues by regulating the translocation and synthesis of AQP1 protein.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Su Ah Sung ◽  
Dong Hee Kim ◽  
Kook-Hwan Oh ◽  
Sang Youb Han ◽  
Kum Hyun Han

Glucose-containing peritoneal dialysis (PD) solution causes peritoneal fibrosis (PF) characterized by accumulation of extracellular matrix (ECM) in the submesothelial layer. Cathepsin B is a lysosomal cysteine protease that degrades ECM, but its role in the PF remains unclear. Thus, we investigated the role of cathepsin B in PF. Procathepsin B was measured in the 73 PD effluents of 68 patients. Procathepsin B and cathepsin B after exposure of glucose and the effects of cathepsin B on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and urokinase-type plasminogen activator (uPA) were measured in the supernatant of cultured human peritoneal mesothelial cells (HPMCs). The effect of cathepsin B and its inhibitor, cystatin C, on PF was investigated in the murine model. Procathepsin B was measured at 3.6 μg/L in serum and 5.4 μg/L in PD effluent and positively correlated to the cancer antigen (CA) 125. The treatment with 4.25% glucose increased procathepsin B by 3.1-fold and cathepsin B by 5.9-fold in the HPMCs. Cathepsin B induced the secretion of MMP-1, -2, and -3 and TIMP-1 in the HPMCs, but uPA was not excreted. In the PF murine models, cathepsin B reduced the thickness of the submesothelial layer and cystatin C attenuated the effect of cathepsin B. HPMCs secrete cathepsin B with exposure of PD solution, and cathepsin B might help protect against PF.


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.


2017 ◽  
Vol 313 (5) ◽  
pp. H1063-H1073 ◽  
Author(s):  
Jimmy Toussaint ◽  
Chirag Bharavi Raval ◽  
Tieuvi Nguyen ◽  
Hadi Fadaifard ◽  
Shripad Joshi ◽  
...  

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop.


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.


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