Objective   To provide guide for prevention and cure of peritonitis in peritoneal dialysis(PD) by comparing the causative organisms and clinical outcome of PD related peritonitis in younger and elderly patients in our center.  Methods    All patients who developed PD related peritonitis between January 2006 and December 2013 in Wuhan NO.1 hospital were included. According to their age, episodes were divided into younger patients group (＜65 years) and elderly patients group (≥65 years). The microbiology and clinical outcome of PD related peritonitis were compared, and the related risk factors of the treatment failure were analyzed.  Results    Three hundred and sixty - six episodes of peritonitis occurred in 258 patients during the study period. The overall rate of peritonitis was 1 episode in 76.8 patient-months. Elderly patients had higher incidence of peritonitis (1 episode every 56.4 months vs 1 episode every 88.7 months, P=0.001), higher incidence of fungus infection (9.6% vs 3.9%, P=0.026) and higher mortality ( 46.2% vs 14.0%, P=0.001) than that in younger patients. Cox regression analysis showed that longer duration of PD treatment and fungal peritonitis were both risk factors of the treatment failure.  Conclusion    Elderly patients had higher incidence of peritonitis, higher incidence of fungus infection and higher PD - related mortality than younger patients.

Objective   To prospectively evaluate the risk factors for the decline of residual renal function (RRF) in new peritoneal dialysis (PD) patients. Methods   A total of 84 new PD patients in our PD center were included in this study. Clinical comprehensive assessment were made, and regression models was established to analyze the relationship between the decline of RRF and clinical indicators, which included the rate of peritonitis, systolic pressure, diastolic pressure, urine volume, 24 h urinary protein, serum albumin, C-reactive protein(CRP), history of diabetes mellitus, and the use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) drugs, cardiac functional grading, sodium and water retention and biochemical indicators. The primary outcome was defined as two consecutive urine volume ≤100 ml/24 h. Results    The mean follow-up time was (11.7± 1.1) months, primary outcome occurred in 20 patients, accounting for 23.8%, and their average period progressed to the primary outcome was (10.5±2.0) months. The 20 patients had higher ultrafiltration volume [(551.6±328.2) ml vs（294.1±288.0) ml, P=0.001], higher systolic blood pressure [(145.2±16.5) mmHg vs (136.0±13.8) mmHg, P=0.016], worse cardiac functional grading [(1.7±0.8) vs (1.3±0.4), P=0.000], more serious water-sodium retention [(1.0±0.7) vs (0.6±0.5), P=0.012], higher peritonitis rates (35.0% vs 4.7% ,P=0.000), lower Kt/V [(1.7 ± 0.4) vs (2.0 ± 0.3), P=0.003], lower hemoglobin levels [(89.0±14.9) g/L vs (99.5±17.8) g/L, P=0.020], higher C - reactive protein levels [(19.4±34.4) mg/L vs(8.7±12.6) mg/L, P=0.017], higher Scr levels [(1 004.6±291.1) μmol/L vs (753.1± 254.3) μmol/L, P=0.000], lower serum calcium levels[(1.86±0.1) mmol/L vs (2.02±0.2) mmol/L, P=0.000], higher serum phosphorus [(2.1±0.6) mmol/L vs (1.6±0.4）mmol/L, P=0.001] and higher calcium phosphorus product [(3.8±1.1) mmol2/L2 vs (3.1±0.8) mmol2/L2, P=0.010] as compared with those of the patients without the primary outcome. Based on the results of multivariable Cox regression analysis, ultrafiltration volume, cardiac functional grading, peritonitis, Kt/V and serum phosphorus level contributed to the decline of RRF significantly. Conclusion   The higher Kt/V in PD patients plays a protective role, the higher ultrafiltration volume, the worse heart function, the more peritonitis rate and higher serum phosphorus predict more rapid declination of RRF.

