Erythropoietin Resistance Index Research Articles

#2895 Erythropoietin Resistance Index (ERI) between mortality and metabolic changes in a cohort of hemodialysis patients. What acts below the surface?

Abstract Background and Aims The management of anemia in hemodialysis patients (HD-ps) is influenced by many factors, including inflammation, martial balance (MB) and mineral metabolism (MM). Recent data would identify the Erythropoietin Resistance Index (ERI) as an indicator of mortality risk in HD-ps. The objective of the present study was to evaluate the relationship of ERI with inflammation, MB and MM, as well as all-cause mortality in a cohort of HD-ps. Method An observational-retrospective study was performed on 100 HD-ps, excluding those with acute or chronic infections (3 months), neoplasia, or immunosuppressive therapy. Mortality was considered primary outcome along a 2-year follow-up (FU). Results HD-ps, predominantly males, had advanced mean age, good Hb values and fair biochemical control. ERI showed significant correlations with some elements of inflammation, MM and BM (Table 1), including c-terminal fragment of Fibroblast Growth Factor 23 (cFGF23). At multivariate, ERI remained influenced by cFGF23 (p = 0.009), iron (p = 0.002) and transferrin (p = 0.007). Furthermore, after 2 years of FU, 42% of HD-ps died. As shown in Table 2, HD-ps that faced the primary outcome (death) were older, had lower levels of albumin, hemoglobin and transferrin, and higher levels of IL6, parathormone (PTH), reactive C protein (PCR), and ERI (p < 0.035). In multivariate, ERI (p = 0.011), age (p = 0.001) and albumin (p = 0.010) remained significant for the outcome studied. Conclusion Our data, albeit on few HD-ps, show a possible association between ERI and mortality. ERI was found to be related to several factors, including cFGF23, itself a factor implicated in maintaining a baseline inflammatory state. The results suggest the possible presence of some pathological mechanisms that can act silently with a negative impact on survival. Certainly, increased numbers and a prospective design could better clarify the explored relationships in the future.

#1351 Assessment of safety and efficacy of expanded hemodialysis in comparison to HDF

Abstract Background and Aims In end-stage kidney disease, solutes with a wide spectrum of molecular weight, called uremic toxins, are retained due to impaired kidney cleansing capacity. Particularly, the retention of toxins in the middle molecular weight range 15–45 kDa might negatively affects multiple organ systems and metabolic pathways. The removal of such large uraemic toxins is still a challenge. HDF has produced some results although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium Cut-Off, high Retention Onset membrane have been recently developed introducing the concept therapy called “expanded haemodialysis” (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress. Method A prospective longitudinal single-center study was conducted for 3 months among 18 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Throughout the treatment, a proportional part of the dialysis fluid was collected to quantify albumin loss. Blood samples were taken before and after dialysis session in order to calculate the Removal Ratio and at two different intradialytic timepoints from arterial and venous line of the circuit in order to calculate instantaneous clearance. Results Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane (ANOVA, p<0.001) without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we didn't find differences in removal ratio. Reduction of Erythropoietin resistance index was observed in patients treated with ViE-X membrane but it was related to their lower dialysis vintage. Conclusion HDx with Theranova membrane was associated with higher albumin loss without any effect on pre-dialysis serum albumin. Moreover, patients treated Theranova membrane, in the presence lower Qb, lower convective dose and lower instantaneous clearance reached same dialysis efficacy compared to HDF.

Iron indices mediate but not modify association of parathyroid hormone with erythropoietin resistance in hemodialysis patients.

Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the cor-relations of iron indices, PTH and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. The average ERI value of 10.3 ± 5.3 IU w-1 kg-1 (g/dL) -1. ERI was linked to PTH, hepcidin, CHr and TSAT (all P<0.05). PTH was associated with ERI levels (β=0.007, 95%CI: 0.002-0.012, P=0.007). Hepcidin and PTH were closely correlated with each other (r = 0.28, P = 0.020). No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-fourth of the total association between PTH and ERI in hemodialysis population (25.71%, P=0.020). Iron indices and PTH levels were related to ERI values. Hepcidin ap-peared to be closely correlated to PTH and partly mediate the association between PTH and ERI in he-modialysis population.

