hTERT promotes gastric intestinal metaplasia by upregulating CDX2 via NF-κB signaling pathway.

BACKGROUND: hTERT has been reported involved in the proliferation and metastasis of gastric cancer, but the role of hTERT in gastric intestinal metaplasia, a premalignant lesion of the gastric mucosa was unknown. The aim of the present study was to investigate the role of hTERT in GIM and the effect of hTERT on CDX2 expression in gastric cells. RESULTS: Experiments showed that expression of hTERT was significantly higher in GIM than in normal gastric mucosa. Moreover, hTERT increased the KLF4 level via NF-κB during GIM. Furthermore, KLF4 is involved in the up-regulation of CDX2 induced by hTERT, and hTERT can interact with p50, thereby increasing the level of CDX2. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expression of hTERT in gastric intestinal metaplasia tissue. Then, effect of hTERT on the expression of CDX2 was detected by qRT-PCR, WB and dual luciferase experiment. The role of p65 and p50 in the regulation of CDX2 were further detected by WB, CO-IP and ChIP. CONCLUSIONS: We may conclude that hTERT promotes GIM by up-regulating CDX2 via NF-κB signaling pathway.

Prolonged QT interval is linked to all-cause and cardiac mortality in chronic peritoneal dialysis patients.

AIM: Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS: The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS: Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (P = 0.03, log-rank test) and cardiac mortality free survival (P = 0.05, log-rank test). CONCLUSIONS: Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.

Multidisciplinary care in patients with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Multidisciplinary care (MDC) was widely used in multiple chronic illnesses but the effectiveness of MDC in patients with chronic kidney disease (CKD) was inconclusive. The aim of this meta-analysis is to estimate the effectiveness of MDC for CKD. METHODS: We searched PubMed, Web of Science, Google Scholar, Cochrane Library, and China Journal Full-text Database for relevant articles published in English or Chinese. Studies investigating MDC and non-MDC in patients with CKD were included. Random effect model was used to compare all-cause mortality, dialysis, risk of temporal catheterization, and hospitalization in the two treatment entities. RESULTS: We analyzed 8853 patients of 18 studies in patients with CKD stages 3-5, aged 63±12 years. MDC was associated with lower risk of all-cause mortality with an odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.44-0.88, p=0.01], mainly in cohort studies. MDC was associated with a lower risk of starting dialysis (p=0.02) and lower risk of temporal catheterization for dialysis (p<0.01). MDC was not associated with a higher chance of choosing peritoneal dialysis (p=0.18) or a lower chance of hospitalization for dialysis (p=0.13). CONCLUSIONS: Limited evidence from randomized controlled trials is currently available to support the benefit of MDC in patients with CKD. MDC is associated with lower all-cause mortality, lower risk of starting dialysis, and lower risk of temporal catheterization for dialysis in cohort studies. MDC is not associated with a higher chance of choosing peritoneal dialysis or a lower chance of hospitalization for dialysis. More studies are needed to determine the optimal professional that should be included in MDC.

Upper gastrointestinal bleeding in patients with CKD.

BACKGROUND AND OBJECTIVES: Patients with CKD receiving maintenance dialysis are at risk for upper gastrointestinal bleeding. However, the risk of upper gastrointestinal bleeding in patients with early CKD who are not receiving dialysis is unknown. The hypothesis was that their risk of upper gastrointestinal bleeding is negatively linked to renal function. To test this hypothesis, the association between eGFR and risk of upper gastrointestinal bleeding in patients with stages 3-5 CKD who were not receiving dialysis was analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with stages 3-5 CKD in the CKD program from 2003 to 2009 were enrolled and prospectively followed until December of 2012 to monitor the development of upper gastrointestinal bleeding. The risk of upper gastrointestinal bleeding was analyzed using competing-risks regression with time-varying covariates. RESULTS: In total, 2968 patients with stages 3-5 CKD who were not receiving dialysis were followed for a median of 1.9 years. The incidence of upper gastrointestinal bleeding per 100 patient-years was 3.7 (95% confidence interval, 3.5 to 3.9) in patients with stage 3 CKD, 5.0 (95% confidence interval, 4.8 to 5.3) in patients with stage 4 CKD, and 13.9 (95% confidence interval, 13.1 to 14.8) in patients with stage 5 CKD. Higher eGFR was associated with a lower risk of upper gastrointestinal bleeding (P=0.03), with a subdistribution hazard ratio of 0.93 (95% confidence interval, 0.87 to 0.99) for every 5 ml/min per 1.73 m(2) higher eGFR. A history of upper gastrointestinal bleeding (P<0.001) and lower serum albumin (P=0.004) were independently associated with higher upper gastrointestinal bleeding risk. CONCLUSIONS: In patients with CKD who are not receiving dialysis, lower renal function is associated with higher risk for upper gastrointestinal bleeding. The risk is higher in patients with previous upper gastrointestinal bleeding history and low serum albumin.

