COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Evolution of Peritoneal Dialysis-Associated Peritonitis: Pathogen, Antibiotic Resistance, and the Impact of Lymphocyte Count on Treatment Outcomes.

Purpose: Antibiotic administration leads to alterations in pathogenic organisms and antibiotic resistance, posing a significant risk to peritoneal dialysis patients' health. This study aimed to investigate changes in the cause-specific peritonitis, pathogen profiles, antibiotic resistance, and the prognostic factors among patients with peritoneal dialysis-associated peritonitis (PDAP) at our center. Patients and Methods: We included 463 PDAP patients who attended Peking University Shenzhen Hospital between 2002 and 2023. We analyzed the effects of empirical treatment regimens with cefazolin and ceftazidime or gentamicin. Results: From 2002 to 2023, we observed that gram-positive staphylococci emerged as the primary causative agents, while the proportion of gram-negative bacillary, enteric peritonitis, and catheter-associated peritonitis decreased significantly. However, the overall cure rate for PDAP and gram-negative bacillary peritonitis declined significantly from 2014 to 2023. Notably, we observed no increase in antibiotic resistance associated with antibiotic drugs use. In addition, reduced lymphocyte counts due to the prevalence of 2019 coronavirus disease (COVID-19) emerged as an independent risk factor for treatment failure in cases of gram-negative bacillary peritonitis. Conclusion: We did not observe elevated antibiotic resistance in our center when employing empirical dosing strategies involving cefazolin, ceftazidime, or gentamicin. Additionally, we found that a decrease in lymphocyte count due to the COVID-19 epidemic was a significant risk factor for treatment failure in cases of gram-negative bacillary peritonitis at our center. This study provides a foundation for developing clinical treatment strategies for PDAP.

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center.

INTRODUCTION: Recent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients. METHODS: A single-center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all-cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan-Meier survival analysis. RESULTS: In our study, the patients were classified into LTBI (n = 47) or non-LTBI (n = 223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064-22.306]), tobacco use (OR 2.903 [1.155-7.299]), and older age (OR 1.027 [1.002-1.053]). After a median follow-up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazard ratio [HR] 2.540 [1.490-4.350]) after adjustment for potential confounders. CONCLUSIONS: Prior TB history, tobacco use, and the elderly can be used to select cost-effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Red cell distribution width to albumin ratio predicts treatment failure in peritoneal dialysis-associated peritonitis.

BACKGROUND: This study aims to investigate the potential correlation between baseline red cell distribution width (RDW) to albumin ratio (RAR) levels and treatment failure in peritoneal dialysis-associated peritonitis (PDAP) patients. METHODS: A retrospective single-center study was conducted on 286 PDAP patients. Logistic regression and generalized estimation equation (GEE) analyses were employed to assess the relationship between RAR and treatment failure. RESULTS: RAR emerged as a robust predictor of treatment failure in PDAP patients. Elevated RAR levels were associated with an increased risk of treatment failure, exhibiting a linear relationship. Even after adjusting for demographic and clinical variables, this association remained statistically significant. ROC analysis revealed that RAR outperformed RDW and albumin individually in predicting PDAP prognosis. CONCLUSION: This study highlights RAR as a superior prognostic marker for treatment failure in PDAP patients, offering new insights into risk assessment and management strategies for this challenging condition.

Decreased Peripheral Blood Lymphocyte Count Predicts Poor Treatment Response in Peritoneal Dialysis-Associated Peritonitis.

