Factors Affecting Flow-Mediated Vasodilatation in Hemodialysis Patients

Clinical manifestation of overt vascular disease may be preceded for years by endothelial dysfunction. Objective: This study was undertaken to evaluate endothelial function in ESRD patients and correlation between endothelial function and clinical and biochemical parameters. Methods: 32 stable ESRD patients (male : female = 16 : 16, average age: 55.2 ± 13.0) on hemodialysis were included. A 10‐MHz ultrasound transducer was used to image the brachial artery. Brachial artery diameter was measured, and reactive hyperemia was induced by inflation to 250 mmHg for 5 min and then deflation of a pneumatic cuff. After release of the cuff, brachial artery diameter was measured. Results: In the entire study population and non‐diabetic group, the %FMD (% flow‐mediated dilatation, % change of brachial artery diameter between before and after cuff inflation) did not show any significant correlation with duration of dialysis, age, hypertension, albumin, CRP, total cholesterol, LDL and HDL cholesterol, and triglyceride. However, the %FMD of diabetic patients was lower than that of non‐diabetics. Among the patients with diabetes, the group of patients with FMD of <5.2% showed significant lower serum albumin and significantly higher ln(CRP) levels compared to the group of patients with FMD ≥5.2%. The %FMD showed significant positive correlation with serum albumin level and significant negative correlation with ln(CRP) in diabetic patients. Conclusion: These findings suggest that endothelial dysfunction, estimated by FMD, was significantly more prominent in diabetic ESRD, especially with low serum albumin and high CRP levels.     

Clinical Characteristics of Upper Gastrointestinal Bleeding in Hemodialysis Patients

Upper gastrointestinal bleeding (UGIB) frequently occurs in hemodialysis (HD) patients. But, clinical characteristics of UGIB in HD patients are not well reported yet.
Objective:  This study was designed to compare the clinical characteristics of UGIB between HD patients and normal population with intact renal function.
Methods:  This study enrolled 24 HD patients with UGIB. Age- and sex-matched 26 patients with UGIB and normal renal function were selected as control group during the same period. Of the cases with UGIB, esophageal variceal bleedings due to liver cirrhosis were excluded in this study. We investigated the results of treatment and UGIB-associated mortality for 3 months after the event and then compared previous gastrointestinal (GI) symptoms (Sx), endoscopic findings, treatment results, and mortality between HD patients and control.
Results:  The results are summarized in the table.  

     

Role of Genetic Factors in Vascular Access Thrombosis in Hemodialysis Patients

Vascular access thrombosis is a frequent complication in hemodialysis (HD) patients. Genetic mutations, inflammation, and changes in the vascular wall are some factors that are thought to increase thrombosis risk. In this study, we tested for possible relationships between vascular thrombosis and some known thrombophilic mutation/polymorphisms in coagulation factors [factor V Leiden (FVL), prothrombin (Pt) G20210A, methylene tetrahydrofolate reductase (MTHFR C677T), factor XIII (F-XIII) Val34Leu, alpha-fibrinogen (AF) Thr312Ala, factor VII (F-VII) R353Q] and angiotensin I converting enzyme (ACE) gene in our HD patients. Patients who had experienced at least 3 episodes of AVF thrombosis composed of the study group, and patients who had never encountered this complication composed of the control group. None of the patients in either group had a history of diabetes mellitus, atherosclerosis, dialysis-related amyloidosis, or vasculitis. In order to find the frequency of F-XIII Val34Leu, AF Thr312Ala, and F-VII R353Q polymorphisms in our population, we also searched persons without renal disease or history of thrombosis (normal group). Results are summarized in Table. There was a tendency toward thrombotic mutation/polymorphisms in the study group for FVL, Pt G20210A, ACE I/D, and AF Thr312Ala. We suggest that patients who develop recurrent AVF thrombosis should be screened for the above-mentioned factors and investigated for other possible risk factors. This screening would allow more effective focus on prophylaxis.  

     

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.     

Volume Control in Hemodialysis Patients

Cardiovascular disease is the main cause of the high mortality of dialysis patients and is largely due to poor control of blood pressure. Establishing and maintaining normal extracellular volume (ECV) is required to achieve normotension. The dry weight concept links ECV and blood pressure by a simple clinical relationship. Dry weight is the ideal postdialysis weight that allows a constantly normal blood pressure to be maintained without using antihypertensive medications. Maintenance of normal ECV requires control of salt intake to reduce interdialytic weight gain ( i.e., saline overload) combined with the diffusive and convective removal of salt and water from the body during dialysis sessions. Several problems are to be faced when using the dry weight method. Clinical evaluation must take into account the following confounding factors: weight varies with nutrition, clinical symptoms are unspecific and sometimes discordant, and there is a lag time between ECV and blood pressure changes. On the other hand, achievement of dry weight is hampered by dialysis times that are too short (and weight gains that are too high), by antihypertensive medications, and by poor heart conditions. A longer session time allows for a slower, easier, and more comfortable ultrafiltration.     

