Anaemia Management in Chronic Kidney Disease

Abstract

Background

Chronic kidney disease (CKD) is recognised as an extremely intrusive condition, with complex, treatments and lifestyle restrictions. Anaemia is a common complication of CKD and is a multifactorial and complex condition. About 15% of patients with CKD stage 3-5 have anaemia according to the World Health Organisation (WHO) criteria. Untreated anaemia can lead to a reduced quality of life, disease progression and adverse clinical outcomes. It is estimated 44% of CKD patients attending the renal clinic are anaemic (WHO, 2013). This literature review aims to identify the most appropriate management of anaemia in people with kidney disease not receiving dialysis.

Method

The online academic database CINAHL Plus, Medline All, EMBASE and Google Scholar were used to search for relevant articles. The keywords used for the search included anaemia, Chronic Kidney Disease, Renal anaemia, iron deficiency, renal insufficiency, early intervention or medication management or pharmacological and biological treatments. After using the inclusion and exclusion criteria and removing the duplicates. Seven relevant articles were identified. The Critical Appraisal Skills Programme (CASP) tool was used to critique the papers.

Results

Five articles were quantitative, one was qualitative and one a literature review. The key methods identified were Early recognition/diagnosis, Erythropoiesis-stimulating agent (ESA) administration/Patient Education (PE) for self-administration and iron supplementation oral or intravenous (IV) for effective anaemia management and to improve quality of life. All of these are priorities in the patient-centred care process, allows patients to be involved in their treatment, medical decisions and to achieve the goal.

Conclusion

This literature review highlights the importance of how anaemia can be best managed in people with kidney disease not receiving dialysis.

Introduction

Chronic Kidney Disease (CKD) is defined by abnormalities of kidney structure or function that occur for more than three months. A CKD audit by Nitsch et al., (2017) estimated the prevalence of CKD stage 3-5 in the UK is around 5.5%-6%. The global prevalence of CKD is estimated as 8-16% and this continues to grow progressively (Wong et al., 2019). CKD is characterised by reduced Erythropoietin production and normochromic normocytic anaemia (Renal Nursing 2019). Anaemia is a common complication of CKD and is a risk factor for poor clinical outcomes and is also associated with a range of adverse effects in CKD patients. Thus, the review is been developed to understand the effective management techniques for anaemia in CKD patients so that their health and well-being can be improved.

Rationale

In normal and CKD patients, severe anaemia is the condition in which the haemoglobin (Hb) level is below 110g/l (NICE, 2018). CKD patients are investigated for their anaemia condition when their Hb falls below 110g/L or less or they develop symptoms of anaemia (NICE, 2018). According to Minutolo et al. (2013), it is estimated that 44% of CKD patients attending the renal clinic are anaemic. In addition, the study by Dmitrieva et al. (2013) mentioned that out of 10% patients in the primary care for CKD in the UK, nearly 6% of them has anaemia as comorbid condition. This indicates the prevalence of anaemia is high in CKD patients. In global context as well as in UK, it is mentioned that iron deficiency is the key reason behind development of anaemia in CKD patients (Ku et al., 2019). Iron Deficiency (ID) is defined as a Ferritin level less than 100ng/l and or transferrin saturation (TSAT) less than 20% (NICE 2015).

The presence of anaemia among the CKD patients is an issue because it supports increased decline of the kidney function leading to increased affinity of early kidney failure in patients CKD. This is because anaemia stimulates the renin-angiotensin-aldosterone system and causes renal vasoconstriction. It results to increased complication related to proteinuria as it increases the level protein in renal tubules which supports increased complication of kidney functioning and early failure (Ueda and Takasawa, 2018). As argued by Covic et al., (2017), anaemia in CKD patients makes them develop increased risk of cardiovascular disease such as tachycardia. This is because the lower level of red blood cell availability in the body is tried to be compensated by the heart through beating faster leading to the cardiac condition. Thus, it can be seen that anaemia in CKD patients is a key issue because it not only worsens the progression of the disease but also causes increased cardiac output leading to cardiac diseases in people.

