Increased leukocyte aggregates are associated with atherosclerosis in patients with hemodialysis

Little data are available on the role of blood rheology in atherosclerosis in hemodialysis (HD) patients. This study sought to assess the relationship between leukocytes conjugated with platelets (leukocyte aggregates [LA]) and atherosclerosis in patients with HD. The present study included 118 patients on HD. As surrogate markers of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were measured. As an assessment of LA, a method, microchannel array flow analyzer, which makes it possible to directly observe the flow of blood cell elements through the microchannel, was used. We measured a number of LA during 50 μL flow of whole blood through microchannels. In 12 age-matched healthy individuals, a number of LA during 50 μL flow of whole blood was 25.7±5.4, whereas in HD patients it was significantly increased up to 48.2±16.4 (P<0.001). Flow cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates were positively associated with plasma levels of fibrinogen (P<0.01), or serum high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001). In conclusion, we demonstrated hemorheologically that monocyte-platelet conjugates play an important role in aortic stiffness and IMT in HD patients.     

Pre‐ and Post Hemodialysis Procalcitonin Levels and Their Relationships with Immunoregulatory,Proinflammatory Cytokines in Chronic Hemodialysis Patients

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Arteriosclerosis is characterized by stiffening of arteries. Metabolic, inflammatory, and hemodynamic alterations cause structural changes and vascular complications in end‐stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty‐two patients (16 men and 16 women) on chronic HD with a mean age of 42.2 ± 19.3 (range, 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high‐resolution echo‐tracking system. Einc measurement was calculated from transcutaneous measurements of carotid arterial internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance (CCC) and distensibility (CCD) were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Serum levels of calcium (Ca), phosphorus (P), parathormone (PTH), ferritin, C‐reactive protein (CRP), predialysis systolic blood pressure (SBP), predialysis diastolic blood pressure (DBP), pulse pressure (PP), age, HD duration, CCC, and CCD were correlated with Einc in all patients. A significant positive correlation was found between Einc and age (r = 0.40, p < 0.02), SBP (r = 0.39, p < 0.02), PP (r = 0.40, p < 0.02), Ca (r = 0.43, p < 0.01), CRP (r = 0.38, p < 0.02). As expected, Einc was correlated inversely with CCD (r = ?0.77, p < 0.0001). The correlation between Einc and HD duration, DBP, ferritin, P, PTH, and CCC was not significant. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP and PP) but also to metabolic (increased Ca) and inflammatory (increased CRP) responses. Carotid Einc is an accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca‐containing P binder should be used carefully in HD patients.     

Changes of Plasma Amino Acid Profile in Hemodialysis Patients

Background:  The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP, and interleukin-6 (IL-6) in HD patients.
Methods:  The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who were treated by on standard HD for at least 6 months. The patients were divided in two groups, depending on the presence (HCV+) or absence (HCV–) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured, and the values were compared with 22 healthy controls.
Results:  The median of hsCRP, IL-6, and the hsCRP/IL-6 ratio were: 3.5 vs. 2.1 mg/L, p < 0.05; 4.3 vs. 0.9 pg/mL, p < 0.0001; and 0.8 vs. 2.7 pg/mL, p < 0.0001 for patients and controls, respectively. Age, gender, S-Alb, IL-6, and hsCRP did not differ between the HCV+ and HCV– patients. However, HCV+ patients had higher ALT (29 ± 21 vs. 21 ± 25 UI/L) and had been a longer time on HD (6.1 ± 3.0 vs. 4.0 ± 2.0 years) (p < 0.0001), respectively. Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs. 0.9; p < 0.05) as compared to the HCV group.
Conclusion:  The finding that the hsCRP/IL-6 ratio was lower in HCV+ patients than in HCV– patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP may be required to define inflammation in HD patients.     

Endotoxins and inflammation in hemodialysis patients

Long‐term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so‐called MIA syndrome. Circulating soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C‐reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM‐1 was estimated using enzyme‐linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre‐HD level of VCAM was 1851.00 ng/mL, while the mean post‐HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post‐HD rise in sVCAM‐1.     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

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.     