Clinical Usefulness of the serum-Soluble Transferrin Receptor in Iron Dysregulation Associated with long-Term Hemodialysis

Background: Soluble transferrin receptor (sTfR) was reported to be a valuable diagnostic marker for iron dysregulation (ID). Hepcidin, which is a key regulator of iron metabolism, has been shown to have increased values in patients undergoing hemodialysis (HD). Either treatment with erythropoietin stimulating agent（ESA） or iron repletion therapy（IRT）had been reported to induce controversial effect on serum levels between sTfR and hepcidin. Thus, we measured serum levels both of sTfR and hepcidin in 97 HD patients and investigated the clinical value of these measures. Methods: We used a commercial enzyme-linked immunosorbent assay kit to measure serum levels both of hepcidin and sTfR. Results: Although serum sTfR levels did not clearly increase, both sTfR levels and its index value correlated with the saturation of transferrin, erythropoietin-stimulating agent dosage, and erythropoietin resistance index (ERI). In addition, a strong negative correlation was found for sTfR and log serum hepcidin values. Conclusions: Serum sTfR levels and the sTfR index were acceptable markers for iron dysregulation (ID) and ERI even in patients undergoing HD whose serum levels of hepcidin increased.

Theranova versus FX80: The impact on anemia management in hemodialysis.

Middle uremic toxins (MUTs) can cause anemia and erythropoietin hyporesponsiveness. Theranova dialyzers may improve anemia management by removing MUTs. Hence, the impact of Theranova dialyzers on erythropoietin responsiveness was studied. This exploratory single-center prospective observational study, encompassing 50 patients undergoing dialysis with either the Theranova-400 or FX80 membrane for 6 months, involved monthly tracking of hemoglobin levels, weight-adjusted erythropoiesis-stimulating agent (w-ESA) dosing, and erythropoietin resistance index (ERI), with ESA treatment decisions guided by a proprietary algorithm. The groups were similar in terms of demographics and baseline laboratory test results. The median hemoglobin levels, w-ESA and ERI, were found to be similar between FX80 and Theranova-400 groups at both baseline (11.06 vs 10.57, p = 0.808; 92.3 vs 105.2, p = 0.838; 8.1 vs 10.48, p = 0.876) and the end of the study (11.43 vs 11.03, p = 0.076; 48.7 vs 71.5; 4.48 vs 6.41, p = 0.310), respectively. There was a trend toward lower w-ESA and ERI at the end of the study compared to baseline in both groups, but the difference was non-significant. Based on this study of 50 patients undergoing high-flux dialysis with near-target hemoglobin levels, switching to Theranova 400 dialyzers compared to FX80 dialyzers did not show statistically significant differences in maintaining hemoglobin levels, reducing ESA dose, or lowering ERI. The non-randomized design and small sample size limit the study's power to detect true differences. Larger, randomized trials are needed to confirm findings and definitively assess Theranova 400's benefits.

The influencing factors of the erythropoietin resistance index and its association with all-cause mortality in maintenance hemodialysis patients

Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929–0.986), white blood cells (OR 0.900, 95% CI: 0.844–0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755–0.993), body mass index (OR 0.860, 95% CI: 0.828–0.892), males (OR 0.708, 95% CI: 0.625–0.801), and albumin (OR 0.512, 95% CI: 0.389–0.673) had a negative association with high ERI baseline (all p < 0.05). There were 176 (13.9%) deaths in total including 89 cardiac/vascular deaths during follow-up. Cox regression analysis showed that ERI was positively associated with all-cause mortality, especially in some subgroups. ERI was associated with increased all-cause mortality in MHD patients, indicating the possibility of death prediction by ERI. Patients with high ERI warrant more attention.

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.

Correlation between ultrafiltration rate and hemoglobin level and erythropoietin response in hemodialysis patients

