Peritoneal microvascular endothelial function and the microinflammatory state are associated with baseline peritoneal transport characteristics in uremic patients

Teng, Ling; Ming, Chang; Liu, Shuxin; Niu, Min; Zhang, Yungang; Liu, Xiangfei; Yu, Xianpeng

doi:10.1007/s11255-014-0775-1

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…In the studies using human tissues, we confirmed that there was a correlation between peritoneal transport rate and VEGF-A or TGF-␤1 concentrations in PD effluent, as previously reported (32,38,43,44). Importantly, we found that the VEGF-A concentration in PD effluent correlated with TGF-␤1 concentrations (Fig.…”

Section: Discussionsupporting

confidence: 90%

TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

Kariya

Nishimura

Mizuno

et al. 2018

American Journal of Physiology-Renal Physiology

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The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) ( P < 0.001) and TGF-β1 ( P < 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels ( P < 0.01) and peritoneal thickness ( P < 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr ( P < 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness ( P < 0.001), the number of vessels ( P < 0.001), and VEGF-A levels ( P < 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.

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Section: Discussionsupporting

confidence: 90%

TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

Kariya

Nishimura

Mizuno

et al. 2018

American Journal of Physiology-Renal Physiology

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“…The peritoneal membrane consists of a mesothelial cell monolayer, a submesothelial space composed of extracellular matrix, numerous small blood vessels and few lymphatic vessels and nerves, mostly organized in three distinct layers [ 53 ]. Peritoneal microvessel density correlates with small solute transport rates [ 17 , 54 ]; the vascular endothelium is considered the primary, rate limiting barrier [ 32 , 33 , 34 ]. Alterations in the endothelial barrier characteristics should significantly modify PD clearance functions.…”

Section: Discussionmentioning

confidence: 99%

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

et al. 2020

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Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.

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“…The pathophysiological mechanism of late acquired high transport induced by long-term peritoneal dialysis is different from that of early inherent high transport [ 23 , 24 ]. After initiating PD, significant changes occur in the transport characteristics, which may be due to the differences in the structure and function of the peritoneum before dialysis; these differences mainly manifest as microvascular endothelial function and microinflammation of the peritoneum [ 11 , 25 ]. Genetic factors are involved in determining initial peritoneal status.…”

Section: Discussionmentioning

confidence: 99%

“…Neovascularization contributes to both initial fast PSTR and fast PSTR in long -term PD. Although more studies have focused on neovascularization in long-term exposure in PD, several studies have shown higher concentrations of VEGF and KDR in peritoneal tissue in PD patients with initial high/high average transport than in patients with low/low average transport, which means that local expression of VEGF and KDR in peritoneal tissue can affect peritoneal baseline transport by increasing the number of new peritoneal vessels and increasing inflammation status [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis

et al. 2022

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Background Peritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR). Methods This study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD. Results The CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039). Conclusion Baseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

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Peritoneal microvascular endothelial function and the microinflammatory state are associated with baseline peritoneal transport characteristics in uremic patients

Cited by 7 publications

References 26 publications

TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis

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