Survival Analysis of Tunneled Cuffed Central Venous Catheters in Maintenance Hemodialysis Patients: A Retrospective Study in China.

Aim: The study aimed to investigate the clinical epidemiological data and the survival rate of maintenance hemodialysis patients with tunneled cuffed central venous catheters (TCCs) in a single hemodialysis center in China. Methods: We retrospectively investigated the general clinical characteristics (including sex, age, primary causes, and catheter outcome) of 316 patients undergoing maintenance hemodialysis (MHD) via TCC for >3 months at Wannan Medical College Affiliated Yijishan Hospital, Wuhu, China, from July 2011 to June 2021. The long-term survival rate of the catheters was determined by Kaplan-Meier survival analyses. Results: A total of 316 patients (137 males, 179 females) were included, with a mean age of 65.0 ± 15.5 years. The right internal jugular vein was the most commonly used central vein, accounting for 89.1% of catheterizations. After censoring for noncatheter-related events leading to the removal of the catheter, the mean survival time of the TCCs was 26.2 ± 19.8 smonths and the median survival time was 58.0 (95% CI, 54.0-62.0) months. Seventy patients had catheter loss-of-function events, with an incidence of 22.2%. Moreover, 97.3% of TCCs survived 1 year and 43.3% survived 5 years, respectively. The sex and age of the patients were not related to the survival rate (p > 0.05). There were also no statistical differences between the primary diseases of patients and the survival rate of TCCs (p > 0.05). Conclusion: In this study, we provide evidence of the mean TCC survival time beyond 2 years. We found that TCC is an effective alternative for MHD patients with poor vessel status or limited survival time or become a bridge waiting for arteriovenous fistula to mature, regardless of age, sex, and primary diseases.

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations.

Cyclophosphamide (CTX) is one of the most commonly used alkylating agents for the treatment of various cancers; however, CTX-induced nephrotoxicity is one of the most prevailing side effects of the drug. Shorea roxburghii is a plant with diverse bioactivities including antioxidant, anti-inflammatory and renoprotective effects. This study investigated the nephroprotective effect of Shorea roxburghii phenolic extract (SRPF) against CTX-induced nephrotoxicity in rats. The rats were treated with SRPF (100 and 400 mg/kg) for 5 weeks and were concomitantly administered with CTX. The results indicated that treatment with SRPF significantly decreased serum creatinine, blood urea nitrogen (BUN), uric acid as well as renal MDA, IL-6, TNF-α, IL-1ß, NF-kB and caspase-3 levels. Furthermore, SRPF augmented the activities of renal SOD, CAT, GSH and GPx. SRPF also improved renal histopathological damages caused by CTX administration. In conclusion, these results suggested that SRPF showed substantial protective effects against CTX-mediated renal toxicity via its antioxidant and anti-inflammatory effects.

Central versus ambulatory blood pressure for predicting mortality and cardiovascular events in hemodialysis patients: a multicenter cohort study.

OBJECTIVE: Studies in the general population suggest that central blood pressure (BP) may be superior to peripheral BP in risk assessment. Although ambulatory brachial BP is recognized as the most reliable BP measurement in the dialysis population, there is no comparison of office central BP with ambulatory BP regarding risk stratification in these patients. METHODS: In a multicenter prospective study of dialysis patients, central BP was measured noninvasively on a midweek nondialysis day, with interdialytic ambulatory BP and predialysis BP also collected. The primary outcomes were a composite of major adverse cardiovascular events (MACE) and all-cause mortality. Agreement between central and ambulatory BP was assessed using Cohen's Kappa index and Bland--Altman plot. Linear and nonlinear Cox regression models were used to determine the association of BP parameters with outcomes. RESULTS: A total of 368 patients were recruited and 366 underwent central BP measurement. Central BP had a moderate agreement with ambulatory BP in defining hypertension (κ = 0.42) with wide limits of agreement in Bland--Altman analysis. After a median follow-up of 51.5 months, central pulse pressure, ambulatory SBP and ambulatory pulse pressure were associated with all-cause mortality, whereas all BP parameters, except for predialysis DBP, were significant predictors of MACE. However, whenever evaluated in a stepwise variable selection Cox model, only ambulatory pulse pressure, but not any central BP, was determined as the best candidate for prediction of both all-cause mortality and MACE. Nonlinear Cox models revealed no significant nonlinear trend of the association between central BP and outcomes. CONCLUSION: Central BP is predictive of all-cause mortality and cardiovascular events in dialysis patients but its prognostic value does not outperform ambulatory peripheral BP. Our data support the superiority of ambulatory BP in the dialysis population.