This study aimed to investigate the correlation between ultrafiltration rate (UFR) and hemoglobin levels and erythropoietin (EPO) response in patients receiving maintenance hemodialysis (MHD). 225 MHD patients were divided into three groups according to the UFR: < 10 ml/h/kg, 10–13 ml/h/kg, and >13 ml/h/kg. Clinical parameters and prognosis were compared among the groups. Multiple linear correlation and regression analyses were conducted. SPSS 26.0 (IBM, Chicago, IL, USA) was used to analyze all statistics. The UFR < 10 ml/h/kg group was older than the other groups (p < 0.05). The UFR > 13 ml/h/kg group had the highest SpKt/V (p < 0.05), monthly EPO dose/weight (p < 0.001), and EPO resistance index (p < 0.001), as well as the lowest dry weight (p < 0.001), BMI (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.05), and red blood cell count (p < 0.05). Multiple linear regression analysis showed that sex, dry weight, UFR, calcium, phosphorus, albumin, and C-reactive protein levels were associated with hemoglobin levels. Multivariate logistic regression analysis revealed that a higher UFR was associated with lower hemoglobin levels, while male sex and higher levels of calcium and albumin were associated with higher hemoglobin levels. High UFR is associated with more severe anemia and EPO resistance in MHD. This study provides new insights into anemia management in patients undergoing hemodialysis.

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.

Association Between the Polymorphism of Angiotensin-Converting Enzyme Gene and Interleukin-1 Beta Gene and the Response to Erythropoietin Therapy in Dialysis Patients with Anemia.

The polymorphism of the angiotensin-converting enzyme (ACE) gene and interleukin-1 beta (IL-1b) gene could be associated with resistance in the treatment of anemia in dialysis patients with recombinant human erythropoietin (rHuEPO). The aim of the study was to evaluate the association between the polymorphism of the ACE and IL-1b genes and the response to rHuEPO therapy in dialysis patients with anemia. The study investigated 69 patients on dialysis with anemia treated with recombinant human erythropoietin for 12 months. Genotyping of ACE and IL-1b polymorphism was done in all study patients at the initiation of the study. The patient's demographic characteristics, dialysis vintage, and laboratory parameters were also evaluated as factors associated with rHuEPO resistance. The erythropoietin resistance index (ERI) was calculated as the weekly rHuEPO dose per kg of body weight, divided by the hemoglobin (Hb) concentration in g/dl. The Hb ≥ 110 g/l was registered in 37 (53.6%) patients. Patients with Hb ≥ 110 g/l were characterized by significantly higher serum levels of albumin, cholesterol, and iron than those with Hb < 110 g/l. The serum level of the CRP, the weekly dose of rHuEPO, and ERI were significantly higher in patients with Hb < 110 g/l compared to patients with Hb ≥ 110 g/l. The ERI value of ≥ 10 IUkg/weekly/g/dl was present in 27 (39.1%) patients. The serum levels of ferritin and CRP, and weekly dose of rHuEPO were significantly higher in patients with ERI value ≥ 10 IU kg/weekly/g/dl compared with the patients with ERI value < 10 IUkg/weekly/g/dl. There was no significant association between the ERI and polymorphism of the ACE and IL-1b genes in study patients. The polymorphism of the ACE and IL-1b genes was not significantly associated with the response to erythropoietin therapy in dialysis patients with anemia. Iron deficiency, malnutrition, and inflammation were factors associated with anemia and resistance to erythropoietin therapy in dialysis patients.

Proton Pump Inhibitors and Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: Results from the Japan Dialysis Outcomes and Practice Patterns Study.

Hyporesponsiveness to erythropoiesis stimulating agents (ESAs) is important problem in dialysis patients. While proton pump inhibitors (PPIs) may inhibit iron absorption, few studies have examined associations between PPIs and ESA-resistant anemia in hemodialysis patients. This study examined the associations between PPIs and ESA-resistant anemia in hemodialysis patients. The present study was a cross-sectional study using repeated 4-month observations, up to eight observations/patient, from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS). The primary outcome was erythropoietin resistance index (ERI). ESA dose, hemoglobin, proportion of erythropoietin-resistant anemia, transferrin saturation (TSAT), and ferritin were also examined. Linear or risk-difference regression models were used with generalized estimating equations to account for repeated measurements. Of 1,644 patients, 867 patients had PPI prescriptions (52.7%). Patients prescribed PPI had higher ERI, higher ESA dose, and lower TSAT levels. Multivariable analysis for 12,048 four-month observations showed significantly greater ERI in PPI users (adjusted difference 0.95 IU/week/kg/[g/dL] [95% CI: 0.40-1.50]). Significant differences were also found in ESA dose (336 IU/week [95% CI: 70-602]) and the prevalence of erythropoietin-resistant anemia (3.9% [2.0-5.8%]) even after adjusted for TSAT and ferritin. Among possible mediators between the association of PPIs and anemia, TSAT was significantly different between PPI users and non-users (adjusted difference, -0.82% [95% CI: -1.56 to -0.07]). This study showed the associations between PPI and ERI, ESA dose, and TSAT in hemodialysis patients; physicians should consider anemia's associations with PPIs in hemodialysis patients.