Objective   To observe insulin resistance (IR) in non-diabetic peritoneal dialysis (PD) patients, and analyze its related factors.  Methods   The non-diabetic PD patients who had been on stable PD at least three months were eligible to enroll． The patients were measured for their height, weight, waist to hip ratio, fasting glucose, fasting insulin, lipids and other biochemical indicators, dialysis adequacy indicators in August 2012, and divided into two groups depended on median HOMA-IR in August 2012.  Results  A total of 56 patients were enrolled and divided into two groups according to median HOMA-IR, including high IR group (HOMA-IR≥1.79, n=29) and low IR group (HOMA-IR＜1.79, n=27). Compared to low IR group, high IR group were older [(57.9±14.2) years vs (48.7±14.5) years], had higher daily dialysate glucose load [(138.7±28.5) mmol/L vs (114.0±21.5) mmol/L], higher waist-to-hip ratio [(0.91±0.08) vs (0.86±0.07)], higher BMI [(23.0±3.0) kg/m² vs (21.2±3.1) kg/m²], higher triglycerides [(2.51±1.36) mmol/L vs (1.42±0.48) mmol/L], lower high-density lipoprotein cholesterol [(1.00±0.27) mmol/L vs (1.23±0.32) mmol/L], and lower Kt/V [(1.74±0.37) vs (2.08±0.56)]. Multivariate logistic regression showed that age (β =0.122, P=0.033), triglycerides (β = 1.798, P=0.030) and daily dialysate glucose load (β =0.094, P=0.031) associated with the degree of insulin resistance.  Conclusion  More dialysate glucose exposure is a risk factor of the occurrence of insulin resistance in non-diabetic patients with peritoneal dialysis.

Objective   To explore the value of endothelial dysfunction assessment in predicating major adverse cardiac and cerebrovascular events (MACCE) in peritoneal dialysis (PD) patients.  Methods   A prospective cohort study included 136 end stage renal disease (ESRD) patients from Jan 1, 2009 to Dec 31, 2011 was conducted. Endothelial function was assessed by flow- mediated dilation (FMD) of brachial artery. Kaplan-Meier method was used to estimate survival rate. The survival difference between the two groups was compared by the log-rank test. Multivariate Cox proportional hazards regression was used to determine the independent risk factors of MACCE.  Results   In the follow-up period, 18 patients in low FMD (FMD≤2.7%) group occurred MACCE, and 13 patients in high FMD (FMD＞2.7%) group occurred MACCE. Compared with high FMD group, MACCE-free survival rate in the low FMD group had a significantly decreased (χ²=4.190, P=0.041). Multivariate Cox proportional hazards regression analysis showed that higher level of total cholesterol, lower FMD, longer PD time and higher levels of hs-CRP were all independent predictors of MACCE.  Conclusion   Reduced brachial artery FMD is an independent risk factor of MACCE, and the application of FMD contributes to the risk stratification of cardiac and cerebrovascular disease in PD patients.

Objective   To find the key miRNA that relative to peritoneal fibrosis associated with peritoneal dialysis (PD) by microarray technology, and verify its expression in vitro and in vivo.  Methods   The peritoneal fibrosis mouse model associated with PD were established by intraperitoneal injection of lipopolysaccharide (LPS) + 4.25% peritoneal dialysate. The expression of miRNA was detected by microarray in peritoneal tissues. The expression of miRNA profiles between fibrotic and normal peritoneal tissues was compared. The differentially expressed miRNA (miR-200a) was validated by real-time PCR in lager sample size cohorts. The expressions of miR-200a were also detected in the epithelial-mesenchymal transition (EMT) process of human peritoneal mesothelium cells.  Results   In mice model of PD, peritoneal tissue was markedly thickened and with a massive extracellular matrix accumulation. In contrast with control, the expression level of epithelial marker E - cadherin was significantly decreased, α - SMA, Col - I and FN were remarkably increased (P ﹤ 0.05). By miRNA microarray analysis, miR - 200a was significantly down - regulated (3.31 folds change, P ﹤ 0.05) in fibrotic peritoneal tissues. The down-regulated expression level of miR-200a was also validated by real- time PCR in larger cohorts (P ﹤ 0.05). Then, the expression level of miR-200a was detected in the EMT process of human peritoneal mesothelium cells. During the process of TGF-β1 induced EMT, miR -200a was significantly down-regulated compared with the control (P﹤0.05).  Conclusions   Down- regulated expression of miR-200a was observed both during peritoneal fibrosis and TGF-β1 induced EMT in vivo and in vitro, suggesting that miR - 200a may be involved in the peritoneum fibrosis by regulating the target genes of EMT.

