Erythropoietin Dose Research Articles

Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin – a multicentre, randomised, double-blind clinical trial

AimThe aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON).MethodsThis study is a multicentre, randomised,...

Adjuvant High Dose Erythropoietin with Delayed Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy

BackgroundTherapeutic hypothermia (TH) is the standard of treatment for moderate to severe HIE. However, half of asphyxiated babies have a disability despite undergoing hypothermia. Erythropoietin (EPO) is a potential neuroprotective agent. ObjectiveTo evaluate the benefits of high-dose EPO combined with TH on brain magnetic resonance imaging (MRI) scores and neurodevelopmental outcomes in neonates with moderate-to-severe HIE, especially in neonates who received TH between 6–12 h of birth. MethodsThis prospective, single-blinded, randomized, placebo-controlled trial enrolled term newborns with moderate to severe HIE admitted to neonatal ICU between April 2018 and April 2022. Hypothermia was started within 12 hours of age. Infants were randomized to receive EPO 1000 units/kg or an equal volume of normal saline (placebo) on days 1,2,3,5 and 7 of age in combination with hypothermia. ResultsFifty-seven neonates with moderate-to-severe HIE were recruited; ten were excluded. Forty-seven patients were included: 32 received TH within 6 hours (group I) and 15 TH was started within 6–12 h of birth (group II). The clinical characteristics of mothers, infants, maternal complications, and resuscitations performed during the perinatal period showed no statistical differences between EPO and placebo groups I and II. The MRI scores and brain injury patterns did not differ between the EPO and placebo groups. There is no statistical significance in either group's seizure and severe EEG background (initial and after rewarming) between EPO and placebo in each group. There were no differences in developmental outcomes (Abnormal Denver II >2 area, GMFCS >1), BSID-III score (cognitive, language, and motor), or disability (hearing impairment and impaired vision) between the EPO and placebo Groups I and II at 12 and 18 months. ConclusionsAmong term infants with moderate-to-severe HIE, TH with EPO administration, compared with TH alone, did not reduce brain injury on MRI or reduce the risk of neurological sequelae both in TH within 6 h and in patients who received TH late later (6–12 h). Further studies on the benefit of EPO injection alone or before TH in situations where TH cannot be performed are required.

A real-world analysis of roxadustat effectiveness and safety in managing renal anemia among patients on maintenance hemodialysis: An observational study.

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.

Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review.

Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy. To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy. An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords. We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328. Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group. Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.

Online Hemodiafiltration: A New Perspective for Patients With End-Stage Renal Disease.

Introduction Online hemodiafiltration (OL-HDF) is the most effective renal replacement therapy (RRT), which allows the enhanced removal of small and large uremic toxins by combining diffusion and convective transport of solutes. Although the goal of OL-HDF is to provide greater clearance of solutes with a preference for intermediate molecules responsible for many of the complications of chronic kidney disease (CKD), the studies reported to date and their meta-analyses are conflicting in nature and do not show a significant advantage of convective therapies on patient prognosis. Materials and methods At the Clinic of Nephrology and Dialysis, University Hospital "St. Marina", Varna, Bulgaria, 41 patients were monitored in a retrospective study for a two-year period, randomized into two groups, conducting OL-HDF after dilution and hemodialysis (HD) with the aim of studying the effect of convective therapies on the clinical outcome, the achieved quality of life, and the prognosis of the patient. Results The study found a significantly higher quality of life in patients undergoing OL-HDF with significantly higher values ​​of indicators of dialysis adequacy and nutritional status, better control of the anemic syndrome with the reduction of erythropoietin doses, significantly lower frequency of episodes of intradialytic hypotension with improved recovery, and 3.6-fold lower risk of death compared with conventional dialysis. Discussion Three major randomized controlled trials have compared survival outcomes in patients receiving HD or post-dilution OL-HDF, reporting conflicting results. Meta-analyses of the published studies have also been unable to provide a clear and definitive answer regarding the potential benefits of choosing one treatment over the other. Overall mortality, anemia, phosphate control, and small molecule clearance appear to be insufficiently influenced by the treatment method. On the other hand, cardiovascular mortality, hemodynamic stability, and clearance of middle and protein-bound molecules seem to be better in patients treated with OL-HDF. Conclusions Despite the conflicting data reported so far, OL-HDF is associated with better clinical outcome and prognosis for end-stage renal disease (ESRD) patient and undoubtedly warrants extensive future study with a view to improved quality of life in the growing dialysis population.

Artificial Intelligence Outcome Prediction in Neonates with Encephalopathy (AI-OPiNE).

