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Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial.
Sugiyama, M, Hazama, T, Nakano, K, Urae, K, Moriyama, T, Ariyoshi, T, Kurokawa, Y, Kodama, G, Wada, Y, Yano, J, et al
Nutrients. 2021;(6)
Abstract
L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.
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Sudden cardiac death in dialysis patients: different causes and management strategies.
Genovesi, S, Boriani, G, Covic, A, Vernooij, RWM, Combe, C, Burlacu, A, Davenport, A, Kanbay, M, Kirmizis, D, Schneditz, D, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2021;(3):396-405
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Abstract
Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.
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Efficacy of ferumoxytol versus sodium ferric gluconate in anemia management in outpatient hemodialysis patients: A prospective cohort study.
El Nekidy, WS, El-Masri, MM, Kadri, A, Soong, DC
Clinical nephrology. 2021;(4):189-194
Abstract
BACKGROUND Intravenous iron is one of the main therapies for anemia management in hemodialysis-dependent patients. Data comparing the efficacy of ferumoxytol versus other parenteral iron supplements are scarce. The objective of the study was to compare the efficacy of ferumoxytol with that of sodium ferric gluconate in outpatient hemodialysis patients. MATERIALS AND METHODS A prospective, observational study was conducted in outpatients receiving ferumoxytol 510 mg once or twice quarterly compared to sodium ferric gluconate 125 mg weekly in a single center hemodialysis center in Ontario, Canada. Patient demographics, hemoglobin levels, iron indices, iron doses, and erythropoiesis-stimulating agent (ESA) doses were collected. RESULTS The study sample consisted of 291 observations from 173 patients. Generalized estimating equations of multiple linear regression modeling were conducted to compare the outcomes while adjusting for baseline scores. Approximately 25% of the study participants received ferumoxytol while 75% received sodium ferric gluconate. Patients treated were mainly males (58.4%), and the mean age was 68.73 (SD ± 13.03) years. Both groups did not show significant differences in their hemoglobin levels (Wald z = 0.54; p = 0.46), ESA utilization at 3 months (Wald z = 0.20; p = 0.65), and TSAT levels (Wald z = 3.45; p = 0.06). However, the iron levels (Wald z = 4.24; p = 0.04) and ferritin levels (Wald z = 5.14; p = 0.02) were higher in the ferric gluconate group (Wald z = 58.78; p ≤ 0.001), and patients who received ferumoxytol received more blood transfusions as compared to those who received sodium ferric gluconate (χ2 = 16.71; p ≤ 0.001). CONCLUSION Both iron products maintained hemoglobin levels, but patients receiving ferumoxytol had lower iron indices and received more blood transfusions compared to patients who received sodium ferric gluconate.
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Continuous plasma exchange with dialysis for thrombotic microangiopathy in intensive care unit: Retrospective observational study.
Satoh, K, Okuyama, M, Irie, Y, Kameyama, K, Kitamura, T, Nakae, H
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(4):377-383
Abstract
Continuous plasma exchange with dialysis is a novel method of blood purification and is a modification of the plasma exchange. Technically, this process suggests a reduction in adverse events, cost-effectiveness, and compatibility with hemodynamic instability. The therapeutic effect of plasma exchange on thrombotic microangiopathies has been established. We present three clinical cases in the intensive care unit that illustrate continuous plasma exchange with dialysis as a flexible blood purification therapy for critically ill patients; a radical treatment, thrombotic microangiopathies; supportive therapy, multiple organ failure; and fluid balance regulator. The retrospective analysis of 13 continuous plasma exchange with dialysis sessions showed that the platelet count increased significantly (p = 0.0096) after its administration. The total protein, albumin, fibrinogen, or calcium did not decrease significantly after continuous plasma exchange with dialysis, suggesting therapeutic efficacy and fewer adverse events. A prospective study on thrombotic microangiopathies for continuous plasma exchange with dialysis is currently underway.
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Potential effective treatment of shortening continuous erythropoietin receptor activator treatment interval combined with iron supplementation in hemodialysis patients.
Kawai, Y, Toya, Y, Wakui, H, Fujikawa, T, Ueda, E, Azushima, K, Kinguchi, S, Mitsuhashi, H, Kawano, T, Kuji, T, et al
Journal of pharmacological sciences. 2021;(1):118-125
Abstract
Our previous randomized controlled trial comparing the total dose of weekly versus biweekly continuous erythropoietin receptor activator (CERA) therapy to maintain optimal hemoglobin (Hb) levels showed no significant differences between the two therapies. This post-hoc analysis assessed whether the total dose of weekly versus biweekly CERA therapy to maintain Hb levels among HD patients differed among groups with or without iron supplementation. Of 107 patients, 40 received intravenous iron supplementation due to iron deficiency (iron group) and 67 did not (non-iron group). In the iron group, the weekly therapy tended to require a lower total CERA dose compared with the biweekly therapy (274 ± 274 vs 381 ± 223 μg/12 weeks, P = 0.051). Changes in circulating hepcidin levels, a negative regulator of intestinal iron uptake, after 2 weeks of CERA treatment were significantly lower in the weekly therapy compared with the biweekly therapy (-4.2 ± 6.3 vs 11.1 ± 7.3 ng/mL, P = 0.015). In the non-iron group, there were no significant differences in total CERA dose or changes in hepcidin levels between the two therapies. Shortening the CERA treatment interval combined with iron supplementation may lead to the more efficient treatment of HD patients with iron deficiency.