Objective    To investigate the role of microRNA-129-5p (miR-129-5p) in the regulation of epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) isolated from peritoneal dialysate effluents and TGF - β1 induced HPMCs line.  Methods    The isolated cells were cultured from peritoneal dialysate effluents overnight of 10 patients just started PD and 12 patients with PD over 6 months. Taqman PCR assay was used to determine the expression of miR-129-5p in the HPMCs. Moreover, the expression of miR-129-5p in HPMCs induced by 5 μg/L TGF-β1 for 0-72 h was also detected by Taqman PCR. HPMCs were pre-transfected with miR-129-5p precursor (pre-mir-129-5p) to overexpress miR-129-5p, then incubated with TGF-β1 for 48 h, and the expression of EMT associated gene and protein was detected by real-time PCR, Western blotting and immunofluorescence, respectively. Furthermore, the effect of TGF - β1 on the expression of Smad interacting protein-1 (SIP1) and the regulation of pre-miR-129-5p on the SIP1 expression also were investigated.  Results    MiR-129-5p expression significantly down-regulated in the HPMCs isolated from PD patients over 6 months than from PD start patients(P＜0.01). Similarly, TGF-β1 remarkably decreased miR - 129 - 5p in HPMCs lines on time - dependent manner (P＜0.01). Pre - mir - 129 - 5p dramatically restored the expression of epithelial marker E-cadherin, while inhibited the expression of Vimentin, a mesenchymal marker, in HPMCs induced by TGF-β1 (all P＜0.01). In addition, TGF-β1 increased SIP1 expression in HPMCs time dependently, while the high level of SIP1 protein was obviously repressed after transfected of pre-miR-129-5p (P＜0.01), but there was no obvious change of its mRNA expression.  Conclusion    MiR-129-5p modulates EMT formation of HPMCs in PD process, possibly by posttranscriptional inhibition of SIP1. Targeting miR - 129 - 5p/SIP1 may provide a new approach for the prevention and treatment of peritoneal fibrosis during PD.

Objective    To investigate cerebrovascular lesions on maintenance hemodialysis (MHD) patients, including types of cerebrovascular disease, and cognitive function changes.  Methods    A cross-sectional study was applied. A total of 270 MHD patients at hemodialysis center of Peking Union Medical College Hospital were screened, and finally 117 cases were enrolled. Demographic information, aboratory data, MRI and MRA data were collected and assessed. Cognitive function was evaluated with C - MMSE (Chinese mini mental test examination) and C - MoCA (Chinese montreal cognitive assessment). The related factors were selected by Spearman correlation analysis, multiple linear regression and logistic regression analysis.  Results    The patients’average age was (56.0± 12.5) years, average hemodialysis age was (73.5±60.8) months. Only 5.1% patients had clinical history of cerebral infarction or hemorrhage. Pre - hemodialysis blood pressure was (142.7/80.3±18.2/12.9) mmHg, Post-hemodialysis blood pressure was (130.2/79.1±23.4/14.9) mmHg. A total of 18.8% patients had intra-hemodialysis hypotension, spKt/V was (1.45±0.25). MR results showed that 12.0% patients had cerebral artery stenosis, 5.1% patients had cortical infarcts, 39.3% patients had lacunar infarcts, 47.0% patients had microbleeds, 7.7% patients had chronic hematoma, 52.1% patients had abnormal brain whiter matter lesions (WMLs). In cognitive function evaluation, 20.9% patients had abnormal C-MMSE scores, but 65.2% patients had abnormal C-MoCA results. Multiple linear regression showed age (b=0.059, P＜0.01), dialysis age (b=0.005, P＜0.05) were associated with WMLs in MHD patients. Intra-hemodialysis hypotension was an independent risk factor of lacunar infarcts (b=2.123, P＜0.01) and microbleeds (b=3.531, P＜0.01). Low serum albumin level was an independent risk factor of cognitive decline (b=0.314, P＜0.05). Logistic regression analysis showed pre - hemodialysis systolic blood pressure was an independent risk factor of cortical infarcts [OR=1.088, 95%CI (1.018-1.152), P＜ 0.05]. Gender, dialysis age and pre - dialysis serum TCO2 level were related with chronic hematoma.  Conclusions    WMLs is related with dialysis voltage. Lacunar infarcts and mirobleeds are related with intra - hemodialysis hypotension. Lacunar infarcts, WMLs and nutritional status are contributed to decline of cognition in MHD patients.