Purpose To develop a deep learning algorithm to predict 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy using MRI and basic clinical data. Materials and Methods In this study, MRI data of term neonates with encephalopathy in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial (ClinicalTrials.gov: NCT02811263), who were enrolled from 17 institutions between January 25, 2017, and October 9, 2019, were retrospectively analyzed. The harmonized MRI protocol included T1-weighted, T2-weighted, and diffusion tensor imaging. Deep learning classifiers were trained to predict the primary outcome of the HEAL trial (death or any neurodevelopmental impairment at 2 years) using multisequence MRI and basic clinical variables, including sex and gestational age at birth. Model performance was evaluated on test sets comprising 10% of cases from 15 institutions (in-distribution test set, n = 41) and 10% of cases from two institutions (out-of-distribution test set, n = 41). Model performance in predicting additional secondary outcomes, including death alone, was also assessed. Results For the 414 neonates (mean gestational age, 39 weeks ± 1.4 [SD]; 232 male, 182 female), in the study cohort, 198 (48%) died or had any neurodevelopmental impairment at 2 years. The deep learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.74 (95% CI: 0.60, 0.86) and 63% accuracy in the in-distribution test set and an AUC of 0.77 (95% CI: 0.63, 0.90) and 78% accuracy in the out-of-distribution test set. Performance was similar or better for predicting secondary outcomes. Conclusion Deep learning analysis of neonatal brain MRI yielded high performance for predicting 2-year neurodevelopmental outcomes. Keywords: Convolutional Neural Network (CNN), Prognosis, Pediatrics, Brain, Brain Stem Clinical trial registration no. NCT02811263 Supplemental material is available for this article. © RSNA, 2024 See also commentary by Rafful and Reis Teixeira in this issue.

Pattern of Monthly Percentage of Hemodialysis Children Achieving the KDIGO Recommended Hemoglobin Targets: A Twelve-Month Prospective Study to Assess the Trend of Anemia

Abstract Background Anemia is one of the common problems in children on maintenance hemodialysis (HD). It leads to poor quality of life and when severe, it is associated with cardiovascular dysfunction, cardiomyopathy, and death. Proper treatment of anemia in these patients results in better physical and mental performance. So, our study aimed to assess the trend of anemia among HD children by following the monthly percentage of patients capable of achieving Hb level between 11-12g/dl. Methods For optimum treatment of anemia, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines (2012) recommended to measure Hb every month in HD children targeting monthly Hb concentration of 11-12 g/dl. So, we conducted this 12-months prospective study to assess the trend of anemia among HD children at Pediatric Dialysis Unit of Ain Shams University by following the monthly percentage of patients capable of achieving Hb level between 11-12g/dl. Results This study was done over 12 month-period from April 1st, 2020, till March 31st, 2021. A total of 78 patients were included with a mean age at the time of enrollment in the study of 12.16 ± 3.3 years. They were 45 (57.7%) males and 33 (42.3%) females. All patients were receiving 3 hours every other day HD session for 3 sessions a week with a HD duration range of 3.0 - 140.88 months and a median of 16.51 months. All patients were receiving proper doses of recombinant human erythropoietin (rHuEPO) and intravenous iron therapy. Our study showed that the monthly reported percentages of patients achieved Hb level between 11-12g/dl ranged from 14.7% to 40.8% and that of patients with Hb level &amp;lt;11g/dl ranged between 51.4 – 73.5%. It also revealed statistical evidence of significant association between the presence of anemia in our patients at the time of enrollment in the study and HD durations &amp;lt; 6 months (p &amp;lt; 0.05). Conclusion Despite proper HD treatment and proper doses of recombinant human erythropoietin (rHuEPO) and intravenous iron therapy, anemia is still a prevalent problem among our HD children.

Impact of a bundle of care (intravenous iron, erythropoietin and transfusion metabolic adjustment) on post-operative transfusion incidence in cardiac surgery: a single-centre, randomised, open-label, parallel-group controlled pilot trial

Red blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions. In this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20mg/kg intravenous ferric carboxymaltose if Hb<13g/dL the day before surgery or at ICU admission, and RBC transfusion if Hb≤8g/dL and ScvO2≤65%, or additional EPO dose if 8<Hb<13g/dL) or to the control group (RBC transfusion if Hb≤8g/dL, or, if 8<Hb<13g/dL, intravenous iron sucrose 200mg or 300mg according to weight). Primary outcome was the incidence of postoperative RBC transfusion up to hospital discharge or postoperative day 28. The trial is registered with ClinicalTrials.gov, NCT04141631. Between Jan 20, 2020, and Sept 6, 2022, among 128 patients enrolled, 123 (male, 54.4%, 67/123) were included in the full analysis set: 62 in the STOP group and 61 in the control group. Nine patients (14.5%, 9/62) in the STOP group required RBC transfusion vs 19 (31.2%, 19/61) in the control group (odds ratio 0.37 [95% CI: 0.15-0.91], p=0.03). The median length of follow up to transfusion was 2.6 days (1.5; 4.6) and 3.3 (1.6; 4.2) in control and STOP groups respectively (p=0.61). The bundle of care may reduce postoperative RBC transfusion. The findings should be taken with caution due to the unblinded and exploratory nature of the study. University of Montpellier Hospital and Vifor Pharma.

