Regular Hemodialysis Patients Research Articles

Unexpected death of regular hemodialysis patients

Unexpected death of regular hemodialysis patients

Tumor necrosis factor gene expression in regular hemodialysis patients.

This study evaluates tumor necrosis factor (TNF)-alfa gene expression in patients with end-stage renal disease (ESRD) on regular hemodialysis as an expression of cardiovascular disease (CVD) risk even on a sub-clinical level and its relation to some of the parameters incriminated in the pathogenesis and the establishment of uremic arteriopathy. A total of 51 patients with ESRD on regular hemodialysis and 20 healthy subjects matching in age and gender as a control group were recruited. All selected cases were subjected to serum lipid profile, Creactive protein (CRP), TNF-alfa gene expression and Doppler study of carotid arteries to estimate carotid intimal media thickness (cIMT). Serum triglycerides (TGS) level (P <0.001), CRP positivity (P = 0.002), relative quantification (RQ) of TNF-alfa gene expression (P = 0.007) and cIMT (P = 0.02) were significantly higher while high-density lipoprotein (HDL) level (P <0.001) was significantly lower among cases compared with controls. RQ showed a significant positive correlation with CRP titer (rho = 0.583, P = 0.011). Results also showed a significant strong negative correlation between with CRP titer and cIMT (rho = -0.590, P = 0.010). CRP titer showed only a significant strong negative correlation with age (rho = -0.589, P = 0.01) and positive correlation with HDL (rho = 0.51, P = 0.031). Patients with ESRD have increased gene expression of TNF-alfa and CRP titer together with increased atherosclerosis as expressed by increased cIMT.

The relationship of serum cortisol levels with depression, cognitive function and sleep disorders in chronic kidney disease and hemodialysis patients.

In the present study, the relationships between cortisol, cognitive function, depressive behavior, and sleep quality in chronic kidney disease (CKD) and hemodialysis (HD) patients was investigated. Patients underwent history taking, physical examination, biochemical analysis, 24-h urine collection (for CKD patients only), measurement of dialysis adequacy (for HD patients only), evaluation of cognitive function, depressive behavior and sleep quality. Among study participants 58 had creatinine clearance ≥60 mL/min/1.73 m(2) (Group 1), 41 had creatinine clearance between 30 and 59 mL/min/1.73 m(2) (Group 2), 25 had creatinine clearance between 15 and 29 mL/min/1.73 m(2) (Group 3) and 12 had creatinine clearance <15 mL/min/1.73 m(2) (Group 4). 38 patients were regular HD patients (Group 5). The cortisol levels in Group 1, 2, 3, 4 and 5 patients were 472.3 ± 138.4, 490.2 ± 214.3, 541.6 ± 172.8, 569.9 ± 101.0 and 637.8 ± 153.7 nmol/L, respectively (P < 0.0001 for trend). In both non-dialysis patient group and dialysis patients linear regression analysis showed that cortisol was independently related with Beck depression inventory (BDI) score (P: 0.013 and 0.001, respectively) but not with cognitive function and sleep quality. In conclusion serum cortisol levels were independently associated with depressive behavior both in CKD and HD patients but not with cognitive function and sleep quality.

Approaches to inverse-probability-of-treatment–weighted estimation with concurrent treatments

ObjectivesIn a setting with two concurrent treatments, inverse-probability-of-treatment weights can be used to estimate the joint treatment effects or the marginal effect of one treatment while taking the other to be a confounder. We explore these two approaches in a study of intravenous iron use in hemodialysis patients treated concurrently with epoetin alfa (EPO). Study Design and SettingWe linked US Renal Data System data with electronic health records (2004–2008) from a large dialysis provider. Using a retrospective cohort design with 776,203 records from 117,050 regular hemodialysis patients, we examined a composite outcome: mortality, myocardial infarction, or stroke. ResultsWith EPO as a joint treatment, inverse-probability-of-treatment weights were unstable, confidence intervals for treatment effects were wide, covariate balance was unsatisfactory, and the treatment and outcome models were sensitive to omission of the baseline EPO covariate. By handling EPO exposure as a confounder instead of a joint treatment, we derived stable weights and balanced treatment groups on measured covariates. ConclusionsIn settings with concurrent treatments, if only one treatment is of interest, then including the other in the treatment model as a confounder may result in more stable treatment effect estimates. Otherwise, extreme weights may necessitate additional analysis steps.

