Xuesen Cao

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

BACKGROUND AND OBJECTIVES Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. RESULTS In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). CONCLUSIONS Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.

Plasma pentraxin 3 is associated with cardiovascular disease in hemodialysis patients.

Abstract This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.

Acute effects of hemodiafiltration versus conventional hemodialysis on endothelial function and inflammation a randomized crossover study

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

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

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

Electrocardiographic Abnormalities and QTc Interval in Patients Undergoing Hemodialysis

Background Sudden cardiac death is one of the primary causes of mortality in chronic hemodialysis (HD) patients. Prolonged QTc interval is associated with increased rate of sudden cardiac death. The aim of this article is to assess the abnormalities found in electrocardiograms (ECGs), and to explore factors that can influence the QTc interval. Methods A total of 141 conventional HD patients were enrolled in this study. ECG tests were conducted on each patient before a single dialysis session and 15 minutes before the end of dialysis session (at peak stress). Echocardiography tests were conducted before dialysis session began. Blood samples were drawn by phlebotomy immediately before and after the dialysis session. Results Before dialysis, 93.62% of the patients were in sinus rhythm, and approximately 65% of the patients showed a prolonged QTc interval (i.e., a QTc interval above 440 ms in males and above 460ms in females). A comparison of ECG parameters before dialysis and at peak stress showed increases in heart rate (77.45±11.92 vs. 80.38±14.65 bpm, p = 0.001) and QTc interval (460.05±24.53 ms vs. 470.93±24.92 ms, p<0.001). After dividing patients into two groups according to the QTc interval, lower pre-dialysis serum concentrations of potassium (K+), calcium (Ca2+), phosphorus, calcium* phosphorus (Ca*P), and higher concentrations of plasma brain natriuretic peptide (BNP) were found in the group with prolonged QTc intervals. Patients in this group also had a larger left atrial diameter (LAD) and a thicker interventricular septum, and they tended to be older than patients in the other group. Then patients were divided into two groups according to ΔQTc (ΔQTc = QTc peak-stress- QTc pre-HD). When analyzing the patients whose QTc intervals were longer at peak stress than before HD, we found that they had higher concentrations of Ca2+ and P5+ and lower concentrations of K+, ferritin, UA, and BNP. They were also more likely to be female. In addition, more cardiac construction abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ΔQTc. Conclusion Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients’ clinical conditions.

Hemodialysis-induced regional left ventricular systolic dysfunction.

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4‐hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD‐induced LV systolic dysfunction and provide some evidences for clinical strategies.

Indoxyl sulfate, a valuable biomaker in chronic kidney disease and dialysis

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

24-h residual urine volume at hemodialysis initiation: A possible predictor for acute ischemic stroke incurrence in hemodialyis patients

BACKGROUND Residual renal function (RRF) recently has been confirmed to be a significant predictor of morbidity and mortality in hemodialysis (HD) patients. As RRF is not exactly the same with 24-h residual urine volume, the aim of our study is to evaluate the association of residual urine volume with acute ischemic stroke (AIS) among HD patients. METHODS 282 patients starting chronic HD in our center during January 2005 and December 2008 were enrolled. The clinical data at HD initiation and the occurrence of AIS since starting HD were recorded and obtained from our database. According to the prevalence of AIS, we divided 282 patients into the AIS group (n=69) and non-AIS (n=213) group. RESULTS A total of 69 (24.5%) patients suffered from AIS since HD initiation. Patients with AIS were much older, with more diabetes, had higher levels of hemoglobin, while lower levels of residual urine volume and serum uric acid. In multivariate logistic regression analysis, old age (OR, 1.036; 95% CI, 1.009-1.063; P=0.008), diabetes (OR, 2.385; 95% CI, 1.074-5.294; P=0.033) and 24-h residual urine volume<1290 ml at HD initiation (OR, 2.446; 95% CI, 1.219-4.907; P=0.012) was significant predictors for future AIS occurrence during HD. CONCLUSION This study indicates that residual urine volume levels at HD initiation are inversely associated with AIS risk in future in chronic HD patients. Besides, aging and diabetes should also be noticed for prevention of AIS.

BMI, spKt/V, and SBP but Not DBP Are Related to LVH in Chinese Maintenance Hemodialysis Patients

Objective: Left ventricular hypertrophy (LVH) is the strongest predictor of cardiovascular mortality, the leading cause of death in hemodialysis (HD) patients. This study aims to identify the potential risk factors for LVH in HD patients. Methods: Exactly, 164 patients (84 men and 80 women) who had been on HD treatment for at least 6 months were enrolled. Clinical data were collected. Anthropometric measurements, biochemical analyses, and echocardiography were performed. The risk factors were determined by multivariate linear and logistic regression. Results: In all the patients, the prevalence of LVH was 66.5%. The patients with LVH had higher body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure, and lower single-pool kt/V (spKt/V) compared with those without LVH. Multivariate linear regression showed that BMI (β = 7.608, p = 0.014), SBP (β = 9.462, p = 0.001), and spKt/V (β = –14.226, p = 0.024) were independently correlated with left ventricular mass index (LVMI). Multivariate logistic regression showed the same results that BMI (β = 7.193, p = 0.032), SBP (β = 9.382, p = 0.02), and spKt/V (β = –12.535, p = 0.001) were independently correlated with LVH. Conclusions: In Chinese maintenance hemodialysis patients, BMI, single-pool Kt/V (spKt/V), and SBP were independently correlated with left ventricular mass index and were independent risk factors for LVH.

Clinical Factors Associated with Sodium Removal in Peritoneal Dialysis Patients

A cross-sectional study was conducted in 156 clinically-stable peritoneal dialysis patients to identify the factors associated with sodium removal. Serum biochemistry, peritoneal function (modified peritoneal equilibration test [PET]) and the adequacy of dialysis were analysed in relation to sodium removal using multivariate linear regression. Factors significantly affecting peritoneal sodium removal included infusion volume and ultrafiltration volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. Factors significantly affecting total sodium removal included ultrafiltration and urine volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. With traditional dialysate, adequate fluid removal is required to ensure sufficient sodium removal, but a low-sodium dialysate may prevent sodium retention. Sodium removal should be included in evaluation of the adequacy of dialysis.