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Objective:To evaluate the influence of cytomegalovirus (CMV) infection on T cell senescence and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:It was a single center cross sectional study. Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay. CD28 - T cell was evaluated by flow cytometry. Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups. Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28 - T cell compartment. Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD. Results:A total of 438 MHD patients (270 men and 168 women) were enrolled in the study. The median age was 62 (51, 70) years. The median time on hemodialysis was 57 (21, 100) months. The primary diseases included chronic glomerulonephritis [213 cases (48.6%)], diabetic nephropathy [82 cases (18.7%)], polycystic kidney disease [34 cases (7.8%)], hypertensive renal disease [34 cases (7.8%)], etc. Of these patients, 430 (98.2%) were seropositive for anti-CMV-IgG, 206 (47.0%) had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml. Patients aged over 70 years old were 100% seropositive for anti-CMV-IgG. Patients on HD for more than 5 years had a higher seropositive rate of 99.1% than those with shorter HD duration, although these results were not statistically significant. Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4 + CD28 - T cells and CD8 + CD28 - T cells ( r=0.316, P<0.001; r=0.272, P<0.001). Multiple linear regression analysis showed that after adjusting for age and gender, lg[CD4 + CD28 - T cells(%)] and lg[CD8 + CD28 - T cells(%)] were positively correlated with lg[anti-CMV-IgG titers (U/ml)], respectively ( β=0.455, t=8.315, P<0.001; β=0.412, t=7.282, P<0.001). In analyzing the relationship between anti-CMV-IgG titers and CVD, patients were divided into six groups according to age and anti-CMV-IgG level. Group 1 included young patients with a lower anti-CMV-IgG titers (age ≤55 years old, anti-CMV-IgG <400 U/ml); Group 2 included young patients with a higher anti-CMV-IgG titers (age≤55 years old, anti-CMV-IgG ≥400 U/ml); Group 3 included middle-aged patients with a lower anti-CMV-IgG titers (55<age≤65 years old, anti-CMV-IgG<400 U/ml); Group 4 included middle-aged patients with a higher anti-CMV-IgG titers (55<age≤65 years old, anti-CMV-IgG≥400 U/ml); Group 5 included old aged patients with a lower anti-CMV-IgG titers (age >65 years old, anti-CMV-IgG<400 U/ml); Group 6 included old aged patients with a higher anti-CMV-IgG titers (age>65 years old, anti-CMV-IgG≥400 U/ml). The incidence of CVD was significantly different among the six groups ( χ2=18.780, P=0.002) and patients aged over 55 years old with higher anti-CMV-IgG level had a higher CVD incidence compared with group 1 ( P<0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.020, 95% CI 1.002-1.038, P=0.033), male ( OR=1.855, 95% CI 1.161-2.965, P=0.010), history of diabetes ( OR=1.867, 95% CI 1.145-3.046, P=0.012), increased lg[NT-proBNP(μg/L)] ( OR=2.848, 95% CI 1.816-4.467, P<0.001) and lg[anti-CMV-IgG (U/ml)] ( OR=3.183, 95% CI 1.582- 6.405, P=0.001) were independent factors associated with CVD in MHD patients. Conclusions:CMV infection is extremely common in MHD patients. Increased anti-CMV-IgG is related to T cell senescence and CVD complications in MHD patients.
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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.
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Linfocitos T CD8-positivos/citología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Uremia/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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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Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/terapia , Fenotipo , Diálisis Renal/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Antígenos Comunes de Leucocito/análisis , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal , Receptores CCR7/análisis , Subgrupos de Linfocitos T/clasificación , Subgrupos de Linfocitos T/citología , Adulto JovenRESUMEN
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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Biomarcadores de Tumor/sangre , Neoplasias/sangre , Receptores de Interleucina-2/sangre , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Neoplasias/etiologíaRESUMEN
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.
