Peritoneal dialysis effluent-derived exosomal miR-432-5p: an assessment tool for peritoneal dialysis efficacy.

Background: Ultrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR). Methods: The PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells. Results: Our results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=-0.376; P<0.05; n=40) and 4 h DSR (r=-0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells. Conclusions: A high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.

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.

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.

Body mass index and mortality risk in Asian peritoneal dialysis patients in Hong Kong-impact of diabetes and cardiovascular disease status.

BACKGROUND: Obesity increases mortality in the general population, but improves survival in hemodialysis patients. In peritoneal dialysis (PD) patients, the reported effect is controversial. We investigated the effect of body mass index (BMI) on patient survival in Asian PD patients. METHODS: The survival of incident Asian PD patients from 2001 to 2008 in a single center in Hong Kong was analyzed retrospectively. Baseline demographic and clinical data were collected from patient records. Patients who had a total Kt/V below 1.7 or who died within 6 months were excluded. The BMI was categorized using the World Health Organization recommendation for Asian populations. RESULTS: In the 274 study patients [154 men (56%); 138 with diabetes (50.4%); mean age: 63.4 ± 14.6 years; mean BMI: 21.97 ± 3.23 kg/m(2); 37 underweight (13.5%); 35 obese (12.8%)], the relative risk (RR) for mortality [adjusted for age, diabetes status, and cardiovascular disease (CVD)] was similar for the normal and overweight groups, but higher for the underweight (RR: 1.909; p = 0.028) and obese groups (RR: 1.799; p = 0.048). The increased mortality in obese patients was more prominent in patients with diabetes (RR: 1.9 vs 1.19 in patients without diabetes; p = 0.074 and 0.76 respectively), and in patients with CVD (RR: 8.895 vs 1.642 in patients without CVD; p = 0.012 and 0.122 respectively). CONCLUSIONS: In Asian PD patients, the relationship between BMI and mortality was U-shaped, with higher mortality in the underweight and obese patients. The negative impact of obesity was more prominent in patients with diabetes and CVD.

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.

Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients--a randomized crossover trial.

BACKGROUND: The aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: In this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP). RESULTS: All 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 µg/mL (range: 2.59 - 34.48 µg/mL) vs 30.44 µg/mL (3.47 - 93.41 µg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function. CONCLUSIONS: Blood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.

Isolated lesser sac infection: an uncommon cause of abdominal pain in CAPD patients.

Peritonitis in peritoneal dialysis (PD) patients is characterized by abdominal pain and dialysate leukocytosis. Abdominal abscesses have been reported in PD patients with relapsing peritonitis. We report here 3 cases of lesser sac infection in PD patients who had severe abdominal pain but not generalized or diffuse peritonitis.

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial].

OBJECTIVE: Leflunomide (LEF) is a selective inhibitor of de novo pyrimidine synthesis, currently used in the treatment of rheumatoid arthritis. To evaluate the efficacy and safety of LEF in the treatment of proliferative lupus nephritis, a prospective multi-center controlled clinical trial was conducted. METHODS: Patients with biopsy-confirmed proliferative lupus nephritis were recruited. Patients of recent onset who had not used any immunosuppressive drug were given either oral LEF (group A) or IV cyclophosphamide (group B); relapsed patients who had received immunosuppressive therapy 3 months before were given LEF (group C). Efficacy and safety were evaluated at 6 months after treatment. RESULTS: Total 51 patients were enrolled, 4 patients withdrew due to adverse events. For those initial treated patients, total response rate were 80% in group A and 75% in group B, complete remission rate were 40% and 25% respectively, not statistically different. Renal parameters (proteinuria, serum albumin and serum creatinine) and systemic lupus erythematosus disease activity index (SLEDAI) improved similarly in both groups. For 14 relapsed patients, total response rate was 60% and complete remission rate was 6.7%. Major adverse events reported in LEF treated patients were infection and alopecia. Herpes zoster was the most often type among infectious events, and one case of severe lung infection was reported. CONCLUSION: LEF combined with steroid was effective in the induction therapy of proliferative lupus nephritis. LEF was generally well-tolerated, its efficacy in maintenance therapy and long-term safety remains to be clarified.