Changes of Dissociative Properties of Hemoglobin in Patients with Chronic Kidney Disease.

Background: The ability of hemoglobin to bind and dissociate oxygen is crucial in delivering oxygen to tissues and is influenced by a range of physiological states, compensatory mechanisms, and pathological conditions. This may be illustrated by the oxyhemoglobin dissociation curve (ODC). The key parameter for evaluating the oxygen affinity to hemoglobin is p50. The aim of this study was to evaluate the impact of hemodialysis on p50 in a group of patients with chronic kidney disease (CKD). An additional goal was to assess the correlation between p50 and the parameters of erythropoiesis, point-of-care testing (POCT), and other laboratory parameters. Methods: One hundred and eighty patients (106 male, 74 female), mean age 62.5 ± 17 years, with CKD stage G4 and G5 were enrolled in this cross-sectional study. Patients were divided into two groups, including 65 hemodialysis (HD) patients and 115 patients not receiving dialysis (non-HD). During the standard procedure of arteriovenous fistula creation, blood samples from the artery (A) and the vein (V) were taken for POCT. The causes of CKD, as well as demographic and comorbidity data, were obtained from medical records and direct interviews. Results: The weekly dose of erythropoietin was higher in HD patients than in non-HD patients (4914 ± 2253 UI vs. 403 ± 798 UI, p < 0.01), but hemoglobin levels did not differ between these groups. In the group of non-HD patients, more advanced metabolic acidosis (MA) was found, compared to the group with HD. In arterial and venosus blood samples, the non-HD group had significantly lower pH, pCO2 and HCO3-. This group had a higher proportion of individuals with MA with HCO3- < 22 mmol/L (42% vs. 24%, p < 0.01). The absolute difference of p50 in arterial and venous blood was determined using the formula Δp50 = (p50-A) - (p50-V). Δp50 was significantly higher in the HD group in comparison to non-HD (0.08 ± 2.05 mmHg vs. -0.66 ± 1.93 mmHg, p = 0,02). There was a negative correlation between pH and the p50 value in arterial (pH-A vs. p50-A, r = -0.56, p < 0.01) and venous blood (pH-V vs. p50-V, r = -0.45, p < 0.01). In non-HD patients, hemoglobin levels correlated negatively with p50 (r = -0.29, p < 0.01), whereas no significant relation was found in HD patients. Conclusions: The ODC in pre-dialysis CKD (non-HD) patients is shifted to the right due to MA, and this is an additional factor influencing erythropoiesis. Hemodialysis restores the natural differences in hemoglobin's dissociation characteristics in the arterial and venous circulation.

The Effect of Egg White Meal on Anemia in Patients on Hemodialysis Taking Erythropoietin and Iron Infusion.

Eggs are a useful and cheap food source. We evaluated the effects of egg white meal on anemia in dialysis patients. In an open-label, clinical trial, conducted in dialysis centers, 107 hemodialysis patients aged ≥18 years with hemoglobin levels below 12 g/dL and requiring treatment with artificial erythropoietin and iron infusion were included in the study. They were divided into a control and an intervention group. The participants in the intervention group consumed an egg white pack (containing six egg whites, 96 calories, 24 g protein) as a substitute for meat products 3 days a week for 8 weeks. Finally, changes in serum albumin, hemoglobin, ferritin and iron/TIBC, erythropoietin dose and iron infusion dose were measured. A total of 107 dialysis patients were studied, (55 patients in egg white and 52 in control groups) with the mean age of 54.31±16.35 years and male majority (57.90%). The mean of hemoglobin concentration had no statistically significant difference at baseline (P=0.13) and after four weeks. (P=0.48), while after eight weeks, the mean hemoglobin concentration in the intervention group was significantly higher than the control group. (P=0.03) mean of synthetic erythropoietin dose after 4 and 8 weeks was significantly lower in the intervention group compared to the control group. (P=0.30, P=0.001) lower ERI values in intervention group was significantly higher than the control group. (P=0.02) CONCLUSION: We observed that consumption of egg whites led to an increase in mean hemoglobin concentration, serum iron, and albumin levels. These results suggest that egg whites could be a useful dietary intervention for dialysis patients with anemia.

