Publications by authors named "XueSen Cao"

35 Publications

Prostaglandin E induced cardiac hypertrophy through EP2 receptor-dependent activation of β-catenin in 5/6 nephrectomy rats.

ESC Heart Fail 2021 Apr 6. Epub 2021 Apr 6.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Aims: Prostaglandin E (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease-associated cardiac hypertrophy and the tentative mechanism remains to be elucidated.

Methods And Results: We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up-regulated in the PGE2-treated cardiomyocyte cells. PGE2 treatment enhanced active β-catenin (non-phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis-related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats.

Conclusions: Our study demonstrated that inhibition of EP2 receptor could improve PGE2-induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.
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http://dx.doi.org/10.1002/ehf2.13269DOI Listing
April 2021

Decreased Peripheral Naïve T Cell Number and Its Role in Predicting Cardiovascular and Infection Events in Hemodialysis Patients.

Front Immunol 2021 17;12:644627. Epub 2021 Mar 17.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Patients with end-stage renal disease (ESRD) are at high risk of morbidity and mortality from cardiovascular and infectious diseases, which have been found to be associated with a disturbed immune response. Accelerated T-cell senescence is prevalent in these patients and considered a significant factor contributing to increased risk of various morbidities. Nevertheless, few studies have explicated the relevance of T-cell senescence to these fatal morbidities in ESRD patients. In this study, we designed a longitudinal prospective study to evaluate the influence of T-cell senescence on cardiovascular events (CVEs) and infections in hemodialysis (HD) patients. Clinical outcomes of 404 patients who had been on HD treatment for at least 6 months were evaluated with respect to T-cell senescence determined using flow cytometry. We found that T-cell senescence was associated with systemic inflammation. High-sensitivity C-reactive protein was positively associated with decreased naïve T cell levels. Elevated tumor necrosis factor-α and interleukin 6 levels were significantly associated with lower central memory T cell and higher T effector memory CD45RA cell levels. Decreased CD4 naïve T cell count was independently associated with CVEs, whereas decreased CD8 naïve T cell count was independently associated with infection episodes in HD patients. In conclusion, HD patients exhibited accelerated T-cell senescence, which was positively related to inflammation. A reduction of naïve T cell could be a strong predictor of CVEs and infection episodes in HD patients.
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http://dx.doi.org/10.3389/fimmu.2021.644627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009982PMC
March 2021

Association of N-Terminal Pro-brain Natriuretic Peptide With Volume Status and Cardiac Function in Hemodialysis Patients.

Front Cardiovasc Med 2021 22;8:646402. Epub 2021 Feb 22.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

N-terminal-pro-brain natriuretic peptide (NT-pro BNP) is secreted by cardiomyocytes in cases of cardiac structure disorder and volume overload. However, the relationship between NT-pro BNP level and body fluid status in dialysis patients with reduced cardiac ejection function (EF) is uncertain. Therefore, we aimed to investigate this relationship. We enrolled patients who had been receiving hemodialysis for >3 months. Blood sample, transthoracic echocardiographic, and bioimpedance spectroscopy measurements were performed during a midweek non-dialysis day. The predictive value of NT-pro BNP in hemodialysis patients with volume overload was analyzed. A total of 129 hemodialysis patients (74 men and 55 women; mean age: 59.4 ± 13.0 years) were recruited. The average hemodialysis duration was 55.5 (23.9-93.4) months, the NT-pro BNP level was 4992 (2,033-15,807) pg/mL, and the value of overhydration was 2.68 ± 0.19 (-1.9 to 12.2) L. The NT-pro BNP level was independently correlated with overhydration in both the LVEF ≥ 60% (β = 0.236, = 0.044) and LVEF <60% (β = 0.516, = 0.032) groups, even after adjustments for potentially confounding variables. In receiver operating characteristic curves of NT-pro BNP for predicting volume overload, the area under the curve was 0.783 [95% CI (0.688-0.879), < 0.001) and 0.788 [95% CI (0.586-0.989), < 0.001] in the LVEF ≥ 60% and LVEF < 60% groups, respectively. NT-pro BNP is a predictive factor for volume overload in hemodialysis patients with or without EF declines.
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http://dx.doi.org/10.3389/fcvm.2021.646402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937607PMC
February 2021

Pro-inflammatory cytokines as potential predictors for intradialytic hypotension.

Ren Fail 2021 Dec;43(1):198-205

Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.

Background: Intradialytic hypotension (IDH) is a common complication in maintaining hemodialysis (MHD) patients. Immune activation might be part of the mechanisms. However, the association between pro-inflammatory cytokines and blood pressure (BP) has not been deeply explored. So we aim to evaluate the potential role of pro-inflammatory cytokines in IDH.

Methods: MHD patients starting hemodialysis before January 2016 were enrolled in our retrospective study. Patients' characteristics, laboratory results, and intradialytic BP were collected. IDH was defined as nadir systolic BP ≤ 90 mmHg during hemodialysis. The definition of IDH group was that those who suffered from more than one hypotensive event during one month after the enrollment (10% of dialysis treatments). Spearman correlation analysis and logistic regression were employed to explore the relationship between pro-inflammatory cytokines and IDH.

Results: Among 390 patients, 72 were identified with IDH (18.5%). High levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were observed in the IDH group ( < 0.001). Both TNF-α and IL-1β positively correlated with predialysis BP ( < 0.01). Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of serum IL-1β and TNF-α for IDH. The area under the curve of IL-1β was 0.772 (95% CI: 0.708-0.836,  < 0.01), and that of TNF-α was 0.701 (95% CI: 0.620-0.781,  < 0.01). After adjusting for patients' characteristics, biochemical parameters, comorbid conditions, predialysis BP, and medications, elevated TNF-α and IL-1β were still risk factors for IDH.

Conclusion: Pro-inflammatory cytokines (TNF-α and IL-1β) could be potential predictors for IDH.
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http://dx.doi.org/10.1080/0886022X.2021.1871921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833080PMC
December 2021

Relationship between Soluble ST2 and Left Ventricular Geometry in Maintenance Hemodialysis Patients.

Blood Purif 2021 8;50(1):84-92. Epub 2020 Dec 8.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China,

Introduction: Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance hemodialysis (MHD) patients. Different left ventricular geometry may provide additional clinical information. Soluble ST2 is a novel cardiac prognostic biomarker in MHD patients and is closely related to cardiac remodeling.

