Anemia In Chronic Kidney Disease Patients Research Articles

ANEMIA PATTERN IN PATIENTS WITH CHRONIC KIDNEY DISEASES PRESENTED AT TERTIARY CARE HOSPITAL

Anemia is a common complication in patients with chronic kidney disease (CKD) and contributes significantly to morbidity. Understanding the patterns and severity of anemia within this population can guide more effective management strategies. Objective: To assess the pattern and severity of anemia in patients with chronic kidney disease. Methods: This cross-sectional study was conducted from January 2024 to July 2024, involving 250 anemic CKD patients aged 18 years and above. The study was carried out at a nephrology care facility, with participants selected based on predefined inclusion and exclusion criteria. Data on demographic information, laboratory profiles, and anemia patterns were collected. Anemia was classified into mild, moderate, and severe categories. Statistical analysis was performed using SPSS version 24 to establish associations between the severity of CKD and the type of anemia. Results: Among the patients, 59.2% had normochromic anemia, 18.8% had hypochromic anemia, and 14% had macrocytic anemia. Moderate anemia was the most prevalent severity, observed in 51.2% of cases, followed by mild anemia in 41.6% and severe anemia in 7.2%. A significant association was noted between the severity of CKD and the type of anemia, particularly with normochromic anemia being more prevalent in patients with moderate CKD. Conclusion: The study concludes that normochromic anemia is the most predominant pattern of anemia in CKD patients, followed by hypochromic and macrocytic anemia. These findings underscore the importance of regular monitoring and tailored anemia management in CKD patients to improve overall patient outcomes.

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.

Anaemia and Chronic Kidney Disease: A Brief Review on the Direction of Their Relationship

Chronic kidney disease (CKD) is a significant global health concern, affecting approximately 10% of the adult population worldwide. Anaemia is the common complication in CKD, which severely impacts patient quality of life and increases the risk of cardiovascular complications. The primary cause of anaemia in CKD patients is insufficient production of erythropoietin (EPO), a hormone essential for red blood cell production, due to impaired kidney function. Other contributing factors include disruptions in iron metabolism, chronic inflammation, and elevated hepcidin levels, which hinder iron absorption and availability. Anaemia exacerbates symptoms such as fatigue, weakness, and cognitive impairment in CKD patients, significantly diminishing their daily functioning and overall well-being. Effective management of anaemia in CKD patients necessitates a comprehensive approach involving regular monitoring of haemoglobin and iron levels, timely administration of treatments such as EPO and intravenous iron, and addressing underlying causes. This review provides an overall overview of the pathophysiological connections, clinical implications, diagnosis, and management strategies for anaemia in CKD patients, highlighting the need for ongoing research and integrated care approaches.

Anemia and Iron Profile in Hemodialysis and Nonhemodialysis Patients with Chronic Kidney Disease

Abstract BACKGROUND: Chronic kidney disease (CKD) is a global health concern, with anemia being a significant complication. Anemia in CKD patients is multifactorial and often leads to poorer outcomes. Assessing the iron profile, including serum ferritin, iron, and transferrin saturation, is crucial for identifying absolute or functional iron deficiency anemia (IDA). An objective evaluation of the iron profile is essential for effective and comprehensive management of anemia. MATERIALS AND METHODS: The study involved 100 adult patients with CKD and anemia, who were divided into two groups based on age and sex. The patients were divided into two groups: one received regular hemodialysis (HD) 2–3 times per week, whereas the other received no dialysis or dialysis infrequently. Exclusion criteria included infections, inflammation, renal injury, neoplasms, acute hemolysis, and thalassemia. RESULTS: Anemia is a common complication in patients with CKD, both those on HD and non-HD. Among the types of anemia observed, 50% of HD patients and 72% of non-HD CKD patients have normochromic anemia. In addition, 46% of HD patients and 24% of non-HD patients have IDA. Specifically, 24% of HD patients have absolute IDA and 22% have functional IDA, compared to 12% of both absolute and functional IDA in non-HD CKD patients, with a significant statistical difference between the two groups. Furthermore, serum iron and transferrin saturation levels show significant differences between HD and non-HD CKD patients. CONCLUSION: Anemia, especially IDA in CKD patients undergoing HD, requires accurate diagnosis through transferrin saturation and serum iron levels, and customized treatment based on dialysis status and anemia type is crucial.

