Relationship between Serum Irisin Level, All-Cause Mortality, and Cardiovascular Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: This study aimed to investigate the prospective role of serum irisin - a novel adipo-myokine - in all-cause mortality and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD). METHODS: A prospectively observational study was conducted with 154 PD patients. Baseline clinical data were collected from the medical records. Serum irisin concentrations were determined using enzyme-linked immunosorbent assay. Patients were divided into the high irisin group (serum irisin ≥113.5 ng/mL) and the low irisin group (serum irisin <113.5 ng/mL) based on the median value of serum irisin. A body composition monitor was used to monitor body composition. Cox regression analysis was utilized to find the independent risk factors of all-cause and CV mortality in PD patients. RESULTS: The median serum irisin concentration was 113.5 ng/mL (interquartile range, 106.2-119.8 ng/mL). Patients in the high irisin group had significantly higher muscle mass and carbon dioxide combining power (CO2CP) than those in the low irisin group (p < 0.05). Serum irisin was positively correlated with pulse pressure, CO2CP, and muscle mass, while negatively correlated with body fat percentage (p < 0.05). During a median of follow-up for 60.0 months, there were 55 all-cause deaths and 26 CV deaths. Patients in the high irisin group demonstrated a higher CV survival rate than those in the low irisin group (p = 0.016). Multivariate Cox regression analysis showed that high irisin level (hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.135-0.858; p = 0.022), age, and diabetic mellitus were independently associated with CV mortality in PD patients. However, serum irisin level failed to demonstrate a statistically significant relationship with all-cause mortality. CONCLUSION: Low serum irisin levels at baseline were independently predictive of CV mortality but not all-cause mortality in PD patients. Therefore, serum irisin could be a potential target for monitoring CV outcomes in PD patients.

Elevated serum fatty acid-binding protein 4 level predicts all-cause and cardiovascular mortality in peritoneal dialysis patients: a five-year study.

BACKGROUND: To explore the prospective role of serum fatty acid-binding protein 4 (FABP4) in the outcomes of peritoneal dialysis (PD) patients. METHODS: A prospective observational study was conducted with 159 patients on PD. Demographic and clinical data at baseline were collected from medical records. Biochemical data were recorded based on blood samples measured in a central laboratory. Serum FABP4 concentrations were determined using enzyme-linked immunosorbent assay. Body composition was measured using a Body Composition Monitor. Abdominal lateral plain radiography was used to evaluate vascular calcification. The primary endpoints were all-cause and cardiovascular death. RESULTS: The median of serum FABP4 concentration was 154.6 ng/mL (interquartile range, 132.8-269.7 ng/mL). Increased serum FABP4 was associated with increased vascular calcification proportion, time on dialysis, body mass index, high-sensitivity C-reactive protein (hs-CRP), intact parathyroid hormone (iPTH), triglycerides, body fat mass, and body fat percentage (p < 0.05). Increased serum FABP4 was associated with decreased residual kidney Kt/V urea (p < 0.05). Patients with hs-CRP≥ 3 mg/L had significantly higher serum FABP4 than those with hs-CRP< 3 mg/L (p < 0.05). Patients with vascular calcification had significantly higher serum FABP4 than those without vascular calcification (p < 0.05). During a median follow-up of 58.0 months, 58 all-cause deaths and 26 cardiovascular deaths occurred. High serum FABP4 levels were independently predictive for all-cause [hazard ratio (HR), 1.003; 95% confidence interval (CI), 1.001-1.005; p = 0.016] and cardiovascular death (HR, 1.005; 95% CI, 1.001-1.008; p = 0.006) in PD patients. CONCLUSIONS: Increased serum FABP4 levels can independently predict all-cause and cardiovascular death in patients on PD.

The Association between Baseline Serum Lipids and Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: Lipid disturbances are common in ESRD patients. In peritoneal dialysis (PD) patients, dyslipidemia is even more common. This study aimed to examine whether serum lipids were associated with prognosis of PD patients. METHODS: Patients from a multicenter retrospective cohort were used for the present study. The primary endpoint was all-cause mortality. Cox regression was used to analyze the association between serum lipids including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides and the prognosis. RESULTS: The results showed that lower total cholesterol and LDL levels at the initiation of PD predicted higher all-cause mortality in PD patients. Multivariate analysis reveal that the association disappeared after adjusting for age, gender, albumin, prealbumin, protein catabolic rate normalized to body weight, C-reactive protein, and residual renal function. Further analysis showed that patients with lower total cholesterol/LDL had a higher mortality only during the first 24 months of follow-up. In the patients who survived >2 years after PD, lower total cholesterol/LDL was not associated with higher long-term all-cause mortality any more. CONCLUSION: Lower total cholesterol/LDL levels at the initiation of PD were associated with overall mortality in PD patients. The association could be potentially modified by malnutrition, inflammation, and residual renal function or disappeared after 24 months.