Objective: This study sought to evaluate the association of sST2 and left ventricular structure in a cohort of MHD patients.

Methods: Two hundred eighty-seven patients were enrolled. Left ventricular structure was assessed via transthoracic echocardiography. Left ventricular geometric patterns were defined according to left ventricular mass index and relative wall thickness (RWT). Serum sST2 levels were measured.

Results: Prevalence of LVH was 44.9% in the study population. In univariate analysis, sST2 levels were correlated with interventricular septal wall thickness, posterior wall thickness, and RWT. After multivariate adjustment, sST2 was independently correlated with only RWT (p = 0.028). Comparing sST2 concentrations across different LV geometric patterns, we found sST2 levels were significantly increased in patients with concentric cardiac remodeling and concentric LVH.

Conclusions: The present study found that sST2 were significantly increased in patients with concentric remodeling and concentric LVH. ST2/interleukin (IL)-33 signaling might participate in the process of cardiac remodeling via its pro-fibrotic action. Future studies on the mechanism of ST2/IL-33 pathway are needed.
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http://dx.doi.org/10.1159/000508402DOI Listing
December 2020

Indoxyl sulfate and high-density lipoprotein cholesterol in early stages of chronic kidney disease.

Ren Fail 2020 Nov;42(1):1157-1163

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: High IS level has been demonstrated to be associated with vascular calcification and lymphocyte functional disorders, which are both risk factors of CVD. Low HDL-c level is a risk factor of CVD in CKD patients. This study was designed to explore the potential relationship between IS and HDL-c levels in early stages of CKD population.

Methods: Patients of CKD stage 1-3 were enrolled in this cross-sectional study. Correlations between HDL-c and IS levels were investigated among various clinicopathological variables through independent samples test and multivariate logistic regression.

Results: A total of 205 CKD patients (96 men) aged 43.27 ± 13.80 years old were included in this research. There were 96 patients (46 men) in CKD stage1 and 109 (50 men) in CKD stage 2 or stage 3. IS levels were significantly higher in CKD 2 + 3 group (1.50 ± 1.74 μg/ml 0.94 ± 0.66 μg/ml,  = 0.007), while HDL-c levels were lower (1.19 ± 0.39 mmol/L 1.33 ± 0.45 mmol/L,  = 0.017) compared to CKD 1 group. Among all the patients, a negative correlation was observed between IS and HDL-c levels (r = -0.244,  = 0.001). IS level was an independent risk factor for low HDL-c (<1.04 mmol/L) incidence even after controlling for potential confounders including concomitant disease, age, sex, blood pressure, BMI and laboratory biochemical test including eGFR (OR = 1.63, 95% CI: 1.11-2.39,  = 0.013). IS and HDL-c were both risk factors for predicting CKD stage 3.

Conclusions: In early CKD stages, low HDL-c level is associated with increased IS levels, which may be an important contributor in the development of dyslipidemia in CKD patients.
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http://dx.doi.org/10.1080/0886022X.2020.1845731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671672PMC
November 2020

Differences between exhausted CD8 T cells in hepatocellular carcinoma patients with and without uremia.

Can J Physiol Pharmacol 2020 Aug 15:1-7. Epub 2020 Aug 15.

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

The purpose of this study was to explore the differences between exhausted CD8 T cells in hepatocellular carcinoma (HCC) patients with and without uremia. We enrolled 45 uremic patients who were recently diagnosed with HCC into the HCC + uremia cohort and similar patients with HCC but without uremia into the HCC-only cohort. Lymphocytes were obtained from the two cohorts, and exhausted CD8 T cells, comprising PD-1CD8, TIM-3CD8, and LAG-3CD8 T cells, were sorted and expanded in vitro. After expansion, the proportions of PD-1CD8, TIM-3CD8, and LAG-3CD8 T cells were significantly higher in the HCC-only cohort than in the HCC + uremia cohort. CD8 T cells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of interferon-γ in vitro; however, these cells demonstrated weaker anti-tumor activity in HCC + uremia patients than in HCC-only patients. Among the expanded lymphocytes, only the decreased proportion of PD-1CD8 T cells significantly correlated with the HCC + uremia cohort (odds ratio of 2.731,  = 0.009). We concluded that peripheral CD8 T cells expressing PD-1, TIM-3, or LAG-3 from the HCC + uremia cohort were dysfunctional in vitro. Among these populations, PD-1CD8 T cells were most evident in HCC patients with uremia.
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http://dx.doi.org/10.1139/cjpp-2019-0641DOI Listing
August 2020

Premature aging of circulating T cells predicts all-cause mortality in hemodialysis patients.

BMC Nephrol 2020 07 13;21(1):271. Epub 2020 Jul 13.

Department of Nephrology, Zhongshan Hospital, Fudan University, NO180, Feng'lin Road, Xuhui District, Shanghai, 200032, P.R. China.

Background: Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of immune system, which is recently concerned as a significant factor for increased risk of various morbidities. Nevertheless, there are few dates explicating the relevancy of T cell senescence to mortality. In this study, we prospectively studied the predictive value of T cell senescence for mortality in hemodialysis patients.

Methods: Patients who had been on hemodialysis treatment for at least 6 months were enrolled. T cell senescence determined by differentiation status was evaluated by flow cytometry. Survival outcomes were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the prognostic impact of T cell premature aging and other clinical factors on all-cause mortality.

Results: A total of 466 patients (277 man and 169 women) were enrolled in this study. Decreased number of naïve T cell, as the most prominent feature of T cell senescence, did not change in parallel with age in these patients. Decreased absolute count of T cell, naïve T cell, CD4 naïve T cell were independently associated with all-cause mortality. Decreased percentage of T cell and increased percentage of CD8central-memory T cell were also independently associated with all-cause mortality. After including all the T cell parameters in one regression model, only decreased count of naïve T cell was significantly associated with increased mortality in these patients.

Conclusions: Aging-associated T cell changes are aggravated in ESRD patients. For the first time, our study demonstrates that naïve T cell depletion is a strong predictor of all-cause mortality in HD patients.
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http://dx.doi.org/10.1186/s12882-020-01920-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359274PMC
July 2020

Transcriptome Profiling Reveals Indoxyl Sulfate Should Be Culpable of Impaired T Cell Function in Chronic Kidney Disease.