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.     

Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis

The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all‐cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron‐beam computed tomography. Fifty‐six patients underwent a second electron‐beam computed tomography after a 15‐month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross‐sectional study, HD vintage and high‐sensitive C‐reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan‐Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all‐cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15‐month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all‐cause deaths.     

Clinical Consequences of Intermittent Elevation of C-Reactive Protein Level in Hemodialysis Patients

The presence of persistently high C‐reactive protein (CRP) levels is well known to be associated with a state of inflammation, malnutrition, and erythropoietin resistance in hemodialysis (HD) population. Meanwhile, a substantial group of patients present with intermittent elevations of CRP levels, and its clinical consequences are unclear. We designed this study to compare the inflammatory and nutritional parameters and erythropoietin requirements in HD patients with persistent or intermittent CRP elevation and those with CRP levels in without. We included 100 HD patients [age: 48.4 ± 14.3 years; HD duration: 69.3 ± 49.0 months (minimum 12 months)]. The 6‐month retrospective clinical and laboratory data were retrieved from the patient records, and those with chronic inflammatory disease, malignancy, infectious complications, and surgery were excluded. The monthly determined CRP levels (at least 6 for each patient) were reviewed, and the patients were grouped according to their CRP levels as those with persistent (group 1), intermittent (at least one level of CRP 10 mg/L) (group 2), and those with CRP in normal ranges set by the laboratory (group 3). We compared the fibrinogen, ICAM‐1, VCAM‐1, albumin, prealbumin, normalized protein catabolic rate (nPCR), interdialytic weight gain (IDWG), and rHuEPO/kg/Hct results of the patient groups. The patient groups revealed significant differences in terms of fibrinogen (p < 0.001), albumin (p < 0.0001), prealbumin (p < 0.007), ICAM‐1 (p < 00.2) levels and nPCR (p < 0.03), IDWG (p < 0.02), and rHuEPO/kg/Hct (p < 0.03) values. Group 2 presented to be in risk of inflammation and malnutrition with a decrease in albumin levels and nPCR and presence of rHUEpo resistance when compared to patients in group 3. We conclude that, similar to HD patients with persistently high CRP levels, those with intermittent elevation of CRP must also be considered to be in a state of chronic inflammatory response associated with malnutrition and erythropoietin resistance. This signifies the importance of regulatory monitoring of CRP in HD population.     

Characteristics of heart rate variability entropy and blood pressure during hemodialysis in patients with end-stage renal disease

Entropy (ENT) is a newly developed measure of the complexity of heart rate variability (HRV). The aim of this study was to characterize the complexity of HRV in patients with end-stage renal disease (ESRD) and to find a possible clinical utility. Healthy subjects and patients with ESRD undergoing hemodialysis (HD) were recruited. The HD population consisted of patients with and without diabetes mellitus (DM). An electrocardiogram was recorded before HD, and blood pressure was measured during HD. The coefficients of variation of R-R intervals, high- and low-frequency components, and ratio of the low- to high-frequency components were measured as variables of HRV. The ENT was used to describe the complexity of HRV. Forty-six healthy subjects and 27 HD patients participated in this study. The ENT negatively correlated with the duration of DM (p = 0.001), systolic blood pressure (p = 0.003), and mean blood pressure (p = 0.004) before a HD session. ENT in HD patients was lower than that in healthy subjects (p < 0.01). ENT in HD patients with DM was lower than that in HD patients without DM (p < 0.01). The change in systolic blood pressure (DeltaSBP) during a HD session showed high correlations to ENT and ultrafiltration rate (UFR) of the dialyzer. The following equation was obtained: DeltaSBP = 2.25 x ENT - 2.28 x UFR - 21.27 (R2 = 0.805; p < 0.0001). ENT decreased with uremic and diabetic status. ENT also represents a possible prediction of hypotension during a HD session.     

