Predialysis fluid overload linked with quality of sleep in patients undergoing hemodialysis.
Hao Guihua,Lu Wei,Huang Jie,Ding Wei,Wang Pengfei,Wang Lili,Ding Feng,Hu Min,Hou Lili
Sleep medicine
OBJECTIVE:Hemodialysis (HD) patients are exposed to dysregulated fluid balance which can lead to overhydration. Poor sleep quality and excessive daytime sleepiness are particularly common in these patients, however the relationship between fluid status and sleep quality and daytime sleepiness has not yet been studied. Therefore, the aim of this study is to evaluate the correlations between fluid status and sleep quality and daytime sleepiness in HD patients. METHOD:This cross-sectional study included 115 HD patients and 30 healthy control subjects from the HD center of Shanghai Ninth People's Hospital. Fluid compartments [total body water (TBW)], extracellular water (ECW)] and overhydration index (OH) were analyzed by multifrequency bio-impedance (BCM). Overhydration was defined as OH/ECW≥7%. HD patients were divided into an overhydration group and non overhydration group according to OH/ECW. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and excessive daytime sleepiness was evaluated by the Epworth Sleepiness Scale (ESS). RESULTS:The prevalence rate of fluid overload in HD patients was 65.2%. Poor sleep quality (PSQI≥5) and excessive daytime sleepiness (ESS≥11) were significantly higher in HD patients compared with the healthy controls [6 (3, 10) vs.2.11 ± 1.59, p = 0.000; 3 (0, 6) vs.1.68 ± 1.07, p = 0.045]. Furthermore, the PSQI scores were higher in HD patients with overhydration (7.8 ± 4.5 vs. 4.8 ± 3.2, p = 0.000). The component scores 1, 2, 3 and 5 of the PSQI showed significant differences between the overhydration and non overhydration groups. The ESS scores did not show differences between the two groups (3.9 ± 4.1 vs. 3.3 ± 3.5, p = 0.508). OH was correlated with Systolic BP and Diastolic BP, and additionally was an independent predictor of poor sleep quality. CONCLUSION:Fluid overload is significantly linked with poor quality of sleep in HD patients, however there is no association with excessive daytime sleepiness. Our study provides new insight into possible treatment strategies. Future studies should examine the effects of optimizing fluid status on quality of sleep.
10.1016/j.sleep.2018.07.011
Evaluation of inflammatory and cardiac-electrophysiological markers in patients undergoing peritoneal dialysis.
Fang Junyan,Su Haixia,Song Ahui,Tong Yan,Huang Zehui,Ding Feng,Liu Yingli
Biomarkers in medicine
The Tp-e/QT (peak to end of T-wave duration/QT interval) ratio is a promising marker of myocardial repolarization and ventricular arrhythmogenesis. Its elevation is associated with sudden cardiac death in different clinical conditions. This study was designed to assess the possible association between increased Tp-e/QT ratio and clinical factors in peritoneal dialysis patients. We devised a prospective cross-sectional study, which included 107 patients who were divided into groups according to their Tp-e/QT ratio. The association of an increased Tp-e/QT ratio with related factors was analyzed with multivariate logistic regression. Thirty-one patients, who had an elevated Tp-e/QT ratio, showed higher values of IL-6, left ventricular end-systolic diameter, Tp-e, percentage of diabetes mellitus, coronary artery calcification, and left ventricular ejection fraction. Multivariate analysis revealed that IL-6 was an independent risk factor for a higher Tp-e/QT ratio after adjustments. Our study revealed that a high serum IL-6 level in peritoneal dialysis patients increased the risk of a higher Tp-e/QT ratio, which indicated a potentially hazardous interplay between inflammation and arrhythmogenesis.
10.2217/bmm-2020-0230
Solutes removal characteristics at various effluent rates during different continuous renal replacement therapy modalities.
The International journal of artificial organs
BACKGROUND:Some studies suggest the effluent as a surrogate solute removal indicator in continuous hemodialysis or hemofiltration, but the delivered clearance is frequently smaller than prescribed. This study aims at testing whether the effluent, represented by mL/kg/h, could measure solute clearance and whether increasing effluent increases clearance proportionately in continuous hemodialysis or hemofiltration. METHODS:Patients treated with continuous renal replacement therapy for various diagnoses were included. The range of dialysate flow rate or substitution fluid flow rate was 1-5 L/h; solutes in the effluent and in the plasma entering the filter were measured, and the ratio of solutes in the effluent and in the plasma entering the filter and the clearance of blood urea nitrogen, creatinine, phosphate, and β-microglobulin were calculated. RESULTS:The ratio of solutes in the effluent and in the plasma entering the filter showed a decreasing trend with increased dialysate flow rate or substitution fluid flow rate ( 0.05), but solute clearance showed an increasing trend. The increase in solute clearance was less than expected from the increased effluent ( < 0.01), and actual delivered clearance was always below the corresponding prescribed clearance ( < 0.001). CONCLUSION:With increasing prescribed clearance of continuous renal replacement therapy, effluent rate overestimated the delivered clearance.