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Objective To assess the risk factors of intradialytic-hypotension (IDH) and the prognosis of IDH among maintenance hemodialysis (MHD) patients for the prevention and treatment of IDH.Methods 276 MHD patients were enrolled during Jan.2009 to Mar.2009.Intradialytic blood pressure was monitored during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mmHg or in mean artery pressure (MAP) more than 10 mmHgassociated with clinical events and need for interventions.Dialysis-related information was collected.Kaplan-Meier method,log-rank test,logistic regression and Cox regression analyses were performed to examine the association between IDH and survival,using a follow-up through 31 May 2014.Results A total of 276 patients were recruited.The incidence rate of IDH was 40.9%.163 patients with no-IDH (< 1/10 hypotensive events/3 months) served as controls.113 patients with IDH (≥ 1/10 hypotensive events/3 months) were identified among all 276 patients.Multivariate logistic regression analysis showed that age,ultrafiltration rate,gender,serum NT-proBNP,serum albumin and aortic rool inside dimension (AoRD) were associated with IDH among MHD patients.During the 5-year follow-up,74 patients died,with a mortality rate 5.2 per 100 person-year.Kaplan-Meier survival curve showed significant difference of overall and CV mortality rates between 2 groups.The multivariate Cox regression model indicated that IDH increased the risk of death (HR=1.572,95%CI 1.077-2.293,P=0.019).So did the rise of LVMI (HR=1.010,95%CI 1.009-1.085,P=0.020).Conclusion Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia and shorter AoRD are independent risk factors for IDH among MHD patients.LVMI can predict the outcome of MHDpatients.Intradialytic hypotension is an independent risk factor for long-term mortality in MHD patients.
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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.
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Objective To evaluate the short-term efficacy and safety of sevelamer hydrochloride in treating maintenance hemodialysis (MHD) patients with hyperphosphemia.Methods A multicenter,open-labeled,self-control study was performed.Phosphate binders were discontinued during a two-week washout period.Patients with more than 1.78 mmol/L serum phosphorus after two-week washout period were eligible for the trial.The dose was adjusted every two weeks as necessary to achieve serum phosphorus control. Sevelamer hydrochloride was administered to 138 MHD patients for 10 weeks and a second two-week washout period followed.Results A total of 111 from 138 patients fulfilled the whole 14-week study. Mean serum phosphorus and calcium-phosphate products starte to decline after two-week sevelamer hydrochloride treatment. By the end of 10-week sevelamer hydrochloride treatment, mean serum level of phosphorus [(1.85±0.50) vs (2.57±0.54) mmol/L,P<0.01],calcium-phosphate product [(4.16± 1.72) vs (5.79 ± 1.50) mmol2/L2,P<0.01 ] and low density lipoprotein [(1.64±0.76) vs (2.31 ±0.87) mmol/L,P<0.01] were significantly decreased,while the adjusted serum level of calcium and serum intact parathyroid hormone kept steady.Both serum phosphorus and calcium-phosphrus product increased after the second washout period, but the levels were still lower as compared to pre-treatment [(2.26±0.71) vs (2.57±0.54) mmol/L; (5.12±1.63) vs (5.79±1.50) mmol2/L2,P<0.01].Of the 138 patients involved,214 episodes in 106 patients and 121 episodes in 89 patients were reported as adverse events and adverse drug reaction respectively. Gastrointestinal symptoms,of which most were mild or moderate,happened to 68.1% (94/138) patients. Conclusions Sevelamer hydrochloride can control serum phosphorus and reduce the levels of calcium-phosphorus product and cholesterol.Slight gastrointestinal symptoms like constipation are common during the treatment.