Contemporary Practice of Anemia Treatment Among Dialysis Patients in the United States

The treatment of anemia is a major activity in the care of patients undergoing maintenance hemodialysis (HD). The comparative effectiveness of new pharmacologic treatments, relative to erythropoiesis-stimulating agents (ESAs), should be anticipated on the bases of controlled trials and current practice. We describe the contemporary practice of anemia treatment in a national cohort of patients undergoing maintenance HD. We analyzed the United States Renal Data System (USRDS) data to identify adult patients undergoing in-facility HD in 2016 to 2019. Using the Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb) dataset, we identified hemoglobin and ESA utilization (agent and cumulative dose) during each patient-month, as well as intravenous (IV) iron utilization, ferritin, and transferrin saturation. We compared ESA dosing during the study era to dosing in the Normal Hematocrit Cardiac Trial (NHCT), conducted in the 1990s. We assessed ESA hyporesponsiveness by estimating the prevalence of the following: (i) high erythropoietin resistance index (ERI) and (ii) either 3 or 6 consecutive months with hemoglobin<10 g/dl. Nearly two-thirds of patient-months had hemoglobin of 10.0 to 11.9 g/dl. Mean ESA utilization was 76.7% per month, with increasing use of pegylated epoetin beta. ESA dosing was stable; epoetin alfa dosing was slightly lower than in the low-target arm of the NHCT. The prevalence of ESA hyporesponsiveness was 22.2% if defined by high ERI, but only 2.1% to 6.0% if defined by 3 to 6 consecutive months with hemoglobin<10 g/dl. Median transferrin saturation was 22.3% with high ERI and persistently low hemoglobin. Hemoglobin and ESA dosing distributions are stable, with epoetin alfa dosing below the low-target arm of the NHCT. Persistently low hemoglobin occurs infrequently and may reflect iron depletion.

Correlation between Erythropoietin Resistance Index and Mortality in Regular Hemodialysis Patients at Haji Adam Malik General Hospital Medan

Correlation between Erythropoietin Resistance Index and Mortality in Regular Hemodialysis Patients at Haji Adam Malik General Hospital Medan

Opportunities to improve the management of anemia in peritoneal dialysis patients: lessons from a national study in routine clinical practice.

Current guidelines establish the same hemoglobin (Hb) and iron biomarkers targets for hemodialysis (HD) and peritoneal dialysis (PD) in patients receiving erythropoiesis-stimulating agents (ESAs) even though patients having PD are usually younger, more active and less comorbid. Unfortunately, specific renal anemia [anemia in chronic kidney disease (aCKD)] trials or observational studies on PD are scanty. The aims of this study were to describe current aCKD management, goals and adherence to clinical guidelines, identifying opportunities for healthcare improvement in PD patients. This was a retrospective, nationwide, multicentre study including patients from 19 PD units. The nephrologists collected baseline data, demographics, comorbidities and data related to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for definitions, drug prescriptions and targets. A total of 343 patients (mean age 62.9years, 61.2% male) were included; 72.9% were receiving ESAs and 33.2% iron therapy [20.7% intravenously (IV)]. Eighty-two patients were receiving ESA without iron therapy, despite 53 of them having an indication according to the European Renal Best Practice guidelines. After laboratory results, iron therapy was only started in 15% of patients. Among ESA-treated patients, 51.9% had an optimal control [hemoglobin (Hb) 10-12g/dL] and 28.3% between 12-12.9g/dL. Seventeen patients achieved Hb >13g/dL, and 12 of them remained on ESA after overshooting. Only three patients had Hb <10g/dL without ESAs. Seven patients (2%) met criteria for ESA resistance (epoetin dose >300IU/kg/week). The highest tertile of erythropoietin resistance index (>6.3 UI/kg/week/g/dL) was associated with iron deficiency and low albumin corrected by renal replacement therapy vintage and hospital admissions in the previous 3months. Iron therapy continues to be underused (especially IV). Low albumin, iron deficiency and prior events explain most of the ESA hyporesponsiveness. Hb targets are titrated to/above the upper limits. Thus, several missed opportunities for adequate prescriptions and adherence to guidelines were identified.