#1809 Twice against thrice-weekly hemodialysis: the TATH trial

Abstract Background and Aims Frequency of hemodialysis is still a debatable topic. Incremental hemodialysis has gained popularity and requires a smooth increase in dialysis frequency while maintaining a sufficient residual diuresis. In developing countries and some developed countries, a twice-weekly schedule independent of residual kidney function is still performed, sometimes because of lack of resources and some other times because of patients’ resistance to undergo three sessions per week. This study aimed to compare the survival of patients on twice versus thrice-weekly hemodialysis. Method This is a prospective, multicenter, non-randomized trial, that included incident patients on chronic hemodialysis between January 2018 and August 2021. Patients terminally ill were excluded. Patients were divided into two arms: twice-weekly and thrice-weekly hemodialysis. CASTOR eCRF (electronic case report form) was used for data capture. Demographics, comorbidities, laboratory tests, medications, residual diuresis and dialysis prescription were collected from the patients' medical records at dialysis initiation. Patients were followed at 1 month, 3 months, 6 months, one year and two years for their mortality, hospitalisations for pulmonary edema or hyperkalemia, uncontrolled severe hypertension and erythropoietin (EPO) dose requirement. This trial was terminated before reaching the required sample size of 800 because of the pandemic and economic crisis in the country. Missing baseline factors and covariates were imputed using multiple imputation algorithms, then entered in a logistic regression model to estimate propensity scores. A survival analysis with a cox-regression model including propensity score as a covariate assessed the difference between twice-weekly and thrice-weekly dialysis. This trial was registered on Clinicaltrials.gov ID NCT03415776. Results A total of 203 consecutive patients of 10 dialysis units were included, 133 in the thrice-weekly arm and 70 in the twice-weekly. Mean age was 67 ± 15 years, 54.2% were males, 55.5% had diabetes, 53.7% had coronary artery disease. Median eGFR at dialysis initiation was 6 (4, 8) mL/min/1.73 m2. Baseline median 24-hour diuresis was 500 (500, 1000) mL with higher diuresis in patients on twice-weekly (P = 0.051). Baseline mean hemoglobin was 9.6 ± 1.6 g/dL. 41.7% were initiated with AV fistula with more patients in the thrice-weekly initiated with temporary catheter. Median number of dialysis hours per week was 12 (10, 12) and 8 (8, 9) in thrice- and twice-weekly respectively. High-flux membranes with ultrapure dialysate were used in 55% of thrice-weekly and 74.3% of twice-weekly. Mean blood flow was 329 ± 76 mL/min. In univariate analysis, residual diuresis was significantly higher in twice-weekly at 1 month, 3 months (P = .002), 6 months (it dropped at 6 months to a median of 100 (0, 500) in thrice-weekly versus 225 (175, 875) in twice-weekly) and at one year (P = .015). Inter-dialytic weight gain and blood pressure levels were not statistically different at 1, 3, 6 months and one year. 22.5% of patients on thrice-weekly did not need antihypertensive medications at 6 months versus 12.1% in the twice-weekly. Serum potassium was significantly higher in twice-weekly at 3 months and at one year. Cumulative dose of EPO administered during 2 years was significantly higher in twice-weekly with a median of 720000 UI versus 500000 UI in thrice-weekly (P = .001) without a difference in hemoglobin but lower ferritin in twice-weekly (P = .005). There was no difference in hospitalisations' rates between the two arms. A cox regression model including propensity scores as a covariate did not show any survival difference between the two arms (Fig. 1). Conclusion Patients on twice-weekly hemodialysis had a similar survival and hospitalisations' rates at two years as patients on thrice-weekly hemodialysis. However, a twice-weekly schedule was accompanied with higher EPO dose requirements, higher serum potassium levels, more antihypertensive therapy despite more preserved residual diuresis.

#2243 The experience from the use of citric acid blood purification solution (CD) with l-ascorbic acid (Vitamin-C) in patients under HD