Front Med (Lausanne) 2020 6;7:178. Epub 2020 May 6.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Chronic inflammation and immune system dysfunction have been evaluated as major factors in the pathogenesis of chronic kidney disease (CKD), contributing to the high mortality rates observed in these populations. Uremic toxins seem to be the potential "missing link." Indoxyl sulfate (IS) is one of the protein-bound renal toxins. It participates in multiple pathologies of CKD complications, yet its effect on immune cell has not been studied. This study aimed to explore the genome-wide expression profile in human peripheral blood T cells under stimulation by IS. In this study, we employed RNA-sequencing transcriptome profiling to identify differentially expressed genes (DEGs) responding to IS stimulation in human peripheral T cells . Flow cytometry and western blot were used to verify the discovery in RNA-sequencing analysis. Our results yielded a total of 5129 DEGs that were at least twofold up-regulated or down-regulated significantly by IS stimulation and half of them were concentration-specific. Analysis of T cell functional markers revealed a quite different transcription profile under various IS concentration. Transcription factors analysis showed the similar pattern. Aryl hydrocarbon receptor (AhR) target genes CYP1A1, CYP1B1, NQO1, and AhRR were up-regulated by IS stimulation. Pro-inflammatory genes TNF-α and IFN-γ were up-regulated as verified by flow cytometry analysis. DNA damage was induced by IS stimulation as confirmed by elevated protein level of p-ATM, p-ATR, p-BRCA1, and p-p53 in T cells. The toxicity of IS to T cells could be an important source of chronic inflammation in CKD patients. As an endogenous ligand of AhR, IS may influence multiple biological functions of T cells including inflammatory response and cell cycle regulation. Further researches are required to promulgate the underling mechanism and explore effective method of reserving T cell function in CKD.
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http://dx.doi.org/10.3389/fmed.2020.00178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218060PMC
May 2020

The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis.

Ren Fail 2020 Nov;42(1):419-427

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

Elevated serum levels of sIL-2R are commonly observed in patients undergoing maintenance hemodialysis (MHD). However, the clinical implications in these subjects are unclear. This study is aimed to assess the significance of elevated sIL-2R levels in MHD patients. A total of 382 MHD patients were followed-up from September 2016 to December 2019. Patients were divided into two groups: high sIL-2R, with sIL-2R levels ≥2-fold of the upper limit of normal (710 U/ml); and low sIL-2R, with sIL-2R levels < 2-fold the upper limit of normal. The relationships between sIL-2R levels and other clinical parameters, as well as patient prognosis were both assessed. The median concentration of sIL-2R was 1268 U/mL. A total of 372 (97.38%) patients exhibited sIL-2R levels higher than the upper limit of the normal range. Multiple linear regression analysis revealed that monocyte count (β = 0.1571,  = 0.01), and β-MG (β = 0.2635,  < 0.0001), hemoglobin (β = -0.1610,  = 0.001), SCr (β = -0.3471,  < 0.0001), and HDL-C (β = -0.1091,  = 0.029) levels were independent factors influencing serum concentrations of sIL-2R. High sIL-2R was significantly correlated with non-cardiovascular-related mortality (OR 2.97 [95% CI 1.59-5.56;  = 0.001), of which 39 (82.98%) were attributed to infection and/or cancer. Elevated sIL-2R is prevalent in MHD patients and related with several unfavorable parameters. sIL-2R appears to have no ability to predict cardiovascular mortality, which accounts for approximately one-half of all deaths. However, sIL-2R may be beneficial in predicting noncardiovascular mortality.
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http://dx.doi.org/10.1080/0886022X.2020.1761388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269077PMC
November 2020

Role of magnesium in the risk of intradialytic hypotension among maintenance hemodialysis patients.

Hemodial Int 2020 07 12;24(3):351-358. Epub 2020 May 12.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai Medical Center of Kidney Disease, Shanghai, China.

Introduction: Intradialytic hypotension (IDH) is a common complication in end-stage renal disease patients on hemodialysis (HD). It has been documented that several factors contribute to IDH. However, the relationship between serum electrolytes and the occurrence of IDH remains unclear. Our study aims to investigate the role of serum magnesium (Mg) for the risk of IDH in maintenance HD patients.

Methods: The retrospective study included adults starting HD before January 2009 in the blood purification center, Zhongshan Hospital, Fudan University, and treated thrice weekly with standard bicarbonate dialysate by low-flux HD. Patients' characteristics including age and sex, laboratory test results were collected. IDH was defined according to kidney disease outcomes quality initiative (K/DOQI) guidelines as a decrease in systolic blood pressure (SBP) by ≥20 mmHg or a decrease in mean arterial pressure (MAP) by ≥10 mmHg associated with clinical symptoms during HD. Multivariate logistic regression was employed to explore independent risk factors for IDH.

Findings: Among 423 patients recruited, 175 patients (41.4%) suffered from IDH. Compared with those with non-IDH, patients with IDH presented higher predialysis serum Mg levels. Univariate correlation analysis showed that predialysis serum Mg level was negatively correlated with SBP at 3 hours, 4 hours after dialysis (3 hours SBP r = -0.134 P = 0.006, 4 hours SBP r = -0.142 P = 0.003) and was positively correlated with the differences of blood pressure (BP) (SBP and MAP) (△SBP r = 0.195 P < 0.001, △MAP r = 0.155, P = 0.001). After adjustment for predialysis blood urea nitrogen, platelet distribution width, cardiac troponin T, fasting blood glucose, β2-microglobulin, and predialysis MAP, multivariate logistic regression analysis demonstrated that predialysis serum Mg level was one of the independent risk factors for IDH (odds ratio [95% confidence interval-CI]: 7.154 (1.568-32.637); P = 0.011). In addition, Mg levels of 1.15 mmol/L or higher were associated with a high incidence of IDH.

Discussion: Our findings suggested that higher predialysis serum Mg level was one of the independent risk factors for IDH among maintenance hemodialysis (MHD patients).
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http://dx.doi.org/10.1111/hdi.12833DOI Listing
July 2020

The Predictive Value of NT-Pro-Brain Natriuretic Peptide for Risk of Pneumonia in Patients on Maintenance Hemodialysis.

