Search

Most treatments for spinal cancer are accompanied by serious side effects including subsequent tumor recurrence, spinal cord compression, and tissue adhesion, thus a highly effective treatment is crucial for preserving spinal and neurological functionalities. Herein, trilayered electrospun doxorubicin@bovine serum albumin/poly(ε-caprolactone)/manganese dioxide (DOX@BSA/PCL/MnO

Background: Little is known about the impact of haemodialysis (HD) and peritoneal dialysis (PD) on health-related quality of life (HRQoL). We compared HRQoL between conventional in-centre HD and home-based PD in 1082 newly diagnosed kidney failure patients. Methods: This was an open-label, randomised, non-inferiority trial of adult patients with a diagnosis of end-stage kidney disease (estimated glomerular filtration rate ≤ 15 mL/min/1.73 m2) requiring maintenance dialysis from 36 sites in China randomised 1:1 to receive PD or conventional in-centre HD. The primary outcome was the ‘Burden of Kidney Disease’ assessed using the Kidney Disease Quality of Life-Short Form (KDQoL-SF) survey over 48 weeks and the main secondary outcomes were the remaining scales of KDQoL-SF and all-cause mortality. The effect of PD versus HD on the primary outcome was compared by their geometric mean (GM) ratio, and non-inferiority was defined by the lower bound of a one-sided 95% confidence interval (CI) >0.9. Results: A total of 725 subjects completed the trial per protocol (395 PD and 330 HD, mean age 49.8 (standard deviation (SD) 14.4) years, 41.4% women). For the primary outcome, the mean (SD) change in ‘Burden of Kidney Disease’ over 48 weeks was 2.61 (1.27) in PD group and 2.58 (1.35) in HD group, and the GM ratio (95% CI) was 1.059 (0.908–1.234), exceeding the limit for non-inferiority. For the secondary outcomes, the PD and HD groups were similar in all scales. There were 17 and 31 deaths in PD and HD groups, respectively. Patients receiving PD had more adverse events, adverse event leading to hospitalisation and serious adverse events compared to those allocated to HD, but adverse events leading to death and discontinuation of the trial were not different between PD and HD. Conclusions: In this trial, PD may be non-inferior to HD on the ‘Burden of Kidney Disease’ among Chinese kidney failure patients who are of younger age and have lower comorbidity after 48 weeks’ follow-up.

Background Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. Methods We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. Results One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. Conclusions The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose‐limiting toxicity remain as major dilemmas for immunotherapy. Stimuli‐responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti‐tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti‐tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long‐term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

Background: Acute kidney injury (AKI) is a common post-cardiac surgery complication. It leads to increased morbidity and mortality. The aim of our study is to identify the prevalence and risk facto...

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. Methods: We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. Results: CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27–9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01–13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27–3.95; p = 0.005). Conclusion: Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.

Background/Aims: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. Methods: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. Results: Postoperative SAKI occurred in 262 ­patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52–12.21), age 61–80 years (vs. age 2O (3.53, 2.38–5.23), and low postoperative cardiac output (4.78, 2.97–7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74–0.85). The difference in the C statistic was 0.21 (95% CI 0.12–0.29, p < 0.001) compared with the Cleveland Clinic score. Conclusion: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Background Both peritoneal small solute transport and peritoneal protein clearance are closely linked to outcomes in peritoneal dialysis (PD) patients. However, the associated factors of these two components are not fully understood so far. This study aimed to investigate the association between a panel of systemic and peritoneal inflammatory and angiogenic factors and peritoneal solute transport properties. Methods Stable PD patients in PD center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled in present study. Serum and overnight effluent markers including angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), sTie-2, VEGF, IL-6 and IL-10 were determined. Mass transfer area coefficient of creatinine (MTACcr) and peritoneal protein clearance (Prcl) were calculated. Multivariable linear regression was used to examine the association between these markers and MTACcr as well as Prcl. Results A total of 320 patients were enrolled in present study, which consisted of 166 (51.9%) males with a mean age of 56.8 ± 14.2 years and a median PD duration of 32.5 (9.0–56.3) months. Multiple regression analyses showed that BSA, history glucose exposure, dialysate IL-6 AR and dialysate Ang-1 AR were independent associated factors of MTACcr, while BSA and serum Ang-1 were independent associated factors of Prcl. Conclusions MTACcr representing peritoneal small-solute transport and Prcl representing peritoneal large molecular transport are associated with slightly different panels of inflammatory and angiogenic factors.

Background FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). Methods In the NDD study, 91 participants were randomized to low (1.1–1.75 mg/kg) or high (1.50–2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1–1.8 mg/kg), medium (1.5–2.3 mg/kg) and high (1.7–2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. Results In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P

Cumulative evidence indicates it may be worthwhile revisiting the twice-weekly hemodialysis (HD) regimen as a valid option for individualized or incremental treatments for selected patients with end-stage renal disease. In this article, we will review the current evidences on the potential pros and cons of twice-weekly HD compared to thrice-weekly HD including China's experience in the practice of twice-weekly HD. A prudent patient selection and close dialysis adequacy monitoring might be necessary for this medical treatment choice. More randomized prospective controlled studies for the critical evaluation of twice-weekly dialysis are encouraged.