Purpose: Peripheral blood lymphocyte counts is a pivotal parameter in assessing the host's immune response during maladies and the equilibrium of the immune system which has been found to correlate with various diseases progression and prognosis. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We sought to investigate the prognostic value of baseline peripheral blood lymphocyte count in PDAP patients. Patients and methods: This retrospective study analyzed data from 286 PDAP patients over nine years. Episodes were categorized according to the tertiles of peripheral blood lymphocyte counts (Very Low Lymphocyte Count (VLLC) Group, <0.72×106/L; Low Lymphocyte Count (LLC) Group, 0.72-1.11×106/L; Normal Lymphocyte Count (NLC) Group, ≥ 1.11×106/L). Demographic, laboratory, and infection-related variables were analyzed. Cox regression and generalized estimating equation (GEE) models were used to estimate the association between lymphocyte counts and PDAP treatment failure, which included PD catheter removal and death. Results: After adjusting for other potential predictors, decreased lymphocyte counts exhibited an incremental relationship with the risk of treatment failure. The VLLC group indicated a 270% (95% CI, 1.168-6.247, P=0.020) and 273% (95% CI, 1.028-7.269, P=0.044) increased venture of treatment failure in Cox regression and GEE analyses, respectively, compared with the NLC group. As a continuous variable, the restricted cubic spline showed a linear negative correlation between lymphocyte counts and the treatment failure risk (P for overall = 0.026). The multivariate model C (combined lymphocyte count with baseline age, sex, dialysis age, Charlson Comorbidity index (CCI), etiology of kidney failure, hemoglobin, albumin, total bilirubin and infection type) showed an area under the curve of 0.824 (95% CI, 0.767-0.881, P=0.001) for the prediction of treatment failure. Conclusion: Lower lymphocyte counts are linked to increased PDAP treatment failure risk. This highlights lymphocyte count's potential as a prognostic indicator for PDAP.

Association of Different Total Bilirubin Levels with Prognosis of Peritoneal Dialysis-Associated Peritonitis.

Background and Objectives: Peritoneal dialysis-associated peritonitis (PDAP) poses significant challenges in peritoneal dialysis (PD) patient management and outcomes. Total bilirubin has gained attention due to its antioxidant and immunomodulatory properties. However, its relationship with PDAP prognosis remains underexplored. Materials and Methods: We conducted a retrospective single-center study involving 243 PDAP patients stratified into tertile-based groups according to total bilirubin levels. The association between total bilirubin levels and treatment failure risk was investigated through statistical analyses and restricted cubic spline curve analysis. Results: Our analysis revealed a non-linear correlation between total bilirubin levels and PDAP treatment failure risk. At total bilirubin levels below 8.24 µmol/L, a protective effect was observed, while levels exceeding this threshold heightened the risk of treatment failure. Conclusions: This study unveils a dual role of total bilirubin in PDAP prognosis. Below a certain threshold, it confers protection, while higher levels exacerbate the risk of treatment failure. These findings emphasize the need for further investigation in larger, multicenter prospective studies to validate and elucidate the mechanisms behind bilirubin's impact on PDAP, potentially guiding the development of targeted therapeutic strategies.

Retinopathy is associated with impaired cognition in patients undergoing peritoneal dialysis.

Objective: Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD). Methods: In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function. Results: The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm-1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: -3.71, 95% confidence interval: -7.09 to -0.33, p = 0.03). Conclusions: Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

The Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study: Design and methods.

OBJECTIVES: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

Value of gamma interferon enzyme-linked immunospot assay in the diagnosis of peritoneal dialysis-associated tuberculous peritonitis.

BACKGROUND: Tuberculous peritonitis is the most common form of extrapulmonary tuberculosis infection in peritoneal dialysis patients. However, diagnosing tuberculous peritonitis quickly and early has always been a challenge for nephrologists. Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay has been widely used in the clinical diagnosis of tuberculous pleurisy and peritonitis, but its use has not been reported for uremia. METHODS: This study mainly verified the feasibility of using the M. tuberculosis antigen-specific IFN-γ ELISPOT assay in the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) patients with tuberculous peritonitis. Taking M. tuberculosis culture as the gold standard, the IFN-γ ELISPOT assay was used to analyze peripheral blood and peritoneal dialysis fluid of patients, and the receiver operating characteristic (ROC) curves in patients with tuberculous peritonitis (TBP) or non-tuberculous peritonitis (NTBP) were analyzed. RESULTS: The area under the receiver operating characteristic curve (AUC) was 0.927 (95% CI 0.816-1.000, P = 0.001) for the ELISPOT assay with peritoneal fluid mononuclear cells (PFMC), which was higher than that for the ELISPOT assay with peripheral blood mononuclear cells (PBMC) (0.825, 95% CI 0.6490-1.000, P = 0.011). The cutoff value for the diagnosis of TBP was 40 spot-forming cells (SFCs)/2 × 105 for the ELISPOT with PBMC, with a sensitivity of 55.6%, a specificity of 92.3%, and a diagnostic efficiency of 77.3%. The cutoff value for the diagnosis of TBP was 100 SFCs/2 × 105 for the ELISPOT on PFMC, with a sensitivity, specificity, and diagnostic efficiency 77.8%, 84.6%, and 81.8%, respectively. Parallel and serial testing algorithms appeared more accurate than single ELISPOT assays with PBMC, but ELISPOT assays with PFMC. CONCLUSIONS: The IFN-γ release test can be used for the early diagnosis of CAPD-related TBP; compared with peripheral blood, peritoneal fluid may be a more effective and accurate medium to diagnose CAPD complicated with tuberculous peritonitis.