10.1177/0391398819836045
Calcium supplementation in CVVH using regional citrate anticoagulation.
Zheng Yin,Xu Zhongye,Fan Qichen,Zhu Qiuyu,Ma Shuai,Lu Jianxin,Zhuang Feng,Hao Guihua,Lu Wei,Ding Feng
Hemodialysis international. International Symposium on Home Hemodialysis
INTRODUCTION:Calcium supplementation is one of the most important factors in maintaining the safety and efficacy of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). The aims of this study were to assess the determinants of calcium requirements in RCA-CVVH and to simplify the calcium supplementation approach. METHODS:Our study consisted of two parts. The first part was a discovery phase to determine the key factors of calcium supplementation. Twenty critically ill patients who required RCA-CVVH were enrolled in this part. Systemic citrate, total calcium, protein-bound calcium, and ionized calcium concentrations were serially measured using the traditional RCA protocol. A two-phase calcium supplementation protocol was then proposed, and algorithms were developed for calcium supplementation. The second part of the study was the validation phase. Another 97 critically ill patients were enrolled and were treated with RCA-CVVH using the new version of the calcium supplementation protocol. FINDINGS:The loss of calcium flux in the extracorporeal circuit and the increase in citrate-calcium complexes in vivo were the main determinants of the required calcium supplementation. In the CVVH mode, the rate of calcium infusion had to be reduced after systemic citrate level reached a steady state. With the aid of mathematical models, systemic calcium levels could be stably maintained in the normal range, and the frequencies of calcium monitoring were reduced. DISCUSSION:Calcium supplementation during RCA-CVVH undergoes two phases. We propose mathematical models to quantify the need for calcium supplementation, which enable individualization of the RCA prescription and simplify the management of RCA in the CVVH mode.
10.1111/hdi.12715
Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation.
Yu Wenyan,Zhuang Feng,Ma Shuai,Fan Qichen,Zhu Mingli,Ding Feng
Nephron
BACKGROUND:It has been confirmed that regional citrate anticoagulation (RCA) plays an effective role in extracorporeal anticoagulation. The current trial-and-error calcium supplementation approach, with intensive monitoring of calcium levels, restricts the widespread use of RCA. Therefore, this study aimed to optimize the calcium supplementation approach for RCA. METHODS:Patients requiring RCA treatment for various reasons were included. Citrate was infused into the arterial port, and the ionized calcium levels in the extracorporeal circulation tubes and body were monitored to maintain them within the target range. Linear regression equations between the clearance of non-protein bound calcium (n-Ca) and prescribed effluent rate were determined; the ratio of the n-Ca concentration to total calcium concentration (fa) after the infusion of citrate was also calculated. Then, we estimated a simplified calcium supplementation approach. RESULTS:Positive correlations were found between the clearance of n-Ca and effluent rate both during continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemofiltration (CVVH; R2: 0.66 and 0.65, respectively, p < 0.01). The fa values at the pre-filter point and after infusion of citrate were constants, but the values differed from CVVHD to CVVH. For CVVHD, fa was 0.93, and for CVVH, fa was 0.80. Using the extracorporeal removal characteristics of n-Ca, the amount of extracorporeally removed calcium per mmol per hour can be quantified with a simplified equation. CONCLUSION:The optimized calcium supplementation approach could provide a more precise and practical method to estimate the amount of extracorporeal calcium removal with regard to different modalities and dosages of RCA.
10.1159/000494693
Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins.
Shi Yuanyuan,Tian Huajun,Wang Yifeng,Shen Yue,Zhu Qiuyu,Ding Feng
Blood purification
BACKGROUND AND OBJECTIVES:While trying to optimize the dialysis clearances of protein-bound uremic toxins (PBUTs), their percentage protein binding (% PB) is an important parameter. We evaluated the effects of ionic strength, pH change and chemical displacers on the dissociation of PBUTs from albumin in vitro. METHODS:PBUTs, such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresylsulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA), were spiked with human serum albumin (HSA) solution prepared with different Nacl concentrations and pH values or in the presence of a series of chemical displacers. Ultrafiltration was performed to separate the free and bound fractions, and the % PB of each PBUT was calculated. RESULTS:For all 4 compounds, their % PB decreased with increasing ionic strength, while only slight changes occurred when the pH of the test solution increased from pH 6.0 to pH 8.5; PCS, IS and 3-IAA were relatively easily dissociated from albumin by drug displacement, while CMPF was released from HSA by all studied drugs with difficulty; the PB % for CMPF, PCS, IS and 3-IAA decreased most remarkably in the presence of free fatty acids, such as oleic acid (41.73% for CMPF, 29.9% for PCS, 23.22% for IS, and 20.34% for 3-IAA) and linoleic acid (43.12% for CMPF, 16.65% for PCS, 29.99% for IS, and 16.29% for 3-IAA). CONCLUSION:The protein binding of PBUTs can be decreased by higher ionic strength, increased pH and the presence of some chemical displacers, including free fatty acids. Effective dialytic removal of PBUTs may be achieved by applying these methods jointly to blood-purification techniques.