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Improvement of clinical outcomes in dialysis: No convincing superiority in dialysis efficacy using hemodiafiltration vs high-flux hemodialysis.
Abdelsalam, M, Demerdash, TM, Assem, M, Awais, M, Shaheen, M, Sabri, A, Alanany, H, Kashgary, A, Alsuwaida, A
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(4):483-489
Abstract
Hemodiafiltration (HDF) is not associated with lower mortality risk compared to standard hemodialysis (HD). However, there are many critical clinical outcomes in dialysis patients in addition to mortality; the impact of HDF on these other outcomes is not clear. This retrospective study included all patients referred to DaVita Clinics in the Kingdom of Saudi Arabia. High-flux HD was the initial modality in all patients. Those who did not achieve adequacy targets or those with poorly controlled phosphorus were switched to postdilution HDF using 18 to 23 L exchange per treatment. Patients dialyzing with a central venous catheter, patients who dialyzed less than 90 days at DaVita, and those with interrupted HDF were excluded. Of the 1115 patients, 215 (19%) were on HDF and 900 on high-flux HD; the median follow-up was 6 months for all patients. The HDF group showed a significant reduction in serum phosphate (P < .001), a significant increase in serum calcium (P < .012) and a significant improvement in Kt/V (P < .0001). The HDF group had significantly higher hemoglobin levels than the HD group (P = .024), with a significant reduction in weekly erythropoiesis-stimulating agent dose after starting HDF (P < .001). A modified protocol that included prolonged dialysis duration, larger-sized dialyzer, faster blood flow rates, and adding hemofiltration fluid may be helpful in achieving the recommended targets. Thus, HDF can enable the achievement of adequate dialysis care in some patients. Randomized-controlled clinical trials are necessary to confirm these findings.
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Risk Factors Associated with All-Cause Death Among Dialysis Patients with Diabetes.
Grzywacz, A, Lubas, A, Smoszna, J, Niemczyk, S
Medical science monitor : international medical journal of experimental and clinical research. 2021;:e930152
Abstract
BACKGROUND Patients receiving dialysis who also have diabetes mellitus have high mortality. This study aimed to investigate the risk factors associated with all-cause death among Polish patients with diabetes receiving dialysis. MATERIAL AND METHODS This prospective observational study included 100 patients with type 1 or type 2 diabetes who were treated with peritoneal dialysis or hemodialysis. Blood laboratory tests, the occurrence of diabetes complications, and comorbidity, using the Charlson Comorbidity Index, were estimated. Survival analysis was performed using the multivariate Cox proportional hazard model, and Kaplan-Meyer survival analyses with log-rank tests were performed to show differences between groups. RESULTS During 16.0±5.0 months, 23 patients died. The deceased group had significantly higher levels of HbA1c (P=0.046) and fructosamine (P=0.011) than the surviving group. The deceased patients also had higher comorbidity scores (P=0.013). In the stepwise multivariate Cox proportional hazard regression model, history of stroke or transient ischemic attack was an independent risk factor of all-cause death (hazard ratio [HR] 3.15, 95% CI 1.34-7.39; P=0.009), while regular physical activity significantly reduced the risk of all-cause death (HR 0.26, 95% CI 0.08-0.87; P=0.029). CONCLUSIONS Deceased patients had higher HbA1c and fructosamine levels and higher comorbidity. However, history of stroke or transient ischemic attack was an independent risk factor of all-cause death, while regular physical activity was associated with the reduction of the risk of all-cause death in patients with type 1 and type 2 diabetes treated with peritoneal dialysis or hemodialysis. Regular physical activity should be recommended to improve survival in this population.
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Phase angle values, a good indicator of nutritional status, are associated with median value of hemoglobin rather than hemoglobin variability in hemodialysis patients.