C-X-C Motif Chemokine Ligand 16 Is a Potent Predictor of Outcomes in Dialysis Patients.

INTRODUCTION: C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. METHODS: This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. RESULTS: Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). CONCLUSION: Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target.

Effectiveness of montelukast for uremic pruritus in hemodialysis patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients. METHODS: The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines. STUDY REGISTRATION NUMBER: INPLASY2020100043.

HDAC1-mediated deacetylation of LSD1 regulates vascular calcification by promoting autophagy in chronic renal failure.

Chronic renal failure (CRF) is commonly associated with various adverse consequences including pathological vascular calcification (VC), which represents a significant clinical concern. Existing literature has suggested the involvement of histone deacetylases (HDACs) in the progression of CRF-induced VC. However, the underlying molecular mechanisms associated with HDACs remain largely unknown. Therefore, we established the adenine-induced CRF rat model and in vitro VC models based on vascular smooth muscle cells (VSMCs) to examine HDAC1/lysine demethylase 1A (LSD1)/SESN2 as a novel molecular pathway in CRF-induced VC. Our initial results demonstrated that HDAC1 reduced the formation of VC in vivo and in vitro. HDAC1 was found to deacetylate LSD1, which subsequently led to impaired transcriptional activity in CRF-induced VC. Moreover, our results illustrated that LSD1 diminished the enrichment of H3K4me2 at the SESN2 promoter. Autophagy was identified as a vasculo-protective element against calcification in VC. Finally, we found that the inhibitory effects of HDAC1 overexpression on VC were partially abolished via over-expressed LSD1 in adenine-induced CRF model rats and in high phosphate-induced VSMCs. Taken together, these results highlight the crucial role of HDAC1 as an antagonistic factor in the progression of VC in CRF, and also revealed a novel regulatory mechanism by which HDAC1 operates. These findings provide significant insight and a fresh perspective into promising novel treatment strategies by up-regulating HDAC1 in CRF.

Association of betaine with blood pressure in dialysis patients.

Mechanisms underlying elevated blood pressure in dialysis patients are complex as a variety of non-traditional factors are involved. We sought to explore the association of circulating betaine, a compound widely distributed in food, with blood pressure in dialysis patients. We used baseline data of an ongoing cohort study involving patients on hemodialysis. Plasma betaine was measured by high performance liquid chromatography in 327 subjects. Blood pressure level was determined by intradialytic ambulatory blood pressure monitoring. The mean age of the patients was 52.6 ± 11.9 years, and 58.4% were male. Average interdialytic ambulatory systolic and diastolic blood pressure were 138.4 ± 22.7 mm Hg and 84.4 ± 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 µmol/L. Multiple linear regression analysis revealed significant associations of betaine with both systolic blood pressure (ß = -3.66, P = .003) and diastolic blood pressure (ß = -2.00, P = .004). The associations persisted even after extensive adjustment for cardiovascular covariates. Subgroup analysis revealed that the association between betaine and blood pressure was mainly limited to female patients. Our data suggest that alteration of circulating betaine possibly contributes to blood pressure regulation in these patients.

Interaction of Soluble CXC Ligand 16 and Cardiac Injury Markers in Hemodialysis Patients.