Positive association of SCD1 genetic variation and metabolic syndrome in dialysis patients in China.

Aim: Metabolic syndrome (MetS) diagnosed in the dialysis patients is increasingly reported which worsens the prognosis of the renal diseases. The relationship of SCD1 with MetS is largely unknown. The purpose of this study was to investigate the relationship between SCD1 polymorphism and MetS in dialysis patients. Methods: A cross-sectional study was conducted on 323 Chinese dialysis patients, and the correlation between the seven SNPs of SCD1 gene (rs10883465, rs2060792, rs1502593, rs522951, rs3071, rs3978768 and rs1393492) and MetS was analyzed. Results: One tag-SNP (rs1393492) has significantly associated with the prevalence of MetS. Dialysis patients with rs1393492 AA genotype of SCD1 are more prone to MetS (p = 0.021). Conclusion: This study shows that the rs1393492 variations of SCD1 gene are related with the development of MetS in Chinese dialysis patients.

Pramipexole in peritoneal dialysis patients with restless legs syndrome (RLS): a protocol for a multicentre double-blind randomised controlled trial.

INTRODUCTION: Restless legs syndrome (RLS) is a common neurological sensorimotor disorder among patients with end stage renal disease. This clinical trial aimed to provide evidence on the efficacy and safety of pramipexole in patients with uremic RLS receiving peritoneal dialysis (PD). METHODS AND ANALYSIS: This is a 12-week, multicentre, randomised, double-blind, placebo-controlled clinical trial. In total, 104 patients with uremic RLS receiving PD will be enrolled from four hospitals and randomly assigned in a 1:1 ratio to either placebo or pramipexole. We will determine the efficacy of pramipexole in the improvement of International RLS Study Group Rating Scale as the primary outcome, while responder rates for other RLS scales at week 12, change from baseline to week 12 for psychological status, sleep disorder and quality of life and blood pressure represent the secondary outcomes. ETHICS AND DISSEMINATION: The study was approved by the ethics committees of Peking University First Hospital, Xinqiao hospital of Army Medical University, Cangzhou Center Hospital and Peking University Shenzhen Hospital. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03817554.

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.

Circulating Alpha-Tocopherol and Insulin Sensitivity Among Older Men With Chronic Kidney Disease.

OBJECTIVE: Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD. DESIGN: Observational study. SETTING: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 mg/minute from the third examination cycle of Uppsala Longitudinal Study of Adult Men. SUBJECTS: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 µg/minute. METHODS: Serum α-, ß-, and γ-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as µmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records. MAIN OUTCOME MEASURE: Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols. RESULTS: The mean serum concentration of α-, ß-, and γ- was 37.4 ± 6.58, 0.89 ± 0.23, and 4.32 ± 1.69 µmol/mmol, respectively. Median dietary vitamin E intake was 6.14 (interquartile range, 5.48-6.82) mg/day. In crude and fully-adjusted multivariate regression analyses, serum α-tocopherol levels were directly and strongly associated with M/I (standard ß = 0.17, P = .003). No such association was observed for dietary vitamin E, serum ß-, and γ-tocopherol concentrations. CONCLUSIONS: Serum α-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.