#2621 HEMOGLOBIN VARIABILITY IS ASSOCIATED WITH NUTRITIONAL STATUS IN HEMODIALYSIS PATIENTS UNDERGOING DARBEPOETIN-ALFA TREATMENT

Abstract Background and Aims Anemia is the most common finding in hemodialysis (HD) patients. A significant proportion of patients are taking erythropoietin (EPO) or other erythrocyte-stimulating agents (ESAs), yet the response to treatment is unsatisfactory, and EPO responsiveness is inconsistent in HD patients. Further, although the introduction of EPO has led to a dramatic reduction in blood transfusion requirements and is associated with improved quality of life, fluctuations in hemoglobin (Hb) levels, known as Hb variability, during EPO treatment is a well-documented phenomenon. Malnutrition is a well-known risk factor in the general population and in HD patients. However, few studies have evaluated the association between EPO responsiveness/Hb variability and nutritional status in HD patients. Therefore, our aim was to investigate whether EPO responsiveness and Hb variability can be associated with nutritional status in HD patients undergoing NESP® (darbepoetin-alfa; Kyowa Kirin Korea Co., Ltd.) treatment. Method In this prospective study, we included adult ninety-eight patients aged over 20 years who had been undergoing HD over 6 months. The target hemoglobin (Hb) level is 10–11 g/dL according to the Korean reimbursement guideline. Dose adjustments of NESP® were made according to the Hb level measured monthly in our facility. Every study population have more than 24 monthly Hb data points. We checked average darbepoetin-alfa dose weekly and the EPO resistance index (ERI) as a marker of EPO responsiveness was calculated by dividing the weekly average darbepoetin-alfa dose by the Hb level. In addition, we evaluated the more than 24 month Hb variability, which was expressed by Hb-Coefficient of Variation (Hb-CV). All of them were measured by BCM® (Fresenius Medical Care a Deutschland GmbH, Germany) to assess the nutritional status three times (Baseline, 12 Mos, 24 Mos). Nutritional parameters obtained by BCM® were body mass index (BMI), fat tissue index (FTI), lean tissue index (LTI), body cell mass index, phase angle (PhA). Clinical parameters and routine biochemical tests such as dose of erythropoietin, Kt/Vurea, iron and lipid profiles, C-reactive protein, albumin, calcium, phosphorus, intact-parathyroid hormone were also taken into account. Results In this study, the mean age of the patients was 64.0 ± 11.9 years, and 55.0% were male. Dialysis vintage was 54.9 ± 46.8 months. Follow-up duration was 79.3±47.9 months. Mean Hb was 10.7 ± 1.3 g/dL. We divided into tertiles (T) according to the ERI. The average ERI was 0.02 ± 0.01, 0.04 ± 0.01, and 0.07 ± 0.03 in ERI-T1, ERI-T2, and ERI-T3, respectively. The ERI-T3 group had the lower Hb level (p = 0.038) whereas administration dose of EPO were higher in ERI-T3 (p = 0.001). The ERI-T3 group had the lower PhA (p = 0.044), BMI (p = 0.001) and FTI (p = 0.046) values. We divided into tertiles (T) according to the Hb-CV. The average Hb-CV was 0.06 ± 0.01, 0.08 ± 0.05, and 0.12 ± 0.02 in Hb-CV-T1, Hb-CV-T2, and Hb-CV-T3, respectively. When comparing the three groups, the Hb-CV-T3 group had the lower BMI (p = 0.002) and lower FTI (p = 0.002). Age (r = 0.203, p = 0.036), female sex (r = 0.376, p = 0.001), presence of diabetes mellitus (r = 0.191, p = 0.049), total iron binding capacity (r = 0.205, p = 0.035) and triglyceride (r = 0.227, p = 0.018) were positively correlated with FTI. ERI (r = -0.193, p = 0.046) and Hb-CV (r = -0.268, p = 0.005) were negatively correlated with FTI. In multiple linear regression analysis, FTI was negatively associated with ERI (β = -0.218, p = 0.014), Hb-CV (β = -0.181, p = 0.039), whereas FTI was positively associated with age (β = 0.197, p = 0.017) and female sex (β = 0.386, p = 0.001). Conclusion In HD patients with higher ERI, PhA, BMI and FTI were significantly decreased. Furthermore, in patients with high Hb-CV, BMI and FTI were decreased. In addition, FTI was negatively associated with ERI and Hb-CV. Therefore, EPO responsiveness and Hb-variability is associated with nutritional status, especially fat tissue in hemodialysis patients undergoing darbepoetin-alfa treatment.