Blood Purif 2020 24;49(3):348-355. Epub 2020 Jan 24.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background/aims: Pneumonia is a common type of infection in maintenance hemodialysis (MHD) patients, while the treatment and prevention progress still keep limited. N-terminal-pro-brain natriuretic peptide (NT-proBNP) is an important marker in reflecting cardiac failure which also is a risk factor for pneumonia. This study aimed to determine the possible predictive value of NT-proBNP for pneumonia in MHD patients.

Methods: In this prospective study, the basic information of 276 MHD patients was collected in Fudan university Zhongshan hospital, followed up for 1 year. The primary endpoint was the first pneumonia event during follow-up. The value of NT-proBNP in patients with pneumonia and without pneumonia was analyzed, to elucidate the predictive value of the NT-proBNP in hemodialysis patients with pneumonia.

Results: Two hundred and seventy-six patients were finally enrolled in this prospective study, including 170 men. The mean age was 59.7 ± 14.0 years old. The average duration of hemodialysis is 56 (30-82.8) months. Enrolled patients were followed up for 1 year. During follow-up, 38 patients got pneumonia. After adjustment for other confounding factors, age (hazard ratio [HR] 1.031, 95% CI 1.003-1.060, p = 0.028), log NT-proBNP (HR 2.512, 95% CI 1.124-5.612, p = 0.025), history of smoking (HR 6.326, 95% CI 2.505-15.974, p < 0.001), β2-microglobin (HR 1.042, 95% CI 1.007-1.079, p = 0.019), and history of cerebrovascular disease (HR 2.303, 95% CI 1.107-4.719, p = 0.026) were independent predictors of pneumonia. Receiver operating characteristic curves of log NT-proBNP to predict 1 year pneumonia cases, log NT-proBNP had an area under the curve of 0.647 (95% CI [0.564-0.729], p < 0.01).

Conclusions: NT-proBNP is a predictive factor of pneumonia in hemodialysis patients.
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http://dx.doi.org/10.1159/000504524DOI Listing
January 2020

Acute effect of one session of hemodiafiltration with endogenous reinfusion on uremic toxins and inflammatory mediators.

Int J Artif Organs 2020 Jul 16;43(7):437-443. Epub 2020 Jan 16.

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

Aims: To investigate the acute effects of hemodiafiltration with endogenous infusion on the elimination of uremic toxins and inflammatory mediators in patients with end-stage renal disease.

Materials And Methods: A total of 37 end-stage renal disease patients undergoing chronic hemodialysis received a single hemodiafiltration with endogenous infusion dialysis treatment. The acute effects of one hemodiafiltration with endogenous infusion session on uremic toxins and inflammatory mediators were assessed by comparing the pre- and post-hemodiafiltration with endogenous infusion concentrations.

Results: Hemoglobin and albumin were stable during hemodiafiltration with endogenous infusion therapy. The mean reduction ratios of β-microglobulin, p-cresyl sulfate, and indoxyl sulfate were 43.60%, 40.91%, and 43.64%, respectively. Tumor necrosis factor-α also decreased significantly at a mean rate of 28.10%, while the concentrations of interleukin-6 and high-sensitivity C-reactive protein remained unchanged after one session of hemodiafiltration with endogenous infusion.

Conclusion: The hemodiafiltration with endogenous infusion system is a new dialysis technique that combines diffusion, convection, and adsorption processes. It allows for extensive solute removal, including protein-bound uremic toxins and some pro-inflammatory cytokines, but does not cause nutrient loss and inflammatory response during the treatment. Although the effect after a single hemodiafiltration with endogenous infusion session is limited, it may be improved by repeated and long-term treatment.
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http://dx.doi.org/10.1177/0391398819899102DOI Listing
July 2020

Incidence, Risk, and Prognosis of Cancer in Patients on Chronic Hemodialysis.

Blood Purif 2020 17;49(3):310-321. Epub 2019 Dec 17.

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

Background: Information concerning the cancer issue in Chinese patients on hemodialysis (HD) was lacking. Thus, we examined data from our dialysis registry to investigate the incidence of cancer, identify the possible factors, and explore outcomes after cancer diagnosis in patients on chronic HD.

Methods: A retrospective cohort study of 639 new-onset end-stage renal disease patients who started HD therapy during the period from July 1999 to December 2017 was retrieved from the database in our dialysis center. All eligible patients were followed up until renal transplantation, death, or end of study (March 31, 2019). The definition of a newly diagnosed cancer was that diagnosed 6 months after HD therapy initiation.

Results: Within a median follow-up period of 5.61 years, 58 patients (9.08%) have been diagnosed with cancer with the incidence of 1,494 per 105 person-years. The mean duration from HD initiation to cancer diagnosis was 5.22 ± 3.55 years. Digestive cancer (32.76%) was the most common followed by urologic cancer (18.97%) and lung cancer (15.52%). Advanced age at starting HD therapy (hazard ratio [HR] 1.04) and erythropoietin dosage ≥20,000 U/week (HR 1.95) were independent predictors for cancer occurrence. Of the 256 deaths during the follow-up period, 29 cases (11.33%) were attributed to cancer, with the mortality rate of 717 per 105 person-years. The 1-, 5-, and 10-year cumulative survival rates after cancer diagnosis were 58.73, 34.64, and 20.41%, respectively. A total of 32 patients (55.17%) did not receive any anti-cancer therapy, and the mortality in those patients was significantly increased as compared to patients who received anti-cancer therapy.

Conclusion: Cancer is common in HD patients due to the improved survival, and it has a negative effect on patient prognosis. Many patients have failed to receive optimal anti-cancer therapy, which calls for effective communication and cooperation among patients, dialysis unit, and oncology teams.
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http://dx.doi.org/10.1159/000504243DOI Listing
December 2019

The difference of T cell phenotypes in end stage renal disease patients under different dialysis modality.

BMC Nephrol 2019 08 5;20(1):301. Epub 2019 Aug 5.

Department of Nephrology, Zhongshan Hospital, Fudan University, NO180, Feng'lin Road, Shanghai, 200032, China.

Background: Impaired T cell immune function exists in end-stage renal disease (ESRD) patients. Dialysis treatment may lead to changes in T cell subsets. In the present study, we aimed to identify alterations of T cell phenotypes in ESRD patients, especially in those receiving peritoneal dialysis (PD), and analyze the potential associated factors.

