Differences in Pre-Post Hemodialysis Hemoglobin Levels on

Erythropoietin Alpha and Beta Administration: A Systematic Review

Munuarti Muhawia and Diana Laila Ramatilla

Faculty of Pharmacy, Universitas 17 Agustus 1945 Jakarta, Indonesia

Keywords: Hemodialysis, Erythropoietin, Alpha, Beta, Hemoglobin.

Abstracts: Background: Anemia Is Becoming a Complication of Chronic Kidney Disease Caused by Erythropoietin,

along with Increasing Comorbidities. Erythropoietin Is a Glycoprotein Hormone to Stimulates Red Blood

Cells as Its Function. There Are Several Options for Recombinant Erythropoietin, Namely Erythropoietin

Alpha and Erythropoietin Beta. This Literature Review Aims to Determine the Difference in Pre-Post

Hemodialysis Hemoglobin Levels on the Administration of Erythropoietin Alpha and Erythropoietin Beta.

Methods: a Systematic Review of 14 National and International Journals Was Conducted to Identify Studies

That Compared Changes in Hemoglobin Levels before and after Hemodialysis with Alpha and Beta

Erythropoietin Administration.

Results: the Systematic Review Found Several Studies That Compared the Difference in Hemoglobin Levels

before and after Hemodialysis in Patients Receiving Alpha and Beta Erythropoietin. the Analysis Showed

That There Was a Significant Difference in the Increase of Hemoglobin Levels in Both Groups of Patients.

However, There Was No Significant Difference between Alpha and Beta Erythropoietin in Terms of Their

Effects on Increasing Hemoglobin Levels.

Conclusion: Administration of Erythropoietin Alpha and Beta Has a Positive Effect on Increasing

Hemoglobin Levels in Patients Undergoing Hemodialysis. Although There Are Differences in Their

Mechanism of Action, Both Are Effective in Overcoming Anemia in Hemodialysis Patients.

INTRODUCTION

Chronic renal failure is a clinical syndrome caused by

a decrease in kidney function that is chronic,

progressive, and irreversible where the body fails to

maintain metabolism and fluid and electrolyte

balance (Sanjaya, A.A.G.B et all 2019). This disease

is irreversible, meaning that it cannot become normal

again, so the intervention carried out in patients is

only to maintain existing kidney function and carry

out hemodialysis to replace kidney function to

eliminate body metabolism (Juwita L, Kartika IR

2019).

The World Health Organization (WHO) states

that Chronic Kidney Failure (CKD) disease in the

world increases by more than 30% every year.

Meanwhile, in Indonesia, according to the Prevalence

of Chronic Kidney Disease (CKD) aged ≥15 years

based on doctor's diagnosis from 2013 patients with

chronic kidney failure rose to 3.8% in 2018

(Riskesdas, 2018). According to PENEFRI (2018)

from 2007 to 2018 the number of new patients who

underwent hemodialysis in Indonesia with a total of

66,433 people, and 132,142 active patients on

hemodialysis therapy in Indonesia. The World Health

Organization (WHO) estimates that Indonesia will

see a 41.4% increase in the number of people with

GGK between 1995 and 2025.

The results of research by Agustina et al. (2019:

146) that there was a decrease in pre-hemodialysis

hemoglobin levels from 20 respondents who had

hemoglobin levels less than normal. Anemia therapy

caused by CKD with epoetin therapy can improve the

patient's quality of life. The types of erythropoietin

include erythropoietin alpha and erythropoietin beta.

From the background described, the problem

formulation in this study is: "What is the difference

between pre- post hemodialysis hemoglobin levels on

the administration of Erythropoietin alpha and beta".

Furthermore, the purpose of this study is to determine

the difference in pre- post hemodialysis hemoglobin

levels on the administration of Erythropoietin alpha

and beta".

Muhawia, M. and Ramatillah, D.

Differences in Pre-Post Hemodialysis Hemoglobin Levels on Erythropoietin Alpha and Beta Administration: A Systematic Review.

DOI: 10.5220/0012585200003821

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 4th International Seminar and Call for Paper (ISCP UTA ’45 JAKARTA 2023), pages 171-174

ISBN: 978-989-758-691-0; ISSN: 2828-853X

171

METHODS

This systematic review was organized based on the

Preferred Reporting Items for Systematic Reviews

and Meta-analyses (prism). Population, intervention,

control, and outcome (PICO) questions:

P (population) hemodialysis patients

I (intervention) the use of erythropoietin alfa and beta

C (comparison control) -

O (result) hemoglobin

In this method, the steps taken are determining the

topic of the literature, searching and selecting the

most relevant sources and identifying keywords

according to the topic, compiling and analyzing, and

summarizing the findings of the article. The literature

search was conducted using electronic databases that

is Pubmed and Science Direct for articles published

from 2018 to 2023, using words related to

hemodialysis, erythropoietin alpha and beta, and

hemoglobin levels. The literature search was

conducted in June-July 2023 using the keywords in

the database search mentioned above: "hemodialysis

patients" AND "erythropoietin alfa AND beta" AND

"hemoglobin".