#6068 ERYTHROPOIETIN RESISTANCE IN HAEMODIALYSIS PATIENTS POST SARS-COV-2 INFECTION

Abstract Background and Aims During the SARS-CoV-2 pandemic, patients undergoing chronic haemodialysis treatment were at particularly high risk of infection. This was due to their vulnerability given their state of immunosuppression and multiple comorbidities, on the one hand, and the circumstances that limited physical distancing during treatment, on the other. Even after negativation, patients with a previous infection experience symptoms such as persistent asthenia, muscle weakness, widespread pain and deterioration in perceived health status. In our study, we aimed to investigate the parameters of anaemia and the change in the erythropoietin resistance index (ERI) in haemodialysis patients with previous infection. Method We included 25 patients with a dialysis age &amp;gt;6 months, giving a total of 72 measurements. The distribution was assessed with the Kolmogorov-Smirnov test and with a graphical evaluation of the same. We calculated the ERI 3 months before the date of infection and in the 3 and 6 months after. These data were also compared with a control group. Patients were divided into 2 groups: Group A (patients with previous infection) and Group B (control group). Linear mixed models were performed to calculate the slope between the group and the ERI index. Results No statistically significant differences were found. The LMMs showed a significant interaction between the scores obtained at the visits performed and the study group, with a decrease in ERI over time of 0.21 at each visit. Conclusion Our results show that patients with previous Covid 19 infection have higher resistance to erythropoietin and require higher doses even months after infection. The response to erythropoietin in this population should be investigated in studies with larger cohorts, as anaemia is an important factor affecting the quality of life of our patients.

#4445 ANAEMIA MANAGEMENT IN PERITONEAL DIALYSIS: FROM GUIDELINES TO ROUTINE CLINICAL PRACTICE

Abstract Background and Aims The evidence on the management of renal anemia in peritoneal dialysis (PD) is much weaker than in hemodialysis (HD). Current guidelines establish the same haemoglobin (Hb) target for patients under eritropoietin stimulating agents (ESAs) in both dialysis techniques (PD, HD), although patients in PD are usually younger, more active and lesss comorbid. Unfortunately, there is not randomized controlled trials evaluating the efficacy and safety the effect of different Hb target on clinical outcomes. The aim is to describe the current situation of anaemia prevalence, treatments, and achievement of clinical guidelines recommendations in this population. Method Retrospective nationwide multicenter study including patients from 19 PD units. All prevalent PD patients that were active in the technique in November 2019 for at least 3 months was included (to avoid COVID pandemic interferences). Exclusion criteria were a previous kidney transplant failure and being on PD due to a cardiorenal syndrome with a residual renal function over 20 ml/min/1.73 m2. The nephrologists collected baseline data, demographics, comorbidities, and data related to anemia management (ie, laboratory values, previously prescribed treatments, and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for iron and Hb limits, prescriptions and targets. Results A total of 343 patients (mean age 62.9 years, 61.2% male) were included. Regarding anaemia-treatment prescription, 72.9% were receiving ESAs and 33.2% iron therapy (20.7% intravenously-IV and 12.5% orally). Eighty-two (32.8%) patients were receiving ESA without iron therapy, despite to have an indication to do it according ERBP guidelines in 53 out of them. After knowing lab results, iron therapy was only started in 8 (15%) patients. Among ESA-treated patients, 58.8% had an optimal control (Hb 10–12 g/dl). Seventeen patients had haemoglobin over 13 g/dl, and 12 of them continued receiving ESA after knowing lab results. Only three patients had persistent haemoglobin &amp;lt;10 g/dl. Seven patients (2%) met criteria for ESA resistance (epoetin dose &amp;gt;300 IU/kg/week). Patients in the highest tertile of erythropoietin resistance index (ERI) (&amp;gt;6.3 UI/kg/week/g/dl) were more inflamed, had lower albumin levels and lower residual renal function. Conclusion Anaemia prevalence is high in this population and its management in PD Units could be improved according to the ERBP guidelines. The lack of iron therapy in patients who should have received it and the excessive tolerance to high Hb levels are the most relevant opportunities to improve compliance with clinical guidelines.