Objective: The objective of this study is to investigate the relationship between blood pressure changes and all-cause mortality, and between blood pressure changes and cardiovascular mortality, for maintenance hemodialysis (MHD) patients during dialysis. Methods: Data regarding general condition, biochemical indices, and survival prognosis of MHD patients who were treated at the Shanghai Jiao Tong University School of Medicine-affiliated Renji Hospital from July 2007 to December 2012 were collected, in order to evaluate the relationship between patients’ blood pressure changes during hemodialysis and mortality. Results: Among 364 patients, with an average age of 63.07 ± 13.93 years, an average dialysis vintage of 76.00 (range, 42.25–134.00) months, and a follow-up time of 54.86 ± 19.84 months, there were 85 cases (23.4%) of all-cause death and 46 cases (14.2%) of cardiovascular death. All-cause mortality and cardiovascular mortality were lowest (OR, 0.324 and 0.335; 95% CI, 0.152–0.692 and 0.123–0.911; p value, .004 and .032, respectively) in patients whose systolic blood pressure difference (ΔSBP) before and after dialysis was between 7.09 and 14.25 mmHg. Kaplan–Meier analysis indicated that both all-cause mortality and cardiovascular mortality were markedly increased for patients with ΔSBPless than −0.25 mmHg (p value, .001 and .044, respectively). Cox regression analysis showed that ΔSBP

Systemic inflammation is involved in vascular calcification and cardiovascular disease which is the leading cause of mortality in rheumatoid arthritis (RA). A high level of serum interleukin (IL)-6 plays a key role in local and systemic inflammation in RA. However, the underlying mechanisms remain unclear. We established a human umbilical artery smooth muscle cell (HUASMC) culturing method to investigate the possible role of IL-6 on vascular calcification. HUASMCs were obtained from umbilical arteries of healthy neonates. To detect calcification effects, HUASMCs were treated with (experimental group) or without (control group) recombinant human (rh) IL-6. The calcium deposition stain and calcium concentrations were measured, as well as the mRNA and protein levels of the regulating factor of osteogenic differentiation-bone morphogenetic protein (BMP) 2 and those calcifying related molecules including bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG), and osteopontin (OPN). Our study showed that rhIL-6 induced calcification of HUASMCs in a time- and dose-dependent manner, and upregulated expressions of BMP2, BAP, OPG, and OPN of HUASMCs. We then used the anti-BMP2 siRNA to knockdown the expression of endogenous BMP2 to confirm its role. HUASMCs were transfected with negative siRNA (control group) or the valid anti-BMP2 siRNA (experimental group) before they were treated with rhIL-6. Cells transfected with negative siRNA without IL-6 stimulating served as the blank group. The results showed that anti-BMP2 siRNA markedly decreased expressions of BMP2, BAP, OPG, and OPN, and also partly reduced the calcification of HUASMCs induced by rhIL-6. Collectively, according to our study, rhIL-6 could induce the extracellular calcification and osteogenic differentiation of human artery smooth muscle cells through upregulating endogenous BMP2 in vitro. This may be one of the underlying mechanisms of the overwhelming vascular calcification in RA.

Background Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. Methods This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray’s proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. Results Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71–1.03), and corresponding sub-hazard ratio 0.86 (0.71–1.03). There was strong effect modification by age. In those aged 40–60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45–0.94), and sub-hazard ratio also 0.65 (0.45–0.95). Conclusions Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes. Electronic supplementary material The online version of this article (10.1186/s12882-019-1219-z) contains supplementary material, which is available to authorized users.

Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals’ inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day

Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (-1.76 L 95% CI: -2.70, -0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported.Kidney International advance online publication, 14 October 2015; doi:10.1038/ki.2015.294.

Objectives Circulating miRNAs have been reported to have potential in detecting various diseases. However, few studies explored differentially expressed miRNAs in plasma of patients with pulmonary embolism (PE). Our study is to identify plasma miRNAs which can serve as potential biomarkers of PE. Materials and methods Exiqon miRCURY Ready-to-Use PCR Human panel I + II V1.M was conducted to identify differently expressed miRNAs in pooled plasma samples of PE patients compared with normal controls. Expressions of identified miRNAs were assessed in 37 PE patients as well as matched normal individuals followed by validation on six Beagle dogs by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results Twelve miRNAs were identified from the screening phase. Moreover, miR-134, previously reported related with PE, and hypoxia-induced miR-210 were also submitted to the validation phase. Only miR-28-3p was found significantly elevated in the plasma of PE patients. Compared with the level of plasma miR-28-3p of the dogs before PE, the elevated miR-28-3p did not alter significantly at 1, 2, 4 and 6 h after PE. The area under the receiver operating characteristic (ROC) curve of plasma miR-28-3p was 0.792 (95% confidence interval: 0.689–0.896). KEGG pathway analysis showed that miR-28-3p might involve in PE related pathways such as inositol phosphate metabolism and phosphatidylinositol signaling system. Conclusion Our study indicated that elevated plasma miR-28-3p could be used as a non-invasive and stable biomarker in the detection of PE. Further researches on the miRNA are warranted.

Background: As the utilization of hemodialysis increases in China, it is critical to examine anemia management. Methods: Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe hemoglobin (Hgb) distribution and anemia-related therapies. Results: Twenty one percent of China's DOPPS patients had Hgb Conclusion: A large proportion of hemodialysis patients in China's DOPPS do not meet the expressed Hgb targets. Less frequent hemodialysis, patient financial contribution, and lack of a substantial increase in ESA dose at lower Hgb concentrations may partially explain this gap. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=442741.

Background To examine serum angiopoietin-2 (Angpt-2) in relation to malnutrition, inflammation, atherosclerosis and cardiac valvular calcification, so-called MIAC syndrome and its predictive role in outcomes of peritoneal dialysis (PD) patients. Methods A prospective observational study was conducted in 324 chronic PD patients. Biochemical analysis was performed at baseline for serum angiopoietins, albumin and high sensitive C-reactive protein (hs-CRP) and echocardiography was done to detect cardiac valvular calcification. Primary study end points were fatal or nonfatal cardiovascular events and mortality. Results The median of serum Angpt-2 levels was 5.44 ng/mL (interquartile range, 3.41–7.85). Across the three tertiles of serum Angpt-2, a significant trend effect was observed for body mass index, normalized protein catabolic rate, calcium × phosphorus product, hs-CRP, brain natriuretic peptide, lower-density lipoprotein cholesterol, left ventricular ejection fraction, total weekly urea clearance and residual renal function (all p