Evaluation of association between atherogenic index of plasma and intima‐media thickness of the carotid artery for subclinic atherosclerosis in patients on maintenance hemodialysis

Incidence of cardiovascular diseases in the patients having chronic kidney disease (CKD) is between 25% and 60%. This increased rate is proposed to be associated with “accelerated atherosclerosis.” Increased carotid intima‐media thickness (CIMT) is a subclinical atherosclerosis marker. Small‐dense low‐density lipoprotein particles are a strong risk factor for atherosclerosis. It was shown that atherogenic index of plasma (AIP = log(TG/HDL‐c)) is correlated with size of the lipoprotein particles. We investigated the correlation between AIP and CIMT which is a subclinical atherosclerosis marker, in hemodialysis (HD) patients. A total of 62 persons with 31 patients under HD therapy and 31 volunteers were included in the study. In all the participants, CIMT was measured and AIP were calculated. AIP and CIMT values of the participants were compared with blood pressures, lipid profiles and the other risk factors. AIP (0.39 ± 0.32) and CIMT (0.57 ± 0.13) were found significantly higher in the patient group than in the controls (0.04 ± 0.36 and 0.45 ± 0.119, respectively); (P = 0.0001 and 0.0001, respectively). There was a significant correlation between AIP and increased CIMT in the patient group (P = 0.0001, r = 0.430). Among the lipid parameters, the strongest correlation was found between CIMT and AIP. We demonstrated the significant increase of AIP and CIMT in HD patients. A correlation was found between AIP and CIMT. AIP was found to show a correlation with a greater number of risk factors, both classical and CKD specific, than CIMT. These data suggest that AIP might be a method which can be used both in diagnosis of subclinical atherosclerosis and in deceleration processes of its progression.     

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.     

Determinants of C-reactive protein in chronic hemodialysis patients: relevance of dialysis catheter utilization

Biomarkers of inflammation, especially C-reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19-90], 68% African Americans, 39% diabetics [DM]) over a mean follow-up of 12 months (range 2-26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4-16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor.     

Serum matrix metalloproteinase-3 in hemodialysis patients with dialysis-related amyloidosis

Background: Matrix metalloproteinase‐3 (MMP‐3) has been linked to osteoarticular destruction in rheumatic arthritis. To investigate the role of MMP‐3 in dialysis‐related amyloidosis (DRA), we determined serum MMP‐3 in long‐term hemodialysis (HD) patients with and without clinical manifestations of DRA. Methods: Thirty‐three subjects (63% female, 3% diabetic) enrolled in the study between September 2001 and June 2003. All patients underwent standard HD three times per week, using high‐flux dialyzers. Four patients had active DRA complications (DRA patients), whereas the others (n = 29) had no evidence of DRA. We determined serum concentrations of MMP‐3, C‐reactive protein (CRP), β₂‐microglobulin (β₂M), and interleukin‐6 (IL‐6). We also studied the effects of hemodiafiltration (HDF) on inflammatory measures by transferring the DRA patients from regular HD to predilution HDF. Results: The DRA group had been on dialysis significantly longer than the control group. Significant positive correlations were observed between MMP‐3 and IL‐6 (R² = 0.5143, p < 0.0001) and MMP‐3 and CRP (R² = 0.6492, p < 0.0001). IL‐6 levels increased after a single dialysis treatment, but this effect was minimal with predilution HDF (the increment of IL‐6 levels did not exceed 10 pg/mL). Serum MMP‐3 levels decreased in parallel with the decrease of IL‐6. Conclusions: MMP‐3 serum levels increase in accordance with clinical manifestations of DRA and elevated circulating levels of IL‐6. For the evaluation of the pathophysiologic state of DRA, serum MMP‐3 may be a useful predictor indicative of chronic inflammation and osteoarticular disorders in DRA patients.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients

Fibroblast growth factor-23 (FGF-23) has been suggested to play a role in vascular calcification in chronic kidney disease. Common carotid artery intima-media thickness (CIMT) assessment and common carotid artery (CCA) plaque identification using ultrasound are well-recognized tools for identification and monitoring of atherosclerosis. The aim of this study was to test that elevated FGF-23 levels might be associated with carotid artery atherosclerosis in maintenance hemodialysis (HD) patients. In this cross-sectional study, plasma FGF-23 concentrations were measured using a C-terminal human enzyme-linked immunosorbent assay kit. Carotid artery intima-media thickness was measured and CCA plaques were identified by B-Mode Doppler ultrasound. One hundred twenty-eight maintenance HD patients (65 women and 63 men, mean age: 55.5 ± 13 years, mean HD vintage: 52 ± 10 months, all patients are on HD thrice a week) were involved. The mean CIMT were higher with increasing tertiles of plasma FGF-23 levels (0.66 ± 0.14 vs. 0.75 ± 0.05 vs. 0.86 ± 0.20 mm, P<0.0001). Log plasma FGF-23 were higher in patients with plaques in CCA than patients free of plaques (3.0 ± 0.17 vs. 2.7 ± 0.23, P<0.0001). Significant correlation was recorded between log plasma FGF-23 and CIMT (r=0,497, P=0.0001). In multiple regression analysis, a high log FGF-23 concentration was a significant independent risk factor of an increased CIMT. Further studies are needed to clarify whether an increased plasma FGF-23 level is a marker or a potential mechanism for atherosclerosis in patients with end-stage renal disease.     

Hypoalbuminemia is an important risk factor of hypotension during hemodialysis

Hypotension during hemodialysis (HD) is an important problem in patients on HD. To investigate the risk factors that contribute to the hypotension during HD, we compared background factors of hypotensive (HP) patients during HD. Among 58 patients undergoing HD in Tamura Memorial Hospital, 12 patients could not continue full HD because of hypotension. We compared the data of ultrafiltration volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP patients (HP group; n=12) and sex- and age-matched control patients (NP group; n=12). There were no significant differences of age, sex, and duration of HD between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%, p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP 3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2 groups. There is a significant negative correlation between changes of systolic blood pressure (delta systolic blood pressure) and serum albumin in these patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia is a major risk factor of hypotension during HD.     

Relationship between Geriatric Nutritional Risk Index and total lymphocyte count and mortality of hemodialysis patients

We examined the relationships between Geriatric Nutritional Risk Index (GNRI), total lymphocyte count (TLC), and mortality in hemodialysis (HD) patients. We examined GNRI and TLC in 120 maintenance HD patients and followed these patients for 120 months. Predictors of all‐cause death were examined using life table analysis and the Cox proportional hazards model. TLC marginally correlated with GNRI (r = 0.176; p = 0.090) and significantly with phosphorus levels (r = 0.206; p = 0.026). Life table analysis revealed that subjects with a GNRI < 90 (n = 19) had lower survival rates than did those with a GNRI ≥ 90 (n = 101; Wilcoxon's test, p = 0.048), but subjects with a TLC < 1500/mm³ (n = 76) had similar survival rates compared with subjects with a TLC ≥ 1500/mm³ (n = 44; Wilcoxon's test, p = 0.500). Multivariate Cox proportional hazards analyses demonstrated that GNRI is a significant predictor of mortality (hazard ratio 9.315, 95% confidence interval 1.161–74.753, p = 0.036), after adjusting for age, sex, presence of type 2 diabetes mellitus, Kt/V, normalized protein catabolic rate, hematocrit, phosphorus, systolic blood pressure and TLC. Our findings suggest the TLC may be used as a simple nutritional tool, but may not be a predictor of mortality in HD patients. These findings require confirmation by further studies.     

