Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.     

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.     

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.     

Hemodynamic and Volume Changes during Hemodialysis

Background: Volume overload is a factor in the hypertension of hemodialysis (HD) patients. Fluid removal is therefore integral to the hemodialysis treatment. Fluid removal by hemodialysis ultrafiltration (UF) may cause intradialytic hypotension and leg cramps. Understanding blood pressure (BP) and volume changes during UF may eliminate intradialytic hypotension and cramps. Studies (S1, S2, and S3) were carried out to determine the amount and direction of changes in body fluid compartments following UF and to determine the relationships between BP, changes in blood volume (ΔBV), central blood volume (CBV), cardiac output (CO), peripheral vascular resistance (PVR) plus total body water (TBW), and intra‐ and extracellular fluid volumes (ICF, ECF) in both the whole body and body segments (arms, legs, trunk). Methods: Indicator dilution technology (Transonic) was used for CBV, CO, and PVR; hematocrit monitoring (Crit‐Line) was used for ΔBV segmental bioimpedance (Xitron) for TBW, ICF, and ECF. Results: S1 (n = 21) showed UF sufficient to cause ΔBV of ?7% and lead to minor changes (same direction) in CBV and CO, and with cessation of UF, vascular refilling was preferential to CBV. S2 (n = 20) showed that predialysis HD patients are ECF‐expanded (ECF/ICF ratio = 0.96, controls = 0.74 [P < 0.0001]) and BP correlates with ECF (r = 0.47, P = 0.35). UF to cause ΔBV of ?7% was associated with a decrease in ECF (P < 0.0001) and BP directly (r = 0.46, P = 0.04) plus ΔBV indirectly (r = ?0.5, P = 0.024) correlated with PVR, while CBV and CO were maintained. S3 (n = 11) showed that following UF, total‐body ECF changes were correlated with leg ECF (r = 0.94) and arm ECF (r = 0.72) but not trunk ECF. Absolute ECF reduction was greatest from the legs. Conclusions: Predialysis ECF influences BP and UF reduces ΔBV and ECF, but CBV and BP are conserved by increasing PVR. ECF reduction is mainly from the legs, hence may cause cramps. Intradialytic hypotension is caused by failure of PVR response.     

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.     

Important role of blood rheology in atherosclerosis of patients with hemodialysis

Concerning a role of blood rheology for atherosclerosis in patients with hemodialysis (HD), little data are available. It may be due to the fact that the method for evaluating rheologic properties of circulating blood has been limited. We examined blood rheology in 118 HD patients by using microchannel array flow analyzer that makes it possible to directly observe the flow of blood cell elements through the microchannel. Transit time (T(B)) of heparinized whole blood through slit pores (7 x 30 microm) was used as an index of rheology and related with various inflammatory biomarkers such as high-sensitive CRP (hsCRP), monocyte chemotactic protein-1, osteopontin, or fibrinogen (Fg). Moreover, as a surrogate marker of atherosclerosis, carotid intima-media thickness (IMT) and aortic stiffness evaluated by brachial-ankle pulse-wave velocity (baPWV) were studied. In HD patients, T(B) had strong positive correlations with hsCRP (r = 0.427; p < 0.00001), Fg (r = 0.452; p < 0.00001), and osteopontin (r = 0.227; p < 0.0134). Further, T(B) was significantly well correlated with IMT (r = 0.400; p < 0.0001) and PWV (r = 0.470; p < 0.0001). Multivariate regression analysis showed that baPWV, IMT, Fg, hematocrit, white blood cell count, and CRP were chosen as significant explanatory factors for T(B.) These results suggest that blood rheology may play an important role for atherosclerosis in patients with HD.     