To determine the relationship between the variability of serum phosphorus and mortality among maintenance hemodialysis (MHD) patients.A total of 502 MHD cases were studied from the Shanghai Renal Registry Network. Serum phosphorus variability was indicated by a coefficient of variation (CV). According to the CV median of serum phosphorus, patients were divided into two groups: a high-variability group (CV ≥ 0.226 mmol/L) and a low-variability group (CV 0.226 mmol/L). Average phosphorus ≤ 1.78 mmol/L was defined as the standard phosphorus group and serum phosphorus 1.78 mmol/L was defined as the non-standard phosphorus group. The relationship between serum phosphorus variability and all-cause and cardiovascular disease (CVD) mortality was assessed.In the 502 MHD cases, the average age of patients was 63.9 ± 14.60 years, and dialysis vintage was 82.0 (43.0 - 139.0) months. 118 patients (23.5%) died, succumbing to all-cause mortality, while 64 patients (14.3%) died from CVD. The high-variability group had increased all-cause mortality (27.7% vs. 19.3%, p = 0.028). Death from CVD was increased in the high-variability group, but had no statistical significance (15.4% vs. 10.0%, p = 0.082). Cox regression analysis showed that older age, low hemoglobin levels, a higher phosphorus CV, and low serum albumin were independent risk factors for all-cause and CVD mortality. The standard group with low-phosphorus variability had a decreased mortality compared with the non-standard group with high variability (15.3 vs. 29.2%, p = 0.047 and 6.0 vs. 15.0%, p = 0.033, respectively). The Kaplan-Meier method revealed that patients with low phosphorus variability had a decreased all-cause and CVD mortality (p = 0.023 and p = 0.047, respectively) compared with high phosphorus variability patients.Higher phosphorus CV was independently correlated with all-cause and CVD mortality. Low phosphorus variability with on-target levels resulted in decreased patient mortality. Thus, stable serum phosphorus levels may improve survival in MHD patients. .

Background and aims Hyperphosphatemia is an independent predictor for cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the effect of dietary intervention on reducing serum phosphate concentration in hyperphosphatemic PD patients. Methods and results In this single-center clinical trial, 97 prevalent PD patients with serum phosphate concentration ≥1.6 mmol/l were allocated to the intervention ( n = 48) or control ( n = 49) group and followed up for 1 year. In addition to phosphate binder (calcium carbonate) therapy, patients in the intervention group were intensively educated to reduce phosphate-rich food intake and improve cooking methods. While stable in the control group (1.97 ± 0.20 to 1.94 ± 0.35 mmol/l, p > 0.05), the serum phosphate concentration decreased significantly in the intervention group (1.98 ± 0.28 to 1.65 ± 0.33 mmol/l, p = 0.015) concurrently with the drop in dietary phosphate intake (13.03 ± 3.39 to 10.82 ± 3.00 mg/kg ideal body weight/day, p = 0.001). Moreover, after 6 months of intervention, fewer patients needed to use calcium carbonate (from 64.6% to 41.5%, p = 0.029) and the medicine dose reduced significantly (from 2.25 (0, 3.94) to 0 (0, 1.50) g/day, p Conclusions Our data indicated that intensive dietary intervention of reducing phosphate-rich food intake and improving cooking methods attenuated hyperphosphatemia in PD patients. It suggests that regular assessment of dietary phosphate intake and modification of diet recipe and cooking methods are essential for hyperphosphatemia treatment in PD patients in addition to phosphate binder therapy.

We investigated the possible role of miR-143 in the development of cisplatin resistance in human gastric cancer cell line. miR-143 was detected by quantitative real-time PCR. Cisplatin resistance changes of cells was tested via MTT assay. Target genes of miR-143 were verified by dual-luciferase activity assay. Immunohistochemistry, immunofluorescence staining, Western blot, cell proliferation, and clonogenic and apoptosis assay were used to elucidate the mechanism of miR-143 in cisplatin resistance formation. miR-143 was downregulated in gastric cancer tissues and cell lines. It was also downregulated in cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP), which was concurrent with the upregulation of IGF1R and BCL2, compared with the parental SGC7901 cell line, respectively. Overexpressed miR-143 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity suggested that IGF1R and BCL2 were both target genes of miR-143. Enforced miR-143 reduced its target proteins, inhibited SGC7901/DDP cells proliferation, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Our findings suggested that hsa-miR-143 could modulate cisplatin resistance of human gastric cancer cell line at least in part by targeting IGF1R and BCL2.

To investigate the effect of hemoglobin fluctuations on cardiovascular prognosis of patients on peritoneal dialysis (PD). Retrospective descriptive study, with sample composed of 333 patients treated with PD at the Renal Unit. Two indicators were adopted to indicate hemoglobin fluctuations of PD patients: absolute value of hemoglobin variability (HV) and HV trend. Moreover, the new cardiovascular events and recurrent rate of cardiovascular events within 3 months after PD were recorded and were compared in groups of PD patients classified by hemoglobin fluctuation indicators. Patients whose HV value is less than 10 g/l have an increased risk of new cardiovascular events than patients with HV value > 10 g/l (27.2 vs. 12.2%, p

The aim was to identify the risk factors of long-term vascular access complications. The study cohort consisted of 239 incident hemodialysis (HD) patients from 1998 to 2010 in a single center. Among these patients, 59.8% had initially been dialyzing with a temporary catheter. Within 3 months after starting dialysis, all catheters had been converted into permanent accesses. 45 patients incurred long-term access complications after the first 2 years of dialysis, and 34 (75.6%) had used a temporary catheter starting HD. Complication occurrence was associated with age, initiation dialysis with a catheter and heart failure by logistic regression (odds ratios were 1.04, 2.77 and 2.23, respectively; p < 0.05). The 2-year primary patency rates of arteriovenous fistulae were significantly higher than those of arteriovenous grafts (79.5 vs. 50%, p = 0.002). We concluded that age, using a catheter and heart failure in HD initiation had a strong impact on long-term access complications.