Association between novel indices of malnutrition-inflammation complex syndrome and cardiovascular disease in hemodialysis patients

Background: Inflammation and malnutrition are recognized as important risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Owing to substantial short‐term variability of serum C‐reactive protein (CRP), more reliable markers of malnutrition–inflammation complex syndrome should be sought with stronger associations with the risk of CVD in HD patients. We therefore explored the clinical relevance of a composite inflammatory index (prognostic inflammatory and nutritional index [PINI]) and of muscle protein mass indicators, derived from creatinine kinetics. Methods: This cross‐sectional study included 177 HD patients (89 women and 88 men; median age, 67.73 years). CVD and risk factors were assessed using medical charts, clinical examination, and biochemical measurements performed at inclusion. Lean body mass (LBM) was derived from creatinine kinetic modeling, whereas PINI was calculated as the ratio (CRP ×α1‐acid‐glycoprotein)/(albumin × transthyretin). Patients were divided according to the presence or absence of established CVD. Results: The traditional risk factors diabetes (odds ratio [OR], 5.83; p = 0.0045) and smoking (OR, 3.50; p < 0.02) were associated with an increase in prevalent CVD. Low transthyretin (OR, 3.79; p < 0.02) and high levels of CRP (OR, 2.70; p < 0.05), PINI (OR, 3.44; p < 0.02), observed LBM (OR, 3.01; p < 0.05), and the ratio of observed/expected LBM (OR, 4.24; p < 0.01) were associated with CVD after adjustment for age, sex, dialysis center, and dialysis vintage. After additional adjustment for diabetes and smoking, only PINI (OR, 2.85; p = 0.0446) and observed/expected LBM (OR, 2.96; p = 0.0361) were still significant. Conclusion: PINI and LBM are associated with increased relative risk for having CVD and could be used routinely to examine the degree of severity of malnutrition inflammation complex syndrome.     

Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis

Little is known about the magnitude of vitamin D deficiency in patients with stage 5 chronic kidney disease (CKD-5) on hemodialysis (HD). In the present study, we examined the prevalence of vitamin D deficiency in patients with CKD-5 undergoing HD, evaluating the relationship between calcidiol levels with other parameters of mineral metabolism, nutrition/inflammation, functional capacity (FC), and sunlight exposure. Serum 25(OH) vitamin D levels were evaluated in 84 stable patients on chronic HD not receiving vitamin D supplements, with a mean age 58.9+/-16.6 years, during the month of September (end of winter in the southern hemisphere). 25(OH) vitamin D serum levels, intact PTH (iPTH), as well as serum albumin, calcium, phosphorus, and alkaline phosphatase were analyzed in fasting samples. Similarly, protein catabolic rate (PCR) and body mass index (BMI) were determined as nutritional parameters. Functional capacity according to the Karnofsky index, and sunlight exposure were also analyzed. In this study, we considered adequate vitamin D levels those above 30 ng/mL (U.S.A. National Kidney Foundation DOQI Guidelines), vitamin D insufficiency when levels were between 15 and 30 ng/mL, and vitamin D deficiency when levels were below 15 ng/mL. The mean 25(OH) D levels were significantly higher in men than in women (28.6 vs. 18.9 ng/mL; p=0.001). Vitamin D insufficiency was found in 53.5% of the patients (n=45) and vitamin D deficiency in 22.6% (n=19). In the univariate analysis, there were no correlations between 25(OH) D levels with age, iPTH, calcium, or phosphorus. There were positive correlations between serum 25(OH) D levels and degrees of sunlight exposure (R=0.55; p<0.0001), serum creatinine (r=0.38; p<0.001), serum albumin (r=0.22; p=0.04), and a negative correlation with BMI (r=-0.26; p=0.01). In the multiple regression analysis, only sunlight exposure (B=0.361), BMI (B=-0.23), and gender (B=-0.27) were significantly associated with 25(OH) D levels. Patients with FC 1 to FC 2 (n: 70%, 83.3%) had significantly higher 25(OH) D serum levels compared with FC 3 to FC 4 patients (n: 14%, 16.6%): 25.9 vs. 17.1 ng/mL (p=0.03). These results indicate that vitamin D insufficiency/deficiency is highly prevalent (76.1%) at the end of winter, in stage 5 CKD patients on HD, and lower values seem to be related to decreased sunlight exposure, female gender, increased BMI, and worse functional class.