Lipid Metabolism and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Role of Factors Modulating Cytosolic Calcium

Animal studies indicate that insulin resistance and glucose intolerance leading to dyslipidemia in uremic rats are associated with increased cytosolic calcium ([Ca⁺⁺ i]). The resistance and intolerance are reversed with verapamil, but recur after its discontinuation. This finding suggests that hyperparathyroid‐induced [Ca ⁺⁺ i] increase is responsible for the metabolic derangement. We retrospectively examined, over a 12‐year period, the effects of factors that lower [Ca ⁺⁺i] on total serum cholesterol and triglycerides in 332 hemodialysis (HD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on morbidity and mortality outcomes related to atherosclerotic vascular disease. Patients with diabetes mellitus were excluded, because their dyslipidemia and vascular disease are mediated via a different mechanism. Four groups emerged: group I [high parathormone (PTH) in the absence of calcium channel blockers (CCBs), n = 107], representing the highest [Ca⁺⁺ i]; group II (high PTH in the presence of CCBs, n = 76) and group III (lower PTH in the absence of CCBs, n = 66), representing intermediate [Ca ⁺⁺ i]; and group IV (lower PTH in the presence of CCBs, n = 83) representing the lowest [Ca ⁺⁺i]. The theoretically lower [Ca ⁺⁺ i] was achieved via CCB therapy or lower PTH, or both. The mean serum cholesterol in group I was 322 ± 24 mg/dL and the level of triglycerides was 398 ± 34 mg/dL. Group II had mean serum cholesterol of 196 ± 16 mg/dL and triglycerides of 157 ± 17 mg/dL. Group III had a mean serum cholesterol of 202 ± 19 mg/dL and triglycerides of 160 ± 15 mg/dL. Group IV had a mean serum cholesterol of 183 ± 9 mg/dL and triglycerides of 94 ± 6 mg/dL. The differences in cholesterol and triglyceride levels among four groups were significant (p < 0.001) by one‐way analysis of variance (ANOVA). The incidence of cardiovascular morbidity and mortality events was 61% in group I, 24% in group II, 28% in group III, and 18% in group IV (χ ² = 47.7, p < 0.001). We conclude that, in non diabetic HD patients, hyperparathyroidism, especially in the absence of CCBs, is associated with severe dyslipidemia and increased risk of cardiovascular morbidity and mortality. Dyslipidemia may be related to a hyperparathyroid‐induced increase in cytosolic calcium [Ca⁺⁺i]. Lowering [Ca⁺⁺i] by decreasing PTH or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long‐term cardiovascular morbidity and mortality. Prospective randomized studies, with actual measurement of [Ca ⁺⁺i], are needed to verify the results of this study.     

Time Needed to Improve Clinical Parameters By Daily Hemodialysis

Daily hemodialysis therapy (DHD), 2 hours, 6 times per week, is able to cure complications that persist on standard hemodialysis (SHD), 4 hours, 3 times per week. Cardiovascular manifestations (high blood pressure, left ventricular hypertrophy), nutritional deficient states, and postdialysis asthenia are improved during the first month of DHD therapy and are usually cured at 3 months. Daily hemodialysis may be considered as a rescue therapy. The next step will be to select which patients can return to the classical SHD therapy without recurrence of their complications.     

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.     

Physiologic Inhibitors of Coagulation in Patients on Chronic Hemodialysis

Patients on hemodialysis are at increased risk for bleeding and thromboses. The intriguing balance between these risks is more complex than once thought, as endogenous clotting factors and their regulators come into contact with bioincompatible dialyzer membranes, in the setting of an extracorporeal circuit of blood flow, in the face of the uremic state. In this review, we summarize the current data on the interaction between the physiologic inhibitors of coagulation and hemodialysis. Data sources and study selection were obtained from research and review articles related to the endogenous anticoagulation pathway published in English on MEDLINE from 1972 to 2002. While protein C activity and protein S antigen concentrations are increased, there is no change in antithrombin III levels during hemodialysis in relation to predialysis levels. Plasma protein Z, which has only recently been studied in uremic subjects, is increased as well. In addition, hemodialysis leads to elevated tissue factor plasminogen inhibitor, thrombomodulin, tissue plasminogen activator, and plasminogen activator inhibitor-1 activities. The potential functional significance of these observations is discussed. Finally, as erythropoietin is commonly prescribed to uremic patients and is recognized to be prothrombotic, an appraisal of its interaction with the naturally occurring anticoagulants is presented. It is apparent that we are only beginning to realize the complexity of the interplay between this myriad of serum factors and hemodialysis. Further research is needed to shed light on this underexplored area of hemodialysis.     