The main aim of this study is to investigate the incidence and prognosis of acute kidney injury (AKI) and to clarify the risk factors associated with the prognosis of AKI in hospitalized patients.All patients hospitalized from January 1st to December 31st 2012 in Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University were screened by the Lab Administration Network. All the patients with an intact medical history of AKI according to the Acute Kidney Injury Network (AKIN) were enrolled in the study cohort. AKI's incidence and etiology, as well as the patient's characteristics and prognosis, were retrospectively analyzed. Logistic regression analysis was used to investigate the risk factors on the patient prognosis and renal outcome.934 AKI patients were enrolled. The incidence of AKI in hospitalized patients was 2.41%. The ratio of males to females of patients was 1.88:1 and the mean age was 60.82 ± 16.94. The incidence of AKI increased with increase in age. Among hospitalized patients, 63.4% were from the surgical department, 35.4% from the internal medicine department, and 1.2% from the obstetric and gynecologic department. Regarding the cause of AKI, pre-renal AKI, acute tubular necrosis (ATN), acute glomerulonephritis and vasculitis (AGV), acute interstitial nephritis (AIN), and post-renal AKI contributed with 51.7, 37.7, 3.8, 3.5, and 3.3%, respectively. The survival rate on the day 28 after AKI was 71.8%. In addition, 65.7% patients got complete renal recovery, while 16.9% got partial renal recovery and 17.4% got renal loss. The mortality of AKI in hospitalized patients at Stage I, Stage II and Stage III was 24.8, 31.2 and 43.7%, respectively. Multivariate Logistic regression analysis showed that use of nephrotoxic drugs, [Odds Ratio (OR) = 2.313], hypotension in the previous week (OR = 4.482), oliguria (OR = 5.267), the number of extra-renal organ failures (OR = 1.376), and need for renal replacement therapy (RRT) (OR = 4.221) were independent risk factors for mortality. The number of extra-renal organ failures (OR = 1.529) and RRT (OR = 2.117) were independent risk factors for renal loss.AKI is one of the most common complications in hospitalized patients. The mortality is high and renal prognosis is poor after AKI. The prognosis is closely associated with the severity of AKI. Nephrotoxic drugs, hypotension within the last week, oliguria, the number of extra-renal organ failures, and RRT are independent risk factors for mortality, while the number of extra-renal organ failures and RRT are independent risk factors for renal loss.

Background: To evaluate the association of dialysate interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation, with the alteration of peritoneal solute transport rate (PSTR) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Stable CAPD patients were enrolled in the present study. A total of 128 patients were analyzed in this prospective study. IL-6 concentration in the overnight effluent was determined and expressed as the IL-6 appearance rate (IL-6AR). Mass transfer area coefficients of creatinine (MTACcr) were measured at enrollment and 12 months later. Logistic regression was used to examine the association between IL-6AR and change in MTACcr. Results: Multivariable linear regression showed that historical glucose exposure was significantly associated with dialysate IL-6AR level [β = 0.008 (0.001-0.015), p = 0.021]. After 12 months, MTACcr was significantly increased [6.40 (4.70-8.75) vs. 7.14 (5.69-8.73) ml/min, p = 0.004], while ultrafiltration capacity decreased [4 h UF 340 (220-400) vs. 280 (180-380) ml, p = 0.006]. Compared to the patients with stable PSTR, the dialysate IL-6AR in patients with increasing PSTR was significantly higher [277.08 (247.45-349.53) vs. 263.18 (69.94-286.72) pg/min, p = 0.015]. Patients with increasing PSTR had lower residual renal function [0.79 (0-2.12) vs. 1.70 (0.39-3.38) ml/min, p = 0.006] and less urine output [225 (0-600) vs. 500 (125-900) ml/24 h, p = 0.014]. Logistic analysis showed that both high dialysate IL-6AR [OR 1.333 and 95% CI (1.024-1.735), p = 0.033] and low RRF [OR 0.831 and 95% CI (0.699-0.988), p = 0.036] were independent risk factors for increasing PSTR. Conclusions: This prospective study suggests that intraperitoneal IL-6 is a predictor of increasing PSTR in peritoneal dialysis patients.

The study was to evaluate neurotoxicity caused by antibiotics in dialysis patients, including incidence, clinical features, treatments and prognosis.In this retrospective study, we reviewed the medical records of 1066 dialysis patients (254 peritoneal dialysis [PD] cases and 812 hemodialysis [HD] cases) who also received intravenous antibiotics in our hospital during July 2006 - April 2012. Naranjo scale was used for estimating the probability of an adverse drug reaction.The incidence of antibiotic-induced neurotoxicity was 5.66% in patients receiving HD, and 7.87% in patients receiving PD. There was no significant difference between the two dialysis modalities about the incidence of antibiotic-induced neurotoxicity (p 0.05). The risk factors included extremely old age, history of central nervous system disorder, low residual renal function, hypoalbuminemia, and the use of multiple antibiotics that share one mechanism. The neurotoxic antibiotics included cephalosporins, penicillins, carbapenems and quinolones in our study. Most patients could be properly diagnosed early according to their medical history, symptoms, signs, electroencephalography (EEG), other related auxiliary examination, and with the help of experienced neurologists. Most neurotoxic patients showed clinical improvement after the discontinuation of antibiotics and active treatment.The adverse neurotoxic effects of antibiotics were common in dialysis patients due to wide and incorrect usage. Neurotoxicity could be prevented in high-risk cases with dosage adjustments. Better prognosis can be achieved with early and proper diagnosis, decisive withdrawal, and aggressive treatment including enhanced HD.

