Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.     

Relationship between non‐alcoholic fatty liver disease and MIA syndrome

Non‐alcoholic fatty liver disease (NAFLD) is an important factor in the pathogenesis of cardiovascular diseases in the general population. Recently, it has been shown that NAFLD is highly prevalent in chronic kidney disease (CKD) patients. Ninety‐four hemodialysis (HD) patients were followed for a time period of 18 months or until death. Patient's survival rate was determined in relation to their nutritional and inflammatory state, and the presence of NAFLD. We also investigated the association between the presence of NAFLD and the patients' nutritional and inflammatory state. We did not find any significant association between the clinical parameters of nutritional status and the mortality rate. However, the mortality rate was statistically significantly higher in patients with low serum albumin and high high‐sensitive C‐reactive protein (hs‐CRP) levels and in those who had NAFLD. Surprisingly, patients who had received enteral nutrition did not have a better survival rate. The severity of liver steatosis was negatively correlated with the serum albumin levels, while it was positively correlated with hs‐CRP values. Furthermore, serum albumin levels showed a negative correlation with hs‐CRP levels. We did not find any significant association between the presence of NAFLD and clinical parameters of nutrition. We have shown that NAFLD could be one more possible example of reverse epidemiology in patients undergoing HD. NAFLD may be the missing link that causally ties malnutrition, inflammation, and atherosclerosis syndrome to the morbidity and mortality in patients undergoing HD.     

Association between antiinflammatory cytokine,IL‐10, and sleep quality in patients on maintenance hemodialysis

Elevated proinflammatory cytokines have been attributed to poor sleep quality in patients receiving hemodialysis. This is the first investigation about the relationship between sleep quality and circulating levels of antiinflammatory markers in these patients. A total of 72 patients who were receiving maintenance hemodialysis were enrolled in this cross‐sectional study. The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. Patients were divided into two groups: good sleepers (PSQI score < 5) and poor sleepers (PSQI score ≥ 5). Assessments were made for serum biochemical parameters (albumin, parathyroid hormone), inflammatory (interleukin [IL]‐6, tumor necrosis factor‐alpha [TNF‐α], and high‐sensitivity c‐reactive protein [hs‐CRP] ) and antiinflammatory (IL‐10) markers. Fifty‐four patients (75%) were classified as poor sleepers. Poor sleepers showed significantly lower levels of serum IL‐10 and higher serum triglyceride and parathyroid hormone concentrations. These patients were more likely to have more comorbidities. The global PSQI score was significantly correlated with serum IL‐10 (p = 0.03) and triglyceride levels (p = 0.01). Multivariate logistic regression analysis showed a direct correlation between PSQI and having comorbidities (p = 0.011, odds ratio [OR] = 3.918; confidence interval 95% [CI] = 2.742–19.031), between PSQI and serum triglyceride (p = 0.027, OR = 1.027 [95% CI = 1.007–1.048] ), and an inverse correlation between PSQI and serum IL‐10 level (p = 0.021, OR = 0.424 [95% CI = 0.195–0.922]). Reduced circulating levels of the antiinflammatory cytokine IL‐10 were significantly associated with poor sleep quality in hemodialysis patients. Factors including serum IL‐10 and triglyceride concentrations and having comorbidities may predict patients prone to poor sleep quality.     

Effect of serum FGF‐23, MGP and fetuin‐A on calcium‐phosphate metabolism in maintenance hemodialysis patients

This study was aimed to explore the role of serum fibroblast growth factor (FGF)‐23, matrix Gla protein (MGP) and fetuin‐A in the calcium‐phosphate metabolism and their predicting value in coronary artery calcification in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF‐23, MGP and fetuin‐A were analyzed by enzyme‐linked immunosorbent assay (ELlSA). Coronary artery calcification score (CACS) was evaluated by coronary artery computed tomography scan. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average dialysis vintage of 6.88 ± 2.94 years. We divided the CACS into three levels, and 13 (20.31%), 16 (25%), and 35 (54.69%) exhibited a CACS of 0–100, 100–400, and >400, respectively. Dialysis vintage, serum FGF‐23, fetuin‐A, phosphorus and high‐density lipoprotein‐C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF‐23 and fetuin‐A were useful for identifying CAC in MHD patients. The cut‐off value corresponding to the highest Youden's index was serum FGF‐23 ≥ 256 pg/mL and fetuin‐A ≤ 85 μg/mL, which was defined as the optimal predictors of CAC. Different combinations of serum FGF‐23 and fetuin‐A in parallel or in series effectively boosted the identification of CAC. The incidence of CAC is high in MHD patients. Serum FGF‐23 and fetuin‐A levels are closely correlated with CAC.     