Integrin ß4 in EMT: an implication of renal diseases.

Renal fibrosis is a main cause of chronic renal failure. Epithelial-to-mesenchymal transition (EMT) markers play a role in renal fibrosis. Transforming growth factor-ß1 (TGF-ß1) has been shown to initiate and complete the whole EMT process. It is now well accepted that loss of E-cadherin, EMT marker α-SMA, and connective tissue growth factor (CTGF) expression are key events in the EMT process. We found that by stimulating human renal proximal tubular epithelial (HK-2) cells with TGF-ß1, the expression of E-cadherin was down regulated and the expression of α-SMA and CTGF were up regulated in a dose dependent manner. In our present study we also found that integrin ß4 and peroxisome proliferators-activated receptor-γ (PPAR-γ) play roles in EMT process, with TGF-ß1 stimulation increasing integrin ß4 expression in HK2 cells. Integrin ß4 and PPARγ were detected in tubulointerstitial tissues, immunohistochemistry analysis showed enhanced expression of integrin ß4 in early stage, with over-expression at later stage. In contrast, the expression of PPARγ showed little increased in early stage, but was dramatically decreased at later stage. This is consistent with TGF-ß1 inducing EMT. Our immune-precipitation studies show that integrin ß4 disassociation with PPARγ is present in E-cadherin signaling. It suggests that PPARγ has a role in EMT inhibition.

Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD.

BACKGROUND AND OBJECTIVES: Although nonesterified fatty acids (NEFAs) are essential as energy substrate for the myocardium, an excess of circulating NEFAs can be harmful. This study aimed to assess plausible relationships between serum NEFA and mortality due to cardiovascular disease (CVD) in individuals with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of 1221 elderly men aged 70-71 years residing in Uppsala, Sweden. Data collection took place during 1991-1995. All participants had measures of kidney function; this study investigated 623 (51.7%) of these patients with manifest CKD (defined as either eGFR<60 ml/min per 1.73 m(2) or urine albumin excretion rate ≥20 µg/min). Follow-up for mortality was done from examination date until death or December 31, 2007. After a median follow-up of 14 years (interquartile range, 8-16.8), associations of NEFAs with mortality (related to all causes, CVD, ischemic heart disease [IHD], or acute myocardial infarction) were ascertained. RESULTS: The median serum NEFA was 14.1 mg/dl (interquartile range, 11.3-17.8). No association was found with measures of kidney function. Diabetes and serum triglycerides were the only multivariate correlates of NEFA. During follow-up, 453 participants died, of which 209 deaths were due to CVD, including 88 IHD deaths, with 41 attributed to acute myocardial infarction (AMI). In fully adjusted covariates, serum NEFA was an independent risk factor for all-cause mortality (hazard ratio [HR] per log2 increase, 1.22; 95% confidence interval [95% CI], 1.00 to 1.48) and CVD-related death (HR, 1.51; 95% CI, 1.15 to 1.99), including both IHD (HR, 1.51; 95% CI, 1.00 to 2.32) and AMI mortality (HR, 2.08; 95% CI, 1.09 to 3.98). CONCLUSIONS: Elevated serum NEFA associated with CVD mortality, and particularly with mortality due to AMI, in a homogeneous population of older men with moderate CKD.

Prevalence and related factors of the absence of anemia among Chinese chronic hemodialysis patients: a multicenter cross-sectional study.