10.1159/000495343
Increasing the removal of protein-bound uremic toxins by liposome-supported hemodialysis.
Shi Yuanyuan,Wang Yifeng,Ma Shuai,Liu Tingyan,Tian Huajun,Zhu Qiuyu,Wang Wenji,Li Yulin,Ding Feng
Artificial organs
Protein-bound uremic toxins (PBUTs) accumulate at high plasma levels and cause various deleterious effects in end-stage renal disease patients because their removal by conventional hemodialysis is severely limited by their low free-fraction levels in plasma. Here, we assessed the extent to which solute removal can be increased by adding liposomes to the dialysate. The uptake of liposomes by direct incubation in vitro showed an obvious dose-response relationship for p-cresyl sulfate (PCS) and indoxyl sulfate (IS) but not for hippuric acid (HA). The percent removal of both PCS and IS but not of HA was gradually increased with the increased concentration of liposomes in a rapid equilibrium dialysis setup. In vitro closed circulation showed that adding liposomes to the dialysate markedly increased the dialysances of PBUTs without greatly altering that of urea and creatinine. In vivo experiments in uremic rats demonstrated that adding liposomes to the dialysate resulted in higher reduction ratios (RRs) and more total solute removal (TSR) for several PBUTs compared to the conventional dialysate, which was approximately similar to the addition of bovine serum albumin to the dialysate. These findings highlight that as an adjunct to conventional hemodialysis, addition of liposomes to the dialysate could significantly improve the removal of protein-bound uremic solutes without greatly altering the removal of small, water-soluble solutes.
10.1111/aor.13383
Development of liposome as a novel adsorbent for artificial liver support system in liver failure.
Shen Yue,Wang Yifeng,Shi Yuanyuan,Tian Huajun,Zhu Qiuyu,Ding Feng
Journal of liposome research
Artificial liver support systems (ALSS), represented by albumin dialysis, are designed to replace the liver detoxification function and to serve as supportive therapy until liver transplantation or liver regeneration. We introduce liposome, which is majorly formed by soybean lecithin as the adsorbent nanomaterial in dialysate for the removal of protein-bound and liver failure-related solutes. The binding rate was detected by ultrafiltration column. and dialysis was performed in a recirculation system. Unconjugated bilirubin (52.83-99.87%) and bile salts (50.54-94.75%) were bound by liposomes (5-80 g/L) in a dose-response relationship. The i haemodialysis model showed that the concentration of unconjugated bilirubin (45.64 ± 0.90 μmol/L 54.47 ± 3.48 μmol/L, 0.05) and bile salts (153.75 ± 7.72 μmol/L 180.72 ± 7.95 μmol/L, 0.05) were significantly decreased in the liposome dialysis group than in the phosphate buffer saline group. The haemodialysis model showed that 40 g/L liposome-containing dialysate led to a significant higher reduction ratio in total bilirubin (6.56 ± 5.72% -1.86 ± 5.99%, < 0.05) and more total bile acids (7.63 ± 5.27 μmol 2.13 ± 2.32 μmol, < 0.05) extracted in the dialysate in comparison with the conventional dialysate. In conclusion, the liposome-added dialysate proved to impose good extraction effects on the unconjugated bilirubin and bile salts. These findings indicate that conventional dialysate supported by this nanomaterial can markedly improve the removal of protein-bound and liver failure-related solutes, thus suggesting a novel and promising liver dialysis system.
10.1080/08982104.2019.1630644
Linoleic acid-modified liposomes for the removal of protein-bound toxins: An in vitro study.
The International journal of artificial organs
INTRODUCTION:Protein-bound uremic toxins (PBUTs) and liver failure-related cholestatic solutes are associated with adverse outcomes in patients with chronic kidney disease (CKD) and liver failure, respectively, and are not easily removed by traditional dialysis therapies. We constructed linoleic acid-modified liposomes (LA-liposomes) as indirect adsorbent in the dialysate, and evaluated their effects on the clearance of the representative PBUTs and cholestatic solutes. METHODS:The LA-liposomes were prepared by the thin-film hydration method. The binding rates of liposomes and protein-bound solutes were detected by the ultrafiltration column. The in vitro dialysis experiments were performed using both non-current and current devices to assay the clearing efficiency of the dialysate supported by LA-liposomes. RESULTS:The LA-liposomes exhibited good binding properties to the PBUTs, bilirubin and bile acids. The LA-liposome dialysate showed higher solute reduction rates of the representative PBUTs and cholestatic solutes than the traditional dialysate or dialysate supported by the unmodified plain liposomes. Also, albumin binding of the PBUTs was significantly inhibited by the addition of linoleic acid (LA), and the removal efficiency of PBUTs was greatly enhanced by the combination of indirect adsorbent LA-liposomes and LA as the competitive displacer. CONCLUSION:LA-liposomes were efficient in the clearance of the representative PBUTs and liver failure-related solutes. Moreover, the combination of indirect adsorbent LA-liposomes and competitive displacer suggested a potential application for the extremely highly-bound solutes.
