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Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 21-24

Assessment of Erythropoiesis-Stimulating Agents for Anemia Treatment among Chronic Kidney Disease Patients: A Descriptive, Retrospective Study

1 Department of Clinical Pharmacy, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan
2 Department of Clinical Pharmacy, Faculty of Pharmacy, Omdurman Islamic University, Khartoum, Sudan
3 Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan

Date of Submission16-Aug-2020
Date of Acceptance28-Sep-2020
Date of Web Publication12-Jan-2021

Correspondence Address:
Dr. Bashir Alsiddig Yousef
Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Al-Qasr Ave., Khartoum 11111
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/MTSM.MTSM_46_20

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Background: Renal anemia is a cause of significant morbidity, and to lesser extent mortality in patients with chronic kidney disease (CKD), the leading causes of anemia in CKD primarily are the lack of erythropoietin (EPO) and iron. Thus, effective management is possible using oral and intravenous (IV) iron preparation and genetically engineered erythropoiesis-stimulating agents such as EPO. This study aimed to assess the effect of EPO in the treatment of anemia among hemodialysis (HD) patients. Methods: A descriptive, retrospective hospital-based study was conducted in Elshaheeda Salma Hospital, Khartoum, Sudan. All patients who were anemic or had a history of anemia and undergoing HD during the period (January to June 2018) were recruited. Data were collected using a checklist and analyzed with the Statistical Package for the Social Sciences software. Results: A total of 191 anemic patients were included: 60% of them were males, and more than half of the participants were aged between 41 and 65 years. Clinically, the average duration of the dialysis among participants was 7.7 ± 5 years, and 97% of them had two dialysis sessions per week. Patients were used either IV or subcutaneous injection of EPO. 8000 IU/week were the most prescribed (52.2%) EPO dose. Whereas, only 6% and 18% were taking 100 mg IV and 150 mg oral ferrous sulfate, respectively. Furthermore, 70% of them were taking 5 mg folic acid. Moreover, the mean hemoglobin level among the participants at the end of the study was 10 ± 2.1 g/dl. Conclusion: EPO was effective in treating renal anemia in HD patients. Among the studied patients, 8000 IU/week was the most frequently used dose. The present study highlights significant low adherence to international guidelines in the management of anemia in patients on HD.

Keywords: Anemia, chronic kidney failure, Elshaheeda Salma hospital, erythropoietin

How to cite this article:
Elamin ZM, Badi S, Yousef BA. Assessment of Erythropoiesis-Stimulating Agents for Anemia Treatment among Chronic Kidney Disease Patients: A Descriptive, Retrospective Study. Matrix Sci Med 2021;5:21-4

How to cite this URL:
Elamin ZM, Badi S, Yousef BA. Assessment of Erythropoiesis-Stimulating Agents for Anemia Treatment among Chronic Kidney Disease Patients: A Descriptive, Retrospective Study. Matrix Sci Med [serial online] 2021 [cited 2021 Apr 15];5:21-4. Available from: https://www.matrixscimed.org/text.asp?2021/5/1/21/306858

  Introduction Top

Chronic kidney disease (CKD) is usually asymptomatic, but it is detectable, and its treatment can prevent or delay the progression of CKD and reduce or prevent the development of complications.[1] The most frequent causes of CKD include diabetic nephropathy, hypertension, glomerular nephritides, interstitial nephritis, pyelonephritis, polycystic kidney disease, and obstructive nephropathy.[1] The selection of renal replacement therapy depends on the patient's physical and socio-demographic characteristics. Renal transplantation is the best option because it assures a better quality of life and more prolonged survival, nevertheless due to the scarcity of transplants, peritoneal dialysis, and mainly hemodialysis (HD) are applied in most cases.[2],[3] Hemodialysis is a medical procedure to remove the waste products from the blood and to correct the electrolyte imbalance. This is accomplished using a machine and dialyzer and is used to treat both acute and chronic kidney failure.[4],[5]

One of the main complications of CKD is the development of anemia, as the kidney secretes erythropoietin (EPO) hormone that plays a vital role in erythropoiesis process.[6] Thus, using different types of recombinant human EPO, including epoetin alfa and Darbepoetin can be administered to manage CKD-induced anemia.[7],[8] Approximately 5%–10% of patients receiving EPO therapy will show resistance.[9] Causes of hypo-responsiveness to EPO therapy are infection, inflammation, iron deficiency, B12 and folate deficiency, blood loss, hyperparathyroidism, malnutrition, and malignancy.[8],[10] Moreover, anemia in CKD can be the leading cause of morbidity and mortality.