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Objective To examine the association between residual renal function at initiation of dialysis and prognosis in maintenance dialysis patients.Methods Incident patients with end-stage renal diseases initiating dialysis between 1 January 2005 and 30 September 2009,followed up to 31 March 2010 were enrolled in this study.Residual renal function was evaluated using eGFR estimated by the abbreviated MDRD equation.Patients were classified into four groups according to eGFR of ≥10.5,8 to <10.5,6 to <8,<6 ml·min-1·(1.73 m2)-1.The outcome was all-cause and cardiocerebral vascular mortality.Results (1) A total of 562 patients were included.The median eGFR at initiation of dialysis was 5.60 (2.26-12.62) ml·min-1·(1.73 m2)-1.The median follow-up time was 17 (0-58) months from initiation of dialysis and 141 patients died within this period.The median survival time was 45.48 (43.05-47.90) months.With eGFR declined,Scr,BUN,serum uric acid,serum prealbumin,phosphorus,calcium and phosphate product,iPTH,mean arterial pressure (MAP) at initiation of dialysis increased (P<0.05),and hemoglobin,proportion of male,proportion of diabetes comorbidity,proportion of the Charlson comorbidity index ≥5 decreased (P<0.05).Though there was no significant difference among the four groups,the proportion of left ventricular hypertrophy comorbidity increased when eGFR declined.(2) There was no significant difference of all-cause mortality among four groups using Kaplan-Meire survival curve.Cox regression model indicated no significant difference of all-cause mortality in levels of eGFR (HR=1.012,95%CI 0.961-1.065,P=0.654).Without patients died in the first 3 months,the multivariate Cox regression model indicated eGFR at initiation of dialysis was the protective factor to 1 year survival (HR=0.791,95%CI 0.669-0.935,P<0.01).(3) The multivariate Cox regression model indicated the risk of overall and 1 year cardiocerebral vascular death decreased with eGFR at initiation of dialysis increased (HR=0.868,95%CI 0.777-0.971,P<0.05; HR=0.937,95%CI 0.851-0.992,P<0.05,respectively).(4) The multivariate Cox regression model indicated eGFR at initiation of dialysis was benefit to survival of patients treated by peritoneal dialysis,with all-cause death risk decreased by 10% when eGFR increased by 1 ml·min-1·(1.73 m2)-1 (HR=0.90,95%CI 0.81-0.99,P<0.05).In hemodialysis patients,Kaplan-Meire survival curve was significantly different among the four groups (Log-rank test,P=0.047); the survival of the group of 8 to <10.5 ml·min-1·(1.73 m2)-1 was lower as compared to the groups of 6 to <8 (Log-rank test,P=0.033) and <6 ml·min-1(1.73 m2)-1 (Log-rank test,P=0.005); but the multivariate Cox regression model indicated no relationship between survival and eGFR.In the subgroup of chronic glomerulonephritis as primary renal disease,the eGFR at initiation of dialysis was the benefit factor,with all-cause death risk decreased by 16.6% (HR=0.834,95%CI 0.736-0.946,P<0.01) and cardiocerebral vascular death risk decreased by 18.2% (HR=0.818,95%CI 0.669-0.999,P<0.05) when eGFR increased by 1 ml ·min-1 ·(1.73 m2)-1.In the subgroup of chronic glomerulonephritis treated by peritoneal dialysis,the all-cause death risk decreased by 32.1% with eGFR increased by 1 ml·min 1·(1.73 m2)-1 (HR=0.679,95%CI 0.535-0.862,P<0.01).Conclusions Early initiation of dialysis may not be associated with improved overall survival,but may reduce cardiocerebral vascular and 1 year all-cause mortality,improve the survival of chronic glomerulonephritis patients and peritoneal dialysis patients.
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Objective To investigate the risk factors and prognosis influential factors of acute kidney injury (AKI) after cardiac surgery.Methods The clinical data of patients who were hospitalized and underwent cardiac surgery from April 2009 to May 2011 were collected prospectively.Demographic characteristics,types of surgeries,preoperative renal function,pre-and intra-operative conditions and clinical outcomes,etc were recorded.Results A total of 4007 patients underwent cardiac surgery were recruited.The overall incidence of AKI was 31.2% (1250/4007).The incidence of AKI requiring renal replacement treatment (AKI-RRT) was 2.6% (104/4007).The overall hospital mortality was 1.9% (77/4007),and was significantly higher in AKI group than in non-AKI group (5.4% vs 0.3%,P <0.01).The hospital mortality of AKI-RRT group was 36.5% (38/104).Grouped by type of surgery,cardiac transplantation had the highest AKI incidence (73.0%) and highest in-hospital mortality (18.9%),followed by coronary artery bypass grafting (CABG) combined with valve surgery (AKI incidence 57.8%,in-hospital mortality 6.1%) and aneurysm surgery (AKI incidence 52.0%,in-hospital mortality 5.5%).Multivariate logistic regression analysis showed that man,age,BMI,hypertension,chronic heart failure,pre-operative serum creatinine (SCr) > 106.0 μmol/L,intra-operative cardiopulmonary bypass time,intra-operative hypotension and aneurysm surgery were the risk factors of AKI after cardiac surgery.Multivariate logistic regression analysis showed that pre-operative SCr > 106.0 μmol/L and intra-operative hypotension were independent risk factors of renal recovery after cardiac surgery while recovery of urine output was the favorable factor.Conclusions Cardiac surgery usually induces high AKI incidence and poor prognosis,which closely associated with many risk factors in peri-operative stage.The incidence of AKI is related to a number of perioperative risk factors.Heart transplantation,aneurysm surgery,CABG combined valve surgery are high risk surgeries.