Oxidative DNA damage correlates with carotid artery atherosclerosis in hemodialysis patients

Oxidative stress is accepted as a nonclassical cardiovascular risk factor in chronic renal failure patients. The aim of this study was to evaluate the relation between oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine/deoxyguanosine [8‐OHdG/dG] ratio), oxidative stress biomarkers, antioxidant enzymes, and carotid artery intima‐media thickness (CIMT) in hemodialysis (HD) patients. Forty chronic HD patients without known atherosclerotic disease and 48 age‐ and sex‐matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8‐OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. 8‐OHdG/dG ratios and MDA levels were higher; SOD and GPx activities were lower in HD patients compared to controls. HD patients had significantly higher CIMT compared to controls (0.61 ± 0.08 vs. 0.42 ± 0.05, p < 0.001). There was a significant positive correlation between CIMT and 8‐OHdG/dG ratio (r = 0.57, p < 0.01) and MDA levels (r = 0.41, p < 0.01), while there was a significant negative correlation between CIMT and SOD (r = ?0.47, p < 0.01) and GPx levels (r = ?0.62, p < 0.01). It is firstly demonstrated that CIMT is positively correlated with oxidative DNA damage in HD patients without known atherosclerotic disease.     

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.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

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.     

Echocardiographic Evidence of Altered Cardiac Status in Predialysis Diabetics and Those on Dialysis

Cardiovascular complications affect diabetic subjects early and the more susceptible ones are those on hemodialysis. Objective: This study was designed to observe prevalent cardiac involvement in both pre‐ and already on dialysis diabetics. Method: Sixty diabetics, 30 predialysis (predialysis diabetics, group 1), and 30 on maintenance hemodialysis (MHD, group 2) were randomly selected and their different clinical, biochemical, and echocardiographic parameters were compared. Result: Both groups of patients were matched for age, sex, and body mass index (BMI). Features like systolic and diastolic blood pressure were lower in predialysis diabetics group than in MHD group [138 ± 19 vs. 152 ± 32, p < 0.02 and 74 ± 10 vs. 87 ± 10 mmHg (p < 0.001)]; hemoglobin higher [10.3 ± 2.1 vs. 7.5 ± 1.5 g/dL (p < 0.001)]; serum creatinine was lower [3.49 ± 1.8 vs. 9.5 ± 2.5 mg/dL (p < 0.001)] (due to recruitment criteria); left ventricular muscle mass index (LVMI) also lower [137 ± 96 vs. 211 ± 77 g/m² (p < 0.001)]; left ventricular end diastolic volume index (LVEDVI) less [58 ± 21 vs. 85 ± 25 mL/m² (p < 0.001) and fractional shortening (FS, %) higher [33 ± 4.3 vs. 28 ± 5.8 (p < 0.006)]. Only 11% of Pre subjects had LV hypertrophy (LVMI >131 g/m² in male and in female LVMI >110 g/m²) whereas it was 51% in MHD (p < 0.001). Systolic dysfunction (FS = <25%) was 4% in Pre subjects and 24% in MHD (p < 0.03) group. Correlation study showed systolic and diastolic blood pressure; both had positive correlation with LVMI (r = 0.38, p < 0.008 and r = 0.32, p < 0.02) and LVEDVI (r = 0.36, p < 0.01 and r = 0.35, p < 0.01) and also similarly positive with serum creatinine (r = 0.35, p < 0.02 and r = 0.5, p < 0.001). Conclusion: It may be concluded that cardiac parameters are grossly altered in majority of diabetics on dialysis and higher serum creatinine and uncontrolled blood pressure may be responsible for this.     

Acute complicating symptoms during hemodialysis sessions have well correlation with deranged blood pressure regulation