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.     

Cirrhosis Ameliorates Renal Osteodystrophy in Patients on Regular Hemodialysis

Cirrhosis (Cir) is often associated with chronic renal failure (CRF) in Egyptian patients on regular hemodialysis (RHD). This is largely attributed to hepatosplenic schistosomiasis and concomitant Hepatitis C viral infection. As the liver has a major role in vitamin D3 activation, we designed this study to envisage the impact of Cir on renal osteodystrophy (ROD). It included 130 consecutive age‐ and gender‐matched subjects in 4 categories. Group I: 39 patients (34 male and 5 female; mean age 48.8 years) with Cir normal renal function; group II: 37 patients (30 male and 7 female; mean age 49.0 years) with CRF and normal liver function, on RHD for a mean duration of 6 ± 3.9 years; group III: 41 patients (30 male and 11 female; mean age 50.7 years) with CRF and concomitant Cir, stable on RHD for a mean duration of 7.0 ± 4.0 years; and group IV: 16 normal volunteers (13 male and 3 female; mean age 46.3 years). The prevalence of diabetes as well as previous infection with schistosomiasis was similar in all patient groups and that of HCV infection was alike in groups I and III. In all subjects, conventional parameters of liver and renal function were tested; in addition to measurement of serum total protein, albumin, calcium, phosphate, total and bone‐specific alkaline phosphatase (B‐ALP), parathormone (PTH), 5‐hydroxycholecalciferol (5HD), 1,25‐dihydroxycholecalciferol (1,25HD), Cross Laps (CXL) as a marker of bone resorption, and aminoterminal propeptide of type I procollagen (PINP) as a measure of bone formation. Bone mineral density (BMD) was measured by either Dual Energy X‐ray Absorptiometry (DEXA) or Computerized Tomography (CT). Group II patients displayed the typical CRF profile comprising hypocalcemia, hyperphosphatemia, increased total and bone‐specific alkaline phosphatases, high PTH and 25HD, low 1,25HD, increased PINP as well as CXL, and generally decreased BMD. Cir (Group III) significantly (p value at least <0.5) modified this profile in several aspects: it checked hypocalcemia (mean 8.8 vs. 7.9 mg/dL in groups II and III, respectively), hyperphosphatemia (5.15 vs. 4.9 mg/dL), and the elevation of B‐ALP (62 vs. 30.5 μg/L) and PTH (89 vs. 78 pg/mL). It lowered the serum level of 25HD (18.7 vs. 13.7 ng/mL), augmented the deficiency of 1,25HD (13.4 vs. 8.0 pg/mL), did not appreciably affect the increase in bone formation (PINP 77.9 vs. 75.5 ng/mL), but ameliorated its excessive resorption (CXL 21 860 vs. 30 328 pmol/L) noticed in group II. This was associated with amelioration of the dialysis‐associated osteopenia (70 vs. 33.5%) and increased incidence of osteosclerosis (30 vs. 61%), as measured by bone mineral density. Conclusion: Our data indicate that Cir ameliorates ROD through decreased bone resorption. This is associated with better tolerance to 1,25HD deficiency, which initiates the cascade of hypocalcemia, hyperparathyroidism, and increased bone resorption in CRF. Such tolerance may reflect upregulation of vitamin D receptors as a consequence of the humoral perturbation supervening in Cir, involving IGF‐1, estrogens, or other vitamin D metabolites as 24,25 HD.     