Serum fatty acid binding protein 4 levels are associated with abdominal aortic calcification in peritoneal dialysis patients.

BACKGROUND: Fatty acid binding protein 4 (FABP4) is an adipokine that was mainly derived from adipocytes and macrophages. Vascular calcification (VC) is highly prevalent in peritoneal dialysis (PD) patients and could predict their cardiovascular mortality. The pathogenesis of VC is complex, and adipokines may play an important role in it. This study aimed to examine the relationship between serum FABP4 and VC in PD patients. METHODS: Serum FABP4 was measured by enzyme-linked immunosorbent assay. According to the median value of serum FABP4, the participants were divided into the low FABP4 group and the high FABP4 group. Lateral plain X-ray films of abdomen were used to evaluate the abdominal aortic calcification (AAC) score. The participants were divided into the high AAC score group (AAC score ≥4, indicating moderate or heavy VC) and the low AAC score group (AAC score <4, indicating no or mild VC). RESULTS: 116 PD patients were involved in the study. The AAC score and the proportion of patients with an AAC score ≥4 of the high FABP4 group were significantly higher than those of the low FABP4 group. Serum FABP4 of the high AAC score group was significantly higher than that of the low AAC score group [164.5 (138.4, 362.8) ng/mL versus 144.7 (123.8, 170.1) ng/mL, p = 0.002]. Serum FABP4 was positively associated with the AAC score according to the multivariate linear regression analysis. In the multivariate logistic regression analysis, serum FABP4 was the independent influencer of an AAC score ≥4. CONCLUSIONS: Serum FABP4 is positively associated with the AAC score and is an independent marker of AAC in PD patients.

Lower Serum Irisin Levels Are Associated with Increased Abdominal Aortic Calcification in Peritoneal Dialysis Patients.

INTRODUCTION: Vascular calcification (VC), with the mechanisms remaining unclear, is closely related with dialysis patients' cardiovascular mortality and all-cause mortality. Irisin is a newly identified myokine. This study aims to evaluate the serum irisin levels of peritoneal dialysis (PD) patients and their relationship with VC. METHODS: This cross-sectional study enrolled stable PD patients in Peking University Third Hospital who were followed for >6 months. We used plain X-ray films of abdomen to quantitatively evaluate VC of abdominal aorta. VC was evaluated by abdominal aortic calcification (AAC) scores, and PD patients were divided into the high AAC score group (AAC score ≥4) and the low AAC score group (AAC score <4). Demographic data and laboratory indexes were collected. Serum irisin concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: A total of 102 PD patients were enrolled in this study, and 52 patients (51.0%) were found to have a high AAC score of ≥4. Age, diabetic mellitus proportion, pulse pressure, hypercalcemia (corrected calcium >2.54 mmol/L) rate, serum ultrasensitive C reactive protein, and AAC scores were significantly higher in the high AAC score group than those of the low AAC score group (p < 0.05). The high AAC score group had lower diastolic blood pressure, serum albumin, and serum carbon dioxide combining power compared with the low AAC score group (p < 0.05). Serum irisin levels of PD patients with a high AAC score were significantly lower than those of PD patients with a low AAC score (109.7 ± 13.1 ng/mL vs. 115.9 ± 10.1 ng/mL, p = 0.010). The multivariate logistic regression analyses showed that serum irisin, diabetic mellitus, serum ultrasensitive C reactive protein, and age were independent factors influencing the occurrence of VC in PD patients. CONCLUSION: Our results are the first to provide a clinical evidence of the association between serum irisin and abdominal aortic calcification in PD patients. Lower irisin levels, diabetic mellitus, higher serum ultrasensitive C reactive protein, and older age could be potential predictive factors for VC in PD patients.

Serum Sphingosine-1-phosphate level and peritonitis in peritoneal dialysis patients.