Abstract Background and Aims The use of CD offers anticoagulation with a reduced dose of heparin while the use of L-Ascorbic acid offers better management of the patients' anemia. The purpose of the study is to record the experience of using CD solution with Vitamin-C in patients with ESRD under HD Method 45 patients with ESRD under HD (40 new recruits) with an average weight of 75 kgrs received CD solution with vitamin-C (2 g/lt) for a period of 12 months. All changes in heparin dose as well as patients' anemia profile (Hb, Hct, ferritin, TSAT, rhEPO dose) were recorded. Results The initial cumulative heparin dose of 1818 ± 659.28 iu (24 iu/kgrBW) was progressively increased to 2677.41 ± 1053.15 iu (36 iu/kgrBW) at 6 months and to 3323.52 ± 1467.79 iu (44 iu /kgr/GB) at 12 months. With no observed thrombotic events or bleeding tendency, the dose of heparin used was significantly lower than the recommended doses with the classical solution (loading dose 30-50 IU/kgBW and then 10 IU/kgBW/hour). Patients' Hb and Hct progressively increased significantly (10.63 ± 1.55 start-11.79 ± 0.91 end, p &amp;lt; 0.05, 32.25 ± 4.45 start-36.5 ± 2, 92 end, p &amp;lt; 0.05) with constant weekly erythropoietin dose (14000 ± 9500 iu start-14000 ± 10000 iu end, p = NS) and stable ferritin levels (526.73 ± 498.72 iu start-690.44 ± 470.32 iu end, p = NS). The above observation was combined with a significant reduction in monthly iron administration (from 700 mg monthly initially to 200 mg monthly after one year). Conclusion Our findings suggest that the use of CD solution and vitamin C compared to the classic one offers anticoagulation with a significant reduction in the dose of heparin used, while simultaneously increasing hemoglobin with a fixed dose of erythropoietin and reduced iron administration.

#1174 Prevalence and factors contributing to erythropoietin hyporesponsiveness in CKD patients on hemodialysis: a single center, cross sectional study

Abstract Background and Aims Anemia, one of the most frequent early complications of CKD is associated with a reduced QOL, cardiovascular morbidity, accelerated CKD progression, and it is an independent predictor of mortality. The successful management of anemia is a vital part of patient care, that improves clinical outcomes. According to the literature, 90% of renal anemia patients responded in a dose-dependent manner to rHu EPO, whereas the remaining 5–10% of patients had either a blunted or absent response to this agent, despite high-dose therapy. Erythropoietin hyporesponsiveness is a strong, independent predictor of mortality risk. Various factors have been associated with ESA hypo responsiveness in different studies. Both the inability to achieve a target hemoglobin and administration of high dose epoetin -alpha are associated with increased risk of CVD complications. AIMS AND OBJECTIVES Method STUDY PERIOD: December 2021 to DECEMBER 2022 STUDY DESIGN: Observational cross sectional study. SAMPLE SIZE: N = 144: Patients older than 18 years old undergoing hemodialysis for at least 3 months before the study were enrolled. History of inpatient treatment, infection, bleeding or transfusion within the last month, hematologic disorders sickle cell disease, MDS and active malignancies were excluded. Required parameters were recorded on every month follow up;Demographic data, Cause of ESRD, Dialysis vintage, ESAs dose (Unit/week), type, Medications history; Dose (mg/week) of iron preparation &amp; use of medication like ACEi, ARBs, dialysis adequacy(Kt/V), haemogram, Liver function test, Kidney function test Iron profile, Serum parathyroid hormone, Serum calcium &amp; phosphorus, CRP, Anti EPO antibodies(if required). We used the European Best Practice Guideline (EBPG) II definition to define ESA hyporesponsiveness for our study purpose(Increase in erythropoietin dose ≥25% to maintain the same Hgb level or &amp;lt; 1 mg/dL gain in Hgb after 4 weeks. EHRI was calculated by dividing weekly ESA dose per kilogram of body weight (IU/Kg/W) by hemoglobin level (g/dL). Based on EHRI, patients were assigned or divided into 2 groups. Group I (EHRI&amp;lt;16) and Group II (EHRI ≥ 16). Patients in the Group II were labeled as erythropoietin hyporesponsive patients and they were compared with others in order to identify the impact of different factors on ESA. Results Among 144 patients, 80 were male and 64 females and 28.4% were diabetic. Mean EHRI were calculated for all patients and based on EHRI pts were divided into two study groups, Gr-I (EHRI&amp;lt;16) &amp; Gr-II(EHRI ≥16). EHRI ≥16 group was considered as ESA hyporesponsive groups. The study parameters were compared between the groups and its statistical significance measured. The overall prevalence of ESA hyporesponsive in our study was 26.3%. Conclusion The overall prevalence of ESA hyporesponsive in our study was 26.3%. Iron deficiency anemia, inadequate dialysis, chronic inflammation, malnutrition, secondary hyperparathyroidism and increased dialysis vintage were the factors associated with ESA hyporesponsiveness.