In Sudan, there are problems in prescribing and monitoring of treatment of anemia in CKD patients. These problems exacerbate the incidence of anemia leading to many complications of anemia as reduced oxygen utilization, increased cardiac output and left ventricular hypertrophy, increase the progression of CKD, and how much these complications are translated into the adverse outcomes such as impaired quality of life, increased hospitalization, and increased cardiovascular event.[6] Thus, this study was carried to assess the prescribing and monitoring of erythropoiesis-stimulating agents (ESA) for the treatment of anemia among CKD patients.

  Methods Top

Study design and settings

This study was a descriptive, retrospective, cross-sectional, and hospital-based study conducted at Elshaheeda Salma Center for dialysis, Khartoum, Sudan. The present study involved CKD adult patients who were attending during the period of study for HD. The study duration was from January to June 2018.

Inclusion and exclusion criteria

A total coverage sampling technique was used. All patients more than 18 years on HD who were anemic or had a history of anemia were included. While those who were coming to the center for a period of fewer than 6 months from the beginning of the study were excluded from the study. The total number of recruited included patients was 191 patients; all their medical records were also reviewed.

Data collection tools

A data collection sheet was developed based on the guideline for the management of anemia among CKD. It was designed to assess the appropriateness of anemia management in CKD; it contained the following sections: Demographic data, data on dosing of treatments, and questions related to dialysis. A pilot study consisting of 10 initial records was first conducted to check the validity of the data collection sheet.

Statistical analysis

Data were collected and analyzed using the Statistical Package for the Social Sciences program SPSS version 22 (Armonk, NY: IBM Corp). The descriptive statistics were presented in tables. A Chi-square test was used to test the significant association between the readings of different months following EPO treatment. P < 0.05 was considered statistically significant.

Ethical consideration

An ethical clearance (FPEC-10-2018) was obtained from the Ethical Committee of the Faculty of Pharmacy, University of Khartoum. Additional approval for checking the medical records was obtained from Elshaheeda Salma Hospital.

  Results Top

As shown in [Table 1], 191 participants were recruited in the study; the average age of the participants was 51 ± 15 years, with a minimum age of 22 years and a maximum of 87 years. Sixty percent of them were males and more than half of the participants aged 41–65. The average weight was 59.8 ± 16 kg with a minimum weight of 27 kg and a maximum of 107 kg, with 13% their weight was more than 80 kg. About half of the participants were living in Khartoum. Clinically, the average duration of the dialysis among participants was 7.7 ± 5 years, with a minimum of 8 months and a maximum of 22 years. About one-third of the participants were on dialysis for more than 10 years, and 97% of them had two dialysis sessions per week [Table 1].
Table 1: Sociodemographic and clinical characteristics of the participants (n=191)

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More than half of the participants were used either intravenous (IV) or subcutaneous (SC) injection of EPO. 43% and 11% of the patients measured their hemoglobin and iron within 1–3 months [Table 2]. Moreover, more than half the participants were taking 8000 IU of ESA therapy per week, and only 10% were taking 12000 IU while ESA therapy was not prescribed for about 12% of the participants. Regarding ferrous sulfate, 82.5% of the participants were not taking ferrous sulfate IV, whereas 55.4% of them were not taking the oral form. 6% were taking 100 mg ferrous sulfate IV, whereas 18% were taking 150 mg oral ferrous sulfate. Furthermore, 70% were taking folic acid 5 mg, and about 55% of them were not taking oral Vitamin B12 [Table 2]. The average hemoglobin, ferritin, and TSAT levels throughout the 6 months (January to June) are shown in [Table 3], the mean hemoglobin level among the participants was 10.9 ± 2.3, and in the 6th month, it was 10 ± 2.1. Regarding TSAT, no one was doing the test in the 1st month, and the average level of TSAT was fluctuating between 28.1 ± 21.7 in February and 50.7 ± 42.2 in April, whereas the average level of ferritin was fluctuating between 456.8 ± 321.5 in May and 833.2 ± 478 in April.
Table 2: Treatment and monitoring of anemia among the studied population (n=191)