The prevalence of anaemia in CKD has currently become an issue because it is found to increases with the progression of CKD to advanced stages ranging from 44% in stage three to 70% in stage 5 (Wong et al., 2019). This indicates CKD increase in stage also influencing worsening of anaemia and vice-versa in patients. The clinical assessment includes potential sources of blood loss, presence of inflammatory disease, and medication history (Atkinson and Warady, 2018). Effective treatment of anaemia reduces the risk of adverse clinical outcomes, symptom burden, and improve quality of life (Palaka, et al 2020). The common treatment for renal anaemia includes an iron replacement for iron deficiency patients and administration of Erythropoiesis Stimulating Agents (ESA) Mikhail, et al (2017). However, it cannot be ensured from the existing studies if the mentioned treatment is effective in managing anaemia in CKD patients or there are additional health treatments available for the better control of the condition (Toft et al., 2020). Thus, as a clinical nurse I will explore how anaemia can be best managed in people with kidney disease not receiving dialysis so that evidence-based care can be developed to be provided to CKD patients in improving their health and well-being.

Aim

The aim of the study is to identify through reviewing the effective treatment for management of anaemia in CKD patients who are not receiving dialysis.

Methods

The systematic review design is used for executing the study. This is because systematic review helps to analyse, review and summarise findings and evidence based on a clearly formulated question to present systematic results useful in resolving the raised query (Saglimbene et al., 2020). The electronic search strategy is to be implemented in gathering information because is time and cost-effective in nature. For this purpose, the online databases are to be used in partnership with the librarian. The searches were carried out between 2012 to 2021 and the databases like CINAHL PLUS, Medline ALL, and EMBASE are used. This is because the databases like CINHAL, Medline and others contains wide number of medical journals and articles from international places which helps in creating critically analytical information for the stud that has high validity (Gafter-Gvili et al., 2019). The search was further refined by using inclusion, exclusion criteria, which included full text, written in the English language, and removing the duplicates. The keywords used in executing the search are anaemia, anaemia management, iron deficiency, non-dialysis CKD, which were added to narrow down the results. A total of 152 articles were identified (39 articles from CINHAL PLUS, 93 from Medline and 20 from EMBASE) and these findings were reviewed on abstracts and titles and 127 articles without relevance were extracted. The next step involved picking 25 articles that are relevant to the topic and reading them in detail from which seven articles were selected for the final review. Table one shows the search process.

Findings

In the search, seven articles are identified to be relevant for the topic as they described the investigations/Diagnosis and other pharmacological methods for anaemia management in Non-Dialysis (ND) CKD patients. Among the studies, two of them were carried out in the USA, one from Ireland, one in the United Kingdom (UK), one in Italy, one in Japan and another is an international cross-sectional study by Wong et al. (2019). The studies by Wong et al. (2020) and Stack et al. (2017) were cross-section in nature and the studies by Kalra et al. (2020), Ino et al. (2019) and Minutolo et al. (2013) used observational design in gathering information in their studies. The study by Park et al. (2018) executed retrospective cohort analysis and Guedes et al. (2020) executed literature review to gather information on Management of anaemia in Non-Dialysis CKD. (Appendix 2)

The real-world prospective observational study by Kalra et al. (2020) had collected data from 256 patients with iron deficiency anaemia from 11 Hospitals across the UK. Patients were followed for 52 weeks after an initial course of intravenous iron to capture the need for retreatment. Data for IV iron dose, blood and iron parameters were collected from patients’ medical records. Quality of life and fatigue symptoms were assessed after four weeks of treatment. The key point identified is that the use of a higher dose of Intravenous (IV) iron is effective for anaemia management and reduced requirement for retreatment. The single centre prospective study by Ino et al. (2019) used a small number of 35 patients as participants with haemoglobin less than 11g/dl assessed for the effect of a Continuous Erythropoietin Receptor Activator (CERA) and its ability to control anaemia in CKD patients. This study examined the blood and urine markers and vital signs every 1-3months for 24 months and the key point identified is that monthly administration of CERA is a safe and effective first-line treatment for anaemia in CKD. A multicentric prospective study by Minutolo et al. (2013) evaluated anaemia management in 755 stage 3-5 patients from nineteen Nephrology clinics for two visits six months apart to identify areas for therapeutic improvement. This study noted a high prevalence of anaemia due to clinical inertia and increased use of IV iron led to better control of anaemia with less need of ESAs.