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Objective To assess the risk factors of intradialytic-hypotension (IDH) among maintaining hemodialysis (MHD) patients and to explore the relation between NT-proBNP and IDH,thus to provide clinical evidence for the prevention and treatment of IDH.Methods A total of 202 MHD patients during March 2009 to May 2009 in our dialysis center were enrolled in the study.Intradialytic blood pressure (BP) was measured during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mm Hg or in mean artery pressure (MAP) more than l0 mm Hg.Logistic regression analysis was used to assess the risk factors of IDH.ROC curve was used to evaluate the diagnostic efficacy of serum NT-proBNP.Results The incidence of IDH was 42.1%.One hundred and seventeen patients with no-IDH (<1/10 hypotensive events per 3 months) were served as controls.Fifty-five patients with o-IDH (≥ 1/ 10 but ≤1/3 hypotensive events per 3 months) and 30 patients with f-IDH (>1/3 hypotensive events per 3 months) were identified among 202 patients.Multivariate regression analysis showed that age,gender,ultrafiltration rate,serum NT-proBNP,serum albumin,aortic root dimension (AoRD) were associated with IDH among MHD patients.Serum NT-proBNP was positively correlated with IDH.The area under the ROC curve (AUC) of NT-proBNP was 0.76 (95% CI 0.69 to 0.83,P<0.01).The cut-off value of serum NT-proBNP for IDH was 1746.5 ng/L,with a sensitivity of 88.61% and a specificity of 51.10%.Furthermore,the AUC of NT-proBNP for f-IDH was 0.65 (95% CI 0.53 to 0.763,P<0.01).The cut-off value of serum NT-proBNP for f-IDH was 8208.0 ng/L,with a sensitivity of 33.33% and a specificity of 91.30%.Conclusions Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia,shorter AoRD are independent risk factors of IDH among MHD patients.Serum NT-proBNP can be used as a predictor of IDH.
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Objective To investigate the incidence and risk factors of acute kidney injury(AKI)after different types of cardiac valve replacement surgery. Methods A single cohort of 1113 patients who received cardiac valve replacement surgery from April 2009 to March 2010 in Zhongshan Hospital,Fudan University were prospectively analyzed.Multivariate Logistic regression analysis was used to evaluate possible risk factors associated with post-operative AKI.Akl was defined as a relative 50% increase or an absolute increment of 26.4 μmol/L in Scr within 48 hours and/or urine volume <0.5ml·kg-1·h-1 up to 6h.Results Of the 1113 patients, the incidence of AKI was 33.24%.In-hospital mortality of AKI patients was 6.49%,which was 5.373 times higher than that of non-AKI patients(P<0.01).The incidence of AKI in patients who simultaneously received cardiac valve replacement and coronary artery bypass grafting was 75.00%,which was significantly higher as compared to other types of valve replacement surgery(P<0.01).Unconditional multivariate Logistic regression analysis revealed that male,old age,long extracorpeal circulation (CPB)time(≥120 min)and combined with coronary artery bypass grafting surgery were the independent predictors of AKI episodes,and the corresponding OR values were 1.455,2.110,1.768 and 2.994 respectively. Conclusions AKI is a common and serious complication after cardiac valve replacement surgery.Patients who received combined cardiac surgery as valve replacement and coronary artery bypass grafting have higher incidence of AKI.Old age,male,long CPB time(≥120 min)and combined with coronary artery bypass grafting surgery are the independent risk factors of post-operative AKI for patients undergoing cardiac valve replacement surgery.