#460 Digital twin in hemodialysis model, with machine learning algorithms. Data from the Andalusian Hemodialysis Registry. SICATA

Abstract Background and Aims Orthodoxly, a digital twin is a computer simulation of an individual, “in silico”, and in real time. A digital twin can also be created with BIG DATA. The Objective It is the development of a survival digital twin model using Machine Learning algorithms using data from the Andalusian SICATA registry. Method The database was composed of 29,189 records at the time of analysis and contains variables in the areas of comorbidity, anemia, efficacy of renal replacement therapy (RRT), and renal bone disease. The algorithms used were: - XG Boost, AdaBoost, Cat boost. KNN, Random Forest, Decision Trees, Logistic Regression. A survival model was developed with each Machine Learning (ML) algorithm . The metrics of the models were taken into account: precision, calibration, accuracy. The software used was Orange based on Python and Rattle based on R. An explanation of the “black box” type models was carried out using SHAP (Shapley values) based on game theory. Results The characteristics that the digital twin that we have modeled with the greatest survival would have are: 1. Age equal to or less than 45 years, 2. Being included in the kidney transplant waiting list. 3. Longer duration of the hemodialysis session. 4. Low doses of Erythropoietin. 5. Normal or high serum albumin levels. 6. BMI &amp;gt; 21.The sample was stratified according to the Ultrafiltration (UF) ratio during the Hemodialysis session in ml/kg/hour. Group1: UF &amp;lt;4 ml/kg/hour. Group2: UF 5-9 ml/kg/hour. Group3: UF&amp;gt;9 ml/kg/hour. And a mortality study was carried out using multivariate Logistic Regression. We found that the OR for mortality in groups 2 and 3 was 17% and 24% in relation to group 1, which had the lowest mortality. Conclusion ML has revealed that the UF ratio (ml/kg/hour) is an important predictor variable of mortality. In our studio a UF ratio&amp;lt;4 ml/kg/hour is safe ML has found an answer to a question that we had not asked ourselves when beginning the study: What is the optimal UF rate in the hemodialysis session?

Comparison of the hemoglobin variability in non-chronic kidney disease or end-stage renal disease participants and patients with CKD and ESRD.

Hemoglobin (Hb) variability occurs frequently in hemodialysis (HD) patients during erythropoietin (EPO) therapy. Guidelines define a narrow target range for the anemia treatment in these patients that is difficult to adhere to in practice. Our aim was to evaluate whether the Hb variability in HD patients is higher compared to non-chronic kidney disease or end-stage renal disease (ESRD) participants and patients with CKD stage I or II. Monthly blood samples were assessed prospectively in 100 non-CKD or ESRD participants and 57 patients with CKD stage I or II, and retrospectively in 74 HD patients without changes in EPO or iron dose for 6 months. Variability was calculated and compared between the different groups. Hb variability was significantly higher in HD patients compared to the other groups, corresponding to results of previous studies. There were no significant differences between non-CKD or ESRD participants and patients with CKD stage I or II in terms of standard deviation (SD), residual SD, fluctuations across threshold, Hb cycling, and mean absolute change of Hb every 30 days (p>0.05), but a significant difference compared to HD patients (p<0.001). There were no significant differences between the groups in time in target and area under the curve (AUC) (p>0.05). Hb variability is a common phenomenon in all groups independently of the method used for assessment and even without EPO therapy. The target range is difficult to achieve for HD patients and should be reconsidered in the future to avoid unsettling both the patients and the staff.

Abstract 2771: Increased mtDNA copy number via EPOR signaling: A potential mechanism for metastatic dissemination in head and neck squamous cell carcinoma

Abstract Introduction: Head and Neck Squamous cell carcinoma (HNSCC) is characterized by high degree of invasion, locoregional metastasis, relapse which leads to overall poor prognosis. The molecular mechanism responsible for aggressiveness is poorly understood. A better understanding of molecular pathways involved shall precede the identification of newer diagnostic tools and therapeutic targets. We explored EPOR signaling pathway in Circulating tumor cells (CTCs) and HNSCC cell lines. Methods and Results: By using a validated in-house CTC isolation protocol, which addresses various drawbacks of currently available techniques and isolates CTCs suitable for various downstream molecular analysis, we isolated CTCs from HNSCC patients. The whole transcriptome analysis was performed from CTCs using ultra-low cell number RNA sequencing and corresponding primary tumors in 24 paired samples. We found a significant transcriptomic heterogeneity in CTCs, which are associated with overall disease outcome in HNSCC patients. To explore the plausible molecular pathways, we also identified 521 differentially expressed genes in CTCs with respect to primary tumors and various canonical pathways including oxidative phosphorylation, TCA cycle, cytokine-cytokine receptor interaction signaling, and ECM receptor interaction were enriched in CTC samples. Overexpression of erythropoietin receptor (EPOR) along with various genes encoded by mitochondrial genome and genes involved in maintenance of mtDNA in CTCs as compared to primary tumors was an important finding from our data. When analyzed in depth, there was a significant positive correlation between various genes involved in mtDNA maintenance (ABAT, NT5M) and encoded by mitochondrial genome (MT-ND1, MT-ND2, MT-ND4, MT-ND5, MT-ND6, MT-CO1, MT-CO2, MT-ATP6, MT-CYTB) with EPOR expression in our RNA seq data which is also substantiated by analyzing TCGA data. We confirmed these findings experimentally in HNSCC cell lines Cal 27 and FaDu. It was also observed that metastatic cell line FaDu has significantly higher mtDNA content as compared to non-metastatic cell line Cal 27, which was correlated with EPOR expression. Treatment with low dose Erythropoietin (0.1IU/mL) which a natural ligand for EPOR, enhanced mtDNA content in both the cell lines at low doses and boosted the metastatic capability while minimal effect on cell proliferation was observed. Conclusion: EPOR signaling might promote the metastatic ability of cancer cells and may act as a potential target for cancer dissemination and metastasis. Citation Format: Anshika Chauhan, Geeta S. Boora, Sahana Ghosh, Subrata K. Patra, Roshan K. Verma, Jaimanti Bakshi, Debajyoti Chatterjee, Radhika Srinivasan, Sushmita Ghoshal, Arindam Maitra, Arnab Pal. Increased mtDNA copy number via EPOR signaling: A potential mechanism for metastatic dissemination in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2771.

