Plasma vitamin C levels in ESRD patients and occurrence of hypochromic erythrocytes

Introduction: The achievement of erythropoiesis in hemodialysis (HD) patients is typically managed with erythropoiesis‐stimulating‐agents (ESA's) and intravenous iron (IV‐iron). Using this treatment strategy, HD patients frequently show an elevated fraction of red blood cells (RBC) with hemoglobin (Hb) content per cell that is below the normal range, called hypochromic RBC. The low Hb content per RBC is the result of the clinical challenge of providing sufficient iron content to the bone marrow during erythropoiesis. Vitamin C supplements have been used to increase Hb levels in HD patients with refractory anemia, which supports the hypothesis that vitamin C mobilizes iron needed for Hb synthesis. Methods: We conducted a cross‐sectional survey in 149 prevalent HD patients of the percent hypochromic RBC, defined as RBC with Hb < 300 ng/uL of packed RBC, in relation to plasma vitamin C levels. We also measured high‐sensitivity CRP, (hs‐CRP), iron, and ferritin levels. and calculated ESA dose. Findings: High plasma levels of vitamin C were negatively associated with hypochromic RBC (P < 0.003), and high ESA doses were positively associated (P < 0.001). There was no significant association of hs‐CRP with percent hypochromic RBC. Discussion: This finding supports the hypothesis that vitamin C mobilizes iron stores, improves iron delivery to the bone marrow, and increase the fraction of RBC with normal Hb content. Further research is warranted on development of protocols for safe and effective use of supplemental vitamin C for management of renal anemia.     

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.     

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.     

Oxidized low‐density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: Influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene

Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low‐density lipoprotein (ox‐LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox‐LDL and adiponectin were measured using enzyme‐linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox‐LDL/low‐density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A‐I, apo B, ox‐LDL, and TC/high‐density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox‐LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).     

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

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

Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in End‐Stage Renal Disease Patients

In addition to disorders in lipoprotein metabolism, several other factors are involved in the development of atherosclerotic changes in end‐stage renal disease (ESRD) patients. One of these is arterial hypertension. We evaluated serum lipids—total cholesterol (TC), triglycerides (TG), apolipoproteins (A_I , A _II , B, E), lipoprotein(a) [Lp(a)]—in 109 ESRD patients on dialysis [46 on hemodialysis (HD); 63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic patients without renal failure (HL group). Dialysis patients were divided in two groups. Group A included 42 hypertensive patients (mean age: 62.3 ± 15.5 years) whose blood pressure (BP) was satisfactorily controlled with anti‐hypertensive medications. Group B included 67 non hypertensive patients (mean age: 66.6 ± 11.9 years). Levels of Lp(a) were significantly higher in both the HD (p = 0.001) and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a) levels were significantly higher in the hypertensive patients; this difference was not observed among non renal failure patients. These results indicate that arterial hypertension is associated with elevated Lp(a) serum levels in ESRD patients undergoing either HD or CAPD.     

Effects of hemodialysis on ventricular activation time in children with end‐stage renal disease

Patients with end‐stage renal disease are affected by cardiovascular complications, including disturbances of the heart intraventricular conduction. Body surface potential mapping is a non‐invasive electrocardiographic detection method of initial disturbances in heart activation propagation. A goal of the study was to analyze the effects of single hemodialysis (HD) session on ventricular activation time (VAT) maps obtained from hemodialyzed children. The study group consisted of 13 hemodialyzed children (age: 6–18 years). The control group is composed of 26 healthy subjects. In each HD patient, 12‐lead electrocardiogram and echocardiography examinations were performed. Isochrone heart maps, reflecting body surface distribution of VAT isolines, were recorded from an 87‐electrode HPM‐7100 system for body surface potential mapping, before (group B) and after HD session (group A). The distribution of isochrones and VAT values, as recorded in the HD patients, differed significantly from the reference VAT map for controls. The highest VAT maximal value was noted in group B (Me: 110 vs. 62 ms in the control group; P < 0.001), becoming significantly lower after HD session (Me: 98 ms for group A vs. 110 ms for group B; P < 0.001). Ventricular activation time maps, recorded before HD session, showed significant VAT delays with isochrone arrangement specific for the left bundle branch block. After HD session, VAT maps presented significant changes, suggesting a normalization process. Ventricular activation time maps in children with end‐stage renal disease exhibited disturbances of intraventricular conduction within the left bundle branch block, undetectable on standard electrocardiogram. A single HD session resulted in VAT map improvement related to overall HD treatment duration.     

Prevalence of hypothyroidism and thyroid nodule in chronic hemodialysis Iranian patients

Introduction: End stage renal disease (ESRD) reasons several changes in the function of thyroid gland as; lower levels of thyroid hormones, altered hormone metabolism, and increased iodine storage. The aim of this study was to evaluate the prevalence of nodular goiter and hypothyroidism in hemodialysis (HD) patients compared with normal population. Methods: This cross‐sectional study was conducted among HD patients and healthy people as the control group for thyroid function evaluation. Thyroid gland was evaluated by physical examination and ultrasonography. Blood level of FT3, FT4, TSH, TPO Ab, and urinary iodine excretion were checked in both groups. Data were analyzed using SPSS‐17 and P‐value less than 0.05 was considered as the significance level. Findings: Eighty six HD patients (57.2 ± 17.2 mean age, 48 men) and 86 healthy people (56.6 ± 16.8 mean age, 48 men) were enrolled in this study. Goiter was confirmed by physical examination in 29.0% of the HD patients and 12.8% of the control group (P = 0.04). Nodular goiter that was shown by ultrasonography was found in 27.9% and 3.5% of the HD and control groups, respectively (P = 0.01). HD patients had a higher frequency of reduced FT3 (40.9% vs. 4.6%, P < 0.01) and increased TSH (18.6% vs. 8.1%, P < 0.03(. TPO Ab was positive in 15.1% of the HD and 11.6% of the control groups (P = 0.14). Discussion: The high incidence of nodular goiter and hypothyroidism in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests, should be considered in evaluations of ESRD patients.     

