Relationship between the -374T/A receptor of advanced glycation end products gene polymorphism and peritoneal solute transport status at the initiation of peritoneal dialysis.

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.

Encapsulating peritoneal sclerosis is a separate entity: Con.

There is controversy with respect to the issue that encapsulating peritoneal sclerosis (EPS) is a separate entity from simple sclerosis (SS), which is the uniform change of the peritoneum on peritoneal dialysis. These following ideas support the notion that the development of EPS is connected with pathology that is not the same as that responsible for SS: (1) EPS is a rare disorder, (2) certain factors are involved with the etiology, (3) the clinical background of the patients is not uniform, and (4) the histopathological findings of EPS are different from those of SS. There are pitfalls in these concepts and they need be revised. This paper discusses the issue against the idea that EPS is a separate entity, supporting the idea that it has a strong connection with SS in its primary pathophysiology.

Hyper-vascular change and formation of advanced glycation endproducts in the peritoneum caused by methylglyoxal and the effect of an anti-oxidant, sodium sulfite.

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 degrees 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.

Association between an increased surface area of peritoneal microvessels and a high peritoneal solute transport rate.

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 post-capillary 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, beta2-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 beta2-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 II). 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 beta2-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.

[Long-standing high-transport membrane as a risk factor for EPS development after PD withdrawal: an analysis based on changes in peritoneal function during and after CAPD withdrawal].

The pathophysiology of encapsulating peritoneal sclerosis (EPS) that develops after withdrawal from long-standing dependence on CAPD remains unclear. The aim of this study was to clarify the risk factors for EPS as expressed in the peritoneal function. Fourteen patients who had shifted to standard hemodialysis after long-term CAPD (average, 105 months) were studied: 3 developed EPS after PD withdrawal while 11 did not. Analysis of the data obtained from the peritoneal equilibration test (PET) revealed that: (1) the dialysate/plasma creatinine ratio (D/Pcr) was significantly higher in the EPS group than in the non-EPS group during the course of PD as well as after PD withdrawal; and (2) eight patients, including the 3 with EPS, were classified as being in a high-transport membrane state (HTS) at PD withdrawal. The duration of HTS during PD was longer in those patients with EPS. During the periods after PD withdrawal, none of these EPS patients recovered from HTS, whereas 4 of the 5 non-EPS patients did. These data suggest that long-standing HTS during the course of PD as well as post-withdrawal, may be risk factors for EPS development. For this reason, it is indicated that PET has clinical relevance in examining sequential changes in peritoneal function and in detecting those patients at risk of EPS.