Erythropoietin Deficiency Research Articles

EPO Deficiency Upregulates GADD45b/p38 MAPK Axis, Mediating Schizophrenia-Related Synaptic and Cognitive Impairments.

Schizophrenia (SZ) is a chronic and severe mental illness associated with psychiatric symptoms, cognitive deficits, and social dysfunction. Current clinical interventions only limit relief of psychiatric symptoms and have minimal impact on cognitive impairments. Erythropoietin (EPO), known for its role in neurogenesis and synaptic plasticity, is significantly low in SZ patients. However, the role of EPO deficiency in SZ-associated cognitive deficits remains unclear. In this study, we used the MK801-induced SZ rat model to show that EPO levels were significantly decreased, correlating with cognitive impairments. EPO supplementation mitigated apoptosis, synaptic damage, and cognitive impairments caused by MK801. RNA-sequencing and Western blot analysis revealed increased expression of growth arrest and DNA damage 45b (GADD45b) in MK801-treated rats, reversed by EPO supplementation. Moreover, overexpression of GADD45b exacerbated neuronal loss and cognitive impairments in male Sprague-Dawley rats, while downregulation of GADD45b rescued these SZ-related pathologies. Notably, the benefits of EPO supplementation on SZ pathology were blocked by GADD45b overexpression. Inhibition of p38 MAPK, a GADD45b target, reduced MK801-induced apoptosis and synaptic damage. These findings uncover a novel etiopathogenic mechanism of SZ-related cognitive impairments, driven by EPO deficiency and the activation of the GADD45b/p38 MAPK axis.

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease.

Anemia plays an important role in chronic kidney disease (CKD) progression because it worsens the quality of life and increases the risk of cardiovascular complications in CKD patients. In such cases, anemia is mainly caused by endogenous erythropoietin (EPO) and iron deficiencies. Therefore, KDIGO and ERBP guidelines for anemia treatment in CKD patients focus on recombinant EPO and iron supplementation. A recent new treatment option for anemia in CKD patients involves blocking the hypoxia-inducible factor (HIF) system with prolyl hydroxylase inhibitors (PHIs), what causes increasing endogenous EPO production and optimizing the use of iron. Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript-roxadustat, vadadustat, daprodustat, and molidustat-effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. Moreover, these medicines reduce blood lipid levels and do not accelerate CKD progression. However, blockage of the HIF system by HIF-PHIs may be associated with adverse effects such as cardiovascular complications, tumorogenesis, hyperkalemia. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients.

Anemia of Chronic Kidney Disease-A Narrative Review of Its Pathophysiology, Diagnosis, and Management.

Anemia is one of the most common chronic kidney disease (CKD) complications. It negatively affects patients' quality of life and clinical outcomes. The pathophysiology of anemia in CKD involves the interplay of various factors such as erythropoietin (EPO) deficiency, iron dysregulation, chronic inflammation, bone marrow dysfunction, and nutritional deficiencies. Despite recent advances in understanding this condition, anemia still remains a serious clinical challenge in population of patients with CKD. Several guidelines have been published with the aim to systematize the diagnostic approach and treatment of anemia; however, due to emerging data, many recommendations vary between publications. Recent studies indicate a potential of novel biomarkers to evaluate anemia and related conditions such as iron deficiency, which is often present in CKD patients. Our article aims to summarize the pathophysiology of anemia in CKD, as well as the diagnosis and management of this condition, including novel therapeutic approaches such as hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI). Understanding these complex subjects is crucial for a targeted approach to diagnose and treat patients with anemia in CKD effectively.

#2815 Single center, single arm, prospective, observational study of desidustat in chronic kidney disease-induced anemia