10.1177/0391398820968837
Improving the clearance of protein-bound uremic toxins using cationic liposomes as an adsorbent in dialysate.
Shen Yue,Wang Yifeng,Shi Yuanyuan,Bi Xiao,Xu Jingyi,Zhu Qiuyu,Ding Feng
Colloids and surfaces. B, Biointerfaces
Anionic and protein-bound uremic toxins, represented by indoxyl sulfate (IS), may be associated with cardiovascular outcomes and the progression of chronic kidney disease in cases of injured kidney function and are not easily cleared by traditional dialysis therapy. We fabricated cationic liposomes that were modified with polyethyleneimine (PEI), octadecylamine (Oct), and hexadecyl trimethyl ammonium bromide (CTAB), and evaluated the effects on the clearance of the representative protein-bound uremic toxins (PBUTs). The binding rate was obtained by ultrafiltration and in vitro dialysis was performed in a Rapid Equilibrium Dialysis (RED) device to assay the clearing efficiency of the dialysate supported by three types of cationic liposomes. The cationic liposomes showed a higher binding rate with IS (1.24-1.38 fold higher) and p-cresol (1.07-1.09 fold higher) than in the unmodified plain liposomes. The dialysate supported by cationic liposomes also exhibited better clearing efficiency for IS (PEI-20: 57.65 ± 1.74 %; Oct-5: 62.80 ± 0.69 %; CTAB-10: 66.54 ± 0.91 %; p < 0.05) and p-cresol (PEI-20: 67.05 ± 3.09 %; Oct-5: 79.26 ± 0.43 %; CTAB-5: 68.45 ± 1.72 %; p < 0.05) than for phosphate buffer saline (IS: 29.70 ± 2.38 %; p-cresol: 33.59 ± 3.44 %) or dialysate supported by bovine serum albumin (IS: 50.00 ± 4.01 %; p-cresol: 53.06 ± 0.97 %). In conclusion, cationic liposomes are efficient in the clearance of anionic PBUTs, and these modified liposomes suggest a potential application in blood purification.
10.1016/j.colsurfb.2019.110725
The possibility of using effluent ionized calcium to assess regional citrate anticoagulation in continuous renal replacement therapy.
The International journal of artificial organs
AIM:This study aimed to investigate whether effluent ionized calcium was an appropriate indicator to assess anticoagulant effect in continuous renal replacement therapy with regional citrate anticoagulation instead of post-filter ionized calcium. METHODS:In total, 48 paired samples of effluent fluid and post-filter blood were obtained from critically ill patients who required continuous renal replacement therapy. All samples were taken for ionized calcium measurements and were assessed by point-of-care analyzer. Correlations and agreements between two methods were performed by Pearson linear analysis and Bland-Altman analysis accordingly. RESULTS:The mean post-filter ionized calcium was 0.42 ± 0.12 mmol/L, and mean ionized calcium level of effluent fluid was 0.39 ± 0.11 mmol/L. The ionized calcium level of effluent fluid was significantly correlated with post-filter ionized calcium in all continuous renal replacement therapy patients. Bland-Altman analysis showed that the mean difference of ionized calcium between two sampling sites in all continuous renal replacement therapy patients was -0.02 mmol/L with 95% confidence interval ranging from -0.09 to 0.04 mmol/L. The significant correlations and agreements were also demonstrated in continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, and continuous veno-venous hemodiafiltration modalities separately. CONCLUSION:The effluent ionized calcium could be a considerable substitute for post-filter ionized calcium to monitor the validity of regional citrate anticoagulation in continuous renal replacement therapy with less blood loss.
10.1177/0391398819894595
Removal of Protein-Bound Uremic Toxins by Liposome-Supported Peritoneal Dialysis.