BACKGROUND: Given the important role of Sphingosine-1-phosphate (S1P) in maintaining the hemostasis in intestinal barrier function and regulation of inflammation and immune, we hypothesize that S1P might be a biomarker to predict peritonitis in peritoneal dialysis (PD) patients. METHODS: In this case-control study, 78 stable, continuous ambulatory peritoneal dialysis patients were enrolled and followed for the episode of PD associated peritonitis. Patients were divided into two groups by whether or not they had peritonitis during follow-up: non-peritonitis (n = 65) and peritonitis (n = 13) group. S1P was analyzed by enzyme-linked immunosorbent assay. Logistic regression analysis was used to assess factors associated with peritonitis. The variables identified by univariable regression models (p < 0.1) were further selected into the multivariable logistic regression model to determine whether they could independently affect peritonitis. RESULTS: Patients with peritonitis had a lower level of S1P than that of patients without peritonitis (1.3 ng/mL IQ 0.8, 3.6 ng/mL vs. 2.8 ng/mL IQ 1.5, 5.4 ng/mL, p = 0.018). The peritonitis group had lower serum albumin, lower blood leukocyte, lower hemoglobin and lower platelet count as compared to the non-peritonitis group. Logistic regression analysis showed that S1P (OR = 0.381, 95% CI = 0.171-0.848, p = 0.018), blood leukocyte count (OR = 0.438, 95% CI = 0.207-0.925, p = 0.030), and serum albumin (OR = 0.732, 95% CI = 0.556-0.962, p = 0.025) were independent factors associated with peritonitis in the present PD population. CONCLUSION: Our study showed that S1P was an independent determinant of subsequent peritonitis in PD patients. S1P might serve as a biomarker to predict peritonitis in PD patients.

Peritoneal dialysis outcomes in patients with nephrotic syndrome: a propensity score-matched cohort study.

INTRODUCTION: It is unclear whether patients with end-stage renal disease (ESRD) and nephrotic syndrome (NS) can be treated with peritoneal dialysis (PD). OBJECTIVES: To investigate the outcomes of PD treatment in ESRD patients with or without NS. METHODS: In this retrospective cohort study, all incident patients with ESRD and NS who started PD from 1 February 2006 to 31 December 2017, were matched with patients without NS using propensity scores based on age, sex, diabetes mellitus status, and serum albumin. RESULTS: Fifty-three patients in the NS PD group and 53 matched controls were included. The median survival of the NS PD group was comparable to that of the non-NS PD group. An interaction effect was observed between survival time and baseline NS status. Thus, patients' outcomes within and after 1.5 years were analyzed separately. Both mortality (log-rank test, p= .235) and technique failure (log-rank test, p= .543) rates within 1.5 years in patients with NS were comparable to those of the non-NS group. After 1.5 years, however, the NS status at baseline was associated with lower all-cause mortality (p= .020) and lower technique failure (p= .008) rates in PD patients compared with the non-NS group. The multivariable Cox regression analysis showed that compared with the patients in the non-NS PD group, PD patients with NS had both significantly lower all-cause mortality and lower technique failure rate after adjusting for other factors. CONCLUSIONS: Our study indicates that PD may be considered as a long-term renal replacement therapy for patients with ESRD and baseline NS.

Serum albumin changes and mortality risk of peritoneal dialysis patients.

PURPOSE: Initial or single time point serum albumin levels have been shown to be important in predicting the prognosis of peritoneal dialysis (PD) patients. However, we assume the dynamic change and trend of albumin after PD are essential. We aimed to investigate the association between baseline albumin levels, albumin trajectories, and patient mortality in a retrospective cohort study. METHODS: In this retrospective cohort study, 547 incident PD patients were enrolled from Peking University Third Hospital. Date were collected by medical records review, including age, gender, body mass index, primary disease, comorbidities, and laboratory tests. A joint model for longitudinal data and time-to-event data was used to establish the relationship between serum albumin trajectories and mortality risk of PD patients. RESULTS: The albumin trajectories was negatively correlated with risk of death. The increase in the current value of albumin trajectories at time points t after PD was associated with decreased risk of death (HR = 0.881, p < 0.0001). There was no statistical association between initial albumin and risk of death (HR = 1.030, 95% CI 0. 995-1.066). The results showed that increased age, higher albumin-corrected Ca levels, and higher eGFR values were risk factors for death. In addition, predictors of low albumin levels are increased PD time, increased age, increased albumin-corrected Ca, and decreased BMI as well as initial albumin levels. CONCLUSION: This study demonstrates that albumin trajectories after PD is better than initial serum albumin level in predicting mortality risk. Increasing albumin level over time can improve the prognosis of PD patients.