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Objective To explore the role of brief ischemia pretreatment in the induction of renal ischemic tolerance,and investigate its effects on tubular cell necrosis,apoptosis and proliferation. Methods Male Sprague-Dawley rats were randomly divided into three groups,including sham-operated group (Sham),ischemia/reperfusion injured group subjected to theocclusion of both renal pedicles for 40 min followed by reperfusion(I/R),and preconditioned group with 20-min ischemia pretreatment induced 4 days before I/R(IPC).Histological changes were evaluated by PAS staining.The ultra-structure of tubular cells was observed by transmission electron microscopy(TEM).Apoptosis was confirmed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL).The proliferation of tubular cells was evaluated with proliferating cell nuclear antigen(PCNA). Results Twenty-minites ischemia pretreatment offered both promising functional and histological protection against 40-min ischemia/reperfusion injury (P<0.01).The mortality rate wag reduced from 33%in I/R group to 0 in IPC group.The renopmtection offered by 20-min ischemia pretreatment was accompanied with reduced postischemic tubular cell apoptosis and necrosis (P<0.05), and increased cell proliferation (PCNA positive) (P< 0.01). Conclusions Brief and sublethal prior ischemia can render the kidney more tolerant to subsequent prolonged I/R injury. Its ability to tilt the balance of tubular cell fate toward survival, reducing postischemic cell death and enhancing cell proliferation, may play an important role in renal protection of ischemic preconditioning.
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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.
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Objective To study the urea rebound after hemodialysis in maintenance hemodialysis (MHD) patients and its impact factors. Methods From 124 stable MHD patients, blood samples were collected at the beginning, immediate post-hemodialysis, 15 minutes and 30 minutes after hemodialysis. The urea rebound was quantified, and its effect on URR and spKt/V was investigated. The impact factors on urea rebound were analyzed. Results In this group of patients, average post-hemodialytic urea rebound was 13.6%, leading to over-estimation of URR and spKt/V of 0.04 and 0.14, respectively. Hemodialysis efficiency expressed as K/V determined urea rebound most significantly. Other impact factors included higher hemoglobin, higher relative ultrafiltration, arteriovenous access, and male patients. Conclusions Urea rebound is common after the hemodialysis. For specific patients and hemodialysis sessions, ignoring it would result in significant over-estimation of delivered hemodialysis dose.
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Objective To investigate the effects of repeated low dose intravenous infusion of low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure (CRF) rats. Methods CRF model was established by 5/6 subtotal nephrectomy (5/6 Nx). Four weeks after removing the right kidney, successful rats were randomly divided into low molecular weight iron dextran group, sucrose iron group and CRF control group. The sham group was established simultaneously. The dose of iron administrated in each rat was similar in iron dextran group and sucrose iron group. There were 6 rats in each group. Animals were observed for 6weeks, then the blood, urine and renal tissue samples were collected, and indexes of renal function,anemia, iron status and oxidative stress were investigated. Results The hemoglobulin (Hb) level in iron groups was significantly higher as compared to control group (P<0.05) but was not significantly different between two iron groups. The levels of serum iron, ferritin and saturation rate of transferring (TS) were obviously lower in control group as compared to sham group (P<0.05).Levels of above 3 indexes were significantly higher in two iron groups as compared to control group (P<0.05), but were not significantly different between two iron groups. Concentration of plasma advanced oxidation protein products (AOPP) was obviously higher in two iron groups than that in control group [(127.84±21.19) μmol/L, (134.21±29.38) μmol/L vs (81.83±19.93) μmol/L, P<0.05]. Plasma malonaldehyde (MDA) was significantly higher in iron sucrose group than that in iron dextran group [(6.06±0.73) nmol/L vs (4.99i0.80) nmol/L, P<0.05]. Serum levels of superoxide dismutase (SOD) and total anti-oxidant capacity (TAOC) had no significant differences among three CRF groups. Concentration of plasma glutathione peroxidase (GSH-Px) was significantly decreased in three CRF groups as compared to sham group (P<0.05), while plasma GSH-Px was significantly lower in sucrose iron group than that in iron dextran group and control group [(2123.11±74.78)nmol ·ml-1 ·min-1 vs (2352.84±163.90) nmol· ml-1 ·min-1, (2310.23±125.99) nmol ·ml-1 ·min-1, P<0.05]. Conclusions Injection of intravenous iron can partially improve the anemia and the iron status indexes in 5/6 Nx CRF rats. Repeated low dose intravenous infusion of iron dextran and iron sucrose can aggravate the oxidative stress state in CRF rats, and the iron sucrose is worst.