Abstract Background and Aims Anemia in chronic kidney disease (CKD) is multifactorial. Relative deficiency of erythropoietin is one of the key reasons for decreased RBC production. This anemia is associated with poor quality of life and increases morbidity in CKD patients. Injectable erythropoietin is the standard of care for CKD-anemia, which has safety concerns. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), stimulates endogenous erythropoiesis and is approved for CKD anemia treatment. Hence, the present study identifies the real-world clinical efficacy and safety of the desidustat treatment for a short duration in CKD anemia. Method This is an open-label, single-center, prospective study. We analyzed the data of 130 patients who are currently in follow-up and received Desidustat as treatment for CKD-anemia. The study is for the duration of 24 weeks. We followed up on patent at 1 month, 3 months, and the end of the study (6 months). Patients were given a 100-mg Desidustat tablet orally three times in a week. The primary outcome is to assess the change in Hb from baseline, and the secondary outcome is the safety of the therapy. Results In this study, we enrolled 130 patients. Of these 130 patients, 58.4% (n = 76) were male and 41.5% (n = 54) were female. The mean age of the study population was 53.6 ± 12.3 years. The majority of the study population was in the pre-dialysis category; 80% (n = 104) and 20% (n = 26) were on dialysis. All the dialysis patients were on three times per week on Dialysis. Diabetes (68%) and hypertension (75%) are the most common co-morbid conditions in patients with CKD anemia. All the patients received desidustat at a 100 mg, three-weekly dose. During each follow-up visit, a significant rise in hemoglobin was observed (p<0.001), as shown in the figure. With desidustat therapy, adverse drug reactions were seen in 5.3% (n = 7) cases: three cases of abdominal pain, two cases of vomiting, and two cases of diarrhea. Conclusion Oral HIF-PHIs and Desidustat showed significant improvement in hemoglobin in CKD anemia patients. More studies require for safety and efficacy in Dialysis dependent CKD - Anemia patients.

Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction.

Chronic kidney disease (CKD) affects around 850 million people worldwide, posing significant challenges in healthcare due to complications like renal anemia, end-stage kidney disease, and cardiovascular diseases. This review focuses on the intricate interplay between iron metabolism, inflammation, and renal dysfunction in CKD. Renal anemia, prevalent in CKD, arises primarily from diminished erythropoietin (EPO) production and iron dysregulation, which worsens with disease progression. Functional and absolute iron deficiencies due to impaired absorption and chronic inflammation are key factors exacerbating erythropoiesis. A notable aspect of CKD is the accumulation of uremic toxins, such as indoxyl sulfate (IS), which hinder iron metabolism and worsen anemia. These toxins directly affect renal EPO synthesis and contribute to renal hypoxia, thus playing a critical role in the pathophysiology of renal anemia. Inflammatory cytokines, especially TNF-α and IL-6, further exacerbate CKD progression and disrupt iron homeostasis, thereby influencing anemia severity. Treatment approaches have evolved to address both iron and EPO deficiencies, with emerging therapies targeting hepcidin and employing hypoxia-inducible factor (HIF) stabilizers showing potential. This review underscores the importance of integrated treatment strategies in CKD, focusing on the complex relationship between iron metabolism, inflammation, and renal dysfunction to improve patient outcomes.

Korelasi Kadar Ureum Dan Kreatinin Pada Pasien Anemia Di RSU Duta Mulya Majenang

Anemia caused by a deficiency of erythropoietin can occur in patients with chronic kidney disease. Kidney function refuses to produce erythropoietin in equal measure, as a result there is a tendency for a linear relationship between hemoglobin level and glomerular filtration rate in patients with kidney disease. One way to diagnose kidney failure is by assessing or measuring serum urea and creatinine levels, because these two compounds can only be excreted by the kidneys. The aim of the study was to determine the correlation between urea and creatinine levels in anemic patients at Duta Mulya Majenang Hospital. This type of research was descriptive with a cross-sectional study design, with a sample of all anemic patients who were examined for urea and creatinine at Duta Mulya Majenang Hospital in January - March 2023 according to the inclusion and exclusion criteria, a total of 66 samples. The results showed that the majority of patients with chronic kidney failure were elderly, namely aged 46-65 years with a total sample of 43 patients (65.2%) and mostly suffered by women as many as 35 patients (53.0%). The correlation between urea and creatinine levels in all samples showed results that exceeded normal values. The conclusion of this study is that there is a correlation between serum urea and creatinine levels in anemic patients at Duta Mulya Majenang Hospital.