Cardiorenal syndrome in incident peritoneal dialysis patients: What is its effect on patients' outcomes?

BACKGROUND: Peritoneal dialysis (PD) is increasingly used for long-term management of Cardiorenal Syndrome (CRS). We compared outcomes in incident PD patients according to their baseline heart failure status. METHODS: This retrospective cohort study evaluated all-cause and cardiovascular mortality in incident PD patients with different heart failure status (non-CRS, acute heart failure [AHF], type II CRS, type IV CRS) who started PD between 2006 and 2016 in the Peking University Third Hospital. RESULTS: Of 748 patients included in the study, there were 466 (62.3%), 214 (28.6%), 27 (3.6%), and 41 (5.5%) patients in the non-CRS, AHF, type II CRS and type IV CRS groups, respectively. Patients with CRS were older (p<0.001), with more diabetes mellitus (p<0.001), coronary heart history (p<0.001), higher estimated glomerular filtration rate (eGFR) (p<0.001), lower serum creatinine (p<0.001) and phosphorus levels (p = 0.003) compared to non-CRS patients. Respective all-cause survival rates for patients with non-CRS, AHF, type II CRS and type IV CRS were 90.6%, 87.1%, 85.2% and 84.8% at 1 year, and 63.1%, 47.7%, 27.3% and 35.1% at 5 years (p<0.001). The corresponding figures for cardiovascular survival were 93%, 92%, 84% and 81% at 1 year, and 67%, 59%, 55% and 54% at 5 years (p<0.001). However, after adjusting for confounding factors, the presence of CRS was not independently associated with all-cause mortality whereas type IV CRS (HR 2.10, 95% CI 1.03-4.28, p = 0.04) was associated with higher cardiovascular mortality as compared to without CRS. CONCLUSION: Incident PD patients with different types of CRS had higher rates of both all-cause and cardiovascular mortality compared with patients without CRS. However, these observed adverse outcomes may be related to associated older age and higher prevalence of comorbidities, rather than CRS per se, except for type IV CRS, treatment strategies to reduce high cardiovascular CVD mortality may needed.

Irisin and Volume Overload are Associated with Protein Energy Wasting in Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Protein energy wasting (PEW) is a common medical phenomenon that is observed in maintenance dialysis patients. PEW also increases morbidity and mortality of these patients. Its pathogenesis is unclear. We hypothesize that serum irisin levels and volume overload may induce PEW in peritoneal dialysis (PD) patients. The aim of this study is to measure serum irisin levels, evaluate volume status of PD patients, and study their correlations with PEW in PD patients. METHODS: This study is a cross-sectional study with 160 PD patients from the PD center of Peking University Third Hospital and 35 healthy control subjects. PD patients were divided into PEW group and non-PEW group according to PEW diagnosis criteria. Serum irisin concentrations were measured by ELISA. Volume overload status (volume overload is defined as overhydration value ≥2 liters) of PD patients was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels were significantly lower in PD patients compared with those of the controls (113.2±11.8 ng/ml vs. 464.2±37.4 ng/ml, P<0.01). The serum irisin levels were lower in PD patients with PEW than those of the patients without PEW (106.5±15.2 ng/ml vs. 117.4±17.6 ng/ml, P<0.01). PEW is more prevalent in patients with volume overload than patients without volume overload (62.5% vs. 43.1%, x2=5.756, P=0.016); however, no direct relationship was found between irisin levels and volume overload status. The independent influencing factors of PEW were serum irisin, serum albumin, and volume overload. CONCLUSION: Our results are the first to provide clinical evidence of the association between serum irisin, volume overload, and PEW in PD patients. PEW may inhibit the release or synthesis of irisin from skeletal muscles, and volume overload may aggravate PEW in PD patients.

What's the Optimal Lipids Level for Dialysis Patients? A Cohort Study from a Chinese Dialysis Center in a University Hospital.