Impact of Hyperuricemia on Cardiovascular System in ESRD Patients

Background: Hyperuricemia was found to be associated with hypertension, coronary heart disease, metabolic syndrome and chronic kidney disease. However there are no specific data about the relationship of uric acid to cardiovascular disease and mortality in ESRD patients on chronic hemodialysis. So, we aimed to study the impact of hyperuricemia on cardiovascular system in chronic kidney disease and in ESRD patients on regular hemodialysis Patients and methods: This study included 100 patients in Ashmoun hospital, nephrology department. Patients were chosen and divided into two groups: Group A, 50cases with chronic kidney disease and Group B, 50cases of ESRD on regular hemodialysis. All cases were subjected to full clinical examination, measurement of eGFR, laboratory tests for blood urea, serum creatinine and serum uric acid and ECG. Results: Serum uric acid was significantly higher in dialysis group than CKD group (p 0.05). Conclusion: In cases of CKD uric acid is involved in the pathogenesis of renal failure and hypertension. In patients with ESRD, hyperuricemia is not a risk factor for the development of cardiac disease; but it shows reversed epidemiology and becomes a marker of good nutritious status. Further studies should be done on wider scales to evaluate the impact of hyperuricemia on cardiovascular system in hemodialysis patients.

Association of Ca×PO4 product with levels of serum C-reactive protein in regular hemodialysis patients.

Introduction: Numerous studies have attempted to identify risk factors for mortality and morbidity in maintenance hemodialysis patients. In this study we sought to examine the association of the levels of serum C-reactive protein (CRP) with value of Ca×PO4 product, in stable hemodialysis patients. Patients and Methods: Based on the severity of secondary hyperparathyroidism, patients being treated with oral active vitamin D3, calcium carbonate/Renagel tablets at various doses. Fasting serum 25-hydroxy vitamin D and intact serum parathormone and also serum blood urea nitrogen, CRP, calcium, phosphorus, alkaline phosphatase was measured. Results: A total of 41 patients, enrolled to the study. The mean patients’ age were 46(17.6) years. The value of serum CRP of patients was 8.6 (6.6) mg/l (median 6 mg/l). The value of Ca×PO4 product was 50.5(15.5) mg2/dl2 (median: 50 mg2/dl2). In this study, a significant inverse association between Ca×PO4 product and the age of the patients was seen. A significant positive correlation of logarithm of serum CRP with Ca×PO4 product was found. Conclusion: The result of this study, revealed the need to further attention to hyperphosphatemia in hemodialysis patients.

Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof-of-concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti-Xa activity during hemodialysis (HD) sessions using a new heparin-grafted HD membrane. In 45 stable HD patients, the use of a heparin-grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse-back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti-Xa activity by 50%. Dose reductions were achieved with both types of heparin (low-molecular-weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti-Xa activity at dialysis session end (low-molecular-weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti-Xa activity at the end of HD sessions was possible in stable HD patients using heparin-grafted membrane. HD patients who require low anti-Xa activity at the end of HD sessions might benefit from a heparin-grafted membrane to reduce bleeding risk and other heparin adverse events.

Correlation of new bone metabolic markers with conventional biomarkers in hemodialysis patients

New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients. One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study. Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH . Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay – with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes – were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean±SD) (5.22±1.57) and also in each of the PreD, HD, and Tx groups [(4.92±1.23), (4.91±1.35), and (5.79±1.94), respectively, vs the healthy children (2.74±2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.

Diabetics on hemodialysis in El-Minia Governorate, Upper Egypt: five-year study

The number of patients with end-stage renal disease (ESRD) due to diabetic nephropathy (DN) is increasing worldwide. In many countries, diabetes mellitus has become the most frequent cause of ESRD. The goal of this work is to critically evaluate the prevalence of DN among chronic regular hemodialysis (HD) patients in El-Minia Governorate, to evaluate changes over the course of 5 years, and to compare data of El-Minia Governorate with data from the United States and other countries, in an attempt to detect factors that might explain causes of the differences. Data of patients on HD enrolled in the annual registry of the causes of ESRD in El-Minia Governorate were evaluated during the period from 2004 to 2008 for prevalence of DN. ESRD related to diabetes was defined as people who were initiated on chronic regular HD with diabetes mellitus as the cause of ESRD. The prevalence of DN among HD patients increased from 5% in 2004 to 16% in 2008. The mean age was significantly higher than that of ESRD patients on HD due to other etiologies. Furthermore, DN was more prevalent in urban areas than rural areas. Diabetic nephropathy among HD patients in El-Minia Governorate is increasing but is less prevalent than in the United States and other Western countries, probably because of a higher incidence of other causes of ESRD in El-Minia governorate, or because of premature death of diabetic patients. Therefore, meticulous management of diabetic patients is mandatory.