Methods: In the present study, 110 PD patients and 110 age/gender-matched hemodialysis (HD) patients who met the inclusion criteria were studied. Pre-dialysis blood samples were obtained and analyzed by flow cytometry to detect the expression of CD45RO and CCR7. Univariate and multivariate regression analyses were used to determine the factors associated with the alteration of T cell phenotypes.

Results: In all dialysis patients, age was associated with the frequencies of both CD4+ and CD8+ naïve T cells, effector memory (EM) T cells and effector memory RA (EMRA) T cells but not central memory (CM) T cells. Dialysis modality was also associated with T cell subsets. Compared with HD patients, PD patients showed an increase in both CD4+ and CD8+ CM T cells and a reduction in both CD4+ and CD8+ EM and EMRA T cells. However, the number of CD4+ naïve T cells was lower and the number of CD8+ naïve T cells was higher in PD patients than those in HD patients. In PD patients, further multivariate analysis revealed that the frequency of CD4+ naïve T cells was positively associated with nPCR, while the frequency of CD8+ naïve T cells was negatively associated with age.

Conclusion: In dialysis patients, the dialysis modality and age influence T cell subsets. There is a progression from naïve to effector T cells in HD patients compared with PD patients. In PD patients, different factors may influence the frequencies of CD4+ and CD8+ naïve T cells.
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http://dx.doi.org/10.1186/s12882-019-1475-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683494PMC
August 2019

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

Int J Clin Oncol 2019 Sep 10;24(9):1151-1160. Epub 2019 Jun 10.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients.

Methods: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables.

Results: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years.

Conclusions: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.
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http://dx.doi.org/10.1007/s10147-019-01455-5DOI Listing
September 2019

Serum Concentration of Indoxyl Sulfate in Peritoneal Dialysis Patients and Low-Flux Hemodialysis Patients.

Blood Purif 2019 30;48(2):183-190. Epub 2019 Apr 30.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China,

Background/aims: To compare the serum concentration of Indoxyl sulfate (IS) in patients on continuous ambulatory peritoneal dialysis (CAPD) and low-flux hemodialysis (HD), and analyze the risk factors associated with IS.

Methods: We performed a single-center, cross-sectional observational study including 169 patients on CAPD and 115 patients on low-flux HD. Patients were divided into the anuric HD group, anuric peritoneal dialysis (PD) group, and non-anuric PD group on the basis of dialysis modality and residual urinary output. Serum concentration of IS was determined by high-performance liquid chromatography electrospray tandem mass spectrometry.

Results: After matching the urinary volume and dialysis vintage, 58 anuric patients on PD and 58 anuric patients on HD were enrolled. The serum level of IS was significantly lower in patients on PD than that in those on HD (28.05 ± 13.98 vs. 39.64 ± 18.25 μg/mL; p < 0.001). This result persisted even after adjustment for confounding risk factors including nutritional status (β = 0.338, p < 0.001). In addition, the serum level of IS was significantly lower in non-anuric PD patients than that anuric PD patients (18.70 ± 11.21 vs. 28.05 ± 13.98 μg/mL; p < 0.001). After the adjustment for risk factors such as dialysis vintage, IS serum concentration in patients on PD was still significantly correlated with residual renal function (RRF; β = -0.355, p < 0.001).

Conclusions: Dialysis modality is the independent risk factor of IS serum concentration and it is substantially lower in patients on CAPD than that in those on low-flux HD. Additionally, RRF was independently associated with IS serum concentration in CAPD patients, and the better the RRF is, the lower IS serum concentration.
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http://dx.doi.org/10.1159/000499749DOI Listing
January 2020

Decreased percentage of memory B cells is independently associated with increased susceptibility to infection in patients on maintenance hemodialysis.

Int Urol Nephrol 2018 Nov 1;50(11):2081-2090. Epub 2018 Oct 1.

Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, 200032, China.

Purpose: Infection is a common complication and cause of death in patients on maintenance hemodialysis (MHD). B lymphocytes, which are an important component of the immune system, play a significant role in defending against pathogen invasion. However, in patients on MHD, the connection between infection and B cell subsets remains largely unknown. Our study aims to clarify the potential role of the distribution of B cell subsets in the infection process in patients on MHD.

Methods: In this cross-sectional study, basic information was collected from 175 patients on MHD from July 2016 to July 2017 at Zhongshan Hospital, Fudan University. The distributions of the B cell subsets in patients with and without infection were analyzed using flow cytometry to determine the role of B lymphocyte subsets in the infection process in patients on MHD.

Results: Among the 175 patients, 45 suffered from infection. The respiratory tract was the most common infection site, accounting for 67.86% of all infections. After adjustment using multivariate logistic regression models, memory B cells [per 1% increase, odds ratio [95% confidence interval (CI)]: 0.949 (0.915, 0.984), P < 0.01], switched memory B cells [per 1% increase, odds ratio (95% CI): 0.939 (0.898, 0.982), P < 0.01], naïve B cells [per 1% increase, odds ratio (95% CI): 1.042 (1.009, 1.075), P < 0.05] and IgG titers [per 1 g/L increase, odds ratio (95% CI): 0.779 (0.630, 0.963), P < 0.05] were independent risk factors for infection in dialysis patients.

Conclusion: A decrease in memory B cells is independently associated with an increased risk of infection in patients on dialysis.
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http://dx.doi.org/10.1007/s11255-018-1977-8DOI Listing
November 2018

Long-term impacts of hemodialysis on the right ventricle: Assessment via 3-dimensional speckle-tracking echocardiography.

Clin Cardiol 2018 Jan 24;41(1):87-95. Epub 2018 Jan 24.

Department of Echocardiography, Zhongshan Hospital of Fudan University, Shanghai, China; Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China.

Background: Right ventricular (RV) dysfunction is a major cause of death in patients undergoing maintenance hemodialysis (MHD). We used 3-dimensional speckle-tracking echocardiography (3DSTE) to evaluate long-term impacts of MHD on RV function.

Hypothesis: In this study, RV dysfunction in MHD patients will be revealed and studied in depth by 3DSTE.

Methods: Echocardiography was performed on 110 consecutively enrolled individuals: 30 controls and 80 patients with MHD. Conventional echocardiographic parameters and 3DSTE parameters were obtained and compared between groups. Univariate and multivariate logistic regression analysis identified independent predictors of intradialytic hypotension (IDH).

