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

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

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients

Clinical guidelines recommend concurrent treatment of anemia in end‐stage renal disease with erythropoiesis‐stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12‐month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4‐week interval for four consecutive intervals (k ? 2, k ? 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k ? 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k ? 2, k ? 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long‐term safety of iron use to improve Hb response to ESA warrants further study.     

Naturally nonanemic dialysis patients: Who are they?

Introduction Not only anemia, but also erythropoiesis stimulating agent (ESA)s for treating anemia may adversely affect prognosis of chronic hemodialysis patients. Various features of naturally (with no ESA usage) nonanemic patients may be useful for defining several factors in the pathogenesis of anemia. Methods Data, retrieved from the European Clinical Database (EuCliD)‐Turkey on naturally nonanemic prevalent chronic hemodialysis patients (n: 201) were compared with their anemic (those who required ESA treatment) counterparts (n: 3948). Findings Mean hemoglobin values were 13.5 ± 0.8 and 11.5 ± 0.9 g/dL in nonanemic and anemic patients, respectively (P < 0.001). Nonanemia status was associated with younger age, male gender, longer dialysis vintage, nondiabetic status, more frequent hepatitis‐C virus seropositivity and more frequent arteriovenous fistula usage. Serum ferritin and CRP levels and urea reduction ratio were higher in ESA‐requiring patients. One (99%) and two (95.3%) years survival rates of the “naturally nonanemic” patients were superior as compared to anemics (91.0% and 82.6%, respectively), (P < 0.001). Discussion “Naturally nonanemic” status is associated with better survival in prevalent chronic hemodialysis patients; underlying mechanisms in this favorable outcome should be investigated by randomized controlled trials including large number of patients.     

Inflammation,high ferritin,and erythropoietin resistance in indigenous maintenance hemodialysis patients from the Top End of Northern Australia

Use of erythropoiesis‐stimulating agents (ESAs) has improved the management of anemia in patients on maintenance hemodialysis (MHD). Iron deficiency and inflammation cause ESAs resistance and are both common among indigenous people of Northern Australia. As part of quality assurance in our Renal Anaemia Management program, we observed that there was use of higher doses of ESAs and adjuvant iron therapy in our MHD patients. This study aimed to explore the relationship among iron studies, inflammation, ESA responsiveness, and ESAs and iron requirements in indigenous patients on MHD from the Top End of Northern Australia. We performed a retrospective cohort analysis of anemia management in a cohort of our patients on MHD. We extracted data for 178 indigenous and 19 non‐indigenous patients from 1 March 2009 to 28 February 2010 from the Renal Anaemia Management database, which collects data prospectively in MHD patients. Ninety‐nine percent of the whole sample had a ferritin level above the international guidelines threshold of >500 µg/L. Indigenous patients had higher ferritin (1534 ± 245.5 µg/L vs. 1013 ± 323.3 µg/L, P = 0.002). C‐reactive protein (CRP) was high in 56.9% of the total cohort. One hundred percent of those with normal CRP had high ferritin (>500 µg/L). C‐reactive protein was higher in indigenous than in non‐indigenous patients. Erythropoiesis‐stimulating agents hyporesponsiveness was higher in indigenous patients (P < 0.0001). There was no significant difference in ESAs hyporesponsiveness among different levels of CRP (P = 0.116), ferritin (P = 0.408), and transferrin saturation (P = 0.503). Indigenous patients required higher total iron dose (2820.30 [2000–4350] vs. 2336.12 [1912–2900], P = 0.02). There was no significant relationship between the high ferritin and CRP. In indigenous dialysis patients, iron therapy and ESAs use are higher. The high iron use is due to a lack of published evidence to guide the administration of iron in patients with high ferritin. The high ferritin and ESAs resistance could not be fully explained by inflammation and need further evaluation. Further studies are required to determine the safe use of iron and management of ESAs resistance in our hemodialysis population.     