Cardiovascular Autonomic Neuropathy Studied by a Laser-Doppler Blood Flowmeter in Hemodialysis Patients

Orthostatic hypotension during a hemodialysis (HD) session affects not only the modality but daily quality of life for HD patients because many of them have combined dysfunction of both sympathetic and parasympathetic nervous systems. Although various non-invasive methods have been applied for the evaluation of autonomic function, no monitor has been devised for measuring the dysfunction during blood purification therapy. We evaluated the usefulness of laser-Doppler blood flowmeter (LDF) for measuring autonomic function of stable 34 regular HD patients and 24 healthy controls. The LDF device was applied for autonomic test by measuring periflux blood flow decreasing velocity (PDV) accompanied with Valsalva maneuver. We also evaluated the correlation between PDV and conventional tests for atherosclerosis. The average PDV (3.79±1.77) in HD population level was significantly lower than that of healthy controls (8.72±6.00). We also found a significant correlation between PDV and conventional methods such as heart rate variability and ankle-brachial blood pressure index. Measurement of PDV by LDF is as useful as a conventional method for evaluating autonomic function in HD patients. The convenience of the device offers the benefit of daily and frequent measurement of autonomic dysfunction.

Cross‐sectional audit of blood lead levels in regular outpatient haemodialysis patients dialysing in north London

Blood lead was measured and found to be high in one haemodialysis patient with atypical abdominal pain and peripheral neuropathy. This prompted an audit of blood lead concentrations in prevalent haemodialysis patients under the care of a University Teaching hospital. Blood lead was determined in 271 prevalent adult haemodialysis patients regularly dialysing three times a week, in five dialysis centres and/or on the home dialysis programme. All samples were carefully collected into lead-free plastic containers, and measured by graphite furnace atomic absorption spectrometry. 25.5% of haemodialysis patients had abnormal blood lead concentrations (>200 microg/L), compared with 59% with high-normal values of 100-200 microg/L, and only 15.5% with normal values (<100 microg/L). Blood lead increased with haemodialysis vintage (r = 0.38, P < 0.001), the use of a single carbon filter and reverse osmosis water purification device unit (r = 0.29, P < 0.001), but reduced by urine output (r = -0.44, P < 0.001). Despite UK government legislation to reduce permissible lead contamination of drinking water, blood lead was increased in 84.5% of prevalent haemodialysis patients. Single reverse osmosis machines and carbon filters may not be as effective at filtering out possible lead contamination compared with large industrial reverse osmosis devices and carbon filters, and thus blood lead testing should be considered for home haemodialysis patients, particularly in those areas where monochloramines are used to sterilize domestic water supplies.

β 2-Microglobulin and Phosphate Clearances Using a Wearable Artificial Kidney: A Pilot Study

Additional small-solute clearances during standard thrice-weekly hemodialysis treatments have not improved patient survival. However, these treatments have limited middle-molecule clearances. Thus, newer therapies designed to increase middle-molecule clearances need to be developed and evaluated. Pilot clinical trial to measure beta(2)-microglobulin and phosphate clearances with a wearable hemodialysis device. 8 regular hemodialysis patients under the care of a university teaching hospital. Patients were fitted with a wearable hemodialysis device for 4 to 8 hours. All patients tolerated the treatment. Average amount of beta(2)-microglobulin removed was 99.8 +/- 63.1 mg, with mean clearance of 11.3 +/- 2.3 mL/min, and an average of 445.2 +/- 326 mg of phosphate was removed, with mean plasma phosphate clearance of 21.7 +/- 4.5 mL/min. These clearances compared favorably with mean urea and creatinine plasma clearances (21.8 +/- 1.6 and 20.0 +/- 0.8 mL/min, respectively). Proof-of-concept preliminary trial. Additional studies are warranted to confirm these positive preliminary data. This wearable artificial kidney potentially provides effective beta(2)-microglobulin and phosphate clearances and, by analogy, middle-molecule clearances.