Effects of l‐carnitine supplement on serum inflammatory cytokines,C‐reactive protein,lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia

Inflammation, oxidative stress, and high concentration of serum lipoprotein (a) [Lp (a)] are common complications in hemodialysis patients. The present study was designed to investigate the effects of l ‐carnitine supplement on serum inflammatory cytokines, C‐reactive protein (CRP), Lp (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was an unblinded, randomized clinical trial. Thirty‐six hyper Lp (a) hemodialysis patients (23 men and 13 women) were randomly assigned to either a carnitine or control group. Patients in the carnitine group received 1000 mg/d oral l ‐carnitine for 12 weeks, whereas patients in the control group did not receive any l ‐carnitine supplement. At baseline and the end of week 12, 5 mL of blood were collected after a 12‐ to 14‐hours fast and serum free carnitine, CRP, interleukin‐1β, interleukin‐6 (IL‐6), tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein were measured. Serum free carnitine concentration increased significantly by 86% in the carnitine group at the end of week 12 compared with baseline (P<0.001), while serum CRP and IL‐6 showed a significant decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes were observed in serum free carnitine, CRP, and IL‐6 in the control group. There were no significant differences between the two groups in mean changes of serum interleukin‐1β, tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein concentrations. l ‐carnitine supplement reduces inflammation in hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.     

Hyperprolactinemia in end‐stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods: The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in‐center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health‐related quality of life, self‐reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12‐month follow‐up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings: Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th–75th percentile 48–195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion: Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one‐year period.     

Positive association between plasma levels of oxidized low‐density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end‐stage renal disease

End‐stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low‐density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized‐LDL (ox‐LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox‐LDL levels, plasma MPO levels, and serum high‐sensitivity C‐reactive protein (hs‐CRP) levels during initial HD in patients with diabetic ESRD. Patients (n = 28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox‐LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme‐linked immunosorbent assay kit. Plasma ox‐LDL levels and MPO levels after a single HD session increased significantly (ox‐LDL, P < 0.005; MPO, P < 0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre‐HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox‐LDL levels during HD (R = 0.62, P = 0.0029). No significant change was observed in serum hs‐CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox‐LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox‐LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.     

Lower C‐reactive protein and better hemodialysis survival are associated with regular exercise activity: Longitudinal outcomes from the ACTIVE‐ADIPOSE special study

Introduction Cross‐sectional and longitudinal studies in the general population have shown that a physically active lifestyle may have anti‐inflammatory properties, but evidence from studies conducted with maintenance hemodialysis (HD) patients is limited. Methods A multicenter prospective cohort of 755 HD participants aged 20–92 was evaluated in a USRDS special study 2009–2013. Kilocalories/week (kcal/week) of leisure time physical activity (LTPA) was estimated from the Minnesota Leisure Time Activity questionnaire. Predialysis serum samples were obtained concurrent with LTPA report date. Generalized estimating equations (GEE) examined association of participants’ LTPA and log‐normalized CRP across 24 months. Cox proportional hazards models investigated LTPA and survival over a median follow‐up of 718 days. Findings Baseline median CRP concentration was lower for participants with 500+ kcal/week LTPA vs. those with <500 kcal/week LTPA (3.4 mg/L vs. 4.6 mg/L; P = 0.03). Participants who reported lower LTPA (<500 kcal/week) at both baseline and 12 months had a borderline significant increase in CRP concentration (within‐group change 4.8 [1.9–10.4] to 5.8 [1.6–15.7]; P = 0.08). Lower LTPA was associated with higher log CRP over 24 months in adjusted GEE analyses (β coefficient = 0.16 [95% CI 0.02–0.31]; P = 0.03). 67/364 (18%) and 43/391 (11%) deaths occurred, respectively, among participants reporting <500 vs. 500+ kcal/week LTPA [adjusted mortality hazard ratio 1.63 (CI, 1.07, 2.47)]. Discussion The data suggest that increased estimated levels of LTPA, a physical activity/exercise opportunity widely applicable to HD patients, may be associated with lower CRP concentration as well as better survival outcome.     