BACKGROUND: Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients. METHODS: Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls. RESULTS: The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs. CONTROLS: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; p < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all p < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins. CONCLUSION: We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients.

Association of adipokines with blood pressure, arterial elasticity and cardiac markers in dialysis patients: cross-sectional analysis of baseline data from a cohort study.

BACKGROUND: Adipokines are a set of cytokines secreted by white adipose tissue that have been suggested to be involved in the development of cardiovascular diseases. We aimed to evaluate the cross-sectional associations of a panel of representative adipokines with cardiovascular measures in a cohort of hemodialysis patients. METHODS: We measured plasma adiponectin, resistin, plasminogen activator inhibitor-1 (PAI-1), leptin, monocyte chemotactic protein 1 (MCP-1) and adipsin levels in 366 dialysis patients and 60 healthy controls. The associations of these adipokines with systolic blood pressure (assessed by ambulatory blood pressure monitoring), pulse wave velocity (PWV) and cardiac markers (BNP, NT-proBNP, Troponin I, Troponin T) in these patients were determined by general linear models with stepwise adjustment for covariates. RESULTS: In unadjusted comparison with controls, dialysis patients showed increased adiponectin, resistin, MCP-1 and adipsin levels, decreased PAI-1 concentrations (all p <0.001) and similar leptin levels (p = 0.82). On adjustment for body mass index and diabetes, however, the PAI-1 level was comparable between group (p = 0.06), whereas leptin levels became significantly higher in the patients(p <0.001). Higher adiponectin, lower PAI-1 and leptin levels were associated with higher systolic blood pressure, even after extensive adjustment (all p ≤ 0.01). Adiponectin was also consistently and inversely associated with PWV in fully adjusted models (p = 0.003). Resistin, PAI-1, leptin and adipsin showed negative associations with one or more circulating cardiac markers (all p ≤ 0.02). CONCLUSIONS: We found significant associations between adipokines and cardiovascular measures. Our data suggest the possible involvement of adipokines in cardiovascular modulation in dialysis patients.

Ambulatory arterial stiffness index and its role in assessing arterial stiffness in dialysis patients.

OBJECTIVE: Ambulatory arterial stiffness index (AASI) is a parameter derived from ambulatory blood pressure (ABP) readings. It is calculated as 1 minus the linear slope of DBP on SBP. We tested its value in assessing arterial stiffness in dialysis patients. METHODS: We performed a cross-sectional analysis of the baseline data from a cohort study. A total of 344 patients on maintenance hemodialysis from six tertiary hospitals were included. All patients underwent ABP monitoring and carotid-femoral pulse wave velocity (cfPWV) measurement. Clinical determinants of AASI were analyzed, and the ability of AASI for assessing arterial stiffness was compared with ambulatory pulse pressure (PP). RESULTS: Multiple regression analysis revealed that ambulatory PP (ß = 0.003), current smoker (ß = -0.069), age (ß = 0.003) and ambulatory SBP (ß = 0.001) were independent determinants of AASI. Ambulatory PP correlates better with cfPWV than AASI (r = 0.28 for AASI and 0.59 for PP; P for difference: <0.001). When cfPWV was treated as a categorical variable, receiver operating characteristic curve analysis also showed a more potent predictive value of PP over AASI (area under the curve: 0.64 for AASI, 0.80 for PP; P for difference: <0.001). Net reclassification improvement and integrated discrimination improvement analysis demonstrated no added predictive value of AASI to PP (net reclassification improvement = -2.2%, P = 0.26; integrated discrimination improvement = 0.001, P = 0.51). Sensitivity analysis in patients with more ABP readings (≥49) yielded similar results. CONCLUSION: For dialysis patients, AASI has very limited value in assessing arterial stiffness, whether used alone or added to PP. Our results suggest that this index should not be used as a surrogate marker of arterial stiffness for dialysis patients in future practice and studies.

Masked uncontrolled hypertension in patients on maintenance hemodialysis.