Results: Compared with the control group, RV end-diastolic volume (RVEDV) was markedly enlarged (46.1 ± 11.8 mL/m vs 42.3 ± 8.6 mL/m ; P = 0.047), whereas RV ejection fraction (RVEF) was significantly lower in the MHD group (50.6% ± 5.8% vs 55.2% ± 3.7%; P < 0.001). RV global, septal, and lateral wall longitudinal strains were also decreased in the MHD group (-18.2 ± 3.6 vs -22.6 ± 4.3%; -13.1 ± 3.8 vs -17.5 ± 5.5%; and -23.4 ± 4.7 vs -27.7 ± 4.0%, respectively; all P < 0.001). RVEF (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51 to 1.01, P = 0.038) and history of diabetes (OR: 11.14, 95% CI: 1.16 to 106.71, P = 0.036) were 2 independent predictors of IDH. Ultrafiltration rate was an independent factor associated with RVEF (β = -0.01, 95% CI: -0.019 to 0.001, P = 0.039).

Conclusions: RVEF by 3DSTE could be an important predictor of IDH in MHD patients, and lower ultrafiltration rate was protective for RVEF. 3DSTE may have potential in RV evaluation and risk stratification in MHD patients.
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http://dx.doi.org/10.1002/clc.22857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490018PMC
January 2018

Decreased percentage of peripheral naïve T cells is independently associated with ischemic stroke in patients on hemodialysis.

Int Urol Nephrol 2017 Nov 15;49(11):2051-2060. Epub 2017 Sep 15.

Division of Nephrology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, 200032, China.

Purpose: Cerebrovascular complications, including ischemic stroke, account for poor outcomes in patients on hemodialysis. T cell responses may be involved in the pathogenesis of ischemic stroke. We aimed to evaluate the role of naïve T cells in development of ischemic stroke in patients on hemodialysis.

Methods: In this cross-sectional study, 156 patients on hemodialysis in our blood purification center were included. These patients were divided into the ischemic stroke (IS) group (61 cases) and non-ischemic stroke (non-IS) group (95 cases) according to a new diagnosis after initiation of hemodialysis. After being lysed with red blood cell lysis solution, peripheral blood was tested by flow cytometry to detect the expression of CD45RO and CCR7 in CD4 T and CD8 T cells. Correlation analysis and logistic regression analysis were conducted to identify potential independent risk factors for ischemic stroke.

Results: The percentage of peripheral naïve T cells was lower in the IS group [median (interquartile range (IQR)) 13.9% (8.6-22.9%)] compared with the non-IS group [median (IQR) 22.7% (15.9-32.2%), P < 0.001]. Spearman correlation analysis showed that naïve T cells were negatively associated with ischemic stroke (r = -0.308, P < 0.001). Multivariate logistic regression analysis showed that CD4 naïve T cells had an independent negative association with ischemic stroke in patients on hemodialysis (odds ratio 0.933, 95% CI 0.883, 0.986; P = 0.013).

Conclusion: A decrease in percentage of peripheral CD4 naïve T cells is a risk factor for ischemic stroke in patients on hemodialysis.
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http://dx.doi.org/10.1007/s11255-017-1691-yDOI Listing
November 2017

Factors associated with the elevated percentage of CD4CD69 T cells in maintained hemodialysis patients.

Ren Fail 2017 Nov;39(1):547-554

a Division of Nephrology , Zhongshan Hospital, Shanghai Medical College, Fudan University , Shanghai , China.

Background: CD4 T-cell abnormality, influencing the outcome of the maintained hemodialysis (MHD), is common in patients on dialysis. We try to find out factors associated with the activated CD4 T cells, CD4CD69 T cells, to improve the dialysis quality.

Methods: A cross-sectional study was conducted to evaluate the change of CD4CD69 in MHD patients and healthy controls in our hospital from September 2015 to May 2016. A total of 164 MHD patients and 24 healthy controls were included according to the criteria. Univariate and multivariate logistic regression models after correlation analysis were executed to discover the related factors of CD4CD69 T-cell posterior to the division of the CD4CD69 T cell according to its median.

Results: The lymphocytes were lower, but the percentage of CD4CD69 T cells was higher in MHD patients compared with healthy controls, even after the propensity score matching based on age and sex. The percentage of CD4 T cells showed no significant difference between the two groups. Further multivariate logistic regression models revealed that CD4CD69 T cell was independently associated with serum total protein (OR 95%CI: 0.830[0.696, 0.990], p = .038), transferrin (OR 95%CI: 3.072[1.131, 8.342], p = .028) and magnesium (OR 95%CI: 16.960[1.030, 279.275], p = .048).

Conclusion: The percentage of CD4CD69 T cells, activated CD4 T cells, elevated in hemodialysis patients despite the decrease in lymphocytes. The elevated CD4CD69 T cells were independently associated with serum total protein negatively, but transferrin and magnesium positively. Strengthening nutrition, reducing the concentration of transferrin and magnesium might be beneficial to reduce the activation of CD4 T cells and improve the outcome of MHD patients.
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http://dx.doi.org/10.1080/0886022X.2017.1349672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014306PMC
November 2017

Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all-cause mortality in hemodialysis patients: A prospective cohort study.

Hemodial Int 2018 01 12;22(1):82-92. Epub 2017 Apr 12.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Introduction: Patients with chronic kidney disease, especially those with end-stage renal disease, have an increased risk of death. Previous studies have suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR) has not been evaluated in HD patients. In this study, we prospectively studied the predictive value of MLR for all-cause and cardiovascular mortality in HD patients and compared it with NLR.

Methods: Patients who had been on a HD treatment for at least 6 months were enrolled. MLR was calculated by dividing the monocyte count by the lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of MLR and other clinical factors on all-cause and cardiovascular mortality.

Results: Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65, 7.02, and 11.15, respectively per 100 patient-years. The Kaplan-Meier analysis revealed that survival rates were significantly different among three MLR groups (P < 0.001). In multivariate Cox regression analyses, MLR was independently associated with all-cause mortality (HR 4.842; 95% CI, 2.091-11.214; P < 0.001) and cardiovascular mortality (HR 6.985, 95% CI 1.943-25.115, P = 0.003) as continuous variables. NLR was not an independent predictor of all-cause nor cardiovascular mortality after adjusted with MLR.