Objective    To investigate the quality of life (QOL) of maintenance hemodialysis （MHD）patients and its influencing factors.  Methods    A total of 257 MHD patients in our hospital were recruited in this study. Clinical data of the patients were collected, and the QOL was assessed by MOS 36 item short form health survey(SF-36). Nutritional status of patients was evaluated by modified quantitative subjective global assessment (MQSGA). Univariate analysis of variance，pearson correlation analysis and multiple linear stepwise regression analysis were performed to determine the effect of related factors on QOL scores.  Results    The scores of all scales of SF - 36 evaluation in MHD patients were relatively lower than that of general population as reported before. Their physiological component summary (PCS) score decreased gradually as age grew, nevertheless, the mental component summary (MCS) score was highest in the group aged 41 - 60. The score was lower in patients with moderate to severe malnutrition or diabetic nephropathy when compared with other patients. Univariate analysis of variance also revealed that high SF-36 scores associated with higher education or income. Multivariate analysis indicated that PCS score and total SF-36 score of MHD patients were positively correlated with body mass index (BMI) and cholesterol, but negatively correlated with diabetic nephropathy, pulmonary artery systolic pressure and MQSGA score (all P＜0.05). There was positive correlation between MCS score and income，yet negative correlation between MCS score and MQSGA score (all P＜0.05).  Conclusion    MHD patients had relatively poor QOL. Primary diseases and nutritional status were probably the main influencing factors. Age, educated level, family income and pulmonary artery systolic pressure might also have effects on their QOL.

Objective   To observe the effect of intermedin(IMD) on microvascular injury of renal fibrosis in unilateral ureteral obstruction (UUO) rat model.  Methods    Seventy-two male Wistar rats were randomly divided into two groups: the sham - operation group (n=24) underwent the left ureteral dissection, the other 48 rats were made as unilateral ureteral obstruction models and sub - divided into model group(UUO, n=24) and IMD group (n=24). At the 7, 14, 21, 28 day after the operation, 6 randomly - selected rats from each of the three groups respectively were blooded by abdominal arotic and their obstructive kidneys were taken out. The renal histopathological changes were observed through HE and Masson staining, the contents of BUN, Scr and cystatin C (CysC) of the obstructive kidneys were determined, the expressions of transforming growth factor - β1 (TGF - β1), α-SMA, bone morphogenetic protein-7 (BMP-7), E-cadherin, thrombospondin 1 (TSP-1) and vascular endothelial growth factor (VEGF) were detected by RT - PCR and immunohistochemistry.  Results   Compared with the sham-operated group, the pathological changes of kidney in the model group showed that the degree of fibrosis was obvious, tubular interstitial damage aggravated, the levels of BUN, Scr, CysC in the model group increased (P＜0.05), the mRNA expression and protein content of TGF-β1, α-SMA, TSP-1 increased (P＜0.05), while the levels of BMP-7, E-cadherin and VEGF decreased (P＜0.05). Compared with the UUO group, renal tubular damage, interstitial fibrosis in the IMD group were lighter, the levels of BUN, Scr, CysC in the IMD group were lower (P＜0.05), the mRNA expression and protein content of TGF-β1, α-SMA,TSP-1 were down-regulated (P＜0.05), while the levels of BMP-7, E-cadherin and VEGF were up-regulated (P＜0.05).  Conclusion   IMD can ameliorate the renal interstitial fibrosis, and the mechanism may be related to the fact that VEGF mediated by IMD can reduce vascular injury.

Objective    To explore the relationship between resveratrol and Notch 1 signalling pathway in podocytes.  Methods    Interference RNA (RNAi) and doxycycline (Dox) were used to inhibit the Sirtuin (SIRT) 1 expression in the wild - type and inducible SIRT1 shRNA (CAGGS) podocytes respectively. Recombinant mouse delta - like ligand 4 (DLL4) was used to activate Notch1 signalling. The message RNA of SIRT1, Notch1 downstream gene Hes1 and Hey2, as well as the key enzymes of Notch1 signalling pathway were detected by using real - time PCR. Western blotting was used to detect intracellular domain of Notch 1 (ICD1), SIRT1, and metalloprotease (ADAM) 10 and components of γ-secretase complex protein expression.  Results    In WT murine podoytes, resveratrol up-regulated ICD1 protein production, as well as the mRNA of Hes1 and Hey2 in a dose-dependent manner. Treatment with resveratrol resulted Nicastrin mRNA and protein increase in podocytes (P＜0.05), as well as inhibit ADAM10 expression (P＜0.05), but all these changes were prevented after the use of SIRT1 RNAi(P＜0.05). DLL4 up-regulated the expression of mRNA of Hes1 and Hey2, as well as ICD1 protein production in a dose-dependent manner. Treatment with doxycycline resulted decrease of SIRT1 gene and protein expression in CAGGS podocytes after 24 h and 48 h respectively(P＜0.05),which weakend the role of DLL4 significantly(P＜0.05).  Conclusion    Resveratrol induces Nicastrin expression, as well as activation of Notch1 signalling pathway in a SIRT1-dependent manner.