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Objective To investigate the correlation between plasma pentraxin 3 (PTX3)and cardiovascular disease(CVD) in maintenance hemodialysis(MHD) patients.Methods Plasma was obtained from 98 MHD patients before and after a session of HD and 50 age-matched healthy subjects.Plasma PTX3 was measured by enzyme-linked immunosorbant assay (ELISA).Spearman correlation and linear regression were used to examine the correlation between plasma PTX3 level and other laboratory parameters.Binary Logistic regression was used to assess the correlation between plasma PTX3 level and CVD.Receiver operator characteristic (ROC) curve was used to analyze the correlation among PTX3, high sensitive C-reactive protein(hsCRP) and CVD.Results Plasma PTX3 level was significantly higher in MHD patients compared to healthy controls [1.87 (1.34-2.50) μg/L vs 1.11(0.86-1.51) μg/L, P<0.01], and increased after a single HD session[post-HD 2.18(1.80-3.14) μg/L vs pre-HD 1.87(1.34-2.50) μg/L, P<0.01].Patients with CVD had higher concentrations of PTX3 than those without CVD[2.18 (1.48-2.74) μg/L vs 1.76 (1.25-2.26) μg/L, P<0.05].High plasma PTX3 (>1.87 μg/L) was positively and independently associated with CVD[OR=3.15, 95%CI(1.17-8.50), P<0.05].ROC curve analysis showed the PTX3 was more closely correlated to CVD than hsCRP in MHD patients with hsCRP >3 mg/L, and the area under the curve of PTX3 and hsCRP was 0.655 ±0.083(P<0.05) and 0.562±0.083(P>0.05) respectively.Plasma PTX3 level was negatively correlated with body mass index (ρ=-0.248,P<0.05), pre-albumin(ρ=-0.218, P<0.05), total cholesterol(ρ=-0.265, P<0.01), triglyceride (ρ=-0.246, P<0.05), LDL-cholesterol (ρ=-0.254, P<0.05), hemoglobin (ρ=-0.212, P<0.05), and positively with erythropoietin dose per week(ρ=0.184, P<0.01), cardiac troponin T (ρ=0.287,P<0.01), carotid artery intima-media thickness (ρ=0.294, P<0.05).Conclusions PTX3 level ismarkedly elevated in HD patients.HD procedure induces PTX3 elevation.Plasma PTX3 could be auseful marker of CVD risk factors in MHD patients.