Conclusions: The main finding of the study suggest that higher MLR was a strong and independent predictor of all-cause and cardiovascular mortality and overwhelmed NLR among HD patients.
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http://dx.doi.org/10.1111/hdi.12549DOI Listing
January 2018

Increased Soluble Suppression of Tumorigenicity 2 Level Predicts All-Cause and Cardiovascular Mortality in Maintenance Hemodialysis Patients: A Prospective Cohort Study.

Blood Purif 2017 23;43(1-3):37-45. Epub 2016 Nov 23.

Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.

Background: Soluble suppression of tumorigenicity 2 (sST2) is a novel cardiovascular biomarker. This study aimed to evaluate the prognostic value of sST2 in hemodialysis patients.

Methods: Four hundred and fourteen maintenance hemodialysis (MHD) patients were enrolled and followed up prospectively. Serum sST2 levels were measured. The endpoint was all-cause and cardiovascular mortality.

Results: During a median follow-up of 22.3 months, 58 patients died, including 31 cardiovascular deaths. sST2 was an independent predictor of all-cause mortality with a relative risk (RR) of 1.31 (95% CI 1.000-1.717, p = 0.050) and cardiovascular mortality with an RR of 2.10 (95% CI 1.507-2.927, p < 0.001). The prognostic value of sST2 was additive to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT), as the combined use of sST2 and NT-proBNP or hs-cTnT better identified higher-risk patients.

Conclusion: Elevated sST2 is an independent predictor of all-cause and cardiovascular mortality in MHD patients. A combined use of sST2 and NT-proBNP or hs-cTnT helps identify individuals of higher risk.
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http://dx.doi.org/10.1159/000452924DOI Listing
March 2017

Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis.

Hemodial Int 2017 04 12;21(2):161-167. Epub 2016 Sep 12.

Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.

Chronic kidney disease (CKD) is an increasingly recognized disease with high global incidence and mortality. Yet, the existing diagnostic tools are not sufficient enough to predict prognosis of CKD and CKD comorbidities. Indoxyl sulfate, a typical uremic toxin, is of great importance in the development of CKD with its nephrotoxicity, cardiovascular toxicity, and bone toxicity. Some reports suggest that indoxyl sulfate directly associate with renal function loss and mortality in CKD patients. This review discusses the diagnostic value of indoxyl sulfate from its biological characteristics, pathophysiological effects, related therapies, and its diagnostic value in clinical studies.
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http://dx.doi.org/10.1111/hdi.12483DOI Listing
April 2017

The Prognostic Value of Red Blood Cell Distribution Width in Patients on Maintenance Hemodialysis.

Blood Purif 2016 6;42(4):314-321. Epub 2016 Oct 6.

Blood Purification Center, Zhongshan Hospital of Fudan University, Shanghai, PR China.

Aims: To examine the association between red blood cell distribution width (RDW) and mortality in hemodialysis (HD) patients.

Methods: Three hundred fifty six patients on HD for >3 months were enrolled and followed for 2 years. Patients were divided into 2 groups according to the median RDW value. Patient survival and risk factors for mortality were investigated.

Results: The 2-year survival rate was significantly lower in the high-RDW group (>14.9%; log-rank = 10.00, p = 0.0016). RDW (hazard ratio (HR) 1.34, 95% CI 1.04-1.71, p = 0.021), hemoglobin (HR 0.98, 95% CI 0.96-1.00, p = 0.023) and albumin (HR 0.90, 95% CI 0.82-0.99, p = 0.026) were independent predictors of mortality. Receiver operating characteristic curves of RDW to predict 2-year mortality had an area under the curve of 0.6487 (95% CI 0.5714-0.7260).

Conclusions: Abnormal RDW was common in HD patients and significantly related with poor outcomes in these patients.
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http://dx.doi.org/10.1159/000449421DOI Listing
December 2016

Hemodialysis-induced regional left ventricular systolic dysfunction.

Hemodial Int 2016 10 17;20(4):564-572. Epub 2016 Jun 17.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4-hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD-induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD-induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Higher cTnT (0.060 ± 0.030 vs. 0.048 ± 0.015 ng/mL, P = 0.023), phosphate (2.07 ± 0.50 vs. 1.49 ± 0.96 mmol/L, P = 0.001), UFR (11.00 ± 3.89 vs. 8.30 ± 2.66 mL/Kg/h, P = 0.039) and lower albumin (37.83 ± 4.48 vs. 38.38 ± 2.53 g/L, P = 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR = 1.047, 95%CI 1.155-4.732, P = 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate.
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http://dx.doi.org/10.1111/hdi.12434DOI Listing
October 2016

Electrocardiographic Abnormalities and QTc Interval in Patients Undergoing Hemodialysis.

PLoS One 2016 12;11(5):e0155445. Epub 2016 May 12.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.

Background: Sudden cardiac death is one of the primary causes of mortality in chronic hemodialysis (HD) patients. Prolonged QTc interval is associated with increased rate of sudden cardiac death. The aim of this article is to assess the abnormalities found in electrocardiograms (ECGs), and to explore factors that can influence the QTc interval.

Methods: A total of 141 conventional HD patients were enrolled in this study. ECG tests were conducted on each patient before a single dialysis session and 15 minutes before the end of dialysis session (at peak stress). Echocardiography tests were conducted before dialysis session began. Blood samples were drawn by phlebotomy immediately before and after the dialysis session.

Results: Before dialysis, 93.62% of the patients were in sinus rhythm, and approximately 65% of the patients showed a prolonged QTc interval (i.e., a QTc interval above 440 ms in males and above 460ms in females). A comparison of ECG parameters before dialysis and at peak stress showed increases in heart rate (77.45±11.92 vs. 80.38±14.65 bpm, p = 0.001) and QTc interval (460.05±24.53 ms vs. 470.93±24.92 ms, p<0.001). After dividing patients into two groups according to the QTc interval, lower pre-dialysis serum concentrations of potassium (K+), calcium (Ca2+), phosphorus, calcium* phosphorus (Ca*P), and higher concentrations of plasma brain natriuretic peptide (BNP) were found in the group with prolonged QTc intervals. Patients in this group also had a larger left atrial diameter (LAD) and a thicker interventricular septum, and they tended to be older than patients in the other group. Then patients were divided into two groups according to ΔQTc (ΔQTc = QTc peak-stress- QTc pre-HD). When analyzing the patients whose QTc intervals were longer at peak stress than before HD, we found that they had higher concentrations of Ca2+ and P5+ and lower concentrations of K+, ferritin, UA, and BNP. They were also more likely to be female. In addition, more cardiac construction abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ΔQTc.