Masked uncontrolled hypertension (MUCH) has been proven to be associated with increased cardiovascular risk in the general population. We performed the current analysis to determine its prevalence in dialysis patients and its association with pulse wave velocity (PWV). From 368 participants of another cohort study, we selected 145 subjects with controlled predialysis blood pressure (BP). All subjects underwent ambulatory BP monitoring and PWV measurement. MUCH was defined as controlled predialysis BP with daytime BP⩾135/85 mm Hg (definition-1); total ambulatory BP⩾130/80 mm Hg (definition-2); and either daytime BP⩾135/85 mm Hg or nighttime BP⩾120/70 mm Hg (definition-3). The prevalence of MUCH was 43.4% (definition-1), 55.9% (definition-2) and 74.5% (definition-3). Multivariable logistic regression analysis showed that the use of antihypertensive medication was the most consistent predictor of MUCH within all 3 definitions (all odds ratio (OR)⩾4.28, P<0.001). Predialysis systolic BP (both OR>1, P⩽0.04), predialysis diastolic BP (both OR>1, P⩽0.001) and hemoglobin (both OR<1, P=0.02) were all significantly associated with MUCH in two models. Interdialytic weight gain (OR=0.52, P=0.02) was associated with MUCH under definition-2, and BMI (OR=0.86, P=0.03) was associated with MUCH under definition-3. Patients with MUCH had significantly elevated PWV compared with their counterparts according to all three definitions with or without adjusting for covariates (all P⩽0.03). In conclusion, MUCH affects a large proportion of dialysis patients with controlled predialysis BP and is associated with increased PWV. Patients on antihypertensive medications and with higher predialysis BP are more likely to have MUCH.

Reactive Hyperemia Index in Patients on Maintenance Hemodialysis: Cross-sectional Data from a Cohort Study.

Previous studies suggested that the reactive hyperemia index (RHI) is a promising cardiovascular risk predictor. We aimed to evaluate clinical determinants of RHI and its association with circulating endothelial injury and cardiac markers in hemodialysis patients. Among 368 patients recruited, RHI was evaluated by peripheral arterial tonometry (PAT) on a midweek nondialysis day. Clinical determinants of RHI were explored by multiple stepwise regression analysis and associations between RHI and circulating markers were evaluated by general linear models. The major cause of a failed PAT test was poor signal (82.1%). Intraclass correlation coefficient for reproducibility evaluation was 0.74. Multiple regression analysis showed traditional clinical factors only explained 7% of the variance of natural logarithm RHI (LnRHI) in the patients. In association analyses, LnRHI showed significant positive associations with Von Willebrand factor (vWF) (p = 0.04) and tissue factor (p = 0.047). It also associated positively with troponins (p ≤ 0.02 for both). In conclusion, performance of the PAT test was acceptable in dialysis patients and traditional clinical variables had very limited influence on RHI in these subjects. Among a panel of conventional endothelial injury markers, RHI showed very modest associations with only vWF and tissue factor. RHI associated positively with troponins in the patients.

[Comparison of two equations for calculating glomerular filtration rate in evaluation of the prevalence of chronic kidney disease in healthy population].

OBJECTIVE: To compare two equations for calculating glomerular filtration rate (GFR) in the evaluation of the prevalence of chronic kidney disease (CKD) and the risk factors of CKD in urban healthy population. METHODS: A total of 40377 subjects (24164 males and 16213 females) participated in this study. Body height, weight and blood pressure were measured, and morning urine and venous blood samples were collected for routine urine and blood tests with measurements of blood glucose, total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and uric acid. RESULTS AND CONCLUSION: Using Japanese CKD Epidemiology Collaboration (J-EPI) equation and Chinese modified Modification of Diet in Renal Disease (C-MDRD) equation, the prevalence of CKD calculated was 3.9% and 6.3% in this population, respectively. The independent risk factors of CKD included an age over 60 years, high uric acid, and high blood glucose.