Living on High Altitudes Associated with Reduced Requirements of Exogenous Erythropoietin in Patients on Chronic Hemodialysis

Introduction: During the last decades the use of erythropoiesis stimulating agents has significantly diminished the prevalence of anemia in patients receiving chronic hemodialysis. Currently, residing at higher altitudes is associated with higher levels of endogenous erythropoietin. Objective: This study aims to analyze how residing at higher altitudes influences the requirements of exogenous erythropoietin in patients receiving hemodialysis as renal replacement therapy. Methodology: Descriptive observational cross-section, including adult patients from three Ecuadorian centers, receiving chronic hemodialysis, between January and June 2020. Patients were classified into two groups regarding the altitude of residence: those living at low-lying regions (&lt;2000 masl, Santo Domingo de los Tsachilas and Tena) and those living at high altitude (&gt;2000 masl, Quito). Results: We included 580 patients, 45.5% in the high-altitude group and 54.5% at low-lying regions. Median exogenous erythropoietin dose was higher in low-lying regions (22000 international units) versus high altitude (17333.3 international units) (P=0.00003) and the proportion of patients without erythropoietin requirement was higher in high altitude (21.6%), compared to low regions (1.0%) (P&lt;0.01). The multivariate analysis associated residing in low regions (HR 58.9, P&lt;0.01), age (HR 0.98, P=0.03) and Kt/V (HR 38.5, P&lt;0.01) with higher exogenous erythropoietin requirements. Additionally, among patients who required erythropoietin, residing in lower altitudes was linked with a need for exogenous erythropoietin doses exceeding 15000 international units per week (HR 1.92, P=0.001). Conclusion: In Ecuadorian patients receiving hemodialysis, living at high altitude is associated with a reduced requirement of exogenous erythropoietin compared with those patients residing in low-lying regions.

Association of Dialysis Adequacy, Physical and Emotional Symptoms with Erythropoietin-stimulating agent Responsiveness in Iraqi Patients Undergoing Hemodialysis

Background: Erythropoietin (EPO)-deficient anemia occurs in patients with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are the standard treatment for CKD anemia, but patient responses vary. Hemodialysis patients are often anemic due to hypo erythropoiesis and their chronic inflammatory state. Inadequate dialysis is considered one of the factors that are linked to ESA hypo responsiveness. Dialysis patients may experience many symptoms that lower their quality of life. End stage renal disease (ESRD) symptoms are assessed using Dialysis Symptom Index (DSI). Objective: The current study was designed to measure the association between physical, and emotional symptoms and ESA responsiveness. Also, to determine how dialysis adequacy affects response level.Materials and Methods: The current study included 150 CKD anemic patients in a multicenter dialysis units. patients were examined for the response to Epoetin alfa (Eprex) after 12 weeks in this cross-sectional study. Clinical, demographic, and laboratory data were collected. The erythropoietin resistance index (ERI) evaluated the effect of erythropoietin dosage on hemoglobin levels. Dialysis adequacy (Kt/V) measured the efficacy of dialysis. The severity of symptoms was evaluated using the 30-question Dialysis Symptom Index (DSI). Results: 150 patients in all were enrolled, with a mean age of 51.6 ± 14.9 for the male patients. There was a significant difference in kt/v among study groups, mainly between hypo response and resistance groups (P-value &lt; 0.01). However, there was no statistically significant difference in the DSI mean (P = 0.4). kt/v was positively correlated with the duration of dialysis and parathyroid hormone (PTH) (R = 0.27, P-value &lt; 0.001), (R = 0.19, P-value = 0.01). additionally, The DSI was strongly connected with the age of the patients (R = 0.18, P-value = 0.02). Conclusion: One of the main causes of Eprex resistance in this study was insufficient dialysis. Patients who received longer hemodialysis sessions exhibited higher hemodialysis sufficiency. However, there was no significant association between DSI and degree of response across research groups, and older hemodialysis patients experienced higher dialysis-related symptoms.

