Long noncoding RNA X-inactive specific transcript regulates NLR family pyrin domain containing 3/caspase-1-mediated pyroptosis in diabetic nephropathy.

BACKGROUND: NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology. Long noncoding RNAs (lncRNAs) are active participators of diabetic nephropathy (DN). X inactive specific transcript (XIST) expression has been reported to be elevated in the serum of DN patients. AIM: To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell (RTEC) pyroptosis in DN. METHODS: A DN rat model was established through streptozotocin injection, and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST. Renal metabolic and biochemical indices were detected, and pathological changes in the renal tissue were assessed. The expression of indicators related to inflammation and pyroptosis was also detected. High glucose (HG) was used to treat HK2 cells, and cell viability and lactate dehydrogenase (LDH) activity were detected after silencing XIST. The subcellular localization and downstream mechanism of XIST were investigated. Finally, a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3 (NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p (miR-15b-5p)/Toll-like receptor 4 (TLR4) axis. RESULTS: XIST was highly expressed in the DN models. XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury. The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells; cell viability was decreased and LDH activity was increased after HG treatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically, XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promoting miR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect of silencing XIST on HG-induced RTEC pyroptosis. CONCLUSION: Silencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury in DN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.

Deletion of Smad3 protects against C-reactive protein-induced renal fibrosis and inflammation in obstructive nephropathy.

Introduction and Aims: Elevated plasma levels of C-reactive protein (CRP) are closely associated with progressive renal injury in patients with chronic kidney disease (CKD). Here, we tested a hypothesis that CRP may promote renal fibrosis and inflammation via a TGF-ß/Smad3-dependent mechanism. Methods: Role and mechanisms of TGF-ß/Smad3 in CRP-induced renal fibrosis and inflammation were examined in a mouse model of unilateral ureteral obstruction (UUO) induced in CRP Tg/Smad3 KO mice and in a rat tubular epithelial cell line in which Smad3 gene is stably knocked down (S3KD-NRK52E). Results: We found that mice overexpressing the human CRP gene were largely promoted renal inflammation and fibrosis as evidenced by increasing IL-1ß, TNF-α, MCP-1 expression, F4/80+ macrophages infiltration, and marked accumulation of α-smooth muscle actin (α-SMA), collagen I and fibronectin in the UUO kidney, which were blunted when Smad3 gene was deleted in CRPtg-Smad3KO. Mechanistically, we found that the protection of renal inflammation and fibrosis in the UUO kidney of CRPtg-Smad3KO mice was associated with the inactivation of CD32-NF-κB and TGF-ß/Smad3 signaling. Conclusion: In conclusion, Smad3 deficiency protects against CRP-mediated renal inflammation and fibrosis in the UUO kidney by inactivating CD32-NF-κB and TGF-ß/Smad3 signaling.

Depression at Baseline Is an Independent Risk Factor for Cognitive Decline in Patients on Peritoneal Dialysis: A Multicenter Prospective Cohort Study.

Background:Depression has been recognized as a risk factor for cognitive impairment (CI) from cross-sectional datasets. This multicenter prospective study investigated the association between depression and cognitive decline in peritoneal dialysis (PD) patients.Methods:This multicenter prospective cohort study included 458 PD patients who were followed up for 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function, Trail-Making Tests A and B for executive function, subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skill, and language ability. Depression was assessed using Zung's Self-Rating Depression Scale.Results:During the 2-year follow-up, patients with moderate/severe depression at baseline showed a significant decline in global cognitive function (80.5 ± 15.2 vs 76.6 ± 15.5, p = 0.008), while patients without depression or with mild depression kept a stable global cognitive function. In the meantime, patients without depression showed significant improvements in immediate memory, visuospatial skill, and language ability. However, no significant improvement in these parameters was shown in depression groups. In multivariable linear regression analysis, depression at baseline was a significant predictor of worsening global cognitive function, whether depression was analyzed as a continuous variable (odds ratio [OR] = -0.14, 95% confidence interval [CI] -0.27, -0.01, p = 0.031) or a rank variable (OR = -1.88, 95% CI -3.30, -0.45, p = 0.010). Moreover, higher depression score or more severe depression degradation was significantly associated with decline of immediate memory, delayed memory, and language skill.Conclusion:Depression was a significant risk factor for worsening of CI in PD patients.

