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

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-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ T cells, were sorted and expanded in vitro. After expansion, the proportions of PD-1+CD8+, TIM-3+CD8+, and LAG-3+CD8+ 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-1+CD8+ T cells significantly correlated with the HCC + uremia cohort (odds ratio of 2.731, p = 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-1+CD8+ T cells were most evident in HCC patients with uremia.

Impact of indoxyl sulfate on left atrial strains in patients with maintenance hemodialysis: a three-dimensional speckle tracking study / 中华超声影像学杂志

Objective:To investigate the influence of indoxyl sulfate(IS), a typical protein-bound uremic toxin, on left atrial (LA) functional strains using three-dimensional speckle tracking echocardiography (3DSTE).Methods:From May 2019 to January 2020, 128 individuals were consecutively enrolled, including 37 healthy controls and 91 patients, who received maintenance hemodialysis (MHD) in the blood purification center of Zhongshan Hospital affiliated to Fudan University. Conventional echocardiographic parameters and 3DSTE datas of LA were obtained on interdialytic days.LA reservoir, conduit and contraction strains (LASr, LAScd and LASct) were calculated and compared. IS concentration in plasma was assessed by high-performance liquid chromatography tandem mass spectrometry in the MHD cohort.According to the IS concentration, the MHD group was divided into high and low IS (HI and LI) groups. The LA data were also compared between the two groups and linear regression analysis was used to identify independent impact factors of LA strains.Results:Compared to the control group, MHD group had markedly enlarged LA volumes( P<0.05). With regard to the LA phasic strains, both of LASr and LAScd were decreased( P<0.05), while LASct remained unchanged( P>0.05). Compared to the LI group, LASr, LAScd and LASct of the HI group were significantly decreased(all P<0.05). Correlation analysis showed IS concentration correlated well with LASr( rs=-0.674, P<0.001), LAScd( rs=0.454, P<0.001) and LASct( rs=0.376, P<0.001). After adjustment of age, systolic blood pressure, left ventricular mass index(LVMI), and pulmonary systolic pressure, IS concentration remained independently associated with LASr (β=-0.206, 95% CI=-0.353--0.059, P=0.007). Conclusions:In MHD patients, LA is enlarged, and its reservoir function and conduit function are impaired.LA strains derived from 3DSTE are independently related to the IS concentration in plasma, which can be used for the monitoring and evaluation of IS induced cardiac injury.

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

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.

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

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.

Evaluation of left ventricular strains in patients with maintenance hemodialysis using layer-specific two-dimensional speckle tracking imaging / 中华超声影像学杂志

Objective To evaluate the impact of maintenance hemodialysis(MHD) on left ventricular(LV) strains via layer-specific speckle-tracking imaging (LSTI).Methods Twenty-eight MHD patients and 28 matched controls were enrolled in the study.Conventional echocardiography and LSTI were performed on patients before and shortly after one hemodialysis session,as well as on controls.Results LV end-diastolic volume (LVEDV) were markedly reduced after one session of HD [(52.3±22.4)ml/m2 vs (55.0±15.3)ml/m2,P=0.033],but still larger than the control group (47.4±6.4) ml/m2.LV ejection fraction (LVEF) decreased in MHD patients after HD [(62.5±8.1)% vs (64.6±7.3)%,P=0.06],which was similar to those in the control group (66.0±4.2)% and in MHD patient before HD (P=0.391).The three layer circumferential and longitudinal strains decreased in the order of the control group,patients before HD and after HD [CS-endo:(-26.3±3.6)% vs (-22.2±4.7)% vs (-19.2±5.4)%;CS-mid:(-19.0±2.7)% vs (-15.3±3.5)% vs (-13.0±3.8)%;CS-epi:(-11.1±2.3)% vs (-8.0±2.6)% vs (-6.5±2.3)%;LS-endo:(-23.7±3.0)% vs (-18.6±3.6)% vs (-16.4±4.5)%;LS-mid:(-20.9±2.7)% vs (-16.3±3.1)% vs (-14.0±4.1)%;LS-epi:(-18.4±2.4)% vs (-14.1±2.8)% vs (-12.0±3.6)%;all P<0.01],while the synchrony index,standard deviation of times to peak longitudinal strain,increased in these three groups [(3.6±1.0)% vs (6.3±1.5)% vs (7.5±2.2)%,all P<0.01].Linear correlation analysis showed ultrafiltration volume was negatively related with the difference of longitudinal strains before and after HD (difference of LS-endo:r=-0.428,P=0.023;difference of LS-mid:r=-0.423,P=0.025;difference of LS-epi:r=-0.422,P=0.025).Conclusions One session of HD may have injurious effects on LV strains and systolic synchrony.The reduction of ultrafiltration volumes may be helpful to protect cardiomyocytes.

The pulmonary arterial hypertension of patients on maintained hemodialysis is positively associated with the decreased percent of CD8 T cell in the peripheral blood independently / 中华肾脏病杂志

Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH.Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently:PAH group (pulmonary artery systolic pressure,PASP ＞ 35 mmHg) and non-PAH group (PASP≤35 mmHg).The related clinical,biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3,CD4,CD8 and CD69 with flow cytometry.Logistic regression analysis was used to find out the relationship between PAH and T cell subsets.Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender,age,mean systolic and diastolic pressure,dialysis durations,morbidities of hypertension and diabetes,smoking rate,and left ventricular diameter.Compared with the non-PAH group,the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells,but a much higher left atrial diameter (LAD),Interventricular septum thickness,left ventricular posterior wall thickness,and NT-proBNP.The percentage of T cells,CD4 T cells and CD4 CD69 T cells showed no difference between the two groups.Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells.Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients,and CD8 T cells may play an important role in the genesis of PAH.