Erythropoietin in Neonates with Perinatal Asphyxia Undergoing Therapeutic Hypothermia—A Prospective Cohort Study

Aims To assess the safety and feasibility of erythropoietin (EPO) in asphyxiated neonates undergoing therapeutic hypothermia (TH). Subjects and methods This study enrolled 60 neonates with HIE undergoing TH. 30 neonates were divided into EPO with TH group, where neonates received EPO (dose), at a dose rate of 1000 IU/kg/48 hours, for four doses and the remaining 30 neonates undergoing TH were into control group. Magnetic resonance imaging brain was undertaken between 10 and 14 days of life in surviving neonates. The Bayley Scales of Infant (BSI) Development IV was performed at regular intervals up to the age of 12 months. Results Amplitude-integrated electroencephalogram (aEEG) showed burst suppression (19% vs. 11%), low voltage (10% vs. 4%), and flat trace (7% vs. 3%) in control group in comparison with EPO concurrent with TH group which was statistically significant. Brain magnetic-resonance imaging (MRI) done at 12 days (±2 days) showed significant brain injury patterns such as severe brain injury (4% vs. 9% P = .05) and regional specific HIE (7% vs. 13%, P = .03) in control group of only TH neonates. At 12 months, neurodevelopment outcomes in EPO with TH group neonates showed a favorable outcome. Conclusion rhEPO concurrent with TH in HIE neonates resulted in significantly less severe brain injuries in MRI brain in HIE neonates. aEEG changes were less statistically significant in EPO with TH group with favorable neurodevelopmental outcomes at 12 months of age.

The Role of Zinc and Copper in Anemia and Erythropoietin Responsiveness in Patients on Hemodialysis and Peritoneal Dialysis

Introduction: Imbalance in copper (Cu) and zinc (Zn) homeostasis is a frequent finding in patients undergoing dialysis. These patients have higher serum Cu and lower serum Zn levels compared to controls. This study is designed to investigate the relationship between blood Cu and Zn levels and Cu/Zn ratio and, ESA (erythropoietin stimulating agent) dosage, erythropoietin responsiveness and anemia in dialysis patients. Methods: Clinical and demographic data for 151 participants (men=79) with a median dialysis vintage of 69.7 months [101 on Hemodialysis (HD), 50 on Peritoneal Dialysis (PD)] and mean age of 56.25±15.6 years was collected in November 2022. Zn and Cu levels were measured with atomic absorption. Erythropoietin responsiveness was evaluated by the erythropoietin resistance index (ERI) and ESA dosing. Results: In HD patients, mean serum Zn and Cu levels were 61.33 ± 15.77 μg/dL and 95.1 ± 21.1 µg/dL, respectively, with a Cu/Zn ratio of 1.58 ± 0.69. In PD patients, mean serum Zn and Cu levels were 54.8 ± 10.3 µg/dL and 97 ± 20.2 µg/dL, respectively, with a Cu/Zn ratio of 1.72 ± 0.55. In Spearman analyses serum Cu was negatively correlated with hemoglobin (p=0.018), serum iron (p=0.03), transferrin saturation (p=0.019), and iron supplementation (p &lt;0.01) in the HD patient group. Serum Cu was found to be positively correlated with erythropoietin (EPO) dosage (p=0.03), ERI (p=0.04), high sensitive C reactive protein (hsCRP) (p=0.01), and Kt/V (p=0.033). Cu/Zn ratio was positively correlated with EPO dosage (p=0.043), ERI (p=0.051) and hsCRP (p=0.015). Conversely, it was negatively correlated with iron supplementation (p=0.014) and serum albumin levels (p=0.049). Serum Zn levels was solely correlated with albumin level (p=0.039). In PD, patient’s serum Cu level was correlated positively with hsCRP (p=0.036); serum Zn levels correlated positively (p=0.01), and Cu/Zn ratio was correlated negatively with albumin (p=0.042). Conclusion: This study has shown a possible association between both serum Cu and Cu/Zn ratio, ESA dosage and hsCRP in HD patients.