The international cross-sectional studies by Wong et al. (2019) used data from the Chronic Kidney Disease Outcomes and Practice Patterns (CKDopps) and evaluated the monitoring frequency, prevalence and management of anaemia and iron deficiency patients with stage 3-5. Participants were sequentially or randomly selected from CKD clinics and a total of 6766 patients were included. The study informs that many CKD patients for whom anaemia variation monitoring and screening is essential were left without screening which lead the patients unable to receive timely treatment. It showcased that effective anaemia management in quality manner is not executed in the care environment for CKD patients. The cross-sectional study by Stack et al. (2017) evaluated clinical characteristics and treatment practice of 530 CKD patients across six regions of Ireland accompanied by a national survey questionnaire to get a better understanding of renal anaemia management. In the study, a standardised data collection tool was used to capture relevant information. Even though anaemia is a well-recognised complication of CKD, suboptimal management both in investigation and treatment were noted.

The retrospective cohort analysis by Park et al. (2018) examined overall anaemia management trends from 2006-2015. The patients included in the study were those who had at least two Outpatient Clinic inputs or one inpatient input for CKD. Databases used from Truven market scan commercial and Medicare supplemental were gathered. This study shows an increase in the use of iron supplementation and blood transfusion and the decreased use of ESAs after Food and Drug Administration (FDA, 2011) safety warnings. The literature review by Guedes et al. (2020) highlights the current challenges and patients’ perspective of anaemia. The study describes despite recommendations to monitor anaemia screen every three months, 50% of the patients didn’t have a measurement. The key methods identified throughout this literature review are Early identification/diagnosis, Erythropoiesis-stimulating agent (ESA) administration /Patient Education (PE) for self-administration and Iron supplementation oral or intravenous as effective anaemia management for CKD patients.

Thematic Analysis

Identification/diagnosis of Anaemia in CKD patients

Research emphasises high rates of low screening of Hb and iron stores and undertreatments (Guedes et al., 2020, Wong et al., 2019, Stack et al., 2017 and Minutolo et al., 2013). The study by Stack et al., (2017) shows variability in anaemia management and iron deficiency along with a low screening rate of haemoglobin and iron stores and undertreatments. This study compared Guedes, et al., (2020) led to identify similar findings where CKD patients with anaemia were left untreated with high rates of discontinuation of therapy. Minutolo et al., (2013) found a high prevalence of anaemia, unmet goals for iron and ESA and failure to modify therapy in CKD patients. Also noted were that anaemia remains underdiagnosed and undertreated in routine clinical practice. Wong et al., (2019) study noted variations in prevalence of anaemia and a high proportion of patients not being measured for haemoglobin and iron stores. These variations may be from the country level, the region, lack of clinical guidelines and low utilization of anaemia algorithms. Renal anaemia occurs because of impaired Erythropoietin synthesis often associated with ID and other contributing factors are infection, inflammation, bone marrow deficiencies (Babitt et al., 2012). Studies by Fishbane et al., (2018), Stack et al., (2017) and Minutolo et al., (2013) described anaemia as an easily identifiable and modifiable risk factor for cardiovascular and renal damage, stroke, high mortality and hospitalisation. The lack of anaemia monitoring leads the patients being left untreated and delayed quality improvement. Therefore, early identification and correction of anaemia is an important care component for patients with advanced CKD.

Administration of EPO/PE for self-administration

The studies by Guedes et al., (2020), Ino et al., (2019), Park et al., (2018), Minutolo et al., (2013) described Erythropoietin Stimulating Agent (ESA) playing an important role in the management of anaemia as it helps to improve quality of life, avoid blood transfusions, and prolong kidney prognosis and survival. The Erythropoietin Stimulating Agent (ESA) are medications which causes bone marrow stimulation to create red blood cells needed among anaemia patients. A recent study by Carrero et al., (2020) noted patients who received moderate ESA doses express relatively low prevalence of iron use and a higher dose associated with inflammation and major cardiac events. Minutolo et al., (2020) found the use of short-acting ESAs may be associated with an increased risk of end-stage kidney disease or death compared with long-acting ESAs. Minutolo et al., (2013) found non-compliance of Erythropoietin (EPO) among patients. In order to manage anaemia especially among non-dialysis patients with low eGFR and haemoglobin levels less than 10g/L, EPO use is in weekly or fortnight manner is prescribed for them as the common care practice (Wong et al., 2019). As anaemia remains the modifiable risk factor for CKD, educating patients for self-administration of EPO to manage their condition is more effective. This is because patients on understanding the function of the kidney and developing knowledge of the disease, they can actively participate in the treatment program by considering the need of EPO use that includes self-administration of the medication. The American Association of Kidney Patients survey showed the provision of patient information is associated with greater willingness to comply with treatment and be active in successful therapy (1999). The use of EPO is convenient and flexible, safe, and effective for anaemia management. Park, et al (2018) study noted a decrease in use of EPO.