Objective: This observational study was undertaken to evaluate the frequency of acute complications occurring during dialysis sessions and their association with other clinical and biochemical parameters. Method: Forty‐six maintenance hemodialysis patients were selected and evaluated. Mean of the weekly evaluations of different parameters over a three‐month period is presented here. Result: Age of study subjects was 39 ± 13 years and body mass index (BMI) 21 ± 4 kg/m². Duration of hemodialysis was 41 ± 29 months. Most of the patients were hypertensive (98%), taking multiple anti‐hypertensive drugs. Mean of the blood pressures before and at the end of dialysis sessions over the three month period were: systolic blood pressure (SBP) 159 ± 18 vs. 163 ± 22 (p < 0.05) and diastolic blood pressure (DBP) 92 ± 13 vs. 87 ± 7 mmHg (p < 0.003). Frequency of acute complicating symptoms during dialysis sessions were: headache (75%), rise in blood pressure (73%), leg cramps (67%), vomiting (60%), palpitation (58%), sweating (52%), and hypotension (35%). Raised blood pressure showed a positive correlation with headache (r = 0.50, p < 0.01) and sweating (r = 0.53, p < 0.05). Vomiting and palpitation were more frequent at low post‐dialysis blood pressure (vomiting vs. post‐SBP‐r = ?0.41, p < 0.05 and palpitation vs. post‐DBP‐r = ?0.48, p < 0.05), and these patients were likely to get inadequate dialysis (hypotension vs. Kt/V‐r = ?0.63, p < 0.01). Pre and post dialysis weight variation was 53 ± 11 vs. 51 ± 11 kg (p < 0.001), average ultrafiltration during dialysis (UF)?2.39 (0.5–4) liter and single session Kt/V was 0.95 ± 0.38. The rising tendency of post‐dialysis blood pressure correlated positively with increasing UF (SBP vs. UF‐r = 0.36, p < 0.01 and DBP vs. UF‐r = 0.25, p < 0.05). Conclusion: From this study it may be concluded that acute complications during dialysis sessions have a significant correlation with deranged blood pressure regulation, and optimum control of blood pressure could provide better dialysis.     

Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3‐dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3‐dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima‐medial thickness, brachial‐ankle pulse wave velocity, ankle‐brachial pressure index, and the cardio‐ankle vascular index. Log‐transformed Kyn/Trp ratio was significantly correlated with log‐transformed time on HD (ρ=0.28, P<0.01), log‐transformed highly sensitive C‐reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=?0.13, P<0.05). A significant association was found between log‐transformed Kyn/Trp ratio and mean carotid artery intima‐medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima‐medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle‐brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.     

Effect of Vitamin E Dialyzer Membrane on Anemia in Hemodialysis Patients

Red blood cell (RBC) survival in patients on chronic maintenance hemodialysis (HD) has been reported to be shortened due to the oxidative damage of RBC membrane. The use of antioxidants might help in the control of anemia and reduce the erythropoietin (EPO) dose needed. Objective: The objective was to determine the effects of vitamin E‐bonded dialyzer membrane (VEM) on anemia and EPO requirements in chronic HD patients. Patients and methods: We prospectively studied 19 stable patients on HD (8 males, age 58.47, range 31–76 years) who were shifted from other dialyzer membranes to VEM for 6 months. At baseline they were given a mean dose of EPO of 90.6 ± 51 U kg^–1 BW^–1 week^–1. Clinical data, dry body weight corrected pre‐dialysis RBC, hemoglobin, reticulocytes, serum iron and ferritin, complete biochemistry, iPTH, and CRP were studied at 3 and 6 months, while therapy scheme was reevaluated monthly. Results: A significant rise, compared to the baseline, was found in hemoglobin and in RBC at 3 months of treatment (12.44 ± 1.16 g/dL vs. 11.2 ± 1.2 g/dL, p = 0.002; and 4.01 ± 0.53 × 10⁶/μL vs. 3.64 ± 0.5 × 10⁶/μL, p < 0.05) and at the end of follow‐up (12.17 ± 1.33 g/dL vs. 11.2 ± 1.2 g/dL, p < 0.05; and 4.03 ± 0.53 × 10⁶/μL vs. 3.64 ± 0.5 × 106/μL, p < 0.05). No significant change in serum iron and ferritin, reticulocytes, EPO dose used, iPTH, Kt/V, or CRP was found at the end of follow‐up compared to the baseline (68.8 ± 17 mg/dL vs. 67.9 ± 18 mg/dL, p = NS; 421 ± 296 mg/dL vs. 478 ± 359 mg/dL, p = NS; 3.76 ± 0.89 × 10⁴/μL vs. 3.82 ± 0.78 × 10⁴/μL, p = NS; 90.2 ± 53 U kg^–1 BW^–1 week^–1 vs. 90.6 ± 51 U kg^–1 BW^–1 week^–1, p = NS; 157 ± 43 pg/dL vs. 148 ± 56 pg/dL, p = NS; 1.21 ± 0.22 vs. 1.2 ± 0.17, p = NS; 7.15 ± 5.42 mg/L vs. 15.38 ± 29.8 mg/L, p = NS, respectively). Conclusions: Despite the small number of patients and the short time interval of treatment, an antioxidant effect of VEM apparently achieved early a better control of anemia in HD patients.     