Purpose Ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression. Methods The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes. The results were validated in the plasma of the selected patients with AKI after cardiac surgery compared with those matched patients without AKI. The performance characteristics of miR-192 were summarized using area under the receiver operator characteristic (ROC) curves (AUC-ROC). Results MiRNA profiling in plasma led to the identification of 42 differentially expressed miRNAs in the IRI group compared to the sham group. MiR-192 was kidney-enriched and chosen for further validation. Real-time PCR showed that miR-192 levels increased by fourfold in the plasma and decreased by about 40% in the kidney of IRI rats. Plasma miR-192 expression started increasing at 3 h and peaked at 12 h, while kidney miR-192 expression started decreasing at 6 h and remained at a low level for 7 days after reperfusion. Plasma miR-192 level in patients with AKI increased at the time of ICU admission, was stable for 2 h and decreased after 24 h. AUC-ROC was 0.673 (95% CI: 0.540–0.806, p = 0.014). Conclusions Plasma miR-192 expression was induced in a time-dependent manner after IRI in rats and patients with AKI after cardiac surgery, comparably to the kidney injury development and recovery process, and may be useful for the detection of AKI.

Background: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. Methods: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). Results: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). Conclusions: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double-blind, multicenter, placebo-controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium-phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.

Angiopoietin-2/Tie2 signaling has been found to play an important role in producing a vasculature in a variety of conditions. However, whether angiopoietin-2/Tie2 signaling is involved in peritoneal angiogenesis induced by TNF-α is not clear. In this study, we investigated the role of TNF-α on the function of human omental tissue microvascular endothelial cells (HOTMECs) and whether angiogenesis is inhibited by blocking angiopoietin-2/Tie2 signaling.Primary cultured HOTMECs were exposed to complete medium as control, medium containing 10 ng/ml TNF-α, a mixture of 10 ng/ml TNF-α plus 2 µg/ml sTie2/Fc or 2 µg/ml sTie2/Fc alone, respectively, as experimental groups. The proliferation of HOTMECs was measured by MTT assay. Expression of vascular endothelial growth factor (VEGF), Angiopoietin-2, and Tie2 were assessed by real-time PCR. We also investigated the angiogenesis of the HOTMECs by tube formation assay, their migration as well as their permeability to FITC-labeled BSA.Compared to the cells in control, exposure to TNF-α or sTie2/Fc had no effect on proliferation of HOTMECs. TNF-α up-regulated the gene expression of VEGF, Angiopoietin-2, and Tie2 (p0.05). TNF-α significantly promoted tube formation, migration and enhanced permeability of HOTMECs (p0.05). Supplement with sTie2/Fc partially inhibited tube formation and migration (p0.05). However, sTie2/Fc did not inhibit the increased permeability induced by TNF-α (p0.05).Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis may provide an alternative way to prevent peritoneal angiogenesis.

We compared patient characteristics, atherosclerosis, left ventricular hypertrophy, and dialysis practice patterns of peritoneal dialysis (PD) patients with change in cardiovascular disease (CVD) status and no change in CVD status in Chinese PD center.This study included all patients who started on PD between 1 January 2003 and 30 June 2009 at the Renji Hospital, Shanghai Jiaotong University School of Medicine, China. They were followed up from the date of PD initiation until new-onset CVD.The median follow-up time was 44.13 months. In patients with preexisting CVD, both high triglyceride (1.43 ± 0.89 mmol/L vs. 2.64 ± 1.58 mmol/L, p0.001) and the duration of dialysis (45.76 ± 13.28 months vs. 58.68 ± 13.74 months, p0.01) were independent predictors of CVD progression and the left atrial dimension, left ventricle septal thickness, left ventricle mass index (LVMI), and intima-media thickness (IMT) also had the difference. On the other hand, in patients without preexisting CVD, the dialysis adequacy and nutritional status are important during the follow-up. Serum albumin in CVD group was lower than in no CVD group (30.86 ± 4.77 g/L vs. 36.04 ± 6.40 g/L, p0.05). Creatinine clearance (CCr) and Kt/V in CVD group were lower than in no CVD group (CCr 57.24 ± 13.86 L/week vs. 71.06 ± 23.96 L/week, p0.05; Kt/V 1.82 ± 0.41 vs. 2.23 ± 0.57, p0.05).In patients with preexisting CVD, it is important to address traditional risk factors such as LVMI, IMT, and lipid profile. In patients without preexisting CVD, we should pay more attention to the nutritional status and PD prescription in order to lower the morbidity of CVD in these PD patients.

Background/Aims: Acute kidney injury (AKI) following surgery is a major complication, but the prevalence and risk factors in the Asian population are unclear. Recently, a consensus definition of AKI (AKIN) was proposed. We studied a cohort of cardiac surgery patients and identified AKI by AKIN and associated risk factors. Methods: We retrospectively evaluated 1,056 consecutive patients undergoing cardiac surgery in Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from January 1, 2004 to June 30, 2007. We recorded AKIN stage, clinical characteristics, perioperative variables and complications, as well as clinical outcomes. Univariate and multivariate regression as well as survival analysis was performed. Results: AKI occurred in 328 (31.1%) patients, stage 1 in 21.1%, stage 2 in 6.3% and stage 3 in 3.7%. Patients with AKI were older (65.8 vs. 53.5 years, p < 0.001), more often male (66.8 vs. 54.1%, p < 0.001), and had higher Charlson Comorbidity Index (CCI) (CCI >2: 22.6 vs. 7.8%, p < 0.001). In logistic regression, advanced age (OR 1.48 per decade, 95% CI 1.32–1.67), CCI >2 (OR 2.82, 95% CI 1.80–4.41), hypertension (OR 2.13, 95% CI 1.47–3.09), left ventricular ejection fraction (LVEF) 2O (OR 13.28, 95% CI 8.72–20.14) and postoperative use of ACEI/ARB (OR 1.90, 95% CI 1.27–2.85) were risk factors of AKI. Mortality rose progressively with increased AKIN stage (non-AKI 0.7%, stage 1 4.9%, stage 2 12.1% and stage 3 48.7%). In ROC analysis, AKIN classification was identified to be associated with in-hospital mortality with an AUC of 0.865 (95% CI 0.801–0.929, sensitivity 0.884, specificity 0.714, p < 0.001). Finally, in a Cox proportional hazards model, AKIN stage (HR 2.40, p < 0.001), re-exploration (HR 6.30, p = 0.002) and multiple organ dysfunction syndrome (MODS) (HR 4.42, p = 0.001) were associated risk factors for in-hospital mortality. Conclusion: We evaluated AKIN as a marker of AKI and mortality risk in a large, unselected Chinese cohort of incident patients undergoing cardiac surgery. AKI following cardiac surgery was diagnosed by AKIN criteria in around one third of the patients, and AKI may be associated with outcome. The value of preventative strategies to reduce AKI and their effect on in-hospital mortality should be studied.

Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients.This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography.Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly.A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

Background/Aims: Acute kidney injury (AKI) is common following cardiac surgery and predicts a poor outcome. However, the early detection of AKI has proved elusive and most cases are diagnosed only following a significant rise in serum creatinine (SCr). We compared a panel of early biomarkers of AKI for the detection of AKI in patients undergoing heart surgery. This study included serum cystatin C (CyC) and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Methods: We retrospectively identified 15 patients undergoing open cardiac surgery who developed AKI within 72 h postoperatively. For these, we identified 15 matched controls also having undergone surgery but without AKI. Serial serum and urine samples had prospectively been postoperatively obtained from all patients at 0, 2, 4, 6, 10, 24, 48 and 72 h after admission to the intensive care unit. AKI was defined as a >50% increase in SCr. CyC was measured by nephelometry, while NGAL, IL-18, and RBP were measured by ELISA and NAG was measured by spectrophotometry. The urinary biomarkers were normalized to urinary creatinine (UCr) concentration. Each marker was assessed at each time point for its predictive value using receiver operating characteristic curves to predict AKI. Results: Following the exclusion of 1 case due to a urinary tract infection, the final cohort consisted of 29 patients aged 62.9 ± 13.7 years with baseline SCr of 73.2 ± 11.9 µmol/l. While there were no differences in the demographics between cases and controls, the aortic clamp time was predictably higher in AKI cases than in controls (60.6 ± 13.9 vs. 43.0 ± 9.2 min, p < 0.05). Each biomarker differed significantly between cases and controls for at least one time point. The optimal area under the curve (AUC) was for CyC at 10 h (sensitivity 0.71, specificity 0.92, cutoff 1.31 mg/l), NGAL at 0 h (sensitivity 0.84, specificity 0.80, cutoff 49.15 µg/g UCr), IL-18 at 2 h (sensitivity 0.85, specificity 0.73, cutoff 285.65 ng/g UCr), RBP at 0 h (sensitivity 0.75, specificity 0.67, cutoff 2,934.65 µg/g UCr) and NAG at 4 h (sensitivity 0.86, specificity 0.67, cutoff 37.05 U/mg UCr). Using a combination of all 5 biomarkers analyzed at the optimal time point as above, we were able to obtain an AUC of 0.98 (0.93–1.02, p < 0.001) in this limited sample. Conclusion: The use of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers urinary NGAL had the best predictive profile. The previously unstudied marker of urinary RBP showed similar predictive power as more established markers. By combining all 5 studied biomarkers we were able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically.

Background. Maintenance dialysis therapy is the only way to remove excess fluid in patients with anuric end-stage renal disease. The optimal ultrafiltration (UF) volume in patients on peritoneal dialysis (PD) remains controversial. Methods. We retrospectively analysed a cohort of 86 prevalent anuric PD patients followed up for a median of 25.3 months (range, 6 to 54 months). Clinical and PD parameters were recorded yearly. Kaplan-Meier analysis and Cox proportional hazards models were used to identify risk factors of mortality and technique failure in patients with a UF ≥1 L/24 h or

Background: The pathogenesis of contrast-induced nephropathy (CIN) remains unclear and is defined by changes in serum creatinine which is not a sensitive biomarker for acute kidney injury. Search for differentially expressed urinary protein or peptide could contribute to further understanding of the disease and may provide new biomarkers. Methods: This is a small sample research. Urine samples were obtained from patients who underwent percutaneous coronary intervention and were labeled with 3 different fluorescent dyes. After 2-dimensional electrophoresis was run, the differentially regulated spots were picked out and identified by mass spectrometry. Another 31 patients were used as validation group. Results: Among 56 significantly changed spots, mannose-binding lectin (MBL) and MBL-associated serine protease 2 were both significantly upregulated. Compared to the baseline value, urinary MBL was significantly increased in the CIN group (2.08, 1.42–5.72, vs. 1.09, 0.516–1.411; p < 0.01). Postprocedure urinary MBL in the CIN group was also significantly higher than that in the non-CIN group (2.08, 1.42–5.72, vs. 1.057, 0.738–1.885; p < 0.05). Conclusion: The studies suggested that MBL may be associated with contrast-induced acute kidney injury. It leads to an attempt to define a new pathogenesis and a novel biomarker for CIN.

Background and objectives: While peritoneal dialysis with icodextrin is commonly used in patients with poor peritoneal membrane characteristics, the data on the usefulness of this solution in patients with lower transport characteristics are limited. The study was designed to compare icodextrin to glucose in Chinese prevalent peritoneal dialysis patients of different peritoneal transport characteristics (PET) categories. Design, setting, participants, & measurements: This was a randomized, double-blind, perspective control study. Stable prevalent continuous ambulatory peritoneal dialysis (CAPD) patients were randomized to either 7.5% icodextrin (ICO) or 2.5% glucose (GLU) solution for 4 wk. Peritoneal membrane function was measured to define PET category in baseline. Creatinine clearance (Ccr), urea nitrogen clearance (CBUN), ultrafiltration (UF) during the long night dwell, dialysate, and metabolic biomarkers were measured at baseline, 2, and 4 wk. UF, Ccr, and CBUN were compared among different PET categories. Results: A total of 201 CAPD patients were enrolled in the study. There were no baseline differences between the groups. Following 2 and 4 wk of therapy, Ccr, CBUN, and UF were all significantly higher in the ICO versus the GLU group. Additionally, switching to ICO resulted in a significant increase in UF in high, high-average, and low-average transporters as compared with baseline. The extent of increased UF was more obvious in higher transporters. Blood cholesterol level in the ICO group decreased significantly than that in the GLU group. Conclusion: Compared with glucose-based solution, 7.5% icodextrin significantly improved UF and small solute clearance, even in patients with low-average peritoneal transport.