Kim, DH, Oh, DJ
Renal failure. 2021;(1):327-334
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Abstract
BACKGROUND Our aim was to elucidate whether Hb variability affects nutritional status in HD patients. METHODS This study included chronic HD patients (n = 76) with available monthly Hb levels up to 24 months prior to the body composition monitoring (BCM) measurement. The parameters obtained in the BCM included body mass index (BMI), lean tissue index (LTI), fat tissue index (FTI), body cell mass index (BCMI), overhydration/extracellular water ratio (OH), and phase angle (PhA). The coefficient of variation (Hb-CV), standard deviation (Hb-SD), and range of Hb (Hb-RAN) were used as indexes of Hb variability. In addition, minimum (Hb-Min), maximum (Hb-Max), average (Hb-Avg), and median (Hb-Med) Hb levels (g/dL) were analyzed. RESULTS There were no significant differences in clinical, biochemical, and nutritional indexes based on the Hb-CV level. Compared to patients with an Hb-Med ≤ 10.77, those with an Hb-Med >10.77 had higher albumin levels, total iron-binding capacity (TIBC), and PhA and lower average weekly prescribed darbepoetin. Age, female sex, OH, and darbepoetin dosage were negatively correlated with PhA. Serum albumin, phosphorus, TIBC, Hb-Med, and Hb-Avg were positively correlated with PhA. In multiple linear regression analysis, PhA was positively associated with Hb-Med and serum albumin level, whereas PhA was negatively associated with age and female sex. The area under the curve (AUC) of Hb-Med was 0.665 (p = 0.040) in predicting PhA >5.00°. CONCLUSIONS PhA was not affected by indexes of Hb variability, whereas PhA was associated with Hb-Med in chronic HD patients.
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Effective glutamate clearance from the systemic circulation by hemodialysis: Potential relevance for cerebral ischemia management.
Martínez-Miguel, P, Albalate, M, Durán-Laforet, V, Peña-Martínez, C, de Sequera, P, Bouarich, H, Peña-Esparragoza, K, López-Ongil, S, Lizasoain, I, Sánchez-Prieto, J, et al
Artificial organs. 2021;(10):1183-1188
Abstract
High glutamate levels after head trauma or cerebral ischemia have neurotoxic effects. The objective of the present study was to evaluate the efficacy of hemodialysis to remove glutamate from the blood and to assess the behavior of this small molecule. Ten patients with end-renal disease on hemodialysis were included in the study. Glutamate clearance was evaluated within the first hour of hemodialysis on a midweek dialysis day on five patients who underwent low flux hemodialysis, whereas the other five patients underwent highly efficient hemodialysis (high flux hemodialysis on one day and online hemodiafiltration on another day). Glutamate clearance with hemodialysis was very effective and did not show any differences between the techniques (low flux: 214 [55], high flux: 204 [37], online hemodiafiltration: 202 [16], median (interquartile range), P = .7). Glutamate clearance was almost equivalent to vascular access plasma flow and it was not affected by dialyzer permeability or ultrafiltration rate. After a hemodialysis session, a significant decrease in glutamate blood level was observed (prehemodialysis: 59.7 [36.1], posthemodialysis 37.0 [49.2], P = .005). Dialysis performed under fasting condition showed higher glutamate reduction rate (60%) than that under feeding condition (20%). Hemodialysis may be an effective method to reduce glutamate blood levels, and the molecule clearance does not differ between the different techniques used. Considering previous results in experimental models, hemodialysis without hemodynamic stress, could be considered for reducing glutamate neurotoxic effects in acute ischemic strokes of patients in chronic hemodialysis programs.
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Modification and Validation of the Phosphate Removal Model: A Multicenter Study.
Zhang, W, Du, Q, Xiao, J, Bi, Z, Yu, C, Ye, Z, Wang, M, Chen, J
Kidney & blood pressure research. 2021;(1):53-62
Abstract
BACKGROUND Our research group has previously reported a noninvasive model that estimates phosphate removal within a 4-h hemodialysis (HD) treatment. The aim of this study was to modify the original model and validate the accuracy of the new model of phosphate removal for HD and hemodiafiltration (HDF) treatment. METHODS A total of 109 HD patients from 3 HD centers were enrolled. The actual phosphate removal amount was calculated using the area under the dialysate phosphate concentration time curve. Model modification was executed using second-order multivariable polynomial regression analysis to obtain a new parameter for dialyzer phosphate clearance. Bias, precision, and accuracy were measured in the internal and external validation to determine the performance of the modified model. RESULTS Mean age of the enrolled patients was 63 ± 12 years, and 67 (61.5%) were male. Phosphate removal was 19.06 ± 8.12 mmol and 17.38 ± 6.75 mmol in 4-h HD and HDF treatments, respectively, with no significant difference. The modified phosphate removal model was expressed as Tpo4 = 80.3 × C45 - 0.024 × age + 0.07 × weight + β × clearance - 8.14 (β = 6.231 × 10-3 × clearance - 1.886 × 10-5 × clearance2 - 0.467), where C45 was the phosphate concentration in the spent dialysate measured at the 45th minute of HD and clearance was the phosphate clearance of the dialyzer. Internal validation indicated that the new model was superior to the original model with a significantly smaller bias and higher accuracy. External validation showed that R2, bias, and accuracy were not significantly different than those of internal validation. CONCLUSIONS A new model was generated to quantify phosphate removal by 4-h HD and HDF with a dialyzer surface area of 1.3-1.8 m2. This modified model would contribute to the evaluation of phosphate balance and individualized therapy of hyperphosphatemia.