scholarly journals Osteopontin levels in the drained dialysate reflect the peritoneal solute transport rate

2020 ◽  
Author(s):  
Jianzhong Li ◽  
Jingjing Lan ◽  
Qing Qiao ◽  
Lei Shen ◽  
Guoyuan Lu

Abstract Background and objectives: Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation, may eventually lead to peritoneal membrane injury with high solute transport rate and ultrafiltration failure. Osteopontin(OPN) is highly expressed with the pro-inflammatory cytokines stimulation in many cell types, and evolves in the process of tissue fibrosis. This study aimed to investigate the potential of OPN as a new indicator of peritoneal injury. Methods: We analyzed a total of 125 PD patients with end-stage renal disease, including 16 patients with continuous ambulatory PD(CAPD)-related peritonitis and 109 patients without peritonitis in a single renal center. The OPN levels in the overnight peritoneal effluents or in serum were analyzed using ELISA. In HMrSV5 cells, The OPN and fibronectin(FN) protein expression were identified using western blot analysis. Results: The OPN levels in overnight drained dialysate were significantly correlated with D/P Cr (P < 0.0001, R =0.54) and D/D0 glucose (P < 0.0001 R=-0.39). Logistical regression analysis showed that the OPN levels in peritoneal effluents was an independent predictive factor for the increased peritoneal solute transport rate (PSTR) (p < 0.001). The area under the receiver operating characteristic (ROC) curve of the OPN-PSTR model for identifying PSTR was 0.88, with 95% confidence interval (CI):0.81-0.95. The OPN was more abundant in peritoneal effluents of the CAPD-related peritonitis group compared with the patients without peritonitis (18.64±13.04 vs. 2.23±1.63 ng/ml, p<0.001). In the in vitro experiment, lipopolysaccharides(LPS) increased the OPN expression in HMrSV5 cells, whereas downregulation of OPN suppressed FN induction with transforming growth factor-β1(TGF-β1)stimulation. Conclusions: The OPN levels in drained dialysate were independently correlated with peritoneal transport status in accordance with the PET results. OPN was highly expressed in effluents in patients with CAPD-related peritonitis. Peritoneal mesothelial cells displayed a high expression of OPN under inflammatory stimuli and OPN was likely to be implicated in the progression of peritoneal fibrosis. Thus, OPN may be a useful indicator of peritoneal injury in patients with PD. Keywords: peritoneal dialysis, osteopontin, peritoneal injury, peritoneal solute transport rate

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 847-853
Author(s):  
Jianzhong Li ◽  
Jingjing Lan ◽  
Qing Qiao ◽  
Lei Shen ◽  
Guoyuan Lu

Abstract Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation and may eventually lead to peritoneal membrane injury with a high solute transport rate and ultrafiltration failure. Osteopontin (OPN) is highly expressed through the stimulation of pro-inflammatory cytokines in many cell types. This study aimed to investigate the potential of OPN as a new indicator of peritoneal deterioration. One hundred nine continuous ambulatory PD patients were analyzed. The levels of OPN and IL-6 in peritoneal effluents or serum were analyzed by ELISA kits. The mean effluent OPN concentration was 2.39 ± 1.87 ng/mL. The OPN levels in drained dialysate were correlated with D/P Cr (p < 0.0001, R = 0.54) and D/D0 glucose (p < 0.0001, R = 0.39). Logistic regression analysis showed that the OPN levels in peritoneal effluents were an independent predictive factor for the increased peritoneal solute transport rate (PSTR) obtained by the peritoneal equilibration test (p < 0.001). The area under the receiver operating characteristic curve of OPN was 0.84 (95% CI: 0.75–0.92) in predicting the increased PSTR with a sensitivity of 86% and a specificity of 67%. The joint utilization of effluent OPN with age, effluent IL-6, and serum albumin further increased the specificity (81%). Thus, OPN may be a useful indicator of peritoneal deterioration in patients with PD.


2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Yeoungjee Cho ◽  
David W Johnson ◽  
David A Vesey ◽  
Carmel M Hawley ◽  
Elaine M Pascoe ◽  
...  

2004 ◽  
Vol 24 (6) ◽  
pp. 597-600 ◽  
Author(s):  
Soon Bae Kim ◽  
Jai Won Chang ◽  
Sang Koo Lee ◽  
Jung Sik Park

Background This study was performed to evaluate the effects of acute systemic inflammation on peritoneal solute transport rate (PSTR) in chronic peritoneal dialysis (CPD) patients. Methods A baseline standard peritoneal equilibration test (PET) was performed on each patient every 6 months, and blood concentration of high-sensitivity C-reactive protein (hs-CRP) was assayed every 2 months in our peritoneal dialysis clinic. Acute systemic inflammation was defined as a greater than 10-fold increase in hs-CRP concentration compared with baseline value, in the absence of peritonitis, and returning to baseline level in 2 months. In patients with acute systemic inflammation, PET and hs-CRP concentration assays were performed during inflammation and after recovery. Ten patients with acute systemic inflammation were enrolled in the inflammation group and 42 other patients served as controls. Results There were no significant changes in hs-CRP and dialysate-to-plasma ratio of creatinine (D/Pcreat) in the control group during the study period. In the inflammation group, median hs-CRP levels at baseline, during acute inflammation, and at recovery were 2.3 mg/L (range 0.3 – 4.5 mg/L), 39.2 mg/L (range 15.1 – 117.4 mg/L), and 3.7 mg/L (range 0.9 – 8.9 mg/L), respectively. Median D/Pcreat increased significantly from baseline (0.64; range 0.55 – 0.98) to time of acute inflammation (0.72; range 0.60 – 0.96) ( p < 0.05). The D/Pcreat at recovery was 0.67 (range 0.52 – 0.94), which decreased significantly from time of acute inflammation ( p < 0.05). There was no correlation between changes in log (hs-CRP) and changes in D/Pcreat. Conclusion We have shown here that acute systemic inflammation is associated with a temporary increase in PSTR in CPD patients.