ERYTHROPOIETIN SYNTESIS IN PATIENTS WITH CHRONIC HEART FAILURE DEPENDING ON COMORBID PATHOLOGY

Introduction. Decreased production of erythropoietin by the kidneys plays crucial role in the development of anemia in patients with chronic heart failure, especially on the background of comorbid diabetes mellitus type 2. In diabetic patients due to early damage of the kidney vessels and following erythropoietin deficiency anemia develops much earlier than clinically significant decrease of glomerular filtration rate.
 The aim of the study was to find out possible dependence of changes in the erythropoietinsynthesizing function of the kidneys on the degree of severity of anemic hypoxia in elderly and senile patients with chronic heart failure, including those with comorbid type 2 diabetes mellitus.
 Materials and methods. 120 patients with chronic heart failure of ischemic origin, type 2 diabetes mellitus and mild and moderate anemia were examined. Control group comprised 12 people with chronic heart failure without comorbid pathology. The examined groups were comparable in terms of gender and age, differing in the presence of comorbid diabetes mellitus and degree of severity of anemic syndrome. The level of erythropoietin in blood serum was determined by standard enzymelinked immunosorbent assay.
 Results. Type 2 diabetes mellitus in patients with chronic heart failure results in a significant decrease in erythropoietin production by 25 % compared to the control group (p<0,05). Comorbid to heart failure anemia leads to an increase in the level of erythropoietin by 74,4 % (р<0,05), and in the case of chronic heart failure and type 2 diabetes mellitus on the background of concomitant anemia – only by 39,5 % (р<0,05). As the severity of anemia in patients with chronic heart failure without diabetes progresses, the severity of the compensatory response of the kidneys to chronic anemic hypoxia is significantly higher than in patients with heart failure and comorbid type 2 diabetes.
 Conclusions. Diabetic nephropathy in patients with chronic heart failure and comorbid anemia leads to a significant deterioration of the erythropoietin-synthesizing function of the kidneys, complicating the course of both main and comorbid diseases.

Low hemoglobin levels are associated with Bowman’s capsule rupture and peritubular capillaritis in ANCA-associated renal vasculitis: a link of vascular injury to anemia?

BackgroundAnemia in anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis is a severe complication that predicts renal survival. We here conducted correlative analyses to evaluate correlations of low hemoglobin levels and histopathological characteristics in ANCA-associated renal vasculitis.MethodsFifty-two patients with biopsy-proven ANCA-associated renal vasculitis observed between 2015 and 2020 were retrospectively evaluated. Spearman’s correlation was performed to assess correlations, and statistical evaluation was performed by simple and stepwise multivariable regression.ResultsRegarding laboratory anemia parameters, no significant association with serum hemoglobin levels was observed. Serum hemoglobin levels were associated with the estimated glomerular filtration rate in the total cohort (β = 0.539, p < 0.001), and in the MPO-ANCA subgroup (β = 0.679, p = 0.008). Among tubulointerstitial lesions, decreased serum hemoglobin levels correlated with peritubular capillaritis in the whole cohort (β = − 0.358, p = 0.013), and was suggested in the MPO-ANCA subgroup (p = 0.029, r = − 0.446). Regarding glomerular lesions, the prevalence of necrotic glomeruli significantly associated with low serum hemoglobin levels in PR3-ANCA (β = − 0.424, p = 0.028). In the total cohort, a significant correlation between decreased serum hemoglobin levels and the occurrence of diffuse Bowman’s capsule rupture was identified (β = − 0.374, p = 0.014), which was implied in the MPO-ANCA subgroup (p = 0.013, r = − 0.546; p = 0.0288, slope = − 16.65).ConclusionPeritubular capillaritis and Bowman’s capsule rupture correlate with low hemoglobin levels; this may indicate that histopathological lesions are linked with inflammatory vascular injury and relative erythropoietin deficiency in ANCA-associated renal vasculitis.Graphical abstract

Serum Erythroferrone in End Stage Renal Disease Patients: Relation to Iron Status, Anaemia and Erythropoiesis Stimulating Agents

