Objective To investigate the incidence of left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients with different hydration statuses, and analyze the risk factors of LVH in PD patients. Methods PD patients in Renji Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled. Demographic data of patients were collected and biochemical parameters were measured. Hydration status index overhydration (OH) was measured by bioimpedance spectroscopy, and LVH was diagnosed by echocardiography. Logistic regression was used to analyze the risk factors of LVH. Results A total of 113 PD patients aged 58.98(48.89, 65.33) years with median PD duration 46.20(18.08, 72.75) months were enrolled in present study, among whom 60 patients (53.1%) had LVH. OH＞1.1 L was detected in 80 patients (70.8%), among whom 34 patients (42.5%) had subclinical overhydration (SCOH). LVH was however diagnosed in 33(71.7%) clinical overhydrated (COH) patients and 17(50.0%) SCOH patients (n=34). In the normal hydrated (OH≤1.1 L) patients (n=33), LVH was detected in 10 patients (30.3%). Multivariate logistic regression showed that high OH (OR=1.730, 95%CI 1.274-2.348, P＜0.001) and low hemoglobin (OR=0.965, 95%CI 0.940-0.991, P=0.008) were the independent risk factors of LVH. Conclusions LVH is common in PD patients, especially in overhydrated patients. High OH and low hemoglobin were the independent risk factors of LVH.

Objective To investigate the association of red cell distribution width (RDW) with all-cause and cardiovascular disease (CVD)-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods A retrospective analysis was performed on 207 patients who initiated CAPD for more than 3 months between July 2005 and March 2016 in the First Hospital Affiliated to Zhengzhou University. Baseline data on demographic, clinical and biochemical variables as well as comorbidities were obtained; medications and clinic outcomes were recorded. According to receiver operator characteristic curve (ROC) analysis, patients were divided into high RDW (RDW＞15.1%) and low RDW (RDW≤15.1%) groups. The data of two groups were compared and Spearman's correlation analysis was used to explore the association of RDW with clinical and biochemical parameters. Survival curves were calculated using Kaplan-Meier method. Cox regression model was employed to analyze risk factors of all-cause and CVD-related mortality. Results In this study, 207 CAPD patients were enrolled. The overall median survival time was 80 months. And the median survival time of high RDW group (68 patients) and low RDW group (139 patients) were 59 months and 96 months, respectively. There were statistical differences in diastole pressure, hemoglobin, hematocrit, serum albumin, intact parathyroid hormone (iPTH), eGFR, cholesterol, lipoprotein a, 4-hour dialysate-to-plasma ratio for creatinine (4hD/Pcr), total Ccr (P＜0.05, respectively); the two groups also varied in the proportion of chronic obstructive pulmonary disease, cardiovascular disease and hyperlipidemia, as well as in the use of iron supplements, angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ receptor blockers (ARB), and beta-receptor blockers (P＜0.05, respectively). Cardiovascular event was a leading cause of mortality. Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality compared with the low RDW group (P＜0.01). The 1-year, 3-year, and 5-year patient survivals of the high RDW and low RDW group were 87.97% vs 97.01%, 58.02% vs 81.53%, and 41.62% vs 67.96%, respectively, demonstrating significant differences (P=0.001). Multivariate Cox regression analysis showed that high RDW was independent risk factor for all-cause mortality (HR=1.212, 95%CI: 1.007-1.458, P=0.042) and CVD-related mortality (HR=1.697, 95%CI:1.030-2.795, P=0.038). Conclusion RDW is associated with mortality risks in CAPD patients and can be stratified as a valuable indicator for the risk of death.

Objective To evaluate the clinical significance of serum Klotho protein levels in the early diagnosis and prognosis of acute kidney injury (AKI) among adult patients in the intensive care units (ICU). Methods The study was prospective and observational. Blood samples and clinical data of AKI patients admitted to the ICU of the First Affiliated Hospital of Xinjiang Medical University between July 1 and August 31, 2016 were collected. ELISA was used for the detection of Klotho and NGAL. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to compare the predictive performance among Klotho, NGAL and serum creatinine, evaluating the sensitivity and specificity of Klotho on the diagnosis of AKI. The correlation between Klotho and prognosis of AKI was investigated by comparing serum Klotho levels and early AKI predictors. Results The patients were divided into AKI group of 52 cases and non-AKI group of 98 cases. The baseline serum Klotho level in AKI group was significantly lower than that in non-AKI group (P＜0.001). The AUC of Klotho predicting for AKI was 0.945(95% CI: 0.892-0.997) and the best cut off value was 1.76 μg/L(sensitivity 92%, specificity 94%). The predictive ability of Klotho was significantly higher than serum creatinine (Scr), and the sensitivity is higher than NGAL (sensitivity 87%, specificity 96%). Serum Klotho combined with Scr predicted better AKI (AUC=0.958, 95% CI: 0.915-1.000, sensitivity 96%, sensitivity 92%). The level of Klotho in patients with AKI was significantly different between the renal function recovery group and non-recovery group (P=0.047), while there was no significant difference between the two groups in the level of NGAL and Scr (P＞0.05). There was no significant correlation between the Klotho level at diagnosis of AKI and peak Scr, peak eGFR, Scr at discharge and eGFR at discharge (r=0.026, P=0.853; r=-0.127, P=0.368; r=0.243, P=0.082; r=-0.187, P=0.184). Conclusion Serum Klotho may be a potential biomarker for early diagnosis of AKI, but the association between serum klotho and the prognosis of AKI requires further study.