Shi Yuanyuan,Tian Huajun,Wang Yifeng,Shen Yue,Zhu Qiuyu,Ding Feng
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Protein-bound uremic toxins (PBUTs) are poorly cleared by peritoneal dialysis (PD). This study aimed to enhance PBUT removal in PD by adding a binder to the peritoneal dialysate and to evaluate the feasibility and efficacy of liposome-supported PD (LSPD) to increase the removal of PBUTs compared with albumin PD.Removal of p-cresyl sulfate (PCS), indoxyl sulfate (IS), and indole-3-acetic acid (3-IAA) was first evaluated in an PD model using artificial plasma preloaded with test solutes. Male Sprague-Dawley rats ( = 24) were then subjected to 5/6 nephrectomy and fed for 16 weeks to establish end-stage renal failure, after which they were treated with either conventional glucose-based PD, albumin-based PD, or liposome-based PD. Removal of PBUTs and small water-soluble solutes was determined during a 6-hour PD dwell.In vitro experiments showed that adding albumin as a toxin binder to the dialysate markedly increased the removal of PCS, IS, and 3-IAA compared with the control. The uptake capacity of liposomes was comparable with that of albumin for PCS and 3-IAA, though slightly inferior for IS. PD in uremic rats demonstrated that LSPD resulted in higher intraperitoneal concentrations and more total mass removal for PBUTs than the conventional glucose-based PD, which was comparable with albumin PD.Supplementing conventional glucose-based PD solutions with a binder could efficiently increase the removal of PBUTs. This preliminary study suggested that LSPD may be a promising alternative to albumin PD for increasing PBUT removal in the development of next-generation PD solutions for PD patients.
10.3747/pdi.2018.00229
Protective effect of COMP-angiopoietin-1 on peritoneal vascular permeability and peritoneal transport function in uremic peritoneal dialysis rats.
Shi Yuanyuan,Xiong Yifan,Lei Yutian,Li Zhenyuan,Yan Hao,Yuan Jiangzi,Ding Feng,Fang Wei
American journal of translational research
The angiopoietin-1 (Ang-1)/Tie-2 signaling pathway plays a crucial role in the maintenance of vascular stabilization and permeability. In this study, we evaluated the protective effect of a designed Ang-1 variant (COMP-Ang-1) on peritoneal vascular permeability and peritoneal transport function in a uremic peritoneal dialysis (PD) model. Compared to the sham controls, uremic rats were characterized by decreased pericyte coverage and downregulated endothelial junction expression. The permeability of the peritoneal vasculature to FITC-BSA and FITC-dextran in uremic rats was also higher than that in the sham controls, as well as increased levels of proinflammatory adhesion molecules and cytokines, increased D/P and decreased ultrafiltration. Such changes were more marked in uremia+PD rats after exposure to glucose-based peritoneal dialysis fluid (PDF) for 4 weeks. Peritoneal Ang-1 protein expression and Tie-2 phosphorylation were significantly lower in uremic rats than in control rats and were further significantly reduced in uremia+PD rats. After COMP-Ang-1 administration, phosphorylation of the Tie-2 receptor was significantly increased. Treatment with COMP-Ang-1 also significantly enhanced pericyte coverage, upregulated endothelial junction protein expression and inhibited leakage of FITC-BSA and FITC-dextran from the peritoneal vasculature induced during PD therapy; these changes were accompanied by reduced peritoneal tissue levels of proinflammatory adhesion molecules and cytokines, decreased D/P and increased ultrafiltration. These findings suggest that COMP-Ang-1 may exert a protective effect against glucose-based PDF-induced peritoneal vascular permeability and inflammation, at least in part, by enhancing pericyte coverage and endothelial junction protein expression, which subsequently significantly improves peritoneal transport function.
Improved dialytic removal of protein-bound uremic toxins by intravenous lipid emulsion in chronic kidney disease rats.
Shi Yuanyuan,Zhang Yumei,Tian Huajun,Wang Yifeng,Shen Yue,Zhu Qiuyu,Ding Feng
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND:Protein-bound uremic toxins (PBUTs) have received extensive attention, as their accumulation leads to pleiotropic toxic biological effects, while the removal of these solutes by conventional dialysis therapies is severely hampered. This study aimed to examine whether increased removal of PBUTs could be achieved with intravenous lipid emulsion (ILE). METHODS:PBUTs such as 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were spiked with human serum albumin (HSA) solution and the inhibitory effects of free fatty acid (FFA) on the binding of CMPF, PCS and IS to HSA were examined separately in vitro by ultrafiltration. In vitro dialysis of albumin solution was then performed to investigate the effects of fatty acid (FAs) mixtures infusion on the fractional removal of PBUTs. Finally, the inhibitory effect of FFA on the binding of PBUTs to albumin was examined in uremic rats, and blood purification therapy was conducted to calculate the reduction ratio (RR) and the total solute removal (TSR) of solutes. RESULTS:The percentage protein binding of CMPF, PCS and IS decreased significantly with increasing FFAs concentrations, and the inhibitory effect was more remarkable with the addition of oleic acid or linoleic acid than that of eicosapentaenoic acid and docosahexaenoic acid. In vitro infusion of FAs increased the fractional removal of CMPF to 14.40 ± 2.38%. PCS, IS and indole-3-acetic acid removal increased from 8.00 ± 2.43%, 11.68 ± 1.54% and 15.38 ± 3.97%, respectively, at baseline to 28.21 ± 5.99%, 35.42 ± 5.27% and 40.18 ± 5.05%, respectively, when FAs were present. In vivo, rat serum concentrations of free PBUTs were significantly higher in the ILE group than in the control group, and administration of ILE resulted in higher RRs and more TSR for PBUTs after 3 h of hemodialysis (HD) therapy compared with the control group. CONCLUSIONS:Administration of ILE effectively increased the dialytic removal of PBUTs. This method could be applied to current HD therapy.