Association of walking with survival and RRT among patients with CKD stages 3-5.

BACKGROUND AND OBJECTIVES: Patients with CKD can benefit from an increase in physical activity. Walking is one of the most common exercises in patients with CKD; however, the association of walking with outcomes in patients with CKD is not clear. This study investigated the association of walking with overall mortality and RRT in patients with CKD stages 3-5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with CKD stages 3-5 in the CKD program of China Medical University Hospital from June 2003 to May 2013 were enrolled. The risks of overall mortality and RRT were analyzed using competing-risks regressions. RESULTS: A total of 6363 patients (average age, 70 years) during a median of 1.3 (range=0.6-2.5) years of follow-up were analyzed. There were 1341 (21.1%) patients who reported walking as their most common form of exercise. The incidence density rate of overall mortality was 2.7 per 100 person-years for walking patients and 5.4 for nonwalking ones. The incidence density rate of RRT was 22 per 100 person-years for walking patients and 32.9 for nonwalking ones. Walking, independent of patients' age, renal function, and comorbidity, was linked to lower overall mortality and lower RRT risk in the multivariate competing-risks regression. The adjusted subdistribution hazard ratio (SHR) of walking was 0.67 (95% confidence interval [95% CI], 0.53 to 0.84; P<0.001) for overall mortality and 0.79 (95% CI, 0.73 to 0.85; P<0.001) for the risk of RRT. The SHRs of overall mortality were 0.83, 0.72, 0.42, and 0.41 for patients walking 1-2, 3-4, 5-6, and ≥7 times per week, and the SHRs of RRT were 0.81, 0.73, 0.57, and 0.56, respectively. CONCLUSIONS: Walking is the most popular form of exercise in patients with CKD and is associated with lower risks of overall mortality and RRT. The benefit of walking is independent of patients' age, renal function, and comorbidity.

Comparison of hepatitis B surface antibody decay rates after vaccination between hemodialysis and peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: The available information about maintaining effective immunity after hepatitis B virus (HBV) vaccination in dialysis patients is limited. The aim of this study was to determine whether a difference exists in the persistence of immunity between hemodialysis (HD) and peritoneal dialysis (PD) patients. We compared the decay rate of hepatitis B surface antibody (anti-HBs) titers after HBV vaccination between HD and PD patients. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: A total of 103 HD and 53 PD patients who were completely vaccinated were enrolled. We examined their anti-HBs titers at the 1st month after vaccination then annually thereafter. Changes in the anti-HBs titers were assessed by comparing annual geometric mean titers (GMTs). RESULTS: The slopes of the anti-HBs titer decay rates plotted on a logarithmic scale for the HD and PD groups were -23.41 and -31.48, respectively. The decay rate of the PD group was significantly faster than that of the HD group (P=0.0053). CONCLUSION: The decay rate of anti-HBs titers in the PD group was faster than that in the HD group. Hepatitis B vaccination could not offer long-term protection in HD or PD patients. Post-vaccination testing every 6-12 months is necessary and revaccination may be protective in dialysis patients, especially in hyper-endemic areas of hepatitis B infection.