A Comparative Study of C‐Reactive Protein Plasma Levels in Patients on Hemodialysis and Peritoneal Dialysis

In dialysis patients, C‐reactive protein (CRP), a well‐recognized marker of inflammation, predicts mortality. Higher levels have been described in hemodialysis (HD) patients as compared with peritoneal dialysis (PD) patients. Our aim was to determine, based on CRP plasma levels, the degree of inflammation in HD patients using low‐permeability polysulfone membranes and relatively pure dialysate, and that in PD patients. A secondary objective was to study factors associated with hypoalbuminemia and inflammation in both populations. We studied 69 stable patients on dialysis (32 on HD and 37 on PD). The mean age was 69.9 ± 8.2 years, and the mean time on dialysis was 27 months. The two populations were comparable for overall and cardiovascular comorbidities. Nephelometry was used to measure CRP plasma levels (normal levels < 0.6 mg/dL). The Kt/V_urea, corrected for residual renal clearance, and the equivalent of protein nitrogen appearance (PNA) were also calculated. Of the patients studied, 53% showed CRP plasma levels higher than 0.6 mg/dL; in 36%, the levels were higher than 1 mg/dL. No significant differences in these percentages were noted between the two dialysis groups. Patients with CRP levels higher than 1 mg/dL showed lower serum albumin, iron, hemoglobin, and transferrin levels, and higher ferritin values and leukocyte counts. Under logistic regression analysis, CRP levels higher and lower than 1 mg/dL were significantly associated with serum albumin [p = 0.01; odds ratio (OR): 0.15], iron (p = 0.006; OR: 0.96), transferrin (p = 0.004; OR: 0.97), and hemoglobin (p = 0.02; OR: 0.67). Serum albumin levels were significantly lower in PD patients. Under regression analysis, serum albumin levels correlated with cholesterol (r: 0.25; p = 0.04), serum iron (r: 0.5; p = 0.0001), transferrin (r: 0.3; p = 0.015), ultrafiltration capacity (r: 0.42; p = 0.008), and CRP values above 0.6 mg/dL (r: –0.65; p = 0.001). In conclusion, the frequent elevation of CRP plasma levels observed in both HD and PD patients suggests the presence of a silent inflammatory state. Hemodialysis performed with biocompatible, low‐permeability membranes is not associated with higher CRP plasma levels than those seen in PD. In both groups, hypoalbuminemia is related to CRP level. Levels of serum albumin, slightly lower in PD patients, are also related to peritoneal ultrafiltration capacity.     

Hemodialysis‐induced acute pancreatitis secondary to kinked hemodialysis blood lines

Objective: Blood‐membrane interaction during hemodialysis may contribute to inflammatory process, which accelerates the development of atherosclerosis in maintenance hemodialysis patients (MHD). Vitamin E has been widely used against oxidative stress in MHD. One of the strategies for the utilization of vitamin E in MHD patients is the usage of vitamin E‐coated membrane dialyzer. We investigated the effects of vitamin E‐coated membrane dialyzer on serum C‐reactive protein and interleukin‐6, the biomarker of inflammation, compared to polysulfone membrane dialyzer. Methods: Vitamin E‐coated membrane dialyzer (1.5‐m² surface area) and synthetic polysulfone dialyzer (1.5‐m² surface area) were manipulated in a crossover clinical study for 24 weeks in 10 non‐diabetic MHD patients. Run‐in and wash‐out periods (Cellulose tri‐acetate) were performed for 4 weeks before the treatment. Pre‐ and post‐dialysis blood samples were taken at the begining and the end of each dialyzer period (12 weeks). High‐sensitivity C‐reactive protein (hs‐CRP) and interleukin‐6 (IL‐6) were examined. Results: Mean age of the patients was 54.9 years old. CRP and IL‐6 levels were similarly increased after dialysis in both groups (4.8 ± 0.7 and 37.2 ± 9.4, respectively). The CRP and IL‐6 level in vitamin E‐coated membrane dialyzer treatment were lower than in polysulfone treatment (5.0 ± 1.2, p < 0.008 and 67.2 ± 12.4, p < 0.04, respectively). Serum albumin, hemoglobin level, and white blood cell count were not affected by types of dialyzer membrane. Conclusions: In our study, hemodialysis stimulated the inflammation as the previous study. Vitamin E‐coated membrane dialyzer may diminish the inflammatory process in MHD patients and may also prevent further atherosclerosis.     

Survival with short‐daily hemodialysis: Association of time,site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.     

IL-6 is an independent risk factor for resistance to erythropoiesis-stimulating agents in hemodialysis patients without iron deficiency

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.     