Hemochromatosis gene mutations and treatment of anemia in patients on hemodialysis

Hemochromatosis causes iron overload by enhanced intestinal absorption. This study examined erythropoietin and intravenous (IV) iron requirements in hemodialysis (HD) patients with HFE mutations. Patients on HD for >90 days with no cause of anemia except chronic kidney disease were tested for HFE mutations (H63D and C282Y). Intravenous iron and erythropoietin doses were adjusted to achieve recommended targets. Monthly hemoglobin (Hb), ferritin, mean corpuscular volume, mean cell hemoglobin, erythropoietin, and IV iron doses for 3 consecutive months were averaged. Of 172 patients, 71 (41.3%) had ≥1 HFE mutation: 24 (14%) C282Y heterozygotes, 40 (23.3%) H63D heterozygotes, 5 compound heterozygotes, and 2 homozygotes. Comparing patients with ≥1 HFE mutation to those without mutations showed no significant difference in Hb or serum ferritin. There was a trend toward lower median weekly erythropoietin dose in patients with ≥1 HFE mutation (94.0 vs. 135.4 U/kg body weight; P=0.13). There was no difference in median weekly IV iron dose (1.0 vs. 0.9 mg/kg body weight; P=0.56). Comparing the 30 patients with a C282Y mutation to patients without HFE mutations produced similar results. Comparing the 47 patients with an H63D mutation, with those without HFE mutations, no discernable trend was observed. In this study, patients with HFE gene mutations on HD for established renal failure do not require less iron supplementation to achieve recommended Hb targets. We observed a trend toward lower erythropoietin requirement in patients possessing C282Y mutations. Larger studies may clarify the role of HFE mutations, regulators of iron metabolism and erythropoiesis in chronic kidney disease.     

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

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

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Relationship between non‐alcoholic fatty liver disease and MIA syndrome

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

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.     

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross‐sectional, 1‐year,retrospective cohort study

Introduction This study aimed to evaluate the association between proton pump inhibitor (PPI) use and serum magnesium levels, and the role of hypomagnesemia and PPI use as a risk factor for mortality in hemodialysis patients. Methods An observational study, including a cross‐sectional and 1‐year retrospective cohort study. The study comprised 399 hemodialysis patients at a single center, and was conducted from January to September 2014. Multiple linear regression analysis was used to investigate the independent relationship between serum magnesium levels and baseline demographic and clinical variables, including PPI and histamine‐2 receptor antagonist use. Cox regression model was used to identify lower serum magnesium level and PPI as a predictor of 1‐year mortality. Findings Serum magnesium levels were lower with PPI use than non‐PPI use (2.39 ± 0.36 vs. 2.56 ± 0.39 mg/dL, P < 0.001). Multiple linear regression analysis showed that PPI use, low serum albumin levels, and low serum potassium and high‐sensitivity C‐reactive protein (hs‐CRP) levels were significantly associated with low serum magnesium levels. A total of 29 deaths occurred during the follow‐up period. According to Cox regression analysis stratified by hs‐CRP, only high serum hs‐CRP levels (>4.04 mg/L) in association with low serum magnesium levels was an independent risk factor for 1‐year mortality (hazard ratio: 2.92; 95% CI: 1.53–6.40, P < 0.001). Discussion Serum magnesium levels are lower in PPI use. In the inflammatory state, a low serum magnesium level is a significant predictor 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.     

Hemodialysis‐induced acute pancreatitis secondary to kinked hemodialysis blood lines

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

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.     

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.     

Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities

Inflammation and lipid abnormalities are two important risk factors for cardiovascular disease in hemodialysis (HD) patients. The present study was designed to investigate the effects of flaxseed consumption on systemic inflammation and serum lipid profile in HD patients with lipid abnormalities. This was an unblinded, randomized clinical trial. Thirty HD patients with dyslipidemia (triglyceride >200 mg/dL and/or high‐density lipoprotein‐cholesterol (HDL‐C) <40 mg/dL) were randomly assigned to either a flaxseed or control group. Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks, whereas patients in the control group received their usual diet, without any flaxseed. At baseline and at the end of week 8, 7 mL of blood was collected after a 12‐ to 14‐hour fast and serum concentrations of triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol (LDL‐C), HDL‐C, and C‐reactive protein (CRP) were measured. Serum concentrations of triglyceride (P < 0.01), total cholesterol (P < 0.01), LDL‐C (P < 0.01), and CRP (P < 0.05) decreased significantly in the flaxseed group at the end of week 8 compared with baseline, whereas serum HDL‐C showed a significant increase (P < 0.01). These changes in the flaxseed group were significant in comparison with the control group. The study indicates that flaxseed consumption improves lipid abnormalities and reduces systemic inflammation in HD patients with lipid abnormalities.     

Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis

Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hb<10.0 g/dL with rHuEPO 9000 U/wk or 15 U/kg/wk treatment) into 2 groups as follows: a TJ-48-treated group (TJ-48 group, 7.5 g/d, n=22) and a TJ-48 nontreated (control group, n=20). At the beginning of this study, there was no significant difference between the groups in age, sex, serum creatinine, blood urea nitrogen, serum iron, and ferritin. After 12 weeks of treatment, the Hb level had significantly increased from 8.4 +/- 1.1 to 9.5 +/- 1.3 g/dL (P=0.0272) in the TJ-48 group. C-reactive protein (CRP) had significantly decreased from 1.4 +/- 1.7 to 0.6 +/- 0.8 mg/dL (P=0.0438). There was a significant negative correlation between Hb and CRP in the TJ-48 group (r(2)=0.121, P=0.0066). In contrast, in the control group, Hb and CRP showed no significant changes throughout this study. Nor was there a significant correlation between Hb and CRP in the control group. In conclusion, TJ-48 was effective in improving erythropoietin-resistant anemia in end-stage renal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.     

Costs of managing anemia with erythropoiesis‐stimulating agents during hemodialysis: A time and motion study

Use of erythropoiesis‐stimulating agents (ESAs) presents a significant time and cost burden in the management of anemia of chronic kidney disease (CKD). We conducted a prospective, observational, activity‐based costing study to estimate the health care personnel time and resulting direct medical costs associated with administering epoetin 3 times weekly to patients with end‐stage renal disease on dialysis. The study was conducted at 5 US hemodialysis centers. The personnel time and costs were derived from time and motion observations. Predicted time and cost savings were modeled for switching patients to once‐monthly ESA therapy. Patients also completed a survey questionnaire to assess their level of CKD knowledge and information needs. Total per‐patient‐per‐year (PPPY) time expended on anemia management with epoetin averaged 608 minutes (range 512–915 minutes), with an average PPPY cost of $548 (range $342–$651). Use of a once‐monthly ESA, compared with epoetin, could decrease average PPPY time expenditure by 79% (127 minutes [range 96–173 minutes]) and reduce PPPY costs by 81% ($104 [range $79–$136]). The patient questionnaire reported insufficient education on CKD. Use of a once‐monthly ESA to correct anemia in dialysis patients may provide substantial time, resource, and cost savings compared with current treatment practices.     

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.     

The level of C‐reactive protein in chronic hemodialysis patients: A comparative study between patients with noninfected catheters and arteriovenous fistula in two large Gulf hemodialysis centers

Hemodialysis (HD) patients have greater morbidity and mortality when they have a central venous catheter (CVC) rather than an arteriovenous fistula (AVF) access. Inflammation associated with dialysis catheter use and resultant higher C‐reactive protein (CRP) levels could have an independent adverse effect on patient outcomes. In this prospective study, we investigated whether HD catheters induce inflammation independent of infection. We compared the mean levels of the inflammatory marker (CRP) in 67 patients on maintenance HD using noninfected catheters with 86 HD patients using AVFs at Prince Salman Center for Kidney Diseases, Saudi Arabia (KSA), and Jahra Hospital, Kuwait, who met our inclusion criteria. C‐reactive protein levels were measured every 2 months over a period of 6 months using immunoturbidimetric assay. One hundred fifty‐three patients on maintenance HD for more than 6 months were included in the study, with mean age of 52.19 ± 16.06 years; 66% were males and 34% were females. Serial levels of mean CRP were statistically and significantly higher in group with noninfected catheters (1.33, 1.24, and 1.10 mg/dL) compared to those with AVFs (0.65, 0.59, and 0.68 mg/dL) with P value of 0.000. In our study, we found no relation between CRP level and age, sex, hemoglobin, albumin, calcium, phosphorus, and iPTH level in both groups. Hemodialysis patients with a catheter have a heightened state of inflammation independent of infection, and thus our study supports the avoidance of catheters and a timely conversion to AVFs with catheter removal.