Publications by authors named "JianZhou Zou"

60 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

Paradoxical Association Between Intradialytic Blood Pressure Change and Long-Term Mortality with Different Levels of Interdialytic Weight Gain.

Int J Gen Med 2021 19;14:211-220. Epub 2021 Jan 19.

Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

Background: A greater interdialytic weight gain (IDWG) implies a greater ultrafiltration rate, which might lead to hemodynamic instability and intradialytic blood pressure (BP) change in hemodialysis patients. However, current studies have not explicated the impact of IDWG on the association between intradialytic BP changes and prognosis, especially in patients without cardiac dysfunction and diabetes. In this study, we aimed to explore the relationship between absolute intradialytic BP changes and mortality with different IDWG levels.

Methods: A total of 204 hemodialysis patients (without cardiac dysfunction and diabetes) were included in this prospective observation study, with a mean follow-up of 55.32±20.99 months. Initially, we collected IDWG, IDWG% (percentages according to dry weight), and pre-/post-BPs of 36 consecutive dialysis sessions during three months enrollment. And the average value of them was defined as baseline value. Patients were divided into 3 cohorts according to IDWG% tertiles (<3.3%, 3.3%-4.6%, ≥4.6%). Comparisons between different tertiles were analyzed.

Results: Compared to the low IDWG% group (tertile 1, T1), patients of high IDWG% group (tertile 3, T3) were younger, had higher ultrafiltration rate, less residual kidney function, lower BMI and dry weight, longer dialysis vintage and higher N terminal pro B type natriuretic peptide levels (<0.05). Correlations were found between IDWG% and intradialytic BP changes. Kaplan-Meier analysis and multivariate Cox regression model adjusted for demographic data, dialysis information and predialysis BPs indicated that greater absolute intradialytic BP changes were associated with worse prognosis in T1 group (<0.05). While in T3 group, less absolute intradialytic BP changes were associated with higher mortality (<0.05).

Conclusion: There is a paradoxical association between absolute intradialytic BP changes and long-term mortality with different IDWG levels. Both BP stability and volume balance are crucial to patients' prognosis.
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http://dx.doi.org/10.2147/IJGM.S288038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829598PMC
January 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

Intradialytic systolic blood pressure variation can predict long-term mortality in patients on maintenance hemodialysis.

Int Urol Nephrol 2021 Apr 2;53(4):785-795. Epub 2021 Jan 2.

Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.

Purpose: It is unclear which time-points of intradialytic blood pressure (BP) best predict prognosis. Thus, it is important to assess the association between different time-points of intradialytic BP and prognosis in clinical practice.

Methods: We recruited patients who underwent hemodialysis from January 2014 to June 2014. Data about dialysis were collected, including intradialytic BP. Cox regression analysis was performed to examine the association between different time-points of intradialytic BP and clinical events, with a follow-up through December 31, 2019. The primary endpoint was all-cause mortality.

Results: A total of 216 patients were recruited and 62 (30.7%) patients died (6.1 per 100-person year) during the follow-up. Intradialytic SBP varied greatly in fatalities. Univariate and multivariate Cox regression models indicated that the adjusted hazard ratio for death was 1.80 and 5.06 when intradialytic systolic blood pressure (SBP) variation was analyzed in increments of 20 mmHg. Furthermore, we divided intradialytic SBP variation into three categories: < 15 mmHg, 15 ~ 30 mmHg,  ≥ 30 mmHg. Kaplan-Meier analysis indicated that both all-cause mortality and cardiovascular mortality increased significantly for patients with intradialytic SBP variation over 30 mmHg (P = 0.006 and 0.021). Univariate and multivariate Cox regression models indicated that the adjusted hazard ratio for death was 3.78 and 12.62 as intradialytic SBP variation ≥ 30 mmHg vs. intradialytic SBP variation < 15 mmHg.

Conclusion: Intradialytic SBP variation, rather than BP of specific intradialytic time-points, has the potential to predict long-term mortality in hemodialysis patients. BP stability is crucial for patients' prognosis.
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http://dx.doi.org/10.1007/s11255-020-02701-wDOI Listing
April 2021

High ultrafiltration rate induced intradialytic hypotension is a predictor for cardiac remodeling: a 5-year cohort study.

Ren Fail 2021 Dec;43(1):40-48

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

Background: Intradialytic-hypotension (IDH) is a common complication of hemodialysis. High ultrafiltration rate (UFR) might lead to IDH. However, the relationships between UFR, IDH, and cardiac remodeling among hemodialysis patients in the long-term have not been deeply explored.