Effect of hemodialysis procedure in prohepcidin serum levels in regular hemodialysis patients

Effect of hemodialysis procedure in prohepcidin serum levels in regular hemodialysis patients

Clinical Study of Cinacalcet in Japan

For the approval of cinacalcet hydrochloride, five clinical trials have been performed excluding pharmacokinetic studies for healthy volunteers and hemodialysis patients. An early phase II dose-finding study was started for regular hemodialysis patients with secondary hyperparathyroidism from a daily dose of 12.5 mg cinacalcet and increasing 25 mg up to 50 mg for 9 weeks. A placebo-controlled double-blind three dose-finding study (late phase II study) was then conducted. By this trial, an adequate initial dose of cinacalcet was determined as 25 mg daily, and the placebo-controlled double-blind study (phase III study) was started using this initial dose. Two long-term (1 year) phase III open trials were also conducted during and after these phase II and III studies. The results of two double-blind trials (phase II and phase III) and safety profiles of cinacalcet in all Japanese clinical trials for approval are summarized in this article.

Association of Prohepcidin and Hepcidin-25 with Erythropoietin Response and Ferritin in Hemodialysis Patients

Hepcidin is a key regulator of iron metabolism. In this study, we examined whether measurement of hepcidin is useful in assessing recombinant human erythropoietin (rHuEPO) responsiveness in regular hemodialysis (HD) patients in a cross-sectional fashion. We examined the association between serum prohepcidin, a prohormone of hepcidin, and rHuEPO dosage and the rHuEPO/hemoglobin (Hb) ratio in 75 HD patients. We also semiquantatively measured the peak intensity of serum hepcidin-25, the major form of mature hepcidin, in 24 HD patients by using surface-enhanced laser desorption ionization time of flight time mass spectrometry, and compared those between rHuEPO-hyporesponsive (rHuEPO 192 ± 10 [126–252] IU/kg/week, n = 15) and responsive patients (rHuEPO 40 ± 9 [0–81] U/kg/week, n = 9). A significant but weak relationship was found between serum prohepcidin and rHuEPO dosage (r = 0.24, p < 0.05) and rHuEPO/Hb ratio (r = 0.22, p = 0.06). However, prohepcidin did not become an indicator of hematopoietic parameters by multiple regression analysis. Serum hepcidin-25 intensity was significantly and positively correlated with ferritin (r = 0.51, p < 0.01) but not with log-transformed C-reactive protein. There was no difference in the intensities of serum hepcidin-25 between rHuEPO-hyporesponsive and responsive patients (64 ± 10 vs. 52 ± 16 AU, p = NS). It follows from these findings that the assessment of serum hepcidin using currently available assays was not valid in predicting rHuEPO responsiveness in chronic HD patients.

Dialyzable Uremic Solutes Contribute to Enhanced Oxidation of Serum Albumin in Regular Hemodialysis Patients

Background: Oxidative stress (OS) is reportedly enhanced in patients receiving regular hemodialysis (HD). However, the in vivo redox state of HD patients, particularly after HD sessions, remains unclear. This study aimed to clarify the influence of HD on OS using the albumin redox state as a marker. Method: Blood samples of 8 regular HD patients were obtained during the course of study. The redox state of albumin was determined using high-performance liquid chromatography. Results: The mean fraction of reversibly oxidized albumin [f(HNA-1)] declined significantly over the course of the session and reached a minimum 4 h after the session had ended (pre-HD, 36.16 ± 7.50%; 4 h after HD, 25.71 ± 6.41%), then gradually rose to predialytic levels. The proportion of irreversibly oxidized albumin did not change significantly over time. Positive correlations were demonstrated between f(HNA-1) and uremic small solutes in each case. Conclusion: Accumulation of dialyzable uremic solutes may contribute to OS in HD patients.