Abstract Background Anaemia is a hallmark of chronic kidney disease (CKD), where erythropoietin deficiency and reduced iron availability by the negative iron regulator, hepcidin, are principal causes of the anaemia. Erythroferrone (ERFE), a hormone synthesized by erythroblasts, is a hepcidin inhibitor and increases iron absorption and mobilization, resulting in erythropoiesis stimulation. Thus, ERFE could be considered as one of potential clinical biomarkers for assessing erythropoiesis. Moreover, it has been found that ERFE is produced in response to erythropoietic stimulating agent (ESA) in CKD and thus could have a role in cure from anaemia in those patients. However, few studies focused on understanding the role of this hormone in the regulation of iron homeostasis. Aim of the Work To study the correlation between ERFE level and iron parameters and its response to iron/ESA in end stage renal disease (ESRD) patients with iron deficiency anaemia. Study design and methods A case-control study was carried out on 40 ESRD patients (GFR &amp;lt; 15 ml/min/1.73 mm3) with evidence of iron deficiency anaemia. Patients were further subdivided into 2 subgroups, where subgroup I included patients who received both iron and ESA (Erythropoietin) (n = 28) and subgroup II patients who were treated with iron only (n = 12). Ten age &amp; sex matched normal healthy subjects were included in the study as a control group. The studied parameters (ERFE, Hb, HCT%, MCV, MCH, serum iron, TSAT% and TIBC) were measured at baseline and then revaluated three months later after iron/ESA therapy. Erythroferrone was measured (baseline and post iron/ESA treatment) by ELISA. Results The present study was conducted on 40 ESRD patients with male to female ratio 1:1.5. Their mean age was 51.03±11.22 years and mean dry weight 73.4±13.08 Kg. The commonest risk factor was hypertension (32.5%). Treatment with iron ± EPO results in significant increase of Hb and serum iron in both patients' subgroups (p ˂ 0.001). Baseline and post treatment ERFE levels were higher in patients’ groups than in the control group with significant statistical difference (p = 0.016 &amp; 0.023 respectively). The highest level was in those patients treated with both iron and EPO (212.31±106.33 ng/L at baseline &amp; 520.00±255.26 post treatment). Positive correlation of ERFE level with both Hb and serum Iron (p-value &amp;lt;0.05) was detected. Conclusion Managing anaemia in ESRD patients remain a significant unmet challenge in those patients. Insight into iron homeostasis is important in order to develop new diagnostic as well as therapeutic modalities. Our study proved that ERFE is associated with iron/EPO therapy and positively correlated with hemoglobin and serum iron levels. Thus, ERFE could play a key role in the assessment of erythropoietic activity, as well as, in the treatment process among those patients in status of iron deficiency or iron overload.

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease.

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.

An Overview of Safety and Efficacy Between Hypoxia-Inducible Factor-Prolyl-Hydroxylase Inhibitors and Erythropoietin-Stimulating Agents in Treating Anemia in Chronic Kidney Disease Patients.

Anemia is one of the common complications in chronic kidney disease (CKD) patients. Erythropoietin and iron deficiencies are the major causes to develop anemia in CKD patients. Untreated anemia is associated with increased morbidity and mortality. Erythropoietin-stimulating agents (ESA) with iron supplementation are the standard for treating renal anemia. Although ESA with iron supplementation is an effective therapy in maintaining serum hemoglobin (Hb) levels, it increases the risk of several life-threatening adverse events such as hypertension, thromboembolism, cardiovascular morbidity, and mortality with long-term use. Therefore, effective alternate therapy with better safety and efficacy is needed to treat renal anemia. The newer oral therapy hypoxia-inducible factor-prolyl-hydroxylase inhibitors (HIF-PHI) can potentially be an effective alternative therapy in treating renal anemia. This review article compares the safety and efficacy between HIF-PHI and ESA in treating anemia in CKD patients. We conducted a comprehensive literature review of articles, including clinical trials, meta-analyses, and reviews, that compared the safety and efficacy between HIF-PHI and ESA. Studies have shown that the newer oral therapy, HIF-PHI, was non-inferior to ESA to maintain serum Hb levels in CKD patients. Moreover, the adverse event profile was almost similar in both groups. However, as the studies we reviewed have small sample sizes and short duration periods, the long-term effectiveness and safety of HIF-PHI over ESA in treating renal anemia cannot be established.