Background. While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a lowprotein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). Methods. To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10days.Second,60stablePDpatients[RRF4.04 ±2.30ml/ min/1.73 m 2 , urine output 1226 ± 449 ml/day, aged 53.6 ± 12.8 years, PD duration 8.8 (1.5–17.8) months] were randomized to receive either a low- (LP: 0.6–0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6–0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or highprotein (HP: 1.0–1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. Results. A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 ± 2.17 to 3.39 ± 3.23 ml/min/1.73 m 2 , P = ns) while it decreased in group LP (4.02 ± 2.49 to 2.29 ± 1.72 ml/min/1.73 m 2 , P < 0.05) and HP (4.25 ± 2.34 to 2.55 ± 2.29 ml/min/1.73 m 2 ,P

The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region.The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan-Meier survival analyses, as appropriate.Data were obtained on 201,590 patients (HD 173,788; PD 27,802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% +/- 5.5% versus 3.0% +/- 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13-0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15-1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05-1.58). HBV infection data were limited, but less clearly influenced by dialysis modality.Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.

Background/Aims: The optimal dose of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. Methods: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Trial tests the hypothesis that higher dose continuous veno-venous hemodiafiltration (CVVHDF) at an effluent rate of 40 ml/kg/h will increase survival compared to CVVHDF at 25 ml/kg/h of effluent dose. Results: This trial is currently randomizing critically ill patients in 35 intensive care units in Australia and New Zealand with a planned sample size of 1,500 patients. This trial will be the largest trial ever conducted on acute blood purification in critically ill patients. Conclusion: A trial of this magnitude and with demanding technical requirements poses design difficulties and challenges in the logistics, conduct, data collection, data analysis and monitoring. Our report will assist in the development of future trials of blood purification in intensive care. This study was registered with ClinicalTrials.gov (NCT00221013).

Aims: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. Methods: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for cardiovascular events. Results: The serum adiponectin concentration was elevated and inversely related to C-reactive protein and interleukin-6 in the patients. The adiponectin level of patients with carotid plaques was significantly lower than in those without plaques (p < 0.01). Kaplan-Meier analysis showed that the cumulative survival without new cardiovascular events was better in patients with higher adiponectin levels than in those with lower adiponectin levels. Conclusion: Serum adiponectin levels are inversely related with markers of systemic inflammation and signs of atherosclerosis which may explain why hyperadiponectinemia in this study was associated with better cardiovascular outcome.

Interleukin-6 (IL-6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL-6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells.Human mesothelial cells (Met-5A) were incubated with different concentrations of glucose and mannitol, and the effect of glucose and mannitol on the expression of IL-6 was determined. Then, the cells were stimulated by IL-6 with or without two soluble receptors of IL-6 (sIL-6R or sgp130), and VEGF synthesis was detected. Finally, the cells were incubated with IL-6/sIL-6R combined with or without the inhibitor of Janus kinases (JAK) AG490. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and its intracellular translocation were examined.1. High glucose and mannitol could upregulate IL-6 mRNA expression and IL-6 secretion in mesothelial cells significantly, and there was no difference of its effect between high glucose and mannitol. 2. Met-5A was a cell line with a single IL-6 receptor. The IL-6/sIL-6R complex induced VEGF synthesis of mesothelial cells, which was alleviated by sgp130 or AG490. IL-6 trans-signalling could induce the phosphorylation of STAT3, which is recruited to the cellular nucleus of Met-5A cells.The present study might provide evidence that high glucose upregulates IL-6 synthesis in Met-5A cells, to some extent, depending on its osmolality and that IL-6 trans-signalling could induce VEGF synthesis partly dependent on the JAK/STAT3 pathway.

This study investigated the associated factors of 6-min walk test (6MWT) and its predictive value of outcome in patients undergoing peritoneal dialysis (PD).This is a single centre prospective observational cohort study. Stable ambulatory PD patients in our centre between 1 May 2010 and 30 April 2011 were enrolled in this study. All included subjects performed 6MWT, and 6-min walk distances (6MWDs) were recorded. Patients were divided into two groups according to 6MWD and prospectively followed up until death, cessation of PD or to the end of the study (30 September 2012).A total of 145 patients were enrolled, including 63 (43%) males. Multiple stepwise regression showed that age (β = -0.295, P = 0.001), diastolic blood pressure (DBP) (β = 0.292, P = 0.001), left ventricular ejection fraction (LVEF) (β = 0.198, P = 0.019) were independently associated with lower 6MWD. By the end of the study, six (8%) patients died in long 6MWD group while 15 (20%) died in the short 6MWD group, a significantly lower patient survival was observed in short 6MWD group (Log-rank = 4.983, P = 0.026). Patients with short 6MWD also showed inferior technique survival (Log-rank = 4.838, P = 0.028). There was no significant difference in peritonitis-free survival between the two groups (Log-rank = 0.801, P = 0.371). However, more patients in short 6MWD group had been transferred to hemodialysis due to peritonitis (25% vs 4.2%, P = 0.013).Age, diastolic blood pressure, LVEF are independent associated factors of 6MWD in patients undergoing PD. Having the advantages of easy applicability and safety, 6MWT may be proposed as an important predictor of outcome in ambulatory PD patients.