D‐dimer levels in maintenance hemodialysis patients: High prevalence of positive values also in the group without predisposing diseases

We aimed to estimate the prevalence of elevated D‐dimer levels in all chronic hemodialysis patients and those without additional disease, and to identify factors associated with increased D‐dimer. In 167 chronic hemodialysis patients from our center, D‐dimer was measured before dialysis. The effects of age, C‐reactive protein (CRP), recent acute illness, vascular access, anticoagulation type, dialysis vintage, and chronic diseases, considered to predispose for increased D‐dimer levels, were analyzed. The median D‐dimer in the whole group was 966 (inter‐quartile range [IQR] 524–1947) μg/L and was positive (>500 μg/L) in 75% of cases. D‐dimer was positive in 91% of patients with acute illness, 76% of those with predisposing chronic diseases, but was still positive in 52% of patients without additional disease (i.e., acute illness or predisposing chronic diseases) – median D‐dimer was 538.5 (IQR 359–966) μg/L. D‐dimer was correlated to patients' age, but not dialysis vintage. In univariate analysis, the D‐dimer levels were significantly higher in patients with atrial fibrillation, ischemic heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and on citrate anticoagulation. Multivariate logistic regression showed that only age >65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07) were independently associated with positive D‐dimer at 500 μg/L cut‐off, while the significance of age disappeared at 2000 μg/L cut‐off. To conclude, the high prevalence of positive D‐dimer values even in hemodialysis patients without additional disease limits the use of D‐dimer for exclusion of thromboembolic diseases in hemodialysis patients.     

Prognostic significance of 25‐hydroxivitamin D entirely explained by a higher comorbidity burden: Experience from a South‐Eastern European Dialysis Cohort

Vitamin D deficiency is still a common problem particularly in the elderly and in individuals with various degrees of renal impairment. The present study aimed to evaluate the association between plasma concentrations of 25(OH)D and death in a large cohort of prevalent patients on hemodialysis (HD) from south‐east Romania, a typical Balkan region. This is an observational prospective study that included a total of 570 patients on maintenance HD. Study patients were classified into three groups by baseline 25(OH)D levels: (1) sufficient 25(OH)D—i.e., >30 ng/mL; (2) insufficient 25(OH)D—i.e., between 10 and 29 ng/mL; and (3) deficient 25(OH)D—i.e., <10 ng/mL. During the follow‐up period of 14 months, 68 patients (11.9%) died, the Kaplan–Meier analysis showing significant differences in all‐cause mortality for chronic kidney disease patients in different 25(OH)D groups (P = 0.002). Unadjusted Cox regression analysis also showed significant differences in survival. The multivariate Cox regression model showed no significant differences in survival according to vitamin D levels. Hazard ratio for death in the “<10 ng/mL” group was 1.619 (P = 0.190) and in the “10–30 ng/mL” group was 0.837 (P = 0.609). In our dialysis population with a high comorbidity burden, low 25(OH)D concentration was not associated with mortality in the adjusted Cox model, suggesting that vitamin D deficiency could represent only a non‐specific marker for a poor health status, with less impact on mortality.     

Inappropriately elevated endothelin‐1 plays a role in the pathogenesis of intradialytic hypertension

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty‐four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age‐matched and sex‐matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N‐terminal fragment brain natriuretic peptide, renin, angiotensin‐II, aldosterone (ALD), angiotensin‐converting enzyme (ACE), endothelin‐1 (ET‐1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post‐dialysis serum ET‐1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post‐dialysis ratio of NO to ET‐1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post‐dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre‐dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre‐dialysis and post‐dialysis determinations. Compared with blood angiotensin‐II, ALD, ACE, NOR, adrenomedullin, N‐terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET‐1 plasma concentrations may play a predominant role in the pathogenesis of IDH.     

Is There Any Relationship between Serum Levels of IL‐10 and Atherosclerosis in Hemodialysis Patients?

Background:  Cardiovascular complications due to atherosclerosis (AS) are the major cause of mortality in hemodialysis (HD) patients. Inflammation may play an important role in the development of AS. Several studies have demonstrated the association of acute-phase proteins and cytokines with AS in the general population and in HD patients. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. The aim of study was to compare serum levels inflammatory and anti-inflammatory indicators in HD patients according to the presence or absence of AS.
Methods:  Thirty-three HD patients were enrolled. AS was defined as the detection of plaques by Doppler ultrasonography. The patients were subgrouped according to the presence or absence of plaques. Serum levels of IL-1, IL-2, IL-6, IL-10, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were measured. The factors for AS such as age, gender, hypertension, hyperlipidemia, and HD duration were also evaluated.
Results:  We found that the patients with AS had significantly higher hs-CRP and lower IL-10. Blood pressure values were also increased in patients with AS. Additionally, there was an increased correlation between CRP and IL-10.
Conclusions:  AS(+) patients undergoing HD had low serum levels of anti-inflammatory cytokine IL-10 and high serum levels of hs-CRP. These results may suggest that the limitation of anti-inflammatory response in atherosclerotic uremic patients is a triggering or contributing factor for AS.     