Objective To determine whether elevated circulating B-type natriuretic peptide(BNP) or N-terminal B-type natriuretic peptide precursor (NT-proBNP) could predict long-term risks of all-cause mortality, cardiovascular mortality or cardiovascular events among maintenance hemodialysis (MHD) patients. Method Data updated by December 2014 in Cochrane Library, Medline Database, Embase Database, CBMdisc and CEBM/CCD were searched. Related research about the relation of BNP or NT-proBNP and the prognosis of MHD patients were included, regardless of language or whether blind method was used. The data were extracted independently by two reviewers. The methodological quality of trails was assessed by recommended evaluation standard. Statistical analysis was performed with STATA 10.0. Results There were 874 papers found by our search strategy, among which 711 articles were in English and 163 articles were in Chinese. Nineteen papers were eligible according to the inclusion criterion and a total of 6185 cases were included. The Meta-analysis results showed that: (1) Elevated BNP or NT-proBNP was significantly related to increased all-cause mortality (HR: 2.64, 95% CI: 1.73-4.02); (2) Elevated BNP or NT-proBNP was associated with increased cardiovascular events (HR: 5.35-7.04, 95% CI: 2.23-22.33). Conclusion BNP or NT-proBNP is a promising prognostic tool to risk-stratify MHD patients.

Objective To investigate the effect of complement C3a on mouse podocytes phenotype transformation. Methods Purified C3a recombinant protein was used to stimulate mature mouse podocytes. The expression of the mature podocyte markers synaptopodin, podocin, nephrin, CD2-associated protein (CD2AP) and the mesenchymal cell markers fibroblast specific protein 1 (FSP-1), α-smooth muscle actin (α-SMA) were detected by RT-PCR, Western blotting, immunochemistry and immunofluorescence, respectively. Some podocytes were transfected with integrin-linked kinase (ILK) siRNA before the administration of C3a, the expression of nephrin and α-SMA were accessed by Western blotting, and the expression of Snail and α-actinin 4 were accessed by Western blotting and immunochemical method. The migration ability of podocytes was observed by scratch test. Results Immunocytochemistry and immunofluorescence analysis showed that synaptopodin, podocin, nephrin, CD2AP were highly expressed by mature mouse podocytes. The expression of these podocyte markers could be markedly inhibited after 24 h of C3a (0.1 μmol/L) treatment, and accompanied by the induction of mesenchymal markers FSP-1 and α-SMA. Compared with control group, the mRNA levels of synaptopodin, podocin, CD2AP and nephrin were significantly repressed by the administration of C3a in a dose-dependent manner, whereas the transcription of FSP-1 and α-SMA were remarkably up-regulated by C3a treatment (P＜0.05, respectively). Western blotting analysis also confirmed the decrease of synaptopodin, podocin, nephrin and CD2AP protein and the increase of FSP-1 and α-SMA protein were closely depend on the C3a concentration (P＜0.05, respectively). To further assess the downstream of C3a, some podocytes were transfected with ILK siRNA before the administration of C3a. Compared with C3a group, the protein levels of nephrin and α-SMA were significantly changed by the administration of ILK siRNA (P＜0.05, respectively). The expression of α-actinin 4 and Snail induced by C3a were inhibited by ILK knockdown (P＜0.05, respectively), accompanied by a decline of cell migration potency. Conclusion Complement fragment C3a can induce transformation of mouse podocytes to mesenchymal cells, and ILK signaling pathway is involved in this cell type transformation.

Objective To investigate the effects of angiotensinⅡ(AngⅡ) on the expression of ATP-binding cassette transporter A1(ABCA1) in AngⅡ-infused rat model and cultured human podocytes, and to explore the role of ABCA1 in AngⅡ-induced cholesterol accumulation of podocytes. Methods Twelve Wistar rats were randomly subjected to normal saline infusion, or AngⅡ infusion at 400 ng?kg-1?min-1 (via subcutaneous osmotic minipumps) for 8 weeks. The expression of glomerular ABCA1 was analyzed by Western blotting and real-time fluorescent quantitative PCR. In vitro, conditionally immortalized human podocytes were divided into normal group, AngⅡ group, AngⅡ+scrambled siRNA group, AngⅡ+ABCA1 siRNA group. The expression of podocyte ABCA1 was assessed by immunofluorescence, Western blotting and real-time fluorescent quantitative PCR. Oil Red O staining was used to observe the lipid droplets in podocytes and cholesterol efflux assay kit was used to measure the cholesterol efflux rate of podocytes. Fluorescein isothiocyanate (FITC)-conjugated phalloidin was used to observe the podocyte cytoskeleton. Results In vivo, compared with normal group, the protein and mRNA expression of glomerular ABCA1 in AngⅡ-infused rats were decreased (P＜0.05). In vitro, ABCA1 was distributed in the cytomembrane of podocytes, and compared with normal group, AngⅡtreatment down-regulated the expression of ABCA1 (P＜0.05). Increased lipid droplets, decreased cholesterol efflux and cytoskeletal rearrangement were observed in AngⅡ-treated podocytes. When compared to AngⅡ group, podocytes stimulated by AngⅡand then transfected with ABCA1 siRNA had lower expression level of ABCA1 mRNA and protein (all P＜0.05). More lipid droplets and lower cholesterol efflux rate could be observed in AngⅡ+ABCA1 siRNA group (P＜0.05). Conclusion The reduced expression of ABCA1 may be involved in AngⅡ-induced cholesterol accumulation in podocytes.