The aim of this study was to clarify the relationship between insulin resistance (IR) and glucose and lipid metabolism in peritoneal dialysis (PD) patients. The study also investigated the prognostic factors for survival in long-term peritoneal dialysis patients.Participants were recruited from July 1 to August 1, 2011, based on selection criteria. Patients were divided into two groups, high (H) and low (L) group according to the median value of homeostasis model assessment of IR (HOMA-IR). Type 2 diabetes mellitus (DM) patients were chosen as positive controls. Clinical, plasma biochemical and metabolic parameters were observed and recorded at the outset and follow-up of this study. Mortality related factors were also detected, and statistical analyses were performed.A total of 157 cases with an average age of 55 ± 15 years were included. There were 26, 66 and 65 cases in the DM, H and L groups, respectively. Younger age, lower body mass index, high sensitive C-reactive protein (hsCRP) level, higher normalized protein catabolic rate (nPCR) were found in the L group compared with the other two groups. HOMA-IR positively correlated with age, leptin and triglyceride levels, and it negatively correlated with BMI. L group had better survival rate than H and DM groups. Dialysis duration, serum leptin level, nPCR and hsCRP were statistically associated with mortality.Insulin resistance may play an important role in the pathophysiology of glucose and lipid metabolism. Dialysis duration, leptin, nPCR and hsCRP may be risk factors for mortality in PD patients.

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b) and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC.

Immunoglobulin A nephropathy (IgAN), the pathogenesis of which remained still unclear is one of the leading courses of end-stage renal disease in approximately 50% affected patients. On the basis of several researches, the activation of complement mannose-binding lectin (MBL) pathway might be the underlying mechanism in disease progress. In order to investigate the relationship between MBL pathway and IgAN, we discussed the MBL gene polymorphism as well as its expressed level in serum, urine and renal parenchymal, with renal outcome in IgAN patients. The significantly down-regulated expression of MBL was discovered, which may serve as a potential urinary biomarker in progressive IgAN according to the results of difference in gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The single nucleotide polymorphisms of MBL gene in promoter and exon region were found and confirmed relating with the poor prognosis of progressive IgAN patients. As a result, the deficient activation of MBL pathway caused by the mutation of MBL accompanied with low expressed level of MBL in serum might be the potential inspiring regulation in IgAN, and will attract a promising insight in remedy of IgAN to inhibit further progress.

Objective To investigate the long-term outcomes of peritoneal dialysis (PD) patients with diabetes as primary renal disease and patients with diabetes as a comorbid condition. Methods All diabetic patients who commenced PD between January 1, 1995 and June 30, 2012 at Ren Ji Hospital, China were included. Patients were divided into diabetic nephropathy group (DN group) and non-diabetic nephropathy group (NDN group) according to their diagnosis of primary renal disease at the initiation of PD. They were followed until death, cessation of PD, transferred to other centers or to the end of study (June 30, 2013). Outcomes were analyzed by Kaplan-Meier method and Cox regression models. Results A total of 163 diabetic patients were enrolled in the study, including 121 (74.2%) in DN group and 42 (25.8%) in NDN group. The 1-, 2-, 3- and 5-year patient survival rates were 89%, 78%, 66% and 51% for DN group, and 85%, 63%, 53% and 25% for NDN group, respectively. Kaplan-Meier analysis showed that patients in NDN group had a worse patient survival compared with DN group (log rank 4.830, P=0.028). Patients in NDN group had a marginally shorter peritonitis-free period (log rank 3.297, P=0.069), however, there was no significant difference in technique survival (log rank 0.040, P=0.841). Multivariate Cox regression analysis showed that older age (HR 1.047, 95% CI 1.022-1.073, p

Aim: We investigated the association of peritoneal glucose exposure and dialysis exchange number with peritonitis outcome in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: The first episodes of bacterial peritonitis were retrospectively analyzed in 187 CAPD patients. Peritoneal glucose exposure was calculated based on PD prescription at the onset of peritonitis. Results: Patients with peritoneal glucose exposure ≤140 g/day showed a higher and complete cure rate of peritonitis (66 vs. 51.7%, p = 0.047), lower occurrence of relapsing/recurrent peritonitis (10.0 vs. 21.8%, p = 0.026) and catheter removal (14.0 vs. 26.4%, p = 0.033). Patients who exchanged more than three times every day demonstrated marginally higher catheter removal rate (24.1 vs. 13.0%, p = 0.085). Logistic analysis indicated that peritoneal glucose exposure >140 g/day was an independent predictor for relapsing/recurrent peritonitis (RR: 1.959, p = 0.042). Conclusion: High peritoneal glucose exposure is associated with increased incidence of relapsing/recurrent peritonitis in CAPD patients.

To investigate the prevalence of metabolic syndrome (MS) in patients with lupus nephritis (LN), and its correlation with carotid atherosclerosis.Two hundred ten patients with LN (age: 38.83 ± 12.41 years, 92.86% women) were enrolled. The control group included 150 lupus patients without nephritis and 200 age-matched healthy persons. The improved criteria in 2009 were used to calculate the prevalence of MS, and carotid artery ultrasound was used to detect plaque and intima-media thickness (IMT). The correlation between MS and carotid atherosclerosis in patients with LN was analyzed.The prevalence of MS in patients with LN was 41.90%, which was significantly higher than that in lupus patients without nephritis (30.67%) and healthy controls (11.50%). LN patients with MS showed a significantly increased carotid plaque ratio (28.41% versus 17.21%, P0.05) and IMT value (0.74 ± 0.25 mm versus 0.64 ± 0.18 mm, P0.01). Stepwise multiple regression further confirmed that age (β = 0.026, P = 0.033), duration of disease (β = 0.057, P = 0.025) and MS (β = 0.074, P0.001) were independent risk factors that affected the carotid IMT value in patients with LN.The prevalence of MS was comparatively high in patients with LN and was significantly correlated with carotid atherosclerosis, indicating that MS screening might be useful in the prevention and treatment of carotid atherosclerosis in patients with LN.

The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program.