Conclusion: Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients' clinical conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155445PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865146PMC
July 2017

Acute Effects of Hemodiafiltration Versus Conventional Hemodialysis on Endothelial Function and Inflammation: A Randomized Crossover Study.

Medicine (Baltimore) 2016 Apr;95(16):e3440

From the Division of Nephrology, Zhongshan Hospital, Fudan University (PJ, WJ, JT, HZ, JZ, ZL, BS, XC, XD), Kidney and Dialysis Institute of Shanghai (PJ, XD), Kidney and Blood Purification Laboratory of Shanghai (PJ, XD), and Division of Nephrology, Central Hospital of Minhang District, Shanghai, China (WJ).

Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation. A prospective, randomized, crossover trial. Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OL-HDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flow-mediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well. Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.7 ± 6.9% at baseline; 21.5 ± 5.4% after the first dialysis; 21.5 ± 5.7% after 2 weeks; P < 0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9-457.0] ng/ml at baseline to 234.7 [174.1-345.5] ng/ml after the first dialysis, and to 191.5 [138.2-255.0] ng/ml after 2 weeks; P < 0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments. OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD.
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http://dx.doi.org/10.1097/MD.0000000000003440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845844PMC
April 2016

Assessed value of high-sensitivity cardiac troponin T for cardiovascular disease among CKD patients.

Ren Fail 2016 Jun 16;38(5):728-37. Epub 2016 Mar 16.

c Dialysis Center , Zhongshan Hospital, Fudan University , Shanghai , P.R. China.

Objective To analyze the relationship between serum high-sensitivity cardiac troponin T (hs-cTnT) and cardiovascular disease (CVD) among non-dialysis chronic kidney disease (CKD) patients, and to further explore its value of evaluating and predicting CVD in this population. Methods Five hundred and fifty-seven non-dialysis CKD patients were involved in this cross-sectional study. The relationship between serum hs-cTnT and CVD was analyzed using comparison between groups and regression analysis, and its value on assessing cardiac structure and function was evaluated by ROC curves. Results Median level of hs-cTnT was 13 (7-29) ng/L, with 1.7% undetectable, 46.4% greater than 99th percentile of the general population. Multivariate analysis suggested that compared with the lowest quartile of hs-cTnT, the highest quartile was approximately six times as likely to develop into LVH (OR, 6.515; 95% CI, 3.478-12.206, p < 0.05) and 18 times as likely to progress to left ventricular diastolic dysfunction(OR, 18.741; 95% CI, 2.422-145.017, p < 0.05). And Ln cTnT level had a more modest association with LVEF (OR, -1.117; 95% CI, -5.839 to -0.594; p < 0.05). When evaluated as a screening test, the area under the curve of ROC curves for hs-cTnT was 0.718, 0.788 and 0.736, respectively (p < 0.05). With a specificity of 90% as a diagnostic criterion, the value of hs-cTnT to evaluate LVH, LVEF < 50%, left ventricular diastolic dysfunction increased across CKD stages, from CKD 1 stage to CKD 5 stage. Conclusions In CKD non-dialysis population, hs-cTnT and NT-proBNP were valuable for evaluating LVH, left ventricular systolic dysfunction and left ventricular diastolic dysfunction.
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http://dx.doi.org/10.3109/0886022X.2016.1158040DOI Listing
June 2016

Global longitudinal strain is an independent predictor of cardiovascular events in patients with maintenance hemodialysis: a prospective study using three-dimensional speckle tracking echocardiography.

Int J Cardiovasc Imaging 2016 May 14;32(5):757-66. Epub 2016 Jan 14.

Department of Echocardiography, Zhongshan Hospital of Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, 21 Room, M-floored,16 Building, No. 1609 Xietu Road, Shanghai, 200032, China.

The aim of this study was to investigate subclinical LV changes in patients with maintenance hemodialysis (MHD) using three-dimensional speckle-tracking echocardiography (3DSTE) and to explore its prognostic value. A total of 88 individuals were consecutively enrolled, including 66 subjects with MHD and 22 age- and sex-matched controls. Conventional and Real-time three-dimensional echocardiography was performed and analyzed. Left ventricular volume, strain and time parameters were calculated and compared. The MHD cohort was then followed to record cardiovascular events (CVE). Univariate and multivariate logistic regression analysis was used to identify independent predictors of CVE. Compared with the controls, MHD patients had significantly lower global longitudinal and radial strain (GLS and GRS), and LVEF (GLS: -17.0 ± 2.3 vs -18.8 ± 2.3 %; GRS: 37.0 ± 3.5 vs 39.4 ± 3.4 %; LVEF: 57.3 ± 4.2 vs 59.5 ± 3.5 %, p < 0.05 for all), as well as enlarged LV volume (EDV: 51.3 ± 14.2 vs 40.4 ± 7.3 ml/m(2); ESV: 22.0 ± 6.9 vs 16.3 ± 3.2 ml/m(2); SV: 29.2 ± 8.0 vs 24.0 ± 4.7 ml/m(2), p < 0.01 for all) and LV mass index (LVMi) (107.7 ± 28.6 vs 83.7 ± 20.6 g/m(2)). Time to minimum end-systolic volume and to peak longitudinal strain (T-msv and T-ls) were delayed in the MHD group (T-msv: 38.1 ± 5.2 vs 41.4 ± 6.4 %; T-ls: 38.1 ± 4.6 vs 42.1 ± 6.8 %, p < 0.05). Systolic dyssynchrony index (SDI) of the MHD group was significant larger than that of the controls (6.4 ± 1.5 vs 4.9 ± 1.8 %, p < 0.01). CVE occurred in 23 patients within a follow-up of 2 years. GLS and LVMi remained significant predictors of CVE [OR = 3.94, 95 % CI (1.33-11.66) for GLS and OR = 1.04, 95 % CI (1.01-1.07) for LVMi, p = 0.013 and 0.009, respectively]. Subclinical LV deformation and dysfunction exist in MHD patients with preserved LVEF. GLS and LVMi are two important predictors of CVE in MHD patients. Strain assessment in MHD patients may contribute to better vascular risk stratification.
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http://dx.doi.org/10.1007/s10554-016-0836-xDOI Listing
May 2016