Relationship of Hypoalbuminemia to Multiple Clinical Factors in Hemodialysis Patients

Research shows that low albumin is correlated with higher morbidity and mortality in the dialysis population. The reasons for this are multi‐factorial and may be related to inadequate protein intake, infection and sepsis, inadequate dialysis, or catabolism of uremia. USRDS data show that ESRD Network 16 tends to have lower albumins compared to other ESRD Networks. Objective: To evaluate albumin status of HD patients at Puget Sound Kidney Centers, Everett, WA (ESRD Network 16) and identify potential factors that may put patients at risk of hypoalbuminemia. Methods: Clinical and biochemical data were collected for 3 months on 221 HD patients. Data included serum albumin (bromcresol purple), calcium, phosphorus, CO₂, Hct, % saturation, ferritin, PTH, BUN, Kt/V, URR, nPCR, hours of HD treatment, interdialytic fluid weight gains, DW changes, incidence of infection and hospitalization, catheter use for dialysis access, presence of diabetes and other co‐morbidities, dialyzer reuse, social/psychological status, and use of nutrition supplements. All biochemical data were collected after the longest interdialytic period and analyzed at the same reference laboratory. Data were averaged for each patient for the 3 months and correlations between parameters were determined using Chi‐square analysis. Results: 25% of all patients had albumins <3.2 g/dL (reference range for normal population 3.5–5.0 g/dL). Patients with lower albumins were significantly more likely to have DM (p < 0.02), use catheters for HD access (p < 0.001), had infections during the previous month (p < 0.001), been hospitalized during the previous month (p < 0.002), have co‐morbid issues (p < 0.001), and use nutrition supplements (p < 0.002). No other factors were significantly correlated with lower albumin. Conclusion: Factors other than nutrition seem to be related to hypoalbuminemia. This study has prompted improved protocols for catheter care and use, infection control, and early intervention for nutrition supplement use. Increased screening and monitoring at‐risk patients (those with diabetes and other co‐morbid conditions) has resulted in improved patient care.     

Dipyridamole stress echocardiography in diagnosis and prognosis of hemodialysis patients with asymptomatic coronary disease

The prevalence of coronary artery disease (CAD) is high in hemodialysis (HD) patients. The aim of the study was to assess the diagnostic and prognostic value of dipyridamole stress echocardiography (DSE) in nondiabetic HD patients without signs or symptoms of CAD. In 51 out of 158 evaluated HD patients (21 females, age 67 [33–85] years, HD duration 38 [9–271] months), resting echocardiography and DSE were performed. Exclusion criteria were known CAD, diabetes mellitus, and pulmonary and oncologic pathologies. Logistic regression analysis was carried out to identify predictors of abnormal DSE response, while Cox regression analysis was performed to determine variables associated with total and cardiovascular mortality, after 43.3 (11–60) months of follow‐up. Seven patients (14%) showed a positive response to DSE (DSE+). In 5/7, CAD was documented by angiography: All of them underwent coronary revascularization. DSE+ patients had significantly smaller body mass index than patients with a negative response (DSE‐): 21.7 ± 1.9 vs. 25.1 ± 3.4 kg/m² (p = 0.018). During follow‐up, 16 (31%) patients died. Older age hazard ratio [HR = 1.07; confidence interval (CI) = 1.01–1.12; p = 0.02] and higher plasma phosphate levels (HR = 10.41; CI = 2.30–47.17; p < 0.01) were predictors of total mortality. Male gender (HR = 22.7; CI = 1.45–354.4; p = 0.03), older age (HR = 1.24; CI = 1.03–1.50; p = 0.02), longer HD duration (HR = 1.13; CI = 1.01–1.26; p = 0.04), and positive response to DSE (HR = 5.82; CI = 1.04–32.65; p = 0.04) were associated with cardiovascular mortality. Ten percent of asymptomatic HD patients had significant CAD, but timely diagnosis did not seem to improve their prognosis. Total survival was associated with age and higher levels of plasma phosphate, while male gender, older age, longer HD duration, and DSE+ were predictors of cardiovascular mortality.     

Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension

Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow-mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid-femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow-mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow-mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross-sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology.     

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 of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.