Objective The peritoneal solute transport rate (PSTR) often increases, especially for small solutes, during long-term peritoneal dialysis (PD) treatment. Although the mechanism by which PSTR increases in PD patients is not known, it is likely that an increased PSTR reflects an increased surface area of the peritoneal capillary and postcapillary venules (microvessels), but this has not previously been investigated. The aim of this study was to clarify the relationship between PSTR and peritoneal microvessel alterations in biopsy specimens of peritoneum obtained from PD patients after various times on PD, and the possible contribution of the duration of PD in relation to these alterations. Design Tissue from the parietal peritoneum was obtained from 22 PD patients (age 48.5± 9.0 years, duration of PD 66.3 ± 46.6 months, incidence of peritonitis 0.3/patient-year). The patients were subdivided into three groups according to duration of PD: zero months (group 0, n = 4), less than 60 months (group I, n = 7), and more than 60 months (group II, n = 11). Methods For each specimen, the relative microvessel area (RVA) calculated as total area of microvessels/total area of peritoneal field, and the relative microvessel number (RVN), calculated as number of microvessels/total area of peritoneal field, were determined. The ratio RVA/RVN was used to assess the average area of microvessels. The PSTR was evaluated for creatinine, glucose, β2-microglobulin, and albumin using the peritoneal equilibration test. Results The dialysate-to-plasma concentration ratio (D/P) for creatinine showed a significant positive correlation with both RVA (rho = 0.77, p < 0.001) and RVA/RVN (rho = 0.51, p = 0.01), but not with RVN. The D/P for β2-microglobulin correlated with RVA (rho = 0.51 p = 0.015) but not with RVN or RVA/RVN. No differences were found between the three groups in the values for RVN, whereas there was an apparent significant increase in RVA with time on PD ( p < 0.001 for group 0 vs both groups I and Furthermore, in high transporters, RVA tended to be higher in group II than in group I. Conclusions The present study demonstrates for the first time that an increased peritoneal solute transport rate (for both creatinine and β2-microglobulin) is associated with an increased surface area of peritoneal microvessels, especially in patients on long-term PD treatment. This indicates that increased vascularization and/or dilatation of peritoneal microvessels may play a key role in the development of a high PSTR.
Objective: Methylglyoxal (MGO) in a heat-sterilized conventional PD solution may damage peritoneal cells directly and/or indirectly by producing advanced glycation endproducts (AGEs). This study was conducted to (a) examine the acute effect of MGO on the peritoneum (including AGE formation) and (b) study the possible AGE suppressive effect of an anti-oxidant, sodium sulfite. Method: (1) Human serum albumin (HAS) was continuously incubated with MGO (50 mM) at 37°C for as long as 14 days and the fluorescence intensity (FI) was determined (em. 440, ex. 370). (2) Three types of test solutions – (i) saline; (ii) MGO (20 mM), and (iii) MGO with sodium sulfite (30 mM) – were administered intraperitoneally to 8-week-old rats once a day for 5 consecutive days. The parietal peritoneum was examined macroscopically on the 6th day for immunostaining of anti-AGE antibodies. Result: (1) An increase in FI of HSA was observed as a function of the incubation period in the MGO solution. (2) Prominent hypervascularity and intense immunostaining of anti-AGE Ab were noted in MGO-treated rats, whereas the macroscopic alterations were suppressed in the rats that had been treated with sodium sulfite. Conclusion: MGO-induced hypervascularity and AGE formation in the peritoneum, as well as macroscopic alterations were suppressed by sodium sulfite. This may indicate that there is a risk of MGO causing a peritoneal injury and that the therapeutic potential of an anti-oxidant for this type of injury may exist.
An increased peritoneal solute transport rate (PSTR) at baseline is well known to be associated with decreased patient and technique survival in patients undergoing peritoneal dialysis (PD). Recently, angiogenesis has been recognized to be associated with PSTR and peritoneal deterioration. To investigate genetic variations in genes related to angiogenesis, 30 incident PD patients were studied. Several single nucleotide polymorphisms of the vascular endothelial growth factor (VEGF), the endothelial nitric oxide synthase (eNOS) and the receptor for advanced glycation end product (RAGE) were analyzed by the pyrosequencing method. The dialysate-to-plasma ratio of creatinine (D/P Cr) obtained from a peritoneal equilibrium test (PET) during the first 12 months after initiation of PD was used for a marker of PSTR. The D/P Cr was assessed both as a continuous and as a categorical variable including high (H), high-average (HA), low-average (LA), and low (L). Baseline D/P Cr was 0.645 +/- 0.083. The RAGE -374 TA genotype had a significantly lower prevalence of the H/HA transporters than the TT genotype (20% vs 63%; P = 0.03). Genetic polymorphisms of the VEGF and eNOS were not associated with initial peritoneal transport type. The RAGE polymorphism may have a considerable effect on the basal PSTR. Further studies will be needed to confirm this hypothesis.
Objective Accumulated evidence suggests that Nε-(carboxymethyl)lysine (CML), which is a dominant antigen of advanced glycation end-products (AGEs), is generated in the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and that this process may be involved in the pathophysiology of the peritoneal injury found with CAPD treatment. Since CML is a sequential product of glycation and oxidation processes, CML generation could be suppressed by antioxidants. The aim of this in vitro study was to clarify the effect of N-acetylcysteine (NAC), an antioxidant, on CML generation from proteins under high glucose settings mimicking peritoneal dialysis solutions. Design Test proteins (bovine serum albumin/type I collagen) were incubated continuously for 16 weeks in glucose solutions (200 mmol/L) with or without NAC (2 mmol/L), and the generation time courses (8 and 16 weeks) of CML and furosine (the biomarker of the glycation products of the early Maillard reaction) were determined. Results In both proteins, furosine and CML were progressively generated in accordance with the duration of the incubation period. No apparent differences were found between solutions with and without NAC in furosine levels at the 8th and 16th weeks. However, the generation of CML was lower in the solution with NAC throughout the test periods. Conclusion The results showed that NAC could suppress the generation of CML. This indicates the therapeutic potential of antioxidants for the glycoxidative stress-related peritoneal injury occurring during CAPD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.