Impact of erythropoietin on anemia in end-stage renal disease patients on hemodialysis

Abstract Background: End-stage kidney disease occurs when the estimated glomerular filtration rate is not more than 15 mL/min/1.73 m2 or when the patient requires long-term renal replacement therapy regardless of estimated glomerular filtration rate. Anemia is observed as a frequent comorbid complication of chronic kidney disease (CKD). Erythropoietin (EPO) deficiency is the crucial cause of CKD-anemia development. Objectives: The aim of study was to determine the impact of EPO on anemia in end-stage renal disease patients on hemodialysis (HD). Materials and Methods: This study was a cross-sectional study. A total of 80 patients (42 men and 38women) at end-stage renal disease planned for HD program at Al-Hakeem general hospital in Al-Najaf city/Iraq in period between November 2020 and February 2021. Many information and analyses were taken such as age, sex, cause of end stage, blood urea, serum creatinine and albumin, hemoglobin, dose of EPO, blood pressure, and body weight. Results: The results of study showed that, the level of hemoglobin (g/dL) significantly increased from (8.24 ± 1.77) to (9.57 ± 1.35) after treatment with EPO (P value &lt; 0.05), whereas the levels of blood urea (mg/dL), albumin (g/L) significantly decreased from (218.51 ± 74.47) to (145.76 ± 42.47) and from (40.65 ± 6.35) to (36.56 ± 6.03) respectively, after treatment with EPO (P value &lt; 0.05). additionally, there are no significant differences in serum creatinine (mg/dL) and blood pressure after treatment with EPO. Conclusion: EPO has a positive role on renal function and in treating anemia in end-stage renal disease patients on HD.

Clinico-pathological correlation study in chronic kidney disease patients undergoing hemodialysis

Chronic Kidney Disease (CKD) is a global health problem and associated with increased morbidity and mortality. Hemodialysis is the most common mode of renal replacement in end stage kidney disease. Variation in hematological and biochemical parameters are the prime factors responsible for morbidity and mortality in CKD patients. Normocytic Normochromic Anemia is a typical morphology seen in CKD patients resulting due to erythropoietin deficiency. Early detection and treatment of these pathologies can improve the quality of life in CKD patients.: 1) To evaluate the clinical manifestations and various pathological changes associated with CKD patients on hemodialysis. 2) To compare and correlate various clinico-pathological parameters in CKD patients on hemodialysis, with special emphasis on diabetic kidney disease.: One year eleven months retrospective study was done at CIMS hospital, which included 50 CKD patients. Complete clinical data were recorded and correlated with various hematological and biochemical parameters. Statistical analysis was performed by chi square test and student’s T test. Out of 50 CKD patients, 86% were male, age group of 41-50 years (62%). The commonest co-morbidity was combined hypertension with diabetes in 44%. Majority (72%) had BP between 140-159mmHg. Most (64%) of the CKD patients were known cases of diabetes. Significantly lower levels of RBC count, hemoglobin, hematocrit and platelet count were found with normocytic normochromic anemia being the commonest morphological type. Significantly increased WBC counts, ESR, serum urea, creatinine and serum phosphate levels were noted in CKD patients. DKD patients showed significant risk compared to NDKD patients. CKD is a progressive, irreversible disease. We found alterations in various haematological and biochemical parameters, which were more severe among DKD patients compared to NDKD patients. Early recognition and management of these changes will have an important impact in improving the quality of life.

FADOI survey on chronic kidney disease and anaemia in internal medicine departments of Italian hospitals

The presence of anaemia in patients with chronic kidney disease (CKD) is associated with decreased quality of life, along with increased morbidity, mortality, and hospitalization rates. This, in turn, affects healthcare costs and the utilization of medical resources. The mechanisms involved in anaemia of CKD are diverse and complex. They include reduced production of endogenous erythropoietin (EPO), absolute and/or functional iron deficiency (due to inflammation leading to elevated levels of hepcidin), the diminished response of the bone marrow to EPO due to uraemic toxins, the shortened lifespan of red blood cells (RBC), and deficiencies in vitamin B12 or folic acid. [...]

Prevalence of anemia in dialysis patients in Northwestern of Libya

Background. Chronic kidney disease (CKD) is renal dysfunction leads to failure in the body's ability to maintain metabolic, fluid electrolytes, and balance. It mostly results in uremia or azotemia and can be classified into stages 1 to 5 based on the deterioration of glomerular filtration rate (GFR. These complications lead to the deficiency of erythropoietin (EPO) possible iron loss in patients on hemodialysis are considered the main factors in contributing anemia in CKD patients.