10.1093/ndt/gfz079
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4 T Cell Polarization.
Stem cells international
PURPOSE:Recent evidence has shown that CD4 T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4 T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4 T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4 T cells in vitro. MATERIALS AND METHODS:We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4 T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4 T cells by enzyme-linked immunosorbent assay (ELISA). RESULTS:Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3 cell infiltration, with a significantly decreased IL17ACD4 T cell/CD4 T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4 T cells were cocultured with PMSCs, CD4IL17A cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF- and IL-10 was significantly increased ( < 0.05), while the secretion of IFN-, IL-17, and IL-6 was significantly decreased ( < 0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3/IL-17 cell infiltration was increased in the kidneys of UUO model animals on day 7. CONCLUSIONS:PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4 T cells and macrophages, inhibiting the inflammatory factors IFN- and IL-17, and upregulating the expression of the anti-inflammatory factors TGF- and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.
10.1155/2020/2685820
Interleukin-27 Ameliorates Renal Ischemia-Reperfusion Injury through Signal Transducers and Activators of Transcription 3 Signaling Pathway.
Zhou Peihui,Deng Bo,Wu Ming,Ding Feng,Wang Li
Kidney & blood pressure research
BACKGROUND:Acute kidney injury (AKI) is a clinical syndrome characterized by significant morbidity and a high death rate. Interleukin (IL)-27 is a newly described member of the IL-6/IL-12 heterodimeric cytokine family and displays anti-inflammatory and antiapoptotic properties. OBJECTIVES:To determine the effect and mechanism of IL-27 in AKI. METHOD:We used a mouse model of renal ischemia/reperfusion (I/R) injury to investigate whether IL-27 has a therapeutic potential for the treatment of AKI. For the IL-27 administration group, IL-27 protein was injected 1 h before ischemia. Human proximal tubular epithelial cells were exposed to ischemia for 2 h and followed by 2 h of reperfusion (I2h+R2h treatment) used as an in vitro model to investigate the effect of IL-27. RESULTS:Two IL-27 subunits, Epstein-Barr virus gene 3 and p28, were upregulated in kidneys 24 h after I/R. Renal expression of IL-27 receptor subunits (gp130 and WSX-1) was also increased. Treatment with IL-27 reduced structural/functional damages, ameliorated renal inflammation, inhibited the cleaved caspase-3 expression, upregulated antiapoptotic protein Bcl-2 and downregulated proapoptotic protein Bax in the kidneys of mice subjected to I/R. Meanwhile, the level of IL-27 receptor on renal tubular epithelial cells was increased after I2h+R2h treatment, and IL-27 administration suppressed I2h+R2h-induced epithelial cell apoptosis. Furthermore, IL-27 treatment led to activation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro, and IL-27-mediated protection against I2h+R2h injury was abolished by STAT3 inhibition. CONCLUSIONS:IL-27 protects against renal I/R injury by activating STAT3, suggesting that IL-27 may represent a novel strategy for the treatment of AKI.
10.1159/000503923
Can Serum Nutritional Related Biomarkers Predict Mortality Of Critically Ill Older Patients With Acute Kidney Injury?
Clinical interventions in aging
BACKGROUND:Critically ill older patients with acute kidney injury (AKI), also referred to as acute renal failure, are associated with high in-hospital mortalities. Preexisting malnutrition is highly prevalent among AKI patients and increases in-hospital mortality rate. This study is to evaluate the predictive power of some serum nutritional related biomarkers predicting the 90 days in-hospital mortality of critically ill older patients with AKI. METHODS:A prospective, observational study was conducted in a university teaching hospital. One hundred and five critically ill older patients with AKI aged 60-95 were enrolled and were divided into survival group (n=44) and non-survival group (n=61) in the light of their final outcomes. Receiver operating characteristic analyses (ROC) were performed to calculate the area under ROC curve (AUC). Sensitivity and specificity of in-hospital mortality prediction were calculated. RESULTS:Significant differences were found between the survival group and non-survival group of critically ill older patients with AKI. AUC of low density lipoprotein (LDL) and albumin were 0.686 and 0.595, respectively. The asymptotic 95% confidence intervals of LDL and albumin were 0.524-0.820 and 0.488-0.696, respectively. Sensitivity of the 90 days in-hospital mortality prediction of LDL and albumin were 68.71% and 69.09%, respectively. Specificity of 90 days in-hospital mortality prediction of LDL and albumin were 69.23% and 50.0%, respectively. CONCLUSION:LDL and albumin did not have sufficient power to predict the 90 days in-hospital mortality of critically ill older patients with AKI. Further research on the association between malnutrition and poor prognosis of critically ill older patients with AKI is needed in the future. ClinicalTrials.gov identifier: NCT00953992.