Left ventricular mass index and aortic arch calcification score are independent mortality predictors of maintenance hemodialysis patients

To analyze predictive factors for all‐cause mortality, cardiovascular (CV) mortality, nonfatal CV events (CVE) in maintenance hemodialysis (MHD) patients, and to compare the effects of standard hemodialysis (HD) and online hemodiafiltration (HDF) on these factors and outcomes. A total of 333 MHD patients were prospectively followed up for 50 ± 15 months and all‐cause death, CV death and CVE were registered. At the baseline, demographic, clinical, and laboratory data of the whole population were recorded. Then, patients were stratified into two groups according to the dialysis modalities, HD (n = 268) and HDF (n = 65). At the end of 6th month, clinical and laboratory data were recorded again. The predictive factors at baseline for all‐cause mortality, CV mortality, and CVE were analyzed by Cox regression. The effects of HD and HDF on these factors at the 6th month and long‐term outcomes were compared by t‐test and Kaplan–Meier method, respectively. Age, gender, left ventricular mass index (LVMI), aortic arch calcification score (AoACS), hemoglobin (Hb) <10 g/dL, and ferritin >500 ng/mL maintained independent associations with all‐cause mortality. C‐reactive protein (CRP), LVMI, AoACS, and Hb <10 g/dL were associated with CV mortality. Prior cardiovascular disease (CVD), AoACS and LVMI were independent predictors of nonfatal CVE. Higher body mass index (BMI), body weight, total serum cholesterol, Hb concentration, and lower CRP level, LVMI, and AoACS were found in patients on HDF at the end of the 6th month. Improved outcomes with longer survival time for all‐cause mortality, CV mortality, and CVE were found in HDF group. Age, gender, LVMI, AoACS, Hb, and ferritin were predictors of all‐cause mortality in MHD patients. CRP, LVMI, AoACS, and Hb were associated with CV mortality. Prior CVD, AoACS, and LVMI were independent predictors of nonfatal CVE. HDF could improve BMI, body weight, total serum cholesterol, Hb, CRP, LVMI, AoACS, and long‐term outcomes, including all‐cause mortality, CV mortality, and CVE.     

Serum sulfatide abnormality is associated with increased oxidative stress in hemodialysis patients

Sulfatides are major glycosphingolipids of lipoproteins that influence atherosclerosis and blood coagulation. Our previous cross‐sectional study of hemodialysis patients showed that serum sulfatide levels decreased markedly with increasing duration of hemodialysis treatment, which may contribute to the development of cardiovascular disease. However, this past study could not demonstrate the time‐dependent change in serum sulfatide levels in each patient, and the underlying mechanism is unknown. To confirm the time‐dependent aggravation of serum sulfatide abnormality, 95 stable hemodialysis outpatients were followed up for 3 years. To show the underlying mechanisms, we statistically analyzed correlations between serum sulfatide levels and clinical factors, including an oxidative stress marker, malondialdehyde. Serum sulfatides were quantified by mass spectrometry after conversion to lysosulfatides. Malondialdehyde was measured using a colorimetric assay. The results showed a time‐dependent decrease in serum sulfatide levels associated with increased malondialdehyde levels, although the absolute level of serum malondialdehyde does not determine the baseline level of serum sulfatides. Multiple linear regression analysis showed a significant correlation only between the time‐dependent change in serum sulfatide levels and the time‐dependent change in serum malondialdehyde levels. This study demonstrated, for the first time, a time‐dependent aggravation of serum sulfatide abnormality in hemodialysis patients, as well as the potential relationship between serum sulfatide abnormality and increasing oxidative stress. These findings suggest that oxidative stress might be an aggravating factor in serum sulfatide abnormality. As continuation of hemodialysis treatment hardly improves abnormal serum sulfatide levels or increased oxidative stress, development of novel therapeutic strategies may be important.     

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients

Introduction: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT‐1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT‐1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT‐1 levels might be a novel biomarker in early atherosclerosis. Methods: Forty‐five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high‐resolution B‐mode ultrasonography. Biomarker levels were measured in serum of patients. Findings: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT‐1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT‐1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT‐1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. Discussion: In conclusion, this is the first report showing that serum CHIT‐1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.     

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

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.