The Switch from Ferric Gluconate to Ferric Carboxymaltose in Hemodialysis Patients Acts on Iron Metabolism, Erythropoietin, and Costs: A Retrospective Analysis.

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out period, the same patients were treated with FCM. Results: The iron switch reduced the administered dose of ESA by 1610.500 UI (31% of reduction; p < 0.001) during the entire study period and reduced the erythropoietin resistance index (ERI) (10.1 ± 0.4 vs. 14.8 ± 0.5; p < 0.0001). The FCM group had the highest percentage of patients who did not require ESA treatment during the study period. The FCM patients were characterized by higher levels of iron (p = 0.04), ferritin (p < 0.001), and TSAT levels (p < 0.001) compared to the FG patients. The annual cost during FG infusion was estimated at EUR 105,390.2, while one year of treatment with FCM had a total cost of EUR 84,180.7 (a difference of EUR 21,209.51 (20%), saving EUR 42.1 per patient/month (p < 0.0001). Conclusions: FCM was a more effective treatment option than FG, reducing ESA dose requirements, increasing Hb levels, and improving iron status. The reduced ESA doses and the decreased number of patients needing ESA were the main factors for reducing overall costs.

Relation between erythropoietin resistance and metabolic syndrome in hemodialysis patients: A multicentric propensity score matched analysis.

Erythropoietin (EPO) resistance is frequently reported in hemodialysis (HD) patients. Metabolic syndrome (MetS) is a common biochemical condition that comprises central obesity, dyslipidemia, hypertension, and hyperglycemia. The present study aimed to assess the relation between MetS and EPO resistance in HD patients. The present multicentric study included 150 patients with EPO resistance and 150 patients without EPO resistance. Short-acting EPO resistance was diagnosed if the erythropoietin resistance index is ≥1.0 IU/kg/gHb. Comparison between patients with EPO resistance and patients without resistance revealed that the former group had significantly higher body mass index, lower hemoglobin levels, lower albumin levels, higher ferritin levels, and higher high-sensitivity C-reactive protein (hsCRP) levels. In addition, patients in the EPO resistance group had significantly higher frequency of MetS (75.3% vs 38.0%, p < 0.001) and higher number of MetS components (2.7 ± 1.3 vs 1.8 ± 1.6, p < 0.001). Multivariate logistic regression analysis identified lower albumin levels (OR (95% CI): 0.072 (0.016-0.313), p < 0.001), higher ferritin levels (OR (95% CI): 1.05 (1.033-1.066), p< 0.001), higher hsCRP levels (OR (95% CI): 1.041 (1.007-1.077), p = 0.018), and MetS (OR (95% CI): 36.68 (2.893-465.05), p = 0.005) as predictors of EPO resistance in the studied patients. The present study identified MetS as a predictor of EPO resistance in HD patients. Other predictors include serum ferritin, hsCRP, and albumin levels.

Perbandingan Efektivitas Latihan Intradialisis dan Profiling Suhu dalam Meningkatkan Mutu Layanan Hemodialisis

This study aims to describe the effectiveness of intradialytic exercises and HD temperature profiling in improving the quality of HD services. The literature search method is based on the compilation of PICO through online database searches on Clinicalkey, Clinicalkey Nursing, ScienceDirect, EBSCO, ProQuest, and Scopus. Journal search results obtained 20,106 articles; after the selection stage, nine reports were obtained for analysis, consisting of 5 RCT articles, one systematic review article, two quasi-experimental articles, and one meta-analysis article. The results showed that HD patients who were routinely given intradialytic exercises would show an increase in HD adequacy achievements, suppress inflammatory reactions, increase albumin and hemoglobin values, reduce the erythropoietin resistance index, increase phosphate clearance, improve the quality of life of HD patients and minimize the risk of both acute and chronic complications. Chronic disease caused by HD. Meanwhile, temperature profiling can reduce the incidence of intradialytic hypotension, pruritus, and fatigue and reduce the severity of Restless Leg Syndrome (RLS) without interfering with the achievement of HD adequacy. This study concludes that intradialytic training and temperature profiling effectively improve the quality of HD services.&#x0D; &#x0D; Keywords: HD Quality, HD Patient Quality of Life, Intradialysis Exercise, Temperature Profiling