10.2147/CIA.S218973
Investigate predictive capacity of in-hospital mortality of four severity score systems on critically ill patients with acute kidney injury.
Gong Yu,Ding Feng,Zhang Fen,Gu Yong
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
Although significant improvements have been achieved in the renal replacement therapy of acute kidney injury (AKI), the mortality of patients with AKI remains high. The aim of this study is to prospectively investigate the capacity of Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II), Sepsis-related Organ Failure Assessment (SOFA) and Acute Tubular Necrosis Individual Severity Index (ATN-ISI) to predict in-hospital mortality of critically ill patients with AKI. A prospective observational study was conducted in a university teaching hospital. 189 consecutive critically ill patients with AKI were selected according Risk, Injury, Failure, Loss, or End-stage kidney disease criteria. APACHE II, SAPS II, SOFA and ATN-ISI counts were obtained within the first 24 hours following admission. Receiver operating characteristic analyses (ROCs) were applied. Area under the ROC curve (AUC) was calculated. Sensitivity and specificity of in-hospital mortality prediction were calculated. In this study, the in-hospital mortality of critically ill patients with AKI was 37.04% (70/189). AUC of APACHE II, SAPS II, SOFA and ATN-ISI was 0.903 (95% CI 0.856 to 0.950), 0.893 (95% CI 0.847 to 0.940), 0.908 (95% CI 0.866 to 0.950) and 0.889 (95% CI 0.841 to 0.937) and sensitivity was 90.76%, 89.92%, 90.76% and 89.08% and specificity was 77.14%, 70.00%, 71.43% and 71.43%, respectively. In this study, it was found APACHE II, SAPS II, SOFA and ATN-ISI are reliable in-hospital mortality predictors of critically ill patients with AKI. Trial registration number: NCT00953992.
10.1136/jim-2019-001003
Bisphenol A analogs in patients with chronic kidney disease and dialysis therapy.
Shen Yue,Liu Tingyan,Shi Yuanyuan,Zhuang Feng,Lu Jianxin,Zhu Qiuyu,Ding Feng
Ecotoxicology and environmental safety
Bisphenol A (BPA) accumulates in patients with chronic kidney disease (CKD), and hemodialysis filters may contribute to bisphenol burden in patients on hemodialysis (HD). The serum levels of BPA and three BPA analogs, namely, bisphenol B (BPB), bisphenol S (BPS), and bisphenol F (BPF), in 58 patients with CKD, 66 patients on dialysis therapy and 30 healthy control were investigated. The content of four bisphenols (BPs) was also examined in three types of dialysis filters, followed by an in vitro elution experiment to test the release of BPs from the dialysis filters. The serum levels of BPA (r = -0.746, p < 0.05) and BPS (r = -0.433, p < 0.05) in 58 CKD patients and 30 healthy control were correlated with the decrease in estimated glomerular filtration rate. The serum levels of BPs in the HD patients were higher than those in the peritoneal dialysis patients (p < 0.05). In the in vitro study on the BP contents in dialysis filters, BPA was the main form of the BPs in the polysulfone membrane (20.86 ± 1.18 ng/mg) and in the polyamide membrane (18.70 ± 2.88 ng/mg), and a modicum of BPS (0.01 ± 0.01 ng/mg) was detected in the polyethersulfone membrane. The results of the elution experiment were in accordance with the results of BPs content in the dialysis filters. Insufficient renal function may lead to BPs accumulation in patients with CKD, and BPs in dialysis products may cause BPs burden in patients on HD.
10.1016/j.ecoenv.2019.109684
Therapeutic Approaches in Mitochondrial Dysfunction, Inflammation, and Autophagy in Uremic Cachexia: Role of Aerobic Exercise.