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Objective To clarify the relationship between clinical manifestation and pathological features of IgA nephropathy (IgAN) patients with mild proteinuria and/or hematuria.Methods Clinicopathological data from 316 biopsy-proven IgAN cases (proteinuria<1 g/24 h and/or hematuria, and Scr<133 μmol/L) from our hospital between January 1993 and October 2009 were studied retrospectively. The renal histopathology was quantified according to Lee's grading and Katafuchi's semi-quantitative standard, and the risk factors for renal pathological lesions were evaluated using multifactor logistic regression analysis. Results Among these 316 patients, 123 were male and 193 patients were female. The mean age at the time of renal biopsy was (33.10±10.69) years old. Clinical features were found as follows: hematuria with proteinuria was found in 267 patients (84.5%), isolated hematuria in 24 patients (7.6%), and isolated proteinuria in 25 patients (7.9%). 16.5% of patients had hypertension. The percentages of CKD stage Ⅰ, Ⅱ, Ⅲ were 76.9%, 20.9% and 2.2%, respectively. 31.3% of patients presented Lee's grade Ⅲ or more severe.52.8% of patients had various degrees of glomerulosclerosis. Crescent formation was observed in 20.3% of patients. 22.5% of patients showed tubular atrophy;16.8% showed interstitial fibrosis and 24.7% also had renal vascular lesions. The extent of glomerulosclerosis was negatively correlated with eGFR levels, but positively correlated with the amount of proteinuria and mean arterial pressure (MAP) level (P<0.05). The score of tubulointerstitial lesion was positively correlated with the amount of proteinuria and negatively correlated with eGFR and hemoglobin (Hb)level (P<0.05). The degree of renal vascular lesion was also correlated to MAP level positively and eGFR level negatively (P<0.05). Multifactor logistic regression analysis revealed that proteinuria, Scr and Hb at the time of renal biopsy were independent risk factors for severe renal pathological lesions (Lee's grade Ⅲ or more severe) with odds ratio of 8.564, 1.031 and 0.975 respectively (all P<0.01). Conclusions Severe renal histological lesions and decrease of renal function may be seen in some IgAN patients with mild proteinuria and/or hematuria. The levels of proteinuria,Scr and Hb are the independent risk factors for severe renal pathological lesions. Renal biopsy is important in these patients in order to make diagnosis and individual treatment.
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Objective To investigate the location and expression of hypoxia inducible factor (HIF) subunits in the remnant kidney of 5/6 nephrectomy rats. Methods Remnant kidneys were produced in adult male SD rats by 5/6 nephrectomy. The renal function and histopathological changes were evaluated at week 1, 2, 4, 6, 8 and 12 after operation. Tissues of remnant kidneys were collected to detect the location and expression of HIF-1α and HIF-2α by immunohistochemistry staining and Western blotting. The mRNA levels of HIF targeted genes vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) were determined by RTPCR. Results (1) 5/6 nephrectomy rats underwent one week of acute renal failure at first[Scr (122.8±22.1) μmol/L] and then developed compensative chronic renal failure [(66.0±3.7)-(66.4±8.4) μmol/L], but the level of Scr increased quickly after week 6 [(66.4±8.4)-(127.8±22.7) μmol/L],concomitantly with progressive tubulointerstitial fibrosis in remnant kidney cortex. (2) In cortex, HIF-1α was expressed only in the atrophic and dilated tubular cells while HIF-2α was located in endothelial, interstitial fibroblasts, and vascular smooth muscle cells. The semiquantitative results of imunohistochemistry and Western blotting revealed that HIF-1α and HIF-2α were both gradually up-regulated during the early stage of remnant kidney, peaked at week 4 and 6, and then gradually down-regulated. (3) The mRNA levels of HIF targeted genes VEGF and HO-1 transiently peeked at week 4 and 6, and then decreased gradually. Conclusions The increased stabilization of HIF-αprotein and transcription of HIF targeted genes at the early stage of this model is a compensation reaction towards hypoxia. The mechanism of decreased expression of HIF-α at the end stage of chronic kidney disease deserves further investigation.
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Objective To study the prevalence,treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control.Methods We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female.Hypertension was defined as systolic blood pressure(SBP) ≥ 140 and/or diastolic blood pressure (DBP) ≥90 mm Hg ( 1 mm Hg = 0.133 kPa).Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey.Hypertension control was defined as blood pressure < 140/90 mm Hg before each dialysis session.Results The prevalence of hypertension in the hemodialysis patients was 86.3%.The treatment rate and control rate in those patients were 96.8% and 25.5% respectively.More than half (50.4% ) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more.Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin Ⅱ receptor blockers ( 56.4% ), centrally acting anti-hypertensive agent ( 26.4% ), beta blockers and alpha, beta-blockers( 14.0% ).The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease.The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension.The hypertension control rate elevated significantly with the adequate hemodialysis.Conclusions There is a very high prevalence of hypertension in maintenance hemodialysis patients.Although the treatment rate is high, the control rate is unsatisfactory.So the control of hypertension in hemodialysis patient is still a clinical challenge.Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.