BACKGROUND: With lipid level being a major contributing factor for cardiovascular health, the high cardiovascular mortality among dialysis patients has raised substantial concerns in regard to the optimal lipid level in these patient population. OBJECTIVE: To explore the optimal lipid level for the survival of dialysis patients. METHODS: The lipid profile was measured for each patient. All participants were followed throughout the course of the study. Cox proportional hazards analysis was performed to analyze the prognostic value of lipid level on the survival of these patients. RESULTS: In our study that included 311 stable maintenance dialysis patients, 54.98% of the participants had LDL-C level ≥100 mg/dl and 82.91% of the patients with triglycerides ≥200 mg/dl had non-HDL level ≥130 mg/dl. During the follow-up period of 48.0 (18.0, 55.5) months, 149 (47.91%) participants died. Among those who died, 59 patients died of cardiovascular disease (CVD) and 33 patients died of ischemic CVD (12.0, 4.7, and 2.7 events per 100 patient-years, respectively). Patients with LDL-C 100-130 mg/dl or non-HDL 130-160 mg/dl had a lower all-cause mortality rate than those who did not meet these criteria. After adjusting for the traditional and ESRD-related risk factors, non-HDL was found to be the independent risk factor for the all-cause mortality. Compared to those patients with non-HDL 130-160 mg/dl, patients with non-HDL <100 mg/dl, 100-130 mg/dl, 160-190 mg/dl, or ≥190 mg/dl all had higher all-cause mortality: HR (95% CI) 3.207 (1.801, 5.713), 2.493 (1.485, 4.184), 2.476 (1.423, 4.307), and 1.917 (1.099, 3.345), respectively. There were no differences in nutrition, comorbidity, and inflammation indices among the patients with different non-HDL groups. However, patients with non-HDL of 130-160 mg/dl had the lowest corrected calcium and calcium phosphate product values as compared with other non-HDL groups. CONCLUSION: Our study demonstrated that non-HDL 130-160 mg/dl might be the most appropriate lipid level in our dialysis patients. Our follow-up data also showed that patients with higher lipid level had poorer prognosis, just as in the general population.

Pre-dialysis renal clinic visits and patients' outcomes on peritoneal dialysis.

PURPOSE: To investigate the effect of pre-dialysis renal care on peritoneal dialysis (PD) patients' outcomes in China. METHODS: In this retrospective cohort study, patients who started PD during January 1, 2006, to December 31, 2014, were included. Patients' medical charts were reviewed to extract the information. To explore the effect of pre-dialysis renal care on patients' outcomes, patient were divided into two groups according to whether or not they had frequent renal clinic visits: Group A (with frequent visits) and Group B (without frequent visits). RESULTS: A total of 668 patients were included. Patients who admitted to emergency room before PD initiations were significantly higher in Group B than in Group A (42.7 vs. 33 %, p = 0.01). However, there was no significant difference in the proportion of patients requiring emergency hemodialysis prior to PD commencement (20.5 vs. 24.6 %, p = 0.21), acute heart failure (30.2 vs. 35.4 %, p = 0.16) and pulmonary infection (15.4 vs. 12.1 %, p = 0.23) between groups. Both the mortality and technical failure rate in Group A were significantly lower as compared to Group B (p = 0.003 and p < 0.01, respectively). Multivariable Cox regression analysis showed frequent pre-dialysis renal clinic visits were associated with both lower mortality rate (HR 0.62, 95 % CI 0.46-0.85, p = 0.003) and technical failure on PD (HR 0.58, 95 % CI 0.36-0.92, p = 0.022). CONCLUSION: Pre-dialysis frequent clinic visits were associated with better PD outcomes. Pre-dialysis renal clinic management was suboptimal in the present cohort. More organized system to ensure people with established chronic kidney disease are well managed is necessary in China.

Barriers to community-based drug dependence treatment: implications for police roles, collaborations and performance indicators.