BACKGROUND: Some chronic hemodialysis (HD) patients can maintain normal hemoglobin levels without requiring erythropoiesis-stimulating agents (ESAs). However, the prevalence and the factors associated with this condition in Chinese chronic HD patients have not been reported. The aim of this study was to investigate clinical features, iron metabolism, and other characteristics to survey the prevalence rate and the related factors of this condition among Chinese chronic HD patients. METHODS: A total of 1,318 chronic HD patients participated in this study. The patients were classified into a non-ESA group (n = 11) and an ESA group (n = 1,307). The r-HuEPO-independent (non-ESA) HD patients were defined as having hemoglobin greater than 12 g/dl for more than 6 months without r-HuEPO injection, blood transfusion, or androgen therapy. Epidemiological and laboratory data were collected. Renal sonography was also performed on each patient to evaluate the formation of renal and liver cysts, and the number and size of the cysts were recorded. RESULTS: Approximately 0.84 % of all HD patients were found to be r-HuEPO independent. The non-ESA group had a higher proportion of men (79.6 vs. 58.3 %), a longer duration of renal replacement therapy (RRT) (8.6 ± 6.1 vs. 5.1 ± 3.3 years), a higher prevalence of adult polycystic kidney disease (APKD) (46.3 vs. 9.7 %), a higher prevalence of hepatitis C virus (HCV) liver disease (26.2 vs. 3.2 %, P < 0.01), and had older patients (63.3 ± 13.6 vs. 49.6 ± 13.5 years). Endogenous erythropoietin levels in the non-ESA group were significantly higher than those in the ESA group (61.8 ± 27.1 vs. 29.3 ± 11.7 mU/ml). Non-ESA patients had a significantly higher number of renal (38.1 vs. 13.2 %) and hepatic cysts (9.3 vs. 1.9 %), which were also larger in size (2.9 ± 1.6 vs. 1.3 ± 0.3 cm) compared with those of patients in the ESA group. No significant difference in iron metabolism was found between two groups. In the multivariate Cox analysis, the independent predictor factors for the absence of anemia in these HD patients were the number of renal cysts >6 cysts (95 % CI 1.058-1.405; P = 0.00), endogenous erythropoietin levels (95 % CI 1.139-1.361; P = 0.05), HCV+ liver disease (95 % CI 1.129-1.316; P = 0.01), and time on RRT (95 % CI 1.019-1.263; P = 0.05). CONCLUSIONS: To our knowledge, this study is the first to report on r-HuEPO independence among Chinese HD patients. The prevalence among Chinese chronic HD patients is significantly lower than that reported in the literature. Factors contributing to this condition are complex and multiple. The frequency of this condition is higher in men and in older patients with long-term RRT, in patients with HCV+ liver disease, and in APKD patients. This condition is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Telmisartan counteracts TGF-ß1 induced epithelial-to-mesenchymal transition via PPAR-γ in human proximal tubule epithelial cells.

Chronic renal failure (CRF) mainly results from kidney fibrosis. Epithelial-to-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells and contributes to renal fibrosis. Transforming growth factor-ß1 (TGF-ß1) has been shown to initiate and complete the whole EMT process. Peroxisome proliferators-activated receptor-γ (PPAR-γ) exerts anti-inflammatory, anti-fibrotic and vaculo-protective effects on different renal diseases. Telmisartan is a member of angiotensin II (Ang II) receptor blocker (ARB) family. Recent studies show that Telmisartan has a partial agonistic effect on PPAR-γ. Therefore, we tested the hypothesis that Telmisartan reverses the progression of induced EMT by TGF-ß1 in cultured human renal proximal tubular epithelial (HK-2) cells. Cultured HK-2 cells were treated with TGF-ß1 (3 ng/ml), a combination of TGF-ß1 and Telmisartan (10-200 umol/L) and a combination of TGF-ß1, Telmisartan and GW9662, a PPAR-γ antagonist for 48 hours. EMT was determined by quantitative real-time PCR analysis of E-cadherin (E-cad), Connective Tissue Growth Factor (CTGF) and PPAR-γ transcript expression and immunocytochemical analysis of E-cad, α-Smooth Muscle Actin (α-SMA) and PPAR-γ protein expression. TGF-ß1 induced phenotypic EMT in cultured HK-2 cell line via significantly reduced E-cad expression and significantly increased CTGF, α-SMA expression in association with the loss of epithelial morphology. Telmisartan reversed all EMT markers in a dose-dependent manner which was inhibited by PPAR antagonist GW9662. In the present study, it was suggested that Telmisartan attenuated TGF-ß1 induced EMT by agonistic activation of PPAR-γ.