Rosiglitazone in Diabetes Control in Hemodialysis Patients With and Without Viral Hepatitis Infection

Thiazolidinedione (TZD) may provide an additional benefit of cardiovascular protection in diabetic patients through targeting of insulin resistance. However, use of a TZD is hampered by possible effects of fluid retention and hepatotoxicity. In this study we aimed to determine whether the risk of TZD-induced fluid retention or hepatic injury is higher in hemodialysis patients with persistent viral hepatitis infection. This was a prospective, cohort study on hemodialysis patients. Type 2 diabetic patients with A1C levels of >8% were followed for at least 12 months. Rosiglitazone was initiated at 2-4 mg/day. The primary outcome was the target A1C (<7%) achieved and dosages of rosiglitazone. Secondary outcomes included changes in lipid profile and inflammatory biomarkers. Safety evaluations were number of hypoglycemic episodes, changes in liver transaminase levels, cardiothoracic ratio (CTR), fluid status control during dialysis, and events of symptomatic heart failure. A total of 78 patients, including 15.4% (n = 12) hepatitis B surface antigen-positive and 16.7% (n = 13) anti-hepatis C virus (HCV)-positive patients, were enrolled. The mean follow-up period was 15.4 +/- 3.8 months. The diabetic response rate (A1C <7%) to rosiglitazone was 86.1%. The serum triglyceride level was reduced (194 +/- 112.5 to 168 +/- 88 mg/dl, P = 0.037) more significantly than the total cholesterol level (178 +/- 42.1 to 174 +/- 46.5 mg/dl, P = 0.13). High-dose rosiglitazone (8 mg/day) reduced the serum level of C-reactive protein and increased the serum adiponectin level significantly. After rosiglitazone, interdialysis weight gain (2.07 +/- 1.6 to 3.2 +/- 1.2 kg, P < 0.01) and mean CTR (48.2 +/- 5.6 to 50.4 +/- 6.2%, P = 0.0213) of individuals increased significantly. Nevertheless, liver aminotransferase (aspartate aminotransferase and alanine aminotransferase) levels did not show a tendency to increase in patients (n = 25) with viral hepatitis B or C infections. Among regular hemodialysis patients with chronic viral hepatitis infections, rosiglitazone may be safely used for diabetes control. However, one must be aware that a possible effect of its use is a deterioration in cardiovascular reserve.

Audit of the Effect of Dialysate Sodium Concentration on Inter-Dialytic Weight Gains and Blood Pressure Control in Chronic Haemodialysis Patients

Background/Aims: Over the last three decades the standard dialysate sodium concentration has increased from 136 to 140 mmol/l (mEq/l) today. There has been great debate as to whether a reduction in dialysate sodium alone can lead to improved blood pressure control, and reduced inter-dialytic weight gain. Methods: An audit was performed in 469 maintenance regular haemodialysis patients who dialysed in seven different centres under the care of one university medical school. Results: Those centres which predominantly used a dialysate sodium of 140 mmol/l (mEq/l) had increased inter-dialytic weight gains, with more difficult blood pressure control, as not only did a greater percentage of patients require anti-hypertensive medication, but also more were prescribed multiple classes of anti-hypertensive agents. There was no difference in the frequency of symptomatic intra-dialytic hypotension. Conclusions: A reduction in dialysate sodium was associated with lower inter-dialytic weight gains, without any additional intra-dialytic hypotensive episodes. Those patients in whom the difference between the time-averaged dialysate sodium concentration and the midweek pre-dialysis serum sodium was positive result had increased inter-dialytic weight gains, compared to those with a negative value. Reduced dialysate sodium alone was not effective in controlling blood pressure without additional proper dietary sodium restriction.

Platelet count and mean volume (MPV) in association with plasma HCO3- in regular hemodialysis patients

End-stage renal failure often is associated with abnormal bleeding that may represent an important complication of this disorder. The hemorrhagic tendency currently is attributed to altered primary hemostasis, mainly platelet dysfunction. The aim of the present study was to elucidate whether and how in patients, with uremia on hemodialysis, the level of plasma HCO3- affects the mean PLT volume (MPV) and count. The total patients were 36 (f=15, m=21). The mean patients' age was 46 (±16) years. The mean length of the time patients had received hemodialysis was 32 (±36) months. The mean PLT count was 165 (±70) [x10³mu/L]. The mean MPV was 9 (±1) fl. The mean plasma HCO3- was 20 (±2.6) mEq/L. In this study a significant inverse correlation of PLT count with MPV and a significant positive association of PLT count with plasma HCO3 and also a significant inverse correlation of MPV with plasma HCO3- were found. Positive association of mild relative acidemia with PLT count and its negative correlation with MPV may further support the reverse epidemiology of serum bicarbonate in end-stage renal disease patients on hemodialysis which needs more attention as a protective role in mild relative acidosis of regular hemodialysis patients.