Zhang Yumei,Liu Yuqing,Bi Xiao,Hu Chun,Ding Feng,Ding Wei
Mediators of inflammation
Chronic kidney disease (CKD) causes several systemic changes, including muscular homeostasis, and eventually results in muscle atrophy. CKD-induced muscle atrophy is highly prevalent, and exercise is well known to enhance muscle function in these cases, although the exact mechanism remains unclear. Here, we aim to assess whether the protective effect of aerobic exercise in 5/6 nephrectomized (CKD) mice is associated with mitochondrial dysfunction, autophagy, or inflammation. C57BL/6J mice were randomly allocated into 3 different experimental groups: Sham, CKD, and CKD+aerobic exercise (CKD+AE). Renal function was assessed via serum creatinine and urea levels, and histological PAS and Masson staining were performed. Muscle wasting was determined based on grip strength, cross-sectional area (CSA), and MyHC protein expression. We also measured mitochondrial dysfunction in mice by assessing mtDNA, ROS, ATP production, and mitochondrial configuration. Autophagy was determined via assessments for Atg7, LC3, and SQSTM1 on western blotting. Inflammation was identified via proinflammatory cytokines and NLRP3 inflammasome components using real-time PCR and western blotting. We found that CKD mice exhibited higher BUN and creatinine levels and more severe glomerulosclerosis in the glomeruli and renal tubulointerstitial fibrosis, relative to the Sham group; all these effects were relieved by aerobic exercise. Moreover, grip strength, CSA, and MyHC protein expression were improved after 8 weeks of aerobic exercise. Furthermore, aerobic exercise significantly decreased MDA levels, increased SOD2 activity and ATP production, and improved mitochondrial configuration, relative to the CKD group. In addition, aerobic exercise downregulated the overexpression of proinflammatory cytokines and NLRP3 inflammasome components and balanced the mitochondrial biogenesis and autophagy-lysosomal system. Thus, we observed that aerobic exercise may ameliorate CKD-induced muscle wasting by improving mitochondrial dysfunction, inflammation, and autophagy-lysosomal system in uremic cachexia.
10.1155/2019/2789014
Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation.
Xu Yao,Wang Jingjing,Xu Wangjie,Ding Feng,Ding Wei
American journal of physiology. Renal physiology
Accumulating evidence demonstrates that mitochondrial dysfunction and inflammasome activation play a critical role in the pathogenesis of renal tubular injury through the production of reactive oxygen species and cytokines. Prohibitin 2 (PHB2) is a newly identified intracellular receptor of mitophagy (a type of autophagy) that mediates selective removal of damaged mitochondria, and it could possibly play a renoprotective role in kidney disease. In this study, we confirmed that autophagy is activated in tubular epithelial cells treated with angiotensin II and that inhibition of autophagy results in tubular cell injury. Strikingly, PHB2 knockdown reduced the level of mitophagy and augmented cell death, while overexpression of PHB2 provided protection against pyrin domain-containing protein 3 (NLRP3)-induced inflammatory pathways through amelioration of mitochondrial dysfunction. Our research is the first to experimentally demonstrate the role of PHB2 in renal proximal tubular cells and thereby to provide a better understanding of how autophagy modulates inflammation in renal tubules. These data highlight PHB2 as a therapeutic target in the future treatment of CKD.
10.1152/ajprenal.00420.2018
The leukotriene B-leukotriene B receptor axis promotes cisplatin-induced acute kidney injury by modulating neutrophil recruitment.
Deng Bo,Lin Yuli,Ma Shuai,Zheng Yin,Yang Xuguang,Li Bingji,Yu Wenyan,Xu Qingqing,Liu Tingyan,Hao Chuanming,He Rui,Ding Feng
Kidney international
Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B (LTB), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB-BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB synthesis and BLT1 expression in the kidney after cisplatin administration. Cisplatin was found to directly upregulate gene expression of leukotriene A hydrolase and stimulate LTB production in renal tubular epithelial cells. Reduced kidney structural/functional damage, inflammation, and apoptosis were observed in BLT1 mice, as well as in wild-type mice treated with the LTA4H inhibitor SC-57461A and the BLT1 antagonist U-75302. Neutrophils were likely the target of this pathway, as BLT1 absence induced a significant decrease in infiltrating neutrophils in the kidney. Adoptive transfer of neutrophils from wild-type mice restored kidney injury in BLT1 mice following cisplatin challenge. Thus, the LTB-BLT1 axis contributes to cisplatin-induced AKI by mediating kidney recruitment of neutrophils, which induce inflammation and apoptosis in the kidney. Hence, the LTB-BLT1 axis could be a potential therapeutic target in cisplatin-induced AKI.
10.1016/j.kint.2017.01.009
Plasmacytoid dendritic cells promote acute kidney injury by producing interferon-α.
Deng Bo,Lin Yuli,Chen Yusheng,Ma Shuai,Cai Qian,Wang Wenji,Li Bingji,Liu Tingyan,Zhou Peihui,He Rui,Ding Feng
Cellular & molecular immunology
Acute kidney injury (AKI) is a common clinical complication associated with high mortality in patients. Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis. Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in type I interferon (IFN) production. Here, we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α. Deletion of pDCs using DTR transgenic (Tg) mice suppressed cisplatin-induced AKI, accompanied by marked reductions in proinflammatory cytokine production, immune cell infiltration and apoptosis in the kidney. In contrast, adoptive transfer of pDCs during AKI exacerbated kidney damage. We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI, as IFN-α neutralization significantly attenuated kidney injury. Furthermore, IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells (TECs) in vitro. In addition, our data demonstrated that apoptotic TECs induced the activation of pDCs, which was inhibited in the presence of an apoptosis inhibitor. Furthermore, similar deleterious effects of pDCs were observed in an ischemia reperfusion (IR)-induced AKI model. Clinically, increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI. Taken together, the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.
10.1038/s41423-019-0343-9