Effect of Valsalva Maneuver on QT Dispersion in Hemodialysis Patients

Increased QT dispersion seems to be related to an increased risk of arrhythmia and sudden death, a common cause of mortality in hemodialysis (HD) patients. Increase in sympathetic tone has been documented in HD patients. In this study, we aimed to investigate the effect of changes in the autonomic tone on QT dispersion (QTd) in HD patients. Twenty HD patients (M/F 13/7; age, mean ±SD, 28 ± 10 years) and 22 age‐ and sex‐matched healthy controls (M/F 12/10; age, 30 ± 10 years) were included. The patients were dialyzed three‐times weekly; time on dialysis was 17 ± 8 months. The QT durations were measured from 12 lead surface EKGs and were corrected for RR intervals. Corrected maximum (QT_c max) and minimum (QT_cmin) QT intervals and their difference (QT _c d) were recorded. The effect of the Valsalva maneuver in the release phase on QT _c intervals and dispersion was assessed. The HD patients had prolonged values compared to controls: QT _c d, 59 ± 17 ms versus 35 ± 7 ms, p < 0.001; QT _c max, 458 ± 41 ms versus 397 ± 21 ms, p < 0.001; and QT _c min, 398 ± 36 ms versus 362 ± 25 ms, p < 0.001. After the Valsalva maneuver no changes were observed in controls: QT _c max, 397 ± 21 ms versus 396 ± 22 ms, p = 0.9; QT _c min, 362 ± 24 ms versus 358 ± 19 ms, p = 0.5; and QT _c d, 35 ± 7 ms versus 38 ± 10 ms, p = 0.15. Whereas, in HD patients all values were significantly shortened: QT_cmax, 458 ± 41 ms versus 427 ± 35 ms, p = 0.003; QT_c min, 398 ± 36 ms versus 379 ± 34 ms, p = 0.04; and QT_c d, 59 ± 17 ms versus 48 ± 15 ms, p = 0.01. The decrease in QTmax was more prominent than the decrease in QTmin, hence QT dispersion was significantly decreased after the Valsalva maneuver, but differences from controls were still significant. In conclusion, increased sympathetic activity may have a role in the prolonged QT duration and increased QT dispersion in HD patients.     

Extracellular Volume Changes and Blood Pressure Levels in Hemodialysis Patients

Background: Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post‐HD body weight (BW) over a period of 3 to 4 months. Methods: During a period of 3–4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143–141 mmol/L to 139–138 mmol/L. Extracellular volume (ECV) was measured with a multiple‐frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical. Results: Group 1 showed a significant reduction during the entire 48‐hour period in systolic (156 ± 16 mmHg vs. 140 ± 14 mmHg, P = 0.030) and diastolic BP (97 ± 12 mmHg vs. 87 ± 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 ± 13 vs. 105 ± 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 ± 15 mmHg vs. 138 ± 14 mmHg, P = 0.007; diastolic BP 97 ± 12 mmHg vs. 85 ± 9 mmHg, P = 0.009) than during the day (157 ± 18 mmHg vs. 142 ± 15 mmHg, P = 0.067; diastolic BP 97 ± 13 mmHg vs. 90 ± 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48‐hour period (76 ± 24% vs. 46 ± 28%, P = 0.043) as well as in night systolic load (75 ± 21% vs. 41 ± 30%, P = 0.015) and night diastolic load (67 ± 32% vs. 39 ± 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2. Conclusions: The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.     

Survival of End-Stage Renal Disease Diabetic Patients on Hemodialysis

Purpose: To analyze survival and causes of mortality in end‐stage renal disease (ESRD) diabetic patients treated by hemodialysis. Methods: Data of 1203 ESRD hemodialyzed patients between 1975 and 2002 were analyzed, 116 patients were excluded and 1087 patients included in the study. We studied the prevalence of the diabetic nephropathy, the rate of survival and causes of death by comparing diabetic patients with a control group of patients without diabetes. Results: Among the 1087 patients requiring dialysis, 272 (25%) were diabetic and 815 non‐diabetic whose causal nephropathy was nephroangiosclerosis 32%, glomerulonephritis 15%, chronic interstitial nephropathy 14%, and others 14%. The diabetics were older at the beginning of dialysis than non‐diabetic patients: 60.33 ± 11.39 years vs. 52.23 ± 17.20 years, p < 0.001. Average time on dialysis is more important in non‐diabetic than diabetic group [5.90 ± 5.73 years vs. 2.71. ± 2.48 years, p < 0.001]. The rate of death was higher in diabetics than in control group [71.7% vs. 55.8%, respectively, p < 0.003]. The difference in survival between the two groups remains significant for the same age. Death caused by cardiovascular disorders is higher in diabetics (68.8%) than non‐diabetics (31.2%) (p < 0.05). Among death causes, stroke is the most frequent cause in diabetics (18.4% vs. 11.6%) in non‐diabetics, p < 0.05. Death by heart failure and infections is higher in diabetics but the difference is not statistically significant (12.3% in diabetics vs. 9.4% in non‐diabetics for heart failure and 13.8% vs. 11.4% for infections). Death due to neoplasms is higher in non‐diabetics (4.39% vs. 1.02% in diabetics, p < 0.05). Conclusion: In our cohort, mortality in diabetic patients is higher than in non‐diabetic patients. Cardio‐vascular disorders are the most cause of death in diabetics and above all stroke, whereas mortality due to neoplasms is higher in non‐diabetic patients. Diabetes is an important risk factor of mortality in hemodialysis 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.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