Research articles obtained from the

Diagram 1: Flow of Article Selection.

search results were then checked for duplication and

if the same article was found, it would be excluded.

In searching for literature, the author selected some of

the literature obtained using literature screening by

reading the abstracts and titles of the studies found.

After exclusion, a total search of the stored studies

was conducted, concerning the PICO criteria. From

the database, there were 105 initial articles due to

irrelevant titles 66 articles were excluded and 11

articles were excluded due to duplicate titles. Titles

and abstracts were reviewed and 14 eligible journals

were identified.

RESULTS AND DISCUSSIONS

The article selection flowchart above with a total of

14 articles selected from the initial 105 articles. All

selected studies were from Indonesia (9), Iran (1),

Japan (1), Saudi Arabia(1), and Pakistan (1),

hemodialysis patients with anemia were assessed by

measuring the patient's Hemoglobin level before and

after hemodialysis.

Research conducted by Insani.N., et al. (2018)

where the use of erythropoietin as part of therapy for

CKD-HD anemia patients showed a relatively good

and safe outcome of hematological parameters. This

is indicated by an increase in the levels of each

hematological parameter measured.

Research conducted by Adnan et al (2018: 276-

280). This study examines the differences in red

blood cell profiles, namely hemoglobin (Hb), Mean

Corpuscular Volume (MCV), Mean Corpuscular

Hemoglobin (MCH), Mean Corpuscular Hemoglobin

Concentration (MCHC) in patients given

erythropoietin and Non-erythropoietin therapy.

However, this study did not explain the use of

erythropoietin therapy given to the patient sample.

There was an increase in hemoglobin levels by 1.00

in patients who received EPO therapy. In this study,

the average MCV was 90.06 ± 6.150, MCH 29.60 ±

1.998, and MCHC 32.89 ± 0.688, so the values of the

three groups were in the normal range. In addition,

research conducted by Insani et al. (2018) that epoetin

administration can improve hematological

parameters such as erythrocytes, hemoglobin,

hematocrit, MCH, MCHC, and MCV.

In research conducted by Setiawan. H., et al.

(2021) where the respondents were 57 patients with

chronic renal failure, analyzed that there was a

significant effect of erythropoietin administration on

increasing hemoglobin levels in patients with chronic

renal failure undergoing hemodialysis with a p-value

of 0.000 < α 0.05. Furthermore, research conducted

Database search result

document

(n=105)

Full-text articles

reviewed for

eligibility

(n=20)

Exempt

documents

(n=19)

Document filtered

(n=39)

The research included in the

qualitative synthesis

(n=14)

Full-text articles

are excluded on

the grounds of

(n=6)

Documents after

duplicates are removed

(n=66)

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by Angin, et al. (2021) the results of the application

of erythropoietin therapy have been proven

successful in 78 patients with a percentage of 73.58%

successful in treating anemia that occurs in patients

with GGK.

Research conducted by Pasek, et all on 26 End

Stage Renal Disease (ESRD) patients undergoing

hemodialysis. The mean hemoglobin level pre-

erythropoietin therapy is 8.1 gr/dl and the mean

hemoglobin level post-erythropoietin therapy is 8.7

gr/dl. The results of the paired T-test of pre and post-

erythropoietin therapy hemoglobin levels found a p-

value of 0.001 (p < 0.05). There is a significant

difference between hemoglobin levels before and

after receiving erythropoietin therapy. Furthermore,

Rahayu's research, et al. (2019) involved 36

respondents of chronic renal failure patients

undergoing hemodialysis. The results showed the

mean value of pre-hemodialysis hemoglobin levels of

9.3 g/dl and post-hemodialysis of 10.7 g/dl, with

91.7% of respondents experiencing an increase in

post- hemodialysis hemoglobin levels. Based on these

results, it is concluded that there is a significant

difference in pre- and post-hemodialysis hemoglobin

levels in patients with chronic renal failure.

Research conducted by Kurniawanto., at all

(2018) The results of research on 10 samples of

hemoglobin profiles before (Hbpre) giving EPO

therapy and after giving hemoglobin (Hb-post) giving

erythropoietin therapy the increase in Hb during the

study, where the therapy given to patients is

erythropoietin alpha (α) with two different doses of

2000 IU dose, namely 16,88%, and erythropoietin

alpha (α) 3000 IU, namely 12.53%, where the results

obtained were an increase of 0.16x from Hb before

erythropoietin therapy was given for erythropoietin

alpha (α) 2000IU and 0.12x from Hb before

erythropoietin therapy was given for erythropoietin

alpha (α) 3000IU. Similarly, in a study conducted by

Weinhandl., (2023) almost two-thirds of the total

number of patients per month had hemoglobin levels

between 10.0 to 11.9 g/dL. The average use of

erythropoietin was 76.7% per month, with increased

use of pegylated epoetin beta. Erythropoietin dosing

remained stable; epoetin alfa dosing was slightly

lower than in the NHCT low target group. The

prevalence of erythropoietin nonresponse was 22.2%.