Platelet‐to‐lymphocyte ratio better predicts inflammation than neutrophil‐to‐lymphocyte ratio in end‐stage renal disease patients

Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end‐stage renal disease (ESRD) patients. Recently, platelet‐to‐lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross‐sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C‐reactive protein, TNF‐α, IL‐6 levels were measured. PLR, NLR, serum high sensitive C‐reactive protein, IL‐6, and TNF‐α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL‐6, and TNF‐α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL‐6, and TNF‐α in this population. When we compared the association of PLR and NLR with IL‐6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF‐α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.     

Effects of enoxaparin on myeloperoxidase release during hemodialysis

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin‐binding protein. We studied if low‐molecular‐weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin‐grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin‐anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6‐fold at 10 minutes and 3.3‐fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin‐free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose‐dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.     

Effect of a hydrogen (H2)‐enriched solution on the albumin redox of hemodialysis patients

Elevated oxidative stress (OS) is associated with severe cardiovascular disease and premature death among patients treated with hemodialysis (HD). Oxidative stress is enhanced by contact between blood and dialysis membranes during HD sessions. This study aimed to clarify whether hydrogen (H₂), which is a known antioxidant, is capable of suppressing increased OS induced during HD sessions. Eight patients on regular HD treatment were studied. Two HD sessions were performed in a cross‐over design trial using standard and hydrogen‐enriched solutions (mean of 50 p.p.b. H₂; H₂‐HD). Blood samples were obtained from the inlet and outlet of the dialyzer during HD to determine changes in plasma levels of glutathione, hydrogen peroxide, and albumin redox state as a marker of OS. Comparison of inlet and outlet blood revealed significant decreases in total glutathione and reduced glutathione, as well as significant increases in hydrogen peroxide in both HD treatments. However, the mean proportion of reversibly oxidized albumin in outlet serum was significantly lower than that in inlet serum following the H₂‐HD session, whereas no significant changes were found in the standard solution session, suggesting that “intra‐dialyzer” OS is reduced by H₂‐HD. In conclusion, the application of H₂‐enriched solutions could ameliorate OS during HD.     

Effects of silymarin on biochemical and oxidative stress markers in end‐stage renal disease patients undergoing peritoneal dialysis

Introduction End‐stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies. Methods To evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8‐iso‐prostaglandin F_2α were measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment. Findings Ferric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration. Discussion It is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications.     

Outcomes of patients with end‐stage renal disease (ESRD) under chronic hemodialysis requiring continuous renal replacement therapy (CRRT) and patients without ESRD in acute kidney injury requiring CRRT: A single‐center study

In most continuous renal replacement therapy (CRRT) studies, end‐stage renal disease (ESRD) patients were excluded and the outcomes of patients with ESRD treated with chronic hemodialysis (HD) were unknown. The purposes of this study were to (1) evaluate short‐term patient survival and (2) compare the survival of conventional HD patients needing CRRT with the survival of non‐ ESRD patients in acute kidney injury (AKI) requiring CRRT. We evaluated adults (>18 years) requiring CRRT who were treated in the intensive care unit (ICU) at Kosin University Gospel Hospital from January 1, 2009 to December 31, 2010. A total of 100 (24 ESRD, 76 non‐ESRD) patients underwent CRRT during the study period. Patients were divided into two major groups: patients with ESRD requiring chronic dialysis and patients without ESRD (non‐ESRD) with AKI. We compared the survival of conventional HD patients requiring CRRT with the survival of non‐ ESRD patients in AKI requiring CRRT. For non‐ESRD patients, the 90‐day survival rate was 41.6%. For ESRD patients, the 90‐day survival rate was 55.3%. Multivariate Cox proportional hazards analyses demonstrated that conventional HD was not a significant predictor of mortality (hazard ratio [HR]: 0.334, 95% confidence interval [CI]: 0.063–1.763, P = 0.196), after adjustment for age, gender, presence of sepsis, APACHE score, use of vasoactive drugs, number of organ failures, ultrafiltration rate, and arterial pH. The survival rates of non‐ESRD and ESRD patients requiring CRRT did not differ; ESRD with conventional HD patients may be not a significant predictor of mortality.     

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.     

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.     

Pathophysiology and Treatment of Hyperhomocysteinemia in End‐Stage Renal Disease Patients

The pathophysiology of hyperhomocysteinemia in end‐stage renal disease (ESRD) patients includes impaired remethylation of homocysteine (Hcy) to methionine, inhibition of extrarenal Hcy metabolism by uremic solutes, a block in decarboxylation of cysteinesulfinic acid, impaired [adenosylmethionine]/[adenosylhomocysteine] ratio, and a probable impairment of renal Hcy metabolism and excretion. Treatment of hyperhomocysteinemia in ESRD patients includes administration of folic acid (1 – 15 mg per day). No additional effects have been observed with higher folic acid doses, folinic acid, or 5‐methyltetrahydrofolate. Oral supplementation with vitamin B ₆ and vitamin B ₁₂ has no effect, but some studies reported a decrease of plasma Hcy with high intravenous vitamin doses. Effective reduction of plasma total Hcy (tHcy) in patients treated with super‐flux hemodialyzers suggests the removal of uremic toxins with inhibitory activities against enzymes involved in the extrarenal Hcy metabolism.     

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.     

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.     

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.     

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

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