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Table 3: The average levels of the hemoglobin, serum transferrin saturation, and ferritin throughout the 6 months

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When Pearson's correlation test was performed to determine the associations between the doses of EPO and hemoglobin level throughout 6 months, we found that EPO doses that were administered to the participants were associated with a significant decrease in the Hb level in February (R = 0.178, P = 0.014) and April (R = 0.150, P = 0.038). The results were statistically insignificant for the rest of the months.

  Discussion Top

In this study, 48.2% of the participants receiving HD for 2–10 years, followed by 36.6% receiving HD for more than 10 years and 15.2% for <2 years either twice/weekly (97.4%), (2.1%) thrice/week and (0.5%) once/week. This result was consistent with a study that was done in Saudi Arabia.[11] On the other hand, the economic state of most patients was poor (73.8%), and 26.2 were a moderate state, due to this result, most of the patients did not do the routine laboratory investigation as recommended by doctors.

In the current study, we found that the hyporesponsiveness to EPO represents 1% of all patients. There were two patients who were hyporesponsive one was due to inflammation, and the other was due to hyperparathyroidism, this result was not found only in this study only; a study was done in Saudi Arabia the authors reported that CKD itself is a central cause of hyporesponsiveness of ESA due to inflammation condition that stimulates hepcidin release from the liver leading to iron deficiency.[11] Furthermore, another study showed that hyperparathyroidism was one of the most causes of hyporesponse to EPO.[12] Furthermore, another report found that inflammation was the major cause of hyporesponse.[13]

The monitoring of anemia did not follow international guidelines as no patient was measured his hemoglobin monthly as recommended by the KIDIGO guidelines.[6] Most patients (56.5%) measured their hemoglobin at a time interval of more than 3 months, and only (43.5%) were measured at the time interval of 1–3 months, and they were followed NICE guidelines according to their recommendation.[6] Furthermore, monitoring of iron by measuring ferritin and transferrin saturation did not follow the guideline, as 89% measuring their iron in time interval more than recommended by guideline, and only 11% followed guidelines as they measure their iron at the time interval recommended by the guideline. There were few patients measuring their ferritin and TSAT in each month of study as these tests are too expensive. The patients were used both IV and oral routes of iron administration, which is not recommended by the guideline. The present study that was done in India showed the same result,[14] but differed from a study done in Saudi Arabia and Lebanon, in which patients were using an IV route, which is the preferable route by the guideline.[11],[15]

Data on folic acid and Vitamin B12 doses were collected, and serum folate and serum B12 were done for only three patients during the study, so they were excluded from the analysis. Patients did not do these laboratory investigations because they are very expensive. All patients used oral Vitamin B12, and only one patient used the IV route. At this point, the prescriber adhered to the guidelines, and these tests were written to patients as recommended, but due to their poor economic state, patients did not do these investigations.

EPO was given according to hemoglobin measure, which matches with the guideline.[16] In Elshaheeda Salma, higher doses of EPO were prescribed to patients with lower hemoglobin levels; this result was also found in a study done in Lebanon. The types of EPO used in our study were epoetin Alfa and epoetin beta. In a study that was done in India and Lebanon, patients have used epoetin alfa, epoetin beta, and darbepoetin alfa.[11],[14]

The route of administration of EPO in this study for 55% of patients was by either IV or SC route at the end of dialysis session. These are preferable routes of administration regarding EPO by the guidelines followed by 33% by SC only and the rest 12% by IV only. This result was inconsistent with the results of the study done in Saudi Arabia, which showed that the administration route for all patients was IV,[11] and studies in Lebanon showed that EPO were administered to all patients by SC route.[17]

Hemoglobin level is the most specific parameter used to establish the presence and severity of anemia in HD patients.[18] Among all months, April showed a high frequency of monitoring hemoglobin because the center did the test, and other months showed low frequency in monitoring hemoglobin, thus assessing target hemoglobin (10–12 g/dl) if it complies with guidelines being difficult because the sample is not representative.