Research by Faizah, et al. (2021) 52 respondents

met the inclusion criteria, of which 29 patients in the

alpha erythropoietin group and 23 patients in the beta

erythropoietin group. The average increase in Hb of

subjects using beta erythropoietin was greater than

that of alpha erythropoietin. The average increase in

Hb levels pre-post administration of erythropoietin

beta was 0.48 g/dl while the average increase in Hb

levels pre-post administration of erythropoietin alfa

was 0.02 g/dl. Furthermore, research by Ahsana, et al.

(2021) as many as 94 participants were involved in

the analysis of patients observed after 3 months of

initiation of erythropoietin preparations a significant

increase in Hb levels (p = 0.025) in beta

erythropoietin compared to alpha erythropoietin. The

average increase in Hb levels was 9.80 ± 1.20 to 10.25

± 1.10 g/l on alpha erythropoietin, and 9.66 ± 1.49 to

10.63 ± 1.52 g/l on beta erythropoietin. Furthermore,

in a study conducted by Dian, et al. (2022) where a

sample of 139 CKD patients used epoetin who

underwent routine hemodialysis. Anemia therapy in

CKD patients with the most widely used

hemodialysis is epoetin alfa compared to epoetin

beta. The average value of Hb increase in 3 months

on epoetin beta therapy is higher than on epoetin

alpha therapy and is not statistically significantly

different with a value of p>0.05.

In Widianti's research, et all, this study calculate

the total cost based on the use of erythropoietin used

as anemia therapy in renal failure patients who

undergo between HemapoR, EpotrexR, and

NeorecormonR, so that it can be seen which one is

more effective by comparing the cost-effectiveness

ratio of the three drugs. The most widely used EPO

consistently for 3 (three) consecutive months is

NeorecormonR as much as 41.05. The most effective

erythropoietin to increase Hb levels is NeorecormonR

with a percentage of the number of patients whose Hb

levels increased by 56.41%. Meanwhile, in

AlKharboush research, et al. (2020) study involved a

comparison of the potential therapeutic and economic

impact of using two erythropoietin drugs (epoetin-

beta and darbepoetin- alfa) in patients with stage 5

CKD for the treatment of associated anemia. Baseline

serum Hb was 10.68 ±0.98 g/dL for darbepoetin-alfa

patients and 11.63 ±0.32 g/dL for epoetin-beta group

(p=0.003).

In contrast, in Prasetya research, et al. (2019) the

mean increase in hemoglobin levels in the alpha

erythropoietin group after treatment was 1.28 ± 0.80

g/dL (p = 0.001) and the beta erythropoietin group

was 0.37 ± 0.95 g/dL (p = 0.254). A comparison of

hemoglobin and hematocrit achievement in both

groups showed that erythropoietin alpha gave better

achievement in hemoglobin parameters (p=0.033).

Similarly, in Azmandian research, et al. (2018) A

total of 156 patients were involved in this clinical trial

to compare the efficacy and safety of CinnaPoietin®

(epoetin beta, CinnaGen) with Eprex® (epoetin alfa,

Janssen Cilag) in the treatment of anemia in ESRD

hemodialysis patients. The results showed that there

Differences in Pre-Post Hemodialysis Hemoglobin Levels on Erythropoietin Alpha and Beta Administration: A Systematic Review

173

was no statistically significant difference between the

treatment groups regarding the change in mean Hb

(P= 0.21). However, the incidence of Hb levels above

13 g/dL was significantly lower with CinnaPoietin®

(epoetin beta, CinnaGen).

CONCLUSIONS

Recombinant erythropoietin therapy (epoetin) in its

use in Chronic Kidney Disease (CKD) patients

undergoing hemodialysis can increase hemoglobin.

Of the 14 journals found, 5 journals explain the

effectiveness of erythropoietin in increasing

hemoglobin levels, 2 journals explain the effect of

either alpha or beta erythropoietin in increasing

hemoglobin levels, 5 more journals explain the

comparison of alpha or beta erythropoietin in

increasing hemoglobin where beta erythropoietin is

higher and 2 other journals explain alpha

erythropoietin is higher.

From various studies that epoetin alfa epoetin beta

in CKD patients undergoing hemodialysis there is no

significant difference in the average change in

hemoglobin. The choice between erythropoietin

alpha and beta can be considered based on other

factors such as side effect profile and cost.

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