Pharmacokinetics, Pharmacodynamics, and Safety of Vadadustat in Healthy Volunteers and Patients with Chronic Kidney Disease.

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). Single ascending dose (SAD) and multiple ascending dose (MAD) studies assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of vadadustat in healthy volunteers. A single-dose, open-label study was conducted in patients with CKD stages 3 and 4 not on dialysis. In the SAD study, 48 healthy adult men (n = 8/cohort) received single doses of vadadustat (80-1,200 mg) or placebo. In the MAD study, 34 healthy adult men (n = 8-9/cohort) received daily vadadustat (500-900 mg) or placebo for 10 days. In the single-dose CKD study, 22 male and female patients with CKD (stage 3: n = 10; stage 4: n = 12) received single doses of vadadustat (500 mg). PK parameters included plasma vadadustat; PD biomarkers were measured, including erythropoietin (EPO) levels, reticulocytes, and others. Plasma vadadustat peaked 3-4 hours after single or multiple dosing in healthy volunteers, with a mean t 1/2 of approximately 4.5 hours. In patients with CKD, plasma vadadustat peaked at 5-6 hours, with a mean t 1/2 of 7.2 (stage 3) and 8.5 (stage 4) hours. Vadadustat AUC∞ and C max increased dose proportionally in SAD and MAD trials. In all trials, EPO concentrations increased in a dose-related manner and returned approximately to baseline by 24 hours. Adverse events were mild and considered not study drug related. The PK and PD results of these studies were utilized for further clinical development of vadadustat for treatment of anemia in CKD patients.

Assessment of the safety of Roxadustat for cardiovascular events in chronic kidney disease-related anemia using meta-analysis and bioinformatics.

This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat. We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as "ESA," "Roxadustat," "MACE," "stroke," "death," "myocardial infarction," and "heart failure." Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for "Roxadustat" and "human," and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis. A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation. The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.

#206 The effect of dapagliflozin on anemia in patients with CKD

Abstract Background and Aims SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients. Method We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy. Results Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p &amp;lt; 0.01) before and after initiating SGLT2i therapy. Conclusion The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.

Iron biology.

Iron is a fundamental element for biological life, from bacteria to humans. Iron is essential for cell function and survival, energy production and metabolism, whereas increased levels cause oxidative stress. It is also a constituent of haemoglobin and thus it is necessary for oxygen transportation through the body. Given these multiple functions, the regulation of iron metabolism is complex and tight coupled with oxygen homeostasis at tissue and cellular levels, thanks to the interaction with the hypoxia inducible factor system. In patients with chronic kidney disease (CKD), iron deficiency significantly contributes to anaemia development. This frequently overlaps with chronic inflammation, causing iron- restricted erythropoiesis. To add further complexity, metabolic hyperferritinemia may, on one hand, increase the risk for CKD and, on the other, overlaps with functional iron deficiency. Excessive intracellular iron in certain cell types during CKD can also mediate cellular death (called ferroptosis), and contribute to the pathogenesis of kidney damage, atherosclerosis and vascular calcifications. This review is aimed at broadening the perspective of iron metabolism in the setting of CKD not just as a contributor to anaemia in CKD patients, but also as an important player with an impact on cell metabolism, renal fibrosis and the cardiovascular system.

Evaluation of Folic Acid Deficiency Anaemia in Predialysis Chronic Kidney Disease Patients: A Hospital-based Study

Background: Chronic kidney disease (CKD) is defined as decreasing kidney function for more than 3 months. Anemia is a common complication of CKD due to a decrease in the hormone erythropoietin related to hemoglobin levels. Folic acid helps with the process of nucleoprotein synthesis and erythropoiesis maintenance.Objectives: The aim of the study was to determine the folic acid level in predialytic anaemic chronic kidney disease patients. Methodology: It was a cross-sectional study conducted in the department of Nephrology of Eastern Medical College &amp; Hospital from September 2020 to August 2021 on predialysis CKD anaemic patient of