Effectivity of Erythropoietin Alpha Compared to Erythropoietin Beta in Patients with Chronic Kidney Disease-Anemia on Hemodialysis

Anemia in patient with chronic kidney disease could cause a lot of complication. The first line therapy of this condition is by treating with erythropoiesis-stimulating agents (ESA) or called erythropoietin. The erythropoietin alpha and beta were two types of the human recombinant erythropoietin that are usually used in Indonesia. The aim of this study was to determine the effectivity of erythropoietin alpha compared to erythropoietin beta especially in haemoglobin and haematocrit level. This prospective observational study was conducted in March – September 2016. The inclusion criteria were CKD stage 5 patients with a minimum of 3 months of regular hemodialysis, Hb <10 g/dL with enough iron status ST > 20% and FS > 200ng/mL. The methology of this study had been approved by the Health Research Ethics Committee of the Bhayangkara H.S. Samsoeri Mertojoso Hospital, Surabaya. Patients received 2000 IU subcutaneous erythropoietin twice a week on both groups. Blood sample was withdrawn in pre-treatment and after 4 weeks of post erythropoietin therapy treatment for measurement of haemoglobin and haematocrit. Target for this erythropoietin therapy are increase of Hb 0.5 – 1.5 g/dL (not to exceed 12 g/dL) and increase of Hct level 2 – 4 % in 4 weeks. Based on the inclusion criteria, there were 20 patients in this study (10 patient each of both erythropoietin alpha either beta group) that consist of 7 women and 13 men. After the treatment, the mean of increased haemoglobin level for erythropoietin alpha group was 1.28 ± 0.80 g/dL (p=0.001) and erythropoietin beta was 0.37 ± 0.95 g/dL (p=0.254). The mean of increased haematocrit level for erytropoietin alpha group was 3.56 ± 3.46 % (p=0.010) and erythropoietin beta was 1.34 ± 2.71 % (p=0.152). In comparison of haemoglobin and haematocrit achievement in both groups showed that erythropoietin alpha gave better achievement in haemoglobin parameter (p=0.033), but there were no differences in both groups on haematocrit parameters (p=0.127).

Factors Affecting Doses of Roxadustat Versus Darbepoetin Alfa for Anemia in Nondialysis Patients

<b><i>Introduction:</i></b> Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia of chronic kidney disease (CKD). This post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in nondialysis-dependent (NDD) CKD patients treated with traditional erythropoiesis-stimulating agents (ESAs) evaluated dosing trends of roxadustat and darbepoetin alfa (DA) required to maintain target hemoglobin concentrations in patients with risk factors associated with ESA hyporesponsiveness. <b><i>Methods:</i></b> Patients enrolled in the 1517-CL-0310 study (NCT02988973) that demonstrated noninferiority of roxadustat to DA for change in average hemoglobin levels of week 18–24 from baseline who had used human recombinant erythropoietin or DA before conversion and who were randomized to either roxadustat or DA were included. The endpoints were the average allocated dose of roxadustat and DA per administration in the last 6 weeks (AAD/6W), assessed by subgroups known to be associated with ESA hyporesponsiveness. The analysis of variance was performed by the treatment group to test the influence of subgroup factors on the AAD/6W of study drug. The ratios between the mean AAD/6W in each subgroup category and the within-arm mean AAD/6W were calculated. <b><i>Results:</i></b> Two hundred and sixty-two patients were randomized to either the roxadustat or DA comparative group and received treatment (roxadustat, <i>n</i> = 131; DA, <i>n</i> = 131). Higher mean (standard deviation) doses of both roxadustat (63.15 [24.84] mg) and DA (47.33 [29.79] μg) were required in the highest ESA resistance index (≥6.8) quartile (<i>p</i> = 0.003 and <i>p</i> &#x3c; 0.001, respectively). Patients with adequate iron repletion had the lowest doses for both roxadustat (45.54 [18.01] mg) and DA (28.13 [20.98] μg). High-sensitivity C-reactive protein ≥28.57 nmol/L and the estimated glomerular filtration rate &#x3c;15 mL/min/1.73 m² were associated with requiring higher DA but not roxadustat doses. <b><i>Discussion/Conclusion:</i></b> The roxadustat dose required to maintain target hemoglobin in NDD patients in Japan with anemia of CKD relative to DA dose may not be impacted by low-grade inflammation. Roxadustat may be beneficial for ESA-hyporesponsive NDD CKD patients.

Proof-of-concept study on improved efficacy of rHuEPO administered as a long-term infusion in rats

Background Human recombinant erythropoietin (rHuEPO) is often used in the treatment of diseases associated with a decreased production of red blood cells (RBC), such as chronic renal failure. rHuEPO is typically administered as an intravenous or subcutaneous (SC) injection every few days. The low minimum effective concentration (MEC) of rHuEPO, compared to the concentrations observed after standard doses, suggests that a low dose of the drug administered as a long-term infusion should be efficacious. This study aimed to compare the efficacy observed after a single subcutaneous administration of rHuEPO with that observed after a long-term infusion of rHuEPO via implanted osmotic pumps at a similar or lower dose. Materials and methods In this study three rats received rHuEPO as a single SC injection at a dose of 1350 IU/kg, nine via osmotic pumps at a rate of 0.25, 0.5 and 1 IU/kg and at a total dose of 333 IU/kg, 667 IU/kg, 1333 IU/kg. Three rats served as a control group. The erythropoietin concentrations, RBC count and hemoglobin were measured. Results An increase in RBC count and hemoglobin was observed after SC infusion of rHuEPO. The baseline corrected area under the effect curve for hemoglobin and RBC count was more than 10-times higher for the SC infusion than for a single SC administration with a comparable dose. Conclusions This study demonstrates that administration of rHuEPO as a long-term infusion at a rate ensuring MEC allows to achieve a high efficacy of therapy using relatively small doses of the drug.

Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson’s Patients

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’s Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs.

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease

Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist of a heterocomplex between the erythropoietin receptor (EPOR) and the beta common receptor (βcR). The present study explored the effects of rEPO to prevent renal fibrosis in adenine-induced chronic kidney disease (Ad-CKD) and their association with the expression of the heterodimer EPOR/βcR. Male Wistar rats were randomized to control group (CTL), adenine-fed rats (Ad-CKD), and Ad-CKD with treatment of rEPO (1050 IU/kg, once weekly for 4 weeks). Ad-CKD rats exhibited anemia, uremia, decreased renal function, increased infiltration of inflammatory cells, tubular atrophy, and fibrosis. rEPO treatment not only corrected anemia but reduced uremia and partially improved renal function as well. In addition, we observed that rEPO diminishes tubular injury, prevents fibrosis deposition, and induces the EPOR/βcR heteroreceptor. The findings may explain the extrahematopoietic effects of rEPO in CKD and provide new strategies for the treatment of renal fibrosis in CKD.

Flanker task-elicited Event Related Potential sources reflect human recombinant Erythropoietin differential effects on Parkinson’s patients

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’ s Disease patients.The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators.Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs.From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.

Effectivity of Erythropoietin Alpha Compared to Erythropoietin Beta in Patients with Chronic Kidney Disease-Anemia on Hemodialysis

Anemia in patient with chronic kidney disease could cause a lot of complication. The first line therapy of this condition is by treating with erythropoiesis-stimulating agents (ESA) or called erythropoietin. The erythropoietin alpha and beta were two types of the human recombinant erythropoietin that are usually used in Indonesia. The aim of this study was to determine the effectivity of erythropoietin alpha compared to erythropoietin beta especially in haemoglobin and haematocrit level. This prospective observational study was conducted in March – September 2016. The inclusion criteria were CKD stage 5 patients with a minimum of 3 months of regular hemodialysis, Hb <10 g/dL with enough iron status ST > 20% and FS > 200ng/mL. The methology of this study had been approved by the Health Research Ethics Committee of the Bhayangkara H.S. Samsoeri Mertojoso Hospital, Surabaya. Patients received 2000 IU subcutaneous erythropoietin twice a week on both groups. Blood sample was withdrawn in pre-treatment and after 4 weeks of post erythropoietin therapy treatment for measurement of haemoglobin and haematocrit. Target for this erythropoietin therapy are increase of Hb 0.5 – 1.5 g/dL (not to exceed 12 g/dL) and increase of Hct level 2 – 4 % in 4 weeks. Based on the inclusion criteria, there were 20 patients in this study (10 patient each of both erythropoietin alpha either beta group) that consist of 7 women and 13 men. After the treatment, the mean of increased haemoglobin level for erythropoietin alpha group was 1.28 ± 0.80 g/dL (p=0.001) and erythropoietin beta was 0.37 ± 0.95 g/dL (p=0.254). The mean of increased haematocrit level for erytropoietin alpha group was 3.56 ± 3.46 % (p=0.010) and erythropoietin beta was 1.34 ± 2.71 % (p=0.152). In comparison of haemoglobin and haematocrit achievement in both groups showed that erythropoietin alpha gave better achievement in haemoglobin parameter (p=0.033), but there were no differences in both groups on haematocrit parameters (p=0.127).

Visual Outcomes of Adding Erythropoietin to Methylprednisolone for Treatment of Retrobulbar Optic Neuritis

Purpose: To compare the short-term visual function results and safety of erythropoietin as an add-on to the standard corticosteroid therapy in retrobulbar optic neuritis (RON). Methods: In this prospective pilot study, adult patients with isolated RON with less than 10 days of onset were enrolled. Patients were consecutively assigned to standard intravenous methylprednisolone treatment either in combination with intravenous erythropoietin (20,000 units/day for three days) (group-1) or alone (group-2). Primary outcome measure was best-corrected visual acuity (BCVA), which was assessed up to 120 days from the day the treatment was begun. Systemic evaluations were performed during and after treatment. Results: Sixty-two patients with RON (mean age = 26.6 ± 5.77 years; range = 18–40 years) were enrolled into the study (group-1, n = 35; group-2, n = 27). BCVA three months after the treatment was 0.19 ± 0.55 logMAR and 0.11 ± 0.32 logMAR in group-1 and group-2, respectively (95% CI: –0.61–0.16; P = 0.62). Change in BCVA after three months was 2.84 ± 3.49 logMAR in group-1 and 2.46 ± 1.40 logMAR in group-2 (95% CI: –0.93–1.91; P = 0.57). Pace of recovery was not significantly different between the groups. No complications were detected among patients. Conclusion: Intravenous erythropoietin as an add-on did not significantly improve the visual outcome in terms of visual acuity, visual field, and contrast sensitivity compared to traditional intravenous corticosteroid. This pilot study supports the safety profile of intravenous human recombinant erythropoietin, and it may help formulate future investigations with a larger sample size.