  Conclusion Top

All recruited patients were received EPO to manage renal anemia, 8000 IU/week were the most frequently used dose. Some of patients were further received ferrous sulfate and folic acid to treat anemia. Furthermore, the present study revealed significant low adherence to the international guidelines in the management of anemia in patients on HD.

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Conflicts of interest

There are no conflicts of interest.

  References Top

National Institute for Health and Care Excellence. Chronic Kidney Disease in Adults: Assessment and Management. National Institute for Health and Care Excellence; 2014.  Back to cited text no. 1
Tzanakaki E, Boudouri V, Stavropoulou A, Stylianou K, Rovithis M, Zidianakis Z. Causes and complications of chronic kidney disease in patients on dialysis. Health Sci J 2014;8:343.  Back to cited text no. 2
Work IGOKHC. KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl 2018;8:91.  Back to cited text no. 3
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.  Back to cited text no. 4
Li PK, Szeto CC. Success of the peritoneal dialysis programme in Hong Kong. Nephrol Transplant Dial 2008;23:1475-8.  Back to cited text no. 5
Padhi S, Glen J, Pordes BA, Thomas ME, Guideline Development Group. Management of anaemia in chronic kidney disease: Summary of updated NICE guidance. BMJ 2015;350:h2258.  Back to cited text no. 6
Aapro M, Gascón P, Patel K, Rodgers GM, Fung S, Arantes LH Jr, et al. Erythropoiesis-stimulating agents in the management of anemia in chronic kidney disease or cancer: A historical perspective. Front Pharmacol 2018;9:1498.  Back to cited text no. 7
Johnson DW, Pollock CA, Macdougall IC. Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology 2007;12:321-30.  Back to cited text no. 8
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.  Back to cited text no. 9
Hayat A, Haria D, Salifu MO. Erythropoietin stimulating agents in the management of anemia of chronic kidney disease. Patient Prefer Adherence 2008;2:195-200.  Back to cited text no. 10
Al-Ageel NA, Al-Aqeel SA, Abanmy NO, Alwakeel JS, Sabry A, Alsaran KA. Appropriateness of anemia management in hemodialysis patients. Saudi Pharm J 2012;20:85-91.  Back to cited text no. 11
Kalantar-Zadeh K, Lee GH, Miller JE, Streja E, Jing J, Robertson JA, et al. Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients. Am J Kidney Dis 2009;53:823-34.  Back to cited text no. 12
Bárány P, Divino Filho JC, Bergström J. High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients. Am J Kidney Dis 1997;29:565-8.  Back to cited text no. 13
Mathew MS, Keerthi NR, Meera NK. Study of management of anemia in chronic kidney disease patients. Indian J Pharm Pract 2016;9:163.  Back to cited text no. 14
Baharvand-Ahmadi B, Asadi-Samani M. A mini-review on the most important effective medicinal plants to treat hypertension in ethnobotanical evidence of Iran. J Nephropharmacol 2017;6:3-8.  Back to cited text no. 15
Panjeta M, Tahirovic I, Karamehic J, Sofic E, Ridic O, Coric J. The relation of erythropoietin towards hemoglobin and hematocrit in varying degrees of renal insufficiency. Mater Sociomed 2015;27:144-8.  Back to cited text no. 16
Hörl WH. Optimal route of administration of erythropoietin in chronic renal failure patients: Intravenous versus subcutaneous. Acta Haematol 1992;87 Suppl 1:16-9.  Back to cited text no. 17
Kesztyüs T, Simonsmeier U, Kesztyüs D. Developing a classification system for haemoglobin management in patients with end-stage renal disease on haemodialysis: A secondary data analysis. BMJ Open 2017;7:e017423.  Back to cited text no. 18


  [Table 1], [Table 2], [Table 3]


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