Objective To investigate whether advanced glycation end products (AGEs) can induce the expression of Ros, JC-1 and its apoptosis-related proteins in glomerular mesangial cells under high glucose environment, induce apoptosis and injury of glomerular mesangial cells. Methods Rat glomerular mesangial cell line HBZY-1 was cultured in vitro. The cells were cultured with different concentrations of AGEs for 0, 12, 24 and 48 hours respectively. MTT assay was used to observe the cell proliferation ability. After the optimal time and concentration of AGEs were selected, the caspase enzyme inhibitor Z-VAD-fmk and reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) were cultured and the apoptosis rate was detected by cell death detection apoptosis ELISA plus and Annexin V-FITC/PI kit. JC-1 staining was used to detect the changes of mitochondrial membrane potential (MMP). Cell ROX deep red flow cytometry was used to detect the total ROS level. The expression of anti-apoptotic protein Bcl-2, pro-apoptotic protein BAX, caspase-9, caspase-3 and poly ADP-ribose polymerase (PARP)-activated fragments was detected by Western blotting. Results AGEs could decrease the activity of glomerular mesangial cells in a time and concentration-dependent manner, and induce cell death. The percentage of apoptotic cells in glomerular mesangial cells was significantly increased after treatment with 250 mg/L AGEs for 24 h (P＜0.01), and Z-VAD-fmk could significantly alleviate AGEs-induced glomerular mesangial cell apoptosis (P＜0.01). Compared with the control group, AGEs increased the level of intracellular reactive oxygen species and decreased MMP in a time-dependent manner, and the two time points that AGEs significantly caused the change were 1 h and 2 h (all P＜0.01). AGEs also reduced the expression of antiapoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP (all P＜0.01). Compared with AGEs group, NAC could significantly stabilize MMP (P＜0.01), increase Bcl-2 expression (P＜0.01), and decrease the expression of BAX, cleaved caspase-9, cleaved caspase-3 and cleaved PARP (all P＜0.01). Conclusion AGEs induce mitochondrial pathway apoptosis in glomerular mesangial cells by increasing intracellular ROS level and destroying MMP.

Objective To investigate the effect and the mechanism of epithelial-mesenchymal transition (EMT) in renal tubular cells induced by uric acid. Methods Normal rat kidney tubular cell line (NRK-52E) were exposed to different concentrations of uric acid (100, 200, 400, 600, 800 μmol/L UA) for 48 hours to induce EMT. Morphological changes of the NRK-52E cells were examined under an inverted phase contrast microscope. The protein expression of E-cadherin, α-SMA, p-Akt and Akt were detected by Western blotting. The distribution of E-cadherin and α-SMA were detected by immunofluorescence. NRK-52E cells were pretreated by different concentrations of LY294002(0, 2.5, 5, 10, 15 μmol/L), the inhibitor of PI3K/p-Akt signaling pathway, and then processed by uric acid (400 μmol/L) for 48 hours. Western blotting was used to detect the protein expression of p-Akt and Akt. NRK-52E cells were then divided into four groups: normal group (N), uric acid group (UA), LY294002 group (LY), uric acid with LY294002 group (UA+LY). The protein expression of E-cadherin and α-SMA were detected by Western blotting, the distribution of E-cadherin, α-SMA and p-Akt were detected by immunofluorescence. Results There was abundant cellular expression of E-cadherin in unstimulated renal tubular cells whereas its expression was significantly decreased in uric acid-stimulated cells (P＜0.05). In addition, uric acid induced de novo expression of α-SMA in contrast to almost negative staining in untreated cells (P＜0.05). p-Akt were obviously increased in high uric acid group (P＜0.05) and Akt changed not significantly (P＞0.05). NRK-52E cells transformed into elongated fibroblast-like cells from cuboidal clustered epithelial cells. These indicated that uric acid has induced EMT and activated PI3K/p-Akt signaling pathway in NRK-52E cells. However, the above effects of uric acid were abolished when p-Akt was blocked by the PI3K inhibitor (10, 15 μmol/L LY294002), indicated that LY294002 has reversed the trend of EMT. Conclusions High uric acid induces phenotypic transition of renal tubular cells probably via activating PI3K/Akt signaling pathway.