INTRODUCTION: Worldwide, people who use drugs (PWUD) are among the populations at highest risk for HIV infection. In China, PWUD are primarily sentenced to compulsory detainment centres, in which access to healthcare, including HIV treatment and prevention services, is limited or non-existent. In 2008, China's 2008 Anti-Drug Law encouraged the development and use of community-based drug dependence rehabilitation, yet there is limited evidence evaluating the efficacy and challenges of this model in China. In this study, we explore these challenges and describe how cooperation between law enforcement and health departments can meet the needs of PWUD. METHODS: In 2015, we conducted semi-structured, in-depth interviews with all four staff members and 16 clients of the Ping An Centre No. 1 for community-based drug treatment, three local police officers and three officials from the local Centre for Disease Control. Interviews explored obstacles in implementing community-based drug dependence treatment and efforts to resolve these difficulties. Transcripts were coded and analyzed with qualitative data analysis software (MAXQDA 11). RESULTS: We identified three challenges to community-based drug treatment at the Ping An Centre No. 1: (1) suboptimal coordination among parties involved, (2) a divergence in attitudes towards PWUD and harm reduction between law enforcement and health officials and (3) conflicting performance targets for police and health officials that undermine the shared goal of treatment. We also identified the take-home methadone maintenance treatment model at the Ping An Centre No. 1 as an example of an early successful collaboration between the police, the health department and PWUD. CONCLUSIONS: To overcome barriers to effective community-based drug treatment, we recommend aligning the goals of law enforcement and public health agencies towards health-based performance indicators. Furthermore, tensions between PWUD and police need to be addressed and trust between them fostered, using community-based treatment centres as mediators. The preliminary success of the take-home methadone maintenance treatment pilot can serve as an example of how collaboration with the police and other government agencies can meet the needs of PWUD and contribute to the success of community-based treatment.

The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.

UNLABELLED: ♦ BACKGROUND: Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ METHODS: Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ RESULTS: A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ CONCLUSIONS: Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis.

MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2.

Colorectal cancer remains the third most common cause of death from cancer worldwide. MicroRNA emerges as a good area of research for current cancer therapy. Here, we identified miR-135b to be a contributor to anti-apoptosis and chemoresistance in colorectal cancer. We observed high levels of miR-135b in colorectal cancer cell lines and clinical tissues, compared to colorectal epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-135b attenuated doxorubicin-induced apoptosis in colorectal cells. (Doxorubicin alone can trigger significant apoptosis). In elucidating the molecular mechanism by which miR-135b participate in the regulation of apoptosis and chemoresistance in colorectal cancer, we discovered that large tumor suppressor kinase 2 (LATS2) is a direct target of miR-135b. The role of miR-135b was confirmed in colorectal tumor xenograft models. The growth of established tumors was suppressed by an inhibition of miR-135b expression and enhanced apoptosis was further assessed by TUNEL assay. Taken together, our results reveal that miR-135b and LATS2 axis may be a novel therapeutic target for colorectal cancer.

The associations between the family education and mortality of patients on peritoneal dialysis.

AIMS: To investigate whether education level of family members predicts all-cause and cardiovascular death and initial-episode peritonitis in patients on peritoneal dialysis (PD). METHODS: A total of 2264 patients on chronic PD were collected from seven centers affiliated with the Socioeconomic Status on the Outcome of Peritoneal Dialysis (SSOP) Study. All demographic, socioeconomic and laboratory data of patients and the education level of all family members were recorded at baseline. Multivariate Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular mortality, and initial-episode peritonitis with adjustments for recognized traditional factors. RESULTS: There were no significant differences in baseline characteristics between patients with (n = 1752) and without (n = 512) complete education information. According to the highest education level of patients' family, included 1752 patients were divided into four groups, i.e. elementary or lower (15%), middle (27%), high (24%) and more than high school (34%). The family highest education (using elementary school or lower group as reference, hazard ratio and 95% confidence interval of middle school group, high school group and more than high school group was 0.68[0.48-0.96], 0.64[0.45-0.91], 0.66[0.48-0.91], respectively) rather than their average education level or patients' or spouse's education was significantly associated with the higher mortality. Neither patients' nor family education level did correlate to the risk for cardiovascular death or initial-episode peritonitis. CONCLUSIONS: Family members' education level was found to be a novel predictor of PD outcome. Family, as the main source of health care providers, should be paid more attention in our practice.

The associations of uric acid, cardiovascular and all-cause mortality in peritoneal dialysis patients.