Iron Management in Hemodialysis Patients: Optimizing Outcomes in Vicenza, Italy

The management of anemia in uremic patients undergoing hemodialysis requires the appropriate combination of erythropoietin treatment, iron supplementation, and on occasion androgen therapy.
Identifying and correcting functional iron deficiency is crucial to optimizing erythropoietin efficiency. Recently, however, the trend to administer maintenance iron with resultant high serum ferritin and high transferrin saturation has led to an increase in reports of iron overload.
Oral iron supplementation is inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit its efficacy. Intravenous iron, on the other hand, is effective, and its safety is related to the iron salt used. Currently available data suggest that iron saccharate may be the safest iron salt available for intravenous administration, although iron gluconate is safer than the dextran forms of intravenous iron. It should be kept in mind, however, that all forms of intravenous iron may have the potential of inducing iron overload.
At this time, the levels of ferritin that define iron overload are not clearly established. The side effects of iron overload are well recognized (infections, malignancies, vascular diseases); however, no guidelines exist for safe practice. There are many markers of iron deficiency, with serum ferritin and hypochromic red cell percentage currently the best markers available in clinical practice.     

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.     

Impact of Ischemic Heart Disease on Early Access Failure in Nondiabetic Hemodialysis Patients

Lynchburg Nephrology Dialysis Inc. started its nightly home hemodialysis (NHHD) program in September 1997.
Purpose of study:  To evaluate episodes of exit site infections, catheter sepsis, safety, and longevity of accesses for patients doing NHHD.
Methods:  If IJ catheter was chosen, patient was started on Coumadin 2 mg/day when catheter was placed. If catheter malfunctioned, it was locked with a thrombolytic agent and Coumadin was adjusted to meet a goal INR of 1.5–2.25. If the problem persisted, the catheter was exchanged. For catheters, the B-D InterLink device was used to prevent air emboli and infection, and a locking device was used to prevent disconnects. If AV fistula was used, 4 buttonholes were established using 16 gauge needles. If AV graft was used, patients were taught the ladder cannulation technique using 16 gauge needles.
Results:  As of September 1, 2003, 45 patients have completed training and have performed 27,063 treatments at home. Total catheter time at home was 930 months. Total AV fistula and AV graft time at home was 190 and 20 months, respectively. Upon completion of training, 34 patients were using tunneled IJ catheters, 10 using AV fistulas, and 1 using an AV graft. The IJ catheter exit site and sepsis infection rate was 0.35 and 0.49 episodes/1000 patient days, respectively. Average catheter life was 8.5 months with the longest 66.7 months and the shortest 0.2 months. The AV fistula and graft exit site and sepsis infection rates were 0.16 and 0 episodes/1000 patient days, respectively. Catheter complications included 1 episode of disconnect due to patient's failure to use locking device, 1 episode of central stenosis, and 1 episode of intracranial hemorrhage, due to prolonged INR, with resolution of symptoms.
Conclusion:  Data support that tunneled IJ catheters, AV fistulas, and AV grafts were effective and safe permanent accesses for patients on NHHD.     

Knowledge of Home Dialysis Among Inner‐City Satellite Hemodialysis Patients

There is limited use of home renal replacement therapies in the U.S.A. One percent of dialysis patients are on home hemodialysis (HHD) and only 9% undergo peritoneal dialysis (PD). In an effort to better understand this, 161 satellite hemodialysis patients in 6 units in Brooklyn were surveyed. Forty‐eight percent of patients were women, 86% were black, 5% white, 8% Hispanic, and 1% other. Mean age was 49.4 years (range 22 – 69 years). Etiology of renal disease was hypertension (41%), diabetes mellitus (31%), polycystic kidney disease (3%), systemic lupus erythematosus (4%), and other or unknown (21%). Patients were queried about knowledge of and attitudes toward home therapies. Seventy‐nine percent of patients knew of home dialysis. The source of this information was the nephrologist (59%), the social worker (14%), a nurse (8%), other patients (4%), and other sources (15%). Only 10% of patients had ever considered HHD. Fifty‐four percent were afraid to do self‐care at home and 35% were not interested. Surprisingly, only 3% felt they had no reliable helper and 8% felt that their housing was not suitable. Similarly, 78% of patients had been spoken to about PD, but only 11% had considered it. Forty‐one percent were afraid of doing self‐care on PD, and 45% were not interested. We conclude that, although the majority of patients in six inner‐city dialysis units had heard of home dialysis, only a small number ever considered it. As many patients were afraid of doing home therapy, better education about the risks and benefits needs to be disseminated.