The Association of Cognitive Impairment with Peritoneal Dialysis-Related Peritonitis.

Background:Research on the association between cognitive impairment (CI) and peritoneal dialysis (PD)-related peritonitis is limited. Therefore, we investigated whether CI contributed to the risk of PD-related peritonitis.Methods:This prospective cohort study enrolled 458 patients from 5 PD centers between 1 March 2013, and 30 November 2013, and continued until 31 May 2016. We used the Modified Mini-Mental State Examination (3MS) to assess general cognition, the Trail-Making Test to assess executive function, and subtests of the Battery for the Assessment of Neuropsychological Status to assess immediate and delayed memory, visuospatial skills, and language ability. Patients were assigned to CI and non-CI groups based on their 3MS scores. The first episode of peritonitis was the primary endpoint event. Treatment failure of peritonitis was defined as peritonitis-associated death or transfer to hemodialysis. We used competing risk models to analyze the association between CI and the risk of peritonitis. The association of CI with treatment failure after peritonitis was analyzed using logistic regression models.Results:Ninety-four first episodes of peritonitis were recorded during a median follow-up of 31.4 months, 18.1% of which led to treatment failure. No significant group differences were observed for the occurrence, distribution of pathogenic bacteria, or outcomes of first-episode peritonitis. Immediate memory dysfunction was independently associated with a higher risk of PD-related peritonitis (hazard ratio [HR] 1.736, 95% confidence interval [CI] 1.064 - 2.834, p < 0.05), adjusting for confounders.Conclusions:Immediate memory dysfunction was a significant, independent predictor of PD-related peritonitis. Neither general nor specific domains of CI predicted treatment failure of peritonitis.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

BACKGROUND: Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). METHODS: In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). CONCLUSIONS: Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Association of Social Support and Family Environment with Cognitive Function in Peritoneal Dialysis Patients.

♦ BACKGROUND: Cognitive impairment (CI) is a common phenomenon and predictive of high mortality in peritoneal dialysis (PD) patients. This study aimed to analyze the association of social support and family environment with cognitive function in PD patients. ♦ METHODS: This is a cross-sectional study of PD patients from Peking University First Hospital and the Second Affiliated Hospital of Harbin Medical University. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), executive function was measured by the A and B trail-making tests, and other cognitive functions were measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Social support was measured with the Social Support Scale developed by Xiaoshuiyuan and family environment was measured with the Chinese Version of the Family Environment Scale (FES-CV). ♦ RESULTS: The prevalence of CI and executive dysfunction among the 173 patients in the study was, respectively, 16.8% and 26.3%. Logistic regression found that higher global social support (odds ratio [OR] = 1.09, 1.01 - 1.17, p = 0.027) and subjective social support predicted higher prevalence of CI (OR = 1.13, 1.02 - 1.25, p = 0.022), adjusting for covariates. Analyses of the FES-CV dimensions found that greater independence was significantly associated with better immediate memory and delayed memory. Moreover, higher scores on achievement orientation were significantly associated with poorer language skills. ♦ CONCLUSIONS: Our findings indicate that social support is negatively associated with the cognitive function of PD patients and that some dimensions of the family environment are significantly associated with several domains of cognitive function.

Performance of the Modified Mini-Mental State Examination (3MS) in Assessing Specific Cognitive Function in Patients Undergoing Peritoneal Dialysis.

PURPOSE: While Cognitive impairment (CI) has been identified as an independent risk factors for mortality in patients undergoing peritoneal dialysis (PD), it is inadequately assessed. We evaluated the applicability of the Modified Mini-Mental State Examination (3MS) in assessing specific cognitive function and compared it to a detailed neuropsychological test battery as the reference standard. METHODS: In this multicentric cross-sectional study, we enrolled 445 clinically stable patients from five PD units, who were undergoing PD for at least 3 months. The 3MS was evaluated for general cognitive function. A detailed neuropsychological battery including domains of immediate memory, delayed memory, executive function, language, and visuospatial ability were evaluated as reference standards. Sensitivity and specificity of the 3MS was determined by using receiver operating characteristic (ROC) analysis. RESULTS: The CI prevalence evaluated by 3MS was 23.6%. PD patients with CI performed worse in all cognitive domains. The 3MS correlated well with specific cognitive domains. However, 18.5%, 57.4%, 12.6%, 8.8%, and 41.2% of patients whom were idendified as normal by 3MS still showed executive dysfunction, immediate memory impairment, delayed memory impairment, and language-ability and visuospatial-ability impairment, respectively. The 3MS identified patients having specific cognitive dysfunction with varied extent of diagnostic value, with 0.50, 0.42, 0.35, 0.34, and 0.26 of Youden index in executive function, delayed memory, language ability, immediate memory, and visuospatial ability, respectively. CONCLUSIONS: The 3MS is not a comprehensive instrument for major cognitive domains in PD patients. It could, however, be used for executive dysfunction and delayed memory impairment screening.