Iron Supplementation Oral or Intravenous

In the study, six of the chosen articles discussed the effective use of iron supplementation oral or IV for iron deficiency anaemia management (Kalra et al., (2020), Wong et al., (2020), Gudedes et al., (2020), Park et al., (2018), Stack et al., (2017) and Minutolo et al., (2013)). Anaemia was found in up to 70% in the advanced stage of CKD patients and among them prevalence of iron deficiency is found to be high (Gudedes et al., 2020). Iron deficiency among CKD stage 4-5 using the WHO criteria was 30% in Ireland (Stack et al., 2017). Agarwal et al., (2015) executed randomised trial to evaluate IV and Oral Iron in CKD. The trial noted the use of IV iron associated with risk of infection and cardiovascular complications. In contrast, the Ferrinject Assessment in patients with iron deficiency and anaemia (FIND-CKD) by Bock et al. (2016) noted the use of IV iron contributed to improving anaemia with no safety concerns. It is also noted ESA induced iron deficiency can increase platelet count and IV iron can reduce platelet count and improve thrombocytosis (Hazara et al., 2015). Iron deficiency is an important clinical concern and replacing the deficiency and correcting anaemia leads to improved quality of life and decreased EPO requirement (Macdougall et al (2014). Kalra et al. (2020) found a higher initial dose of intravenous iron achieved a greater haemoglobin response and reduced the total number of appointments compared with a lower dose.

Discussion

Anaemia management in CKD patients depends on various parameters including intervention, haemoglobin and iron threshold targets, clinical assessment and impact of therapy. In the current pandemic condition, the limited space of availability contributes towards low screening of haemoglobin and iron stores and anaemia monitoring but by maximising the clinical space and effective utilization, the investigation process can be improved. Clinically it is observed that the weekly dose of EPO is as effective as the same total dose administered two or three times weekly. Patient Education (PE) should include a clear explanation of renal function, blood pressure control along with a patient information leaflet that may encourage patients to actively participate in their treatment. Multidisciplinary patient education facilitates improvement in compliance with therapy and better input is needed. This is because educating patients on the management of renal anaemia is vital to facilitate self-administration of EPO and encourage closer collaboration between patients, medical team, pharmacist, and renal nurse for the development of treatment regimens. Subcutaneous administration of EPO is more convenient, flexible, and effective than intravenous due to the lower absorption and longer half-life and enables dose reduction of EPO and results in cost benefits. Early treatment of anaemia with EPO leads to a decrease in cardiovascular morbidity and mortality and delays the disease progression. Checking patients’ compliance and educating more nurses to carry out the patient education section is also vitally important (Golper, 2001).

The delivery of high dose of IV iron low frequency helps to reduce venepuncture and this is an important matter for vein preservation for future Arteriovenous Fistula (AVF) creation in CKD patients with anaemia. It is essential for the nurses to inform the risk related with iron delivery to CKD patients with anaemia through information leaflets so that the patients are aware of the probable actions to be faced as a result of the treatment been provided ineffectively. Reporting adverse effects, record keeping, documentation and follow-up are vitally important. Giving a high dose e.g., 1g of IV iron low frequency helps to reduce hospital visits, especially during this pandemic period and improve clinical benefit. Checking the effects and side-effects of iron supplementation with a patient is important as well as educating patients to take oral iron with a full glass of water according to their fluid allowance. Replacing the iron deficiency and maintaining the replete state is the key for renal anaemia management Macdougall et al (2014).

Conclusion

This literature review highlights the importance of anaemia management by an early identification of anaemia and the effective treatment with various treatment choices e.g., ESAs or iron supplementation. Patient education and self-administration of EPO. As anaemia management merit with the investigation, target threshold of Hb and iron stores, ethiology and impact of treatment and medication history. Empowering patients with the knowledge and encouraging them to self-manage is promoting patient-centred care. The current use of ferric carboxymaltose effectively corrects the iron deficiency and patient experience as well as cost-saving. Therefore, further research needs to evaluate the significant effects of the treatments and to gain insight into anaemia in kidney disease. The use of an anaemia specialist nurse with regards to coordination and implementation of evidence-based practice. The role of the specialist nurse is essential in assisting patients and staff to manage anaemia more effectively and thereby improve quality of life.

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