Decreased lymphocyte and increased monocyte count in peripheral blood is associated with cardiovascular disease and one-year mortality in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients.Methods A total of 371 MHD patients at Zhongshan Hospital,Fudan University between March 2009 and February,2011 were enrolled.Demographic,hematological,nutritional and inflammatory markers were obtained.All patients were followed for one year to investigate the risks for CVD event and mortality.Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters.Difference in categorical factors between two groups were determined with Chi-square test,Difference in continuous values between two groups were assessed with t test.Kaplan-Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors.Results Patients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51,P＜ 0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15,P＜0.01) than those without CVD event.Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk,95％CI:0.136-0.719,P ＜ 0.01) and that an increased monocyte count was associated with increased mortality risk,95％ CI:2.657-74.396,P＜0.01) after adjustment for hsCRP.Conclusion Decreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one-year all-cause mortality risk in MHD patients.

Risk factors for aortic and mitral Valve calcification in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To explore the potential risk factors for aortic and mitral valve calcification in maintenance hemodialysis(MHD)patients. Methods Patients on MHD for at least 6 months.aged≥1 8 years without history of surgery or catheter for heart valve disease were enrolled in the study.Echocardiographic examination was performed to detect the calcification.The risk factors for aortic and mitral valve calcification were analyzed by Logistic regression. Results One hundred and eighty-one MHD patients(98 men and 83 women)were enrolled in the study.Of all the patients,aortic or mitral valve calcification was found in 94 patients(5 1.9%),aortic valve calcification in 90 patients(49.7%),mitral valve calcification in 30 patients(16.6%),aortic and valve calcification in 26 patients(14.4%).Multivariate Logistic regression showed that age(β=5.52,P=0.007),dialysis duration(β=6.99,P=0.039)and pre-albumin(β=-12.616,P=0.004)were independently correlated with aortic valve calcification.Mitral valve calcification was independently correlated with dialysis duration(β=6.057,P=0.002),history of primary hypertension(β=3.054,P=0.008),hemoglobin(β=-0.061,P=0.035)and β2 microglobulin(β=7.63,P=0.01).While the correlation between mitral valve calcification and age was borderline significant(β=0.085,P=0.05).Conclusions Valve calcification is prevalent in MHD patients,and aortic valve calcification is more common than mitral valve calcification.Age,dialysis duration and low serum pre-albumin are independent risk factors for aortic valve calcification.The risk factors for mitral valve calcification include age,dialysis duration,history of primary hypertension,anemia and high serum β2 microglobulin.

Interdialytic body weight gain and associated factors in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To study interdialytic body weight gain(IBWG)in maintenance hemodialysis(MHD)patients,and to analyze the associated factors. Methods A total of 269 patients undergoing maintenance hemodialysis were enrolled in this cross-sectional study.The patients were divided into two groups according to the percentage of IBWG(PIBWG:interdialytic body weight gain/dry weight×100%):PIBWG＞3.50%(190 cases)and PIBWG≤3.50%(79 cases).Associated factors of IBWG were analyzed. Results The average IBWG of 269 MHD patients was(2.42±1.01)kg(0-6.33 kg),and PIBWG was(4.25±1.79)%.In male patients,IBWG was (2.45±1.09)kg,and PIBWG was(3.99±1.79)%.In female patients,IBWG was(2.39±0.85)kg,and PIBWG was(4.64±1.74)%which was significantly higher compared to males(P＜0.01).Patients with PIBWG＜3.00%accounted for 20%,with PIBWG≥3.00%to＜5.00%accounted for 50%,with PIBWG≥5.00%accounted for 30%.Compared to patients with PIBWG＞3.50%,those with PIBWG≤3.50%were characterized by elder age(year)(60.50 ±14.49 vs 54.07±13.78),more males(70.88%vs 54.74%),shorter dialysis duration(month)(41.03±41.92 vs 58.83±43.57),larger BMI(kg/m2)(22.67±3.36 vs 20.91±3.25)and less dry weight(kg)(56.69±10.94 vs 62.82±10.97),more residual urine(ml,In)(6.19±0.94 vs 5.48±0.8),lower predialysis serum β2MG(mmol/L)(31.61±9.82 vs 38.54±10.38)and phosphorus(mmol/L)(1.92±0.66 vs 2.15±0.58).Correlation analysis revealed that PIBWG was positively correlated with dialysis duration,Scr,BUN,β2-MG,phosphorus,decrease and decrease percentage of BP during hemodialysis,and negatively correlated with age,dry weight,BMI,residual urine,and pre-dialysis SBP,MAP. Conclusions PIBWG of about 70%of our patients was below 5%.Young.female.low BMI and dry body weight,long dialysis duration,low residual urine,chronic glomerulonephritis and diabetic nephropathy are associated with more IBWG,which may lead to greater intradialytic BP fluctuation.