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.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

BACKGROUND: Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. STUDY DESIGN: Multicenter cross-sectional study. SETTING & PARTICIPANTS: 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. PREDICTOR: Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. OUTCOMES: Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. LIMITATIONS: The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. CONCLUSIONS: Even mild depression is closely associated with global and specific cognitive impairment in PD patients.

Hyponatremia and Cognitive Impairment in Patients Treated with Peritoneal Dialysis.

BACKGROUND AND OBJECTIVES: Hyponatremia has been identified as a relevant factor for cognitive impairment but has not been investigated in patients receiving peritoneal dialysis (PD). This study investigated the relationship between hyponatremia and cognitive functions in PD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 476 clinically stable patients from five PD units who were older than 18 years of age and had undergone PD for at least 3 months between March 2013 and March 2014 were enrolled in this multicenter cross-sectional study. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS); executive function, by trail making tests A (trails A) and B (trails B); and immediate memory, delayed memory, and language ability, by subtests of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Hyponatremia was defined as serum sodium level ≤135 mmol/L, which was calculated as the mean of measurements taken over the preceding 3 months. RESULTS: Fifty patients (10.5%) had hyponatremia; these patients tended to be older and less educated, to have less inflammation, and to have the higher prevalence of cognitive impairment. They also had lower scores on RBANS subtests. After adjustment for demographic and clinical confounders, hyponatremia was independently associated with lower 3MS score (coefficient, -5.28; 95% confidence interval [CI], -8.44 to -2.13) and longer completion time of trials A (coefficient, 22.68; 95% CI, 3.44 to 41.92) and B (coefficient, 45.56; 95% CI, 1.30 to 89.81). After additional adjustment for laboratory measures, hyponatremia was still associated with 3MS score and completion time of trails A. Hyponatremia was independently associated with CI (odds ratio, 2.17; 95% CI, 1.02 to 4.94) and executive dysfunction (odds ratio, 2.43; 95% CI, 1.01 to 5.87) using multivariate logistic regression analysis. Sensitivity analyses with multivariable models that included propensity score still supported the association between hyponatremia and cognitive impairment. CONCLUSIONS: Hyponatremia was associated with global and specific cognitive impairment in PD patients.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

UNLABELLED: ♦ BACKGROUND: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ METHODS: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ RESULTS: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ CONCLUSIONS: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis.

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.

Associations between serum-intact parathyroid hormone, serum 25-hydroxyvitamin D, oral vitamin D analogs and metabolic syndrome in peritoneal dialysis patients: a multi-center cross-sectional study.

INTRODUCTION: Although previous studies have suggested associations between serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MS) in the general population, these associations are still uncharacterized in peritoneal dialysis (PD) patients. METHODS: In total, 837 prevalent PD patients from 5 centers in China were enrolled between April 1, 2011 and November 1, 2011. The demographic data, biochemical parameters and medical records were collected, except for serum 25(OH)D which was measured in 347 of 837 patients. The definition of MS was modified from National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATPIII). RESULTS: 55.4% of 837 patients were found to have MS. The median concentration of iPTH, 25(OH)D and doses of oral vitamin D analogs for participants with MS was significantly lower than those without MS. The iPTH, 25(OH)D values and doses of vitamin D analogs were all associated with one or more components of MS. After multivariate adjustment, low serum iPTH values and oral vitamin D analogs, rather than serum 25(OH)D, were significantly associated with the presence of MS, abnormal fasting blood glucose (FBG) and high-density lipoprotein cholesterol (HDL-C). Compared to iPTH < 130 pg/mL, iPTH 130-585 pg/mL and > 585 pg/mL were associated with a lower risk of MS with adjusted odds ratio (OR) of 0.59 and 0.33, respectively. Taking vitamin D analogs was also associated with a lower risk of MS with adjusted OR of 0.55. CONCLUSIONS: Serum iPTH and the use of active vitamin D supplements rather than serum 25(OH)D were independently associated with the presence of MS in patients on PD.

SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation.

This study is the first to investigate the anticancer effect of Schisandra chinensis polysaccharide (SCP) in renal cell carcinoma (RCC) cells. The results revealed that SCP treatment showed high cytotoxic potency in Caki-1 cells by inducing apoptosis, which is associated with the disruption of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol, increase of Bax/Bcl-2 ratio, activation of caspase-3/9, and cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, pan-caspase inhibitor (z-VAD-fmk) significantly blocked SCP-induced apoptosis and PARP cleavage in Caki-1 cells. As well, we also observed that SCP inhibited the phosphorylation of ERK1/2, whereas it had no significant inhibition effect on the phospho-p38 and phospho-JNK activity. All the above parameters provided scientific evidence that SCP induced mitochondrial-mediated apoptosis in Caki-1 cells through the inactivation of ERK pathways, which may shed further light on its potential application as a cancer chemopreventive agent against RCC.

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.

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.

Protein-energy wasting and peritoneal function in elderly peritoneal dialysis patients.

BACKGROUND: Nutritional status is important in peritoneal dialysis (PD) patients. We aimed to compare the peritoneal transport (PT) characteristics and indicators of nutritional status in elderly and non-elderly PD patients. METHODS: One-hundred and four consecutive patients were divided into either the elderly (>65 years old; n = 44) or the non-elderly (≤65 years old; n = 60) group. PT was assessed via the peritoneal equilibration test, Kt/V (K dialyzer clearance of urea, t dialysis time, V volume of distribution of urea), total creatinine clearance (CrCl), and glomerular filtration rate. Subjective global assessment (SGA), serum albumin (ALB), hemoglobin, prealbumin (PA), transferrin (TF), fat-free edema-free body mass (fat-free edema-free BM), and normalized protein intake (nPNA) were determined, and were used to indicate nutritional status. RESULTS: Elderly PD patients had higher dialysate to plasma creatinine ratios (D/P Cr) and CrCl, but lower serum creatinine body weights, ALB, PA, TF, fat-free edema-free BM, SGA, and nPNA than the non-elderly group. Multivariate analysis indicated that, after adjusting for PD time, body weight, diabetes mellitus, age, and sex, SGA negatively correlated with D/P Cr, whereas after adjusting for PD time, diabetes mellitus, and sex, D/P Cr positively correlated with age in all patients. CONCLUSIONS: Protein-energy wasting and a high PT are more common in elderly than non-elderly PD patients. Nutritional status should be carefully considered when prescribing the PD dose and frequency, especially in elderly patients.

[Parathyroid hormone 1-34 induce cardiac myocytes hypertrophy via extracellular regulated protein kinase 1/2 pathway].

OBJECTIVE: To investigate the role of mitogen activated protein kinase kinase 1 (MAPKK, MEK1) and regulated kinase1/2 (ERK1/2) on cardiac hypertrophy induced by rat parathyroid hormone1-34 (rPTH1-34). METHOD: Neonatal rat cardiomyocytes was treated with or without 10(-7) mol/L rPTH1-34 in the absence or presence 2 x 10(-5) mol/L PD98059, a MEK1 inhibitor. Cellular diameter was measured by Motic Images Advanced 3.0 software and the synthetic rate of protein in cardiac myocytes was detected by 3H-leucine incorporation, mRNA expression of atrial natriuretic peptide (ANP) was measured by RT-PCR and protein expression of ERK1/2 and p-ERK1/2 was measured by Western blot. RESULTS: rPTH1-34 (10(-7) mol/L) significantly increase cellular diameter (+13.6 microm), 3H-leucine incorporation (+898 cpm/well), ANP mRNA expression (+73.9%), and p-ERK1/2 protein expression (+15%) compared to control cells (all P < 0.05) and these effects could be significantly attenuated by PD98059: cellular diameter (-7.1 microm), 3H-leucin e incorporation (-644 cpm/well), ANP mRNA expression (-52.2%), and protein expression of p-ERK1/2 (-18%) (all P < 0.05 vs. PTH group). PD98059 did not affect control cells without PTH treatment (all P > 0.05). CONCLUSIONS: PD98059 attenuates PTH induced cardiac hypertrophy in vitro via inhibiting the expression of ERK1/2 and p-ERK1/2.