2009 ◽  
Vol 29 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Young-Hwan Hwang ◽  
Min-Jeong Son ◽  
Jaeseok Yang ◽  
Kiwon Kim ◽  
Wookyung Chung ◽  
...  

Objective To study the genetic effects of various inflammatory cytokines on peritoneal solute transport rate (PSTR) in incident Korean peritoneal dialysis (PD) patients. Design Case-control association study. Methods 132 patients with baseline peritoneal equilibration test within 1 – 3 months after starting PD were enrolled. We analyzed the influence of single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6; -572G/C, T15A), tumor necrosis factor-alpha (TNF-α; -1031C/T, -863C/A, -308G/A), and IL-10 (-1082A/G, -592A/C) on baseline PSTR. Clinical parameters such as age, gender, presence of diabetes mellitus, comorbidity, C-reactive protein, and residual renal function were also included as covariates. Results The T15A SNP of IL-6 (rs13306435) was associated with PSTR. Patients with TA genotype ( n = 18) had significantly lower D4/P creatinine (0.65 ± 0.087 vs 0.73 ± 0.110, p = 0.0046) and higher D4/D0 glucose (0.39 ± 0.174 vs 0.31 ± 0.119, p = 0.027) than patients with TT genotype ( n = 114). The log value of the dialysate appearance rate of IL-6 had a strong positive correlation with D4/P creatinine ( r2 = 0.1294, p < 0.0001) and was significantly lower in the TA genotype than the TT genotype (201.7 ± 14.42 vs 116.8 ± 88.91 pg/minute, p = 0.0358). By multiple logistic regression, TA genotype was negatively associated with a higher PSTR (high or high average; odds ratio 0.18; 95% confidence interval 0.048 – 0.666). Conclusions In incident Korean PD patients, T15A polymorphism of IL-6 is associated with dialysate IL-6 concentration and baseline PSTR.


2021 ◽  
Vol 37 (4) ◽  
Author(s):  
Ying Hang ◽  
Hao Yan ◽  
He Zhang ◽  
Zhenyuan Li ◽  
Wei Fang

Objectives: We designed this prospective observational study to clarify the associations between dialysate IL-6, a marker of ongoing peritoneal inflammation, Tie2, an important factor in angiogenesis in the peritoneum, and a high peritoneal solute transport rate (PSTR) in patients undergoing peritoneal dialysis (PD) and to investigate their outcome predictive roles. Methods: A total of 60 stable continuous ambulatory peritoneal dialysis (CAPD) patients from a single center in China were analyzed in this prospective study. We measured dialysate levels of IL-6 and Tie-2 using ELISAs. Our primary study endpoint was all-cause mortality with 10 years’ follow-up. Results: For the evaluation of PSTR, we used the Dialysis/Plasma creatinine (D/Pcr) ratio. We subdivided the patients into two groups for statistical evaluation: low and low average D/Pcr (<0.64; L/A), and high and high average D/Pcr (≥0.65; H/A) transporters. The mean levels of dialysates IL-6 (21.71 ± 8.88 pg/mL) and Tie-2 (1.23 ± 0.43 ng/mL) were significantly higher in the H/A (high and high average, group than those in the L/A group (13.94 ± 5.43 pg/mL, p<0.001 and 0.95 ± 0.43 ng/mL, p=0.019; respectively). Moreover, IL-6 and Tie-2 were positively correlated with D/Pcr (r=0.366, p=0.004 and r=0.402, p=0.001; respectively). Both dialysates IL-6 and Tie-2 were independent determinants of a high peritoneal solute transport rate. After follow-up for 42.65±18.08 months, 30 patients (50.0%) had died. An increased D/Pcr increased the risk of all-cause mortality in patients with CAPD (p=0.018), but the dialysates IL-6 and Tie2 were not independent predictors of all-cause mortality (p>0.05). Conclusion: Our results suggest that patients undergoing CAPD have a high peritoneal solute transport status with local peritoneal inflammation and angiogenesis. Increased D/Pcr is a relative risk factor for mortality and technique failure in patients undergoing CAPD. doi: https://doi.org/10.12669/pjms.37.4.4328 How to cite this:Hang Y, Yan H, Zhang H, Li Z, Fang W. Associations between dialysate interleukin-6 and Tie-2 and peritoneal solute transport rate and outcomes for patients undergoing peritoneal dialysis: A prospective cohort study. Pak J Med Sci. 2021;37(4):---------.  doi: https://doi.org/10.12669/pjms.37.4.4328 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2018 ◽  
Vol 314 (2) ◽  
pp. F167-F180 ◽  
Author(s):  
Tetsuyoshi Kariya ◽  
Hayato Nishimura ◽  
Masashi Mizuno ◽  
Yasuhiro Suzuki ◽  
Yoshihisa Matsukawa ◽  
...  

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.


2010 ◽  
Vol 298 (3) ◽  
pp. F721-F733 ◽  
Author(s):  
Makoto Mizutani ◽  
Yasuhiko Ito ◽  
Masashi Mizuno ◽  
Hayato Nishimura ◽  
Yasuhiro Suzuki ◽  
...  

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents ( n = 178) and tissue CTGF expression ( n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate ( n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF-β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.


Sign in / Sign up

Export Citation Format

Share Document