Anemia in chronic kidney disease

Anemia is one of the earliest and most frequent complications of chronic kidney disease (CKD). Anemia is associated with poor quality of life, increased cardiovascular morbidities and mortalities, and accelerated progression of renal function decline. Although the pathogenesis of anemia in CKD is multifactorial, absolute or relative erythropoietin (EPO) deficiency is central to it. Iron deficiency is the second most important cause of anemia. EPO-stimulating agents and iron replacement had been central in the management of anemia of CKD. Newer information regarding the role of hypoxia-inducible factor (HIF) mediating EPO release has the potential to change the current management paradigm. Orally administered HIF inhibitors are shown to be safer and have similar efficacy compared to ESAs, and may become the mainstay of treatment of CKD anemia.

Anemia on Chronic Kidney Disease: The Role of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors

Anemia is one of the homeostatic abnormalities caused by chronic kidney disease and also frequently problem encountered in end-stage renal disease patients, regardless of the hemodialysis treatment. Anemia in chronic kidney disease significantly impairs kidney function, increases morbidity and mortality risk, and deteriorates the quality of life. Chronic kidney disease’s patients with anemia conditions are affected by numerous factors, including decreased production of endogenous erythropoietin, functional and absolute iron deficiency, and elevated hepcidin levels due to inflammation, particularly in hemodialysis patients. Treatment options for anemia in chronic kidney disease include exogenous erythropoietin and iron supplementation. A new mechanism known as the "hypoxia-sensing system" termed a mediator of erythropoietin synthesis, has been proposed to boost endogenous erythropoietin synthesis. The hypoxia-inducible factor activates specific gene expression and contributes to a physiological response to lower tissue oxygen levels. Chronic kidney disease’s patients who are contraindicated or are hyporesponsive to therapy with erythropoiesis-stimulating drugs may utilize this mechanism as an alternative.

Erythropoietin-Resistant Therapy in Routine Hemodialysis Patients: A Case Report

Background: Anemia in chronic kidney disease can be caused by erythropoietin deficiency. Erythropoietin stimulating agent (ESA) is the treatment of choice for anemia in patients with chronic kidney disease. Some patients for some reason fail to reach target hemoglobin levels despite maximal ESA doses. Case illustration: We reported a 58-year-old man suffering from CKD with recurrent anemia despite the maximum dose of ESA. The investigations showed secondary hyperparathyroidism due to complications of chronic kidney disorders. Discussion: Our patient's resistance to erythropoietin therapy was caused by inadequate dialysis and secondary hyperparathyroidism. The management is focused on the adequacy of hemodialysis and the management of secondary hyperparathyroidism with nutrition and medication. Keywords: anemia, kidney failure, hemodialysis, hyperparathyroidism.

Response to Treatment with Erythropoietin in Chronic Kidney Disease Patients with Protein Energy Wasting in Homa Bay Teaching and Referral Hospital, Kenya

Anemia is one of the major causes of morbidity in Chronic Kidney Disease (CKD). There are many causes of anemia in CKD, but the main cause is erythropoietin deficiency. CKD patients on hemodialysis have a high protein-energy wasting (PEW) prevalence that may explain Erythropoietin's (EPO) hypo-responsiveness. This study aimed to evaluate the response to EPO treatment in CKD patients with PEW in Homa County Teaching and Referral Hospital. The study was a retrospective medical chart review of patients on hemodialysis in 2018 and 2019 at Homa Bay County Teaching and Referral Hospital. The patients were classified according to PEW diagnostic using the Subjective Global Assessment tool and the Malnutrition Inflammation score tools. PEW prevalence was 41.2% while the prevalence for anemia was 85.3%. The mean hemoglobin at the onset of EPO treatment for patients with PEW and patients without PEW was 8.71 ± 1.82 and 9.53±1.90 g/dl while the final mean hemoglobin was 9.35±1.95 and 10.7±1.86 g/dl respectively. Differences between groups with PEW and groups without PEW were analyzed considering their responsiveness and a statistically significant improvement was recorded in patients without PEW after EPO administration (p-value=0.04). The relative risk of EPO resistance, considering 95 % confidence interval, was 0.3 with a range of 0.109 – 0.825. The risk of poor response to EPO treatment was reduced to 30 % in patients without PEW. This study concluded that PEW contributes to poor response to EPO treatment in hemodialysis patients. It is therefore important to correct wasting in these patients to improve response to EPO treatment. Key words: Anaemia, Erythropoietin, Protein Energy Wasting, Chronic Kidney Disease