AIMS: To investigate whether uric acid (UA) is an independent predictor of cardiovascular (CV) and all-cause mortality in peritoneal dialysis (PD) patients after controlling for recognized CV risk factors. METHODS: A total of 2264 patients on chronic PD were collected from seven centers affiliated with the Socioeconomic Status on the Outcome of Peritoneal Dialysis (SSOP) Study. All demographic and laboratory data were recorded at baseline. Multivariate Cox regression was used to calculate the hazard ratio (HR) of CV and all-cause mortality with adjustments for recognized traditional and uremia-related CV factors. RESULTS: There were no significant differences in baseline characteristics between patients with (n = 2193) and without (n = 71) UA measured. Each 1 mg/dL of increase in UA was associated with higher all-cause mortality with 1.05(1.00∼1.10) of HR and higher CV mortality with 1.12 (1.05∼1.20) of HR after adjusting for age, gender and center size. The highest gender-specific tertile of UA predicted higher all-cause mortality with 1.23(1.00∼1.52) of HR and higher CV mortality with 1.69 (1.21∼2.38) of HR after adjusting for age, gender and center size. The predictive value of UA was stronger in patients younger than 65 years without CV disease or diabetes at baseline. The prognostic value of UA as both continuous and categorical variable weakened or disappeared after further adjusted for uremia-related and traditional CV risk factors. CONCLUSIONS: The prognostic value of UA in CV and all-cause mortality was weak in PD patients generally, which was confounded by uremia-related and traditional CV risk factors.

Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis.

BACKGROUND: Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients. METHODS: Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions. RESULTS: Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared. CONCLUSION: Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.

[Analysis of clinical state for arteriosclerosis obliterans in lower extremity of diabetic patients on peritoneal dialysis].

OBJECTIVE: To investigate the prevalence of arteriosclerosis obliterans in lower extremity and its influence factors in diabetic patients on peritoneal dialysis. METHOD: In this single center cross-sectional study, 74 with diabetic patients on peritoneal dialysis were recruited. The general information, dialysis program, laboratory examination and dialysis adequacy test results were recorded.Their symptoms and signs of arteriosclerosis obliterans in lower extremities were investigated and ankle brachial index (ABI) was determined. RESULT: In this study,70.3% of the patients had different degrees of symptoms and signs of arteriosclerosis obliterans in lower extremity. With Fortaine classification, 13.5% of the patients were in early lesions phase, 28.8% in local ischemic phase, 51.9% in nutritional disturbance phase, and 5.8% in gangrene phase. The patients were divided into three groups base on Fontaine classification: control group (no symptoms), mild group(early lesions phase and local ischemic phase) and severe group(nutritional disturbance phase and gangrene phase). There was a significant difference between the insulin dose, left foot ABI levels, plasma albumin levels and total Kt/V levels among the three groups (P<0.05). The plasma albumin levels and insulin doses were independent factors associated with arteriosclerosis obliterans in lower extremity (P<0.05). CONCLUSION: In diabetic patients on peritoneal dialysis, there is a high prevalence of arteriosclerosis obliterans in lower extremity, which is related to high insulin dosage and low serum albumin levels.

Impact of individual and environmental socioeconomic status on peritoneal dialysis outcomes: a retrospective multicenter cohort study.

OBJECTIVES: We aimed to explore the impacts of individual and environmental socioeconomic status (SES) on the outcome of peritoneal dialysis (PD) in regions with significant SES disparity, through a retrospective multicenter cohort in China. METHODS: Overall, 2,171 incident patients from seven PD centers were included. Individual SES was evaluated from yearly household income per person and education level. Environmental SES was represented by regional gross domestic product (GDP) per capita and medical resources. Undeveloped regions were defined as those with regional GDP lower than the median. All-cause and cardiovascular death and initial peritonitis were recorded as outcome events. RESULTS: Poorer PD patients or those who lived in undeveloped areas were younger and less-educated and bore a heavier burden of medical expenses. They had lower hemoglobin and serum albumin at baseline. Low income independently predicted the highest risks for all-cause or cardiovascular death and initial peritonitis compared with medium and high income. The interaction effect between individual education and regional GDP was determined. In undeveloped regions, patients with an elementary school education or lower were at significantly higher risk for all-cause death but not cardiovascular death or initial peritonitis compared with those who attended high school or had a higher diploma. Regional GDP was not associated with any outcome events. CONCLUSION: Low personal income independently influenced all-cause and cardiovascular death, and initial peritonitis in PD patients. Education level predicted all-cause death only for patients in undeveloped regions. For PD patients in these high risk situations, integrated care before dialysis and well-constructed PD training programs might be helpful.