Methods: This retrospective cohort study collected clinical and echocardiographic data. Patients were enrolled from 1 January 2014 to 31 March 2014 and were followed-up for 5-year. Those who suffered from more than four hypotensive events during three months (10% of dialysis treatments) were defined as the IDH group. Subgroup analysis was done according to the UFR of 10 ml/h/kg. Associations between UFR, IDH, and alterations of cardiac structure/function were analyzed.

Results: Among 209 patients, 96 were identified with IDH (45.9%). The survival rate of IDH patients was lower than that of no-IDH patients (65.5% vs. 81.4%,  = .005). In IDH group, decreased ejection fraction (EF), larger left atrium diameter index (LADI), and left ventricular mass index (LVMI) ( < .05) were observed at the end of the follow-up. In multivariate logistic model, the interaction between UFR and IDH was notably associated with LVMI variation ( = 1.37). After adjusting covariates, UFR was still an independent risk factor of LVMI variation ( = 1.52) in IDH group. In subsequent analysis, we divided patients according to UFR 10 ml/h/kg. For IDH-prone patients, decreased EF, larger LADI, and LVMI ( < .05) were observed at the end of the study only in high-UFR group.

Conclusions: UFR and IDH have interactions on cardiac remodeling. High ultrafiltration rate induced IDH is a predictor for cardiac remodeling in long-term follow-up.
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http://dx.doi.org/10.1080/0886022X.2020.1853570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745843PMC
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

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

Can J Physiol Pharmacol 2021 Apr 15;99(4):395-401. 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
April 2021

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

Estimating 24-Hour Urinary Sodium Excretion From Spot Urine Samples in Chronic Kidney Disease Patients.

J Ren Nutr 2020 01 5;30(1):11-21. Epub 2019 Apr 5.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; Shanghai Medical Center of Kidney, Shanghai, People's Republic of China; Shanghai Institute of Kidney and Dialysis, Shanghai, People's Republic of China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, People's Republic of China; Hemodialysis Quality Control Center of Shanghai, Shanghai, People's Republic of China. Electronic address:

Objective: Spot urine sodium and associated estimating equations provide a suitable alternative assessment of 24-hour sodium excretion in many large-scale studies, but not in chronic kidney disease (CKD) patients with decreased renal function. Herein, we aimed to develop a novel predictive equation.

Design And Methods: We retrospectively enrolled all CKD patients at Stage 1-4 who received spot and 24-hour urinary analysis in our single center from January 1, 2014 to December 31, 2017. Multiple linear regression analysis generated a predictive equation for estimating 24-hour sodium excretion from spot urine samples in the derivation cohort admitted from 2014 to 2015, and then we assessed this predictive equation in a validation cohort admitted from 2016 to 2017.

Results: All 5,235 patients were finally analyzed and divided into derivation (n = 2,460) and validation (n = 2,775) cohort according to the admission date. We generated a predictive equation and defined it as "CKDSALT" equation because it was used for the estimation of salt intake in CKD patients. When we measured sodium excretion as the gold standard, we compared this novel validation with other 3 equations: Kawasaki, INTERSALT, and Tanaka. The Bland-Altman plots indicated that the CKDSALT equation showed the lowest bias with limits of agreement (bias = -1.25 mmol, 95% confidence interval -121.3 to 123.8), and the best performance in any subgroup analysis: male and female, old and young, different levels of body mass index, various levels of estimated glomerular filtration rate, and 24-hour urine volume. The CKDSALT equation also had the highest Pearson (0.745) and intraclass correlation coefficient (0.853, 95% confidence interval 0.841-0.863) in all validation cohort and the above subgroups.

Conclusion: Spot urine method by CKDSALT equation may be promising for estimating 24-hour urinary sodium excretion in CKD patients with normal renal function and patients with decreased estimated glomerular filtration rate.
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http://dx.doi.org/10.1053/j.jrn.2019.02.002DOI Listing
January 2020

Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis.

J Cell Mol Med 2019 05 22;23(5):3429-3440. Epub 2019 Feb 22.

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

Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.5 within 10 minutes initiation of ischaemia. Acid-sensing ion channels (ASICs) can be activated by pH drops from 7.4 to 7.0 or lower and permeates to Ca entrance. Thus, activation of ASIC1a can mediate the intracellular Ca accumulation and play crucial roles in apoptosis of cells. However, the role of ASICs in renal ischaemic injury is unclear. The aim of the present study was to test the hypothesis that ischaemia increases renal epithelia cell apoptosis through ASIC1a-mediated calcium entry. The results show that ASIC1a distributed in the proximal tubule with higher level in the renal tubule ischaemic injury both in vivo and in vitro. In vivo, Injection of ASIC1a inhibitor PcTx-1 previous to ischaemia/reperfusion (I/R) operation attenuated renal ischaemic injury. In vitro, HK-2 cells were pre-treated with PcTx-1 before hypoxia, the intracellular concentration of Ca , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca overflow, loss of ∆ψm and apoptosis in HK-2 cells. The results revealed that ASIC1a localized in the proximal tubular and contributed to I/R induced kidney injury. Consequently, targeting the ASIC1a may prove to be a novel strategy for AKI patients.
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http://dx.doi.org/10.1111/jcmm.14238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484315PMC
May 2019

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

Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway.

Transplantation 2018 07;102(7):e331-e344

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

Background: The hepatocyte growth factor (HGF) target pathway plays pivotal renoprotective roles after acute kidney injury. Syndecan-1 (SDC-1) serves as the coreceptor for HGF. Shedding of SDC-1 is involved in various pathological processes. Thus, we hypothesized that ischemia/reperfusion injury induced SDC-1 shedding, and inhibiting SDC-1 shedding would protect against kidney injury by potentiating activation of the HGF receptor mesenchymal epithelial transition factor (c-Met).

Methods: Expression of SDC-1 and its sheddases were observed in kidneys of sham and ischemia/reperfusion (I/R) mice. To inhibit SDC-1 shedding, mice were injected with the sheddase inhibitor GM6001 before I/R surgery, and then, renal inflammation, tubular apoptosis, and activation of the c-Met/AKT/glycogen synthase kinase-3β (GSK-3β) pathway were analyzed. In vitro, human proximal tubular cell lines were pretreated with GM6001 under hypoxia/reperfusion conditions. The apoptosis and viability of cells and expression of c-Met/AKT/GSK-3β pathway components were evaluated. The relationship was further confirmed by treatment with SU11274, a specific inhibitor of phospho-c-Met.

Results: Shedding of SDC-1 was induced after ischemia/reperfusion injury both in vivo and in vitro. GM6001 pretreatment suppressed SDC-1 shedding, alleviated renal inflammation and tubular apoptosis, and upregulated phosphorylation of the c-Met/AKT/GSK-3β pathway. In vitro, pretreatment with GM6001 also decreased hypoxia/reperfusion-induced cell apoptosis and promoted activation of the c-Met pathway. In addition, the cytoprotective role of GM6001 was attenuated by suppressing c-Met phosphorylation with SU11274.

Conclusions: Our findings suggest that inhibiting I/R-induced SDC-1 shedding protected against ischemic acute kidney injury by potentiating the c-Met/AKT/GSK-3β pathway.
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http://dx.doi.org/10.1097/TP.0000000000002170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228646PMC
July 2018

Intradialytic Hypotension as an Independent Risk Factor for Long-Term Mortality in Maintaining Hemodialysis Patients: A 5-Year Follow-Up Cohort Study.

Blood Purif 2018 2;45(4):320-326. Epub 2018 Feb 2.

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

Aims: This study aimed to assess risk factors of intradialytic hypotension (IDH) and the association of prognosis and IDH among maintenance hemodialysis (MHD) patients.

Methods: Among 293 patients, 117 were identified with IDH (more than 4 hypotensive events during 3 months). The association between IDH and survival was evaluated.

Results: The incidence of IDH was 39.9%. Age, ultrafiltration rate, N-terminal pro-B-type natriuretic peptide (NT-proBNP), albumin, β2-microglobulin (β2MG), and aortic root inside diameter (AoRD) were independently associated with IDH. During the 5-year follow-up, 84 patients died with a mortality rate 5.2 per 100 person-year. IDH-prone patients had a higher all-cause mortality rate. IDH and left ventricular mass index were independent risk factors for death (HR 1.655, 95% CI 1.061-2.580; HR 1.008, 95% CI 1.001-1.016).

Conclusion: IDH is an independent risk factor for long-term mortality in MHD patients. Patients with older age, high ultrafiltration rate, high level of serum NT-proBNP and β2MG, hypoalbuminemia, and shorter AoRD are at high risk of IDH.
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http://dx.doi.org/10.1159/000486231DOI Listing
February 2019

Quality Measures in Acute Kidney Injury Management.

Contrib Nephrol 2018 23;193:68-80. Epub 2018 Jan 23.

Acute kidney injury (AKI) is common in clinical practice and associated with increased risk for death and major morbidity. Although some meaningful clinical guidelines were published, the quality of AKI healthcare remains suboptimal. Some AKI quality improvement methods, such as guidelines-based training programs, the referral from nephrology, and electronic data system have been found to be potentially beneficial, but further validation is required. Quality measures (QMs) for structure, process, and outcome of AKI care need to be further developed, evaluated, and implemented to ensure utmost quality of AKI care. However, many unknowns remain in this field. Some commonly used QMs like mortality are still difficult to realize in AKI quality control because of the heterogeneity in AKI practice. More evidence is needed to improve the AKI quality control system. These are challenges that will need to be addressed in the future.
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http://dx.doi.org/10.1159/000484964DOI Listing
April 2019

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

MicroRNA-21 Is Required for Local and Remote Ischemic Preconditioning in Multiple Organ Protection Against Sepsis.

Crit Care Med 2017 Jul;45(7):e703-e710

1Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.2Traditional Chinese Medicine Pharmacology Laboratory, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.3Department of Physiology, Medical College of Wisconsin, Milwaukee, WI.4Kidney and Dialysis Institute of Shanghai, Shanghai, China.5Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China.

Objective: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent.

Design: Laboratory study.

Setting: University laboratory.

Subjects: Mouse renal tubular epithelial cells, C57BL/6 J wildtype (Animal Center of Fudan University, Shanghai, China) and microRNA-21-/- mice (B6.129-Mir21atm1Smoc, Shanghai Biomodel Organism Science & Technology Development Co. Shanghai, China).

Interventions: Mouse renal tubular epithelial cells were treated with hypoxia (2% oxygen). Renal ischemic preconditioning was induced by bilateral renal pedicle clamping for 15 minutes, and sepsis was induced by a single intraperitoneal injection of lipopolysaccharide at a dose of 20 mg/kg or cecal ligation and puncture in mice.

Measurements And Main Results: Mice treated with renal ischemic preconditioning were protected from endotoxemia or polymicrobial sepsis-induced multiple organ injury, including kidneys, heart, liver, and lungs. Renal ischemic preconditioning induced activation of hypoxia-inducible factor-1α in kidneys, which up-regulated microRNA-21 at transcriptional level, subsequently, leading to increased expression of microRNA-21 in serum exosomes and remote organs, resulting in decreased apoptosis and reduced proinflammatory cytokines production in these organs. In vivo knockdown of microRNA-21 or genetic deletion of microRNA-21 abrogated the organoprotective effects conferred by renal ischemic preconditioning. Mechanistically, we discovered that knockdown of microRNA-21 increased programmed cell death protein 4 expression and nuclear factor-kappa B activity, decreased expression of anti-apoptotic B-cell lymphoma-2.

Conclusion: MicroRNA-21 is required for local and remote ischemic preconditioning in multiple organ protection against sepsis, and up-regulation of miR-21 may be a potential therapy for sepsis.
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http://dx.doi.org/10.1097/CCM.0000000000002363DOI Listing
July 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

Incidence and outcomes of acute kidney injury in patients with hepatocellular carcinoma after liver transplantation.

J Cancer Res Clin Oncol 2017 Jul 13;143(7):1337-1346. Epub 2017 Mar 13.

Liver Cancer Institute, Shanghai, 200032, People's Republic of China.

Purpose: To describe the incidence and outcomes linked with acute kidney injury (AKI) after liver transplantation (LT) in hepatocellular carcinoma (HCC) patients.

Methods: From January 2003 to February 2011, HCC patients undergoing LT were retrospectively enrolled. Patient with a glomerular filtration rate (GFR) <60 mL/min/1.73 m was excluded. AKI was defined and classified according to the AKIN criteria.

Results: Of the 566 eligible patients, AKI was found in 109 (19.26%) patients (stage I, 66 cases; stage II, 15 cases; and stage III, 28 cases). Risk factors for AKI were the long anhepatic time (OR = 3.59, P = 0.009) and prolonged duration of systolic blood pressure (SBP) < 90 mmHg (OR = 1.07, P < 0.0001). Post-LT AKI was an independent risk factor associated with 30-day mortality (HR = 4.05, P = 0.047). Complete recovery occurred in 84 (77.06%) of all AKI episodes within 1 month after operation, while 25 patients (22.94%) suffered from prolonged AKI. Patients with prolonged AKI had a poorer 1-year survival than those with transient AKI (40 vs 86.90%; P < 0.0001). Patients with severe AKI more often developed prolonged AKI. 13 patients (52%) of the prolonged AKI progressed to chronic kidney disease (CKD) defined as eGFR <60 mL/min/1.73 m after 1 year post-operation.

Conclusions: Post-LT AKI is not an uncommon complication. Intra-operative hemodynamic instability is crucial in the development of post-LT AKI and deserves more attention. Most post-LT AKI is transient and reversible, while the prolonged form may predict a decrease survival.
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http://dx.doi.org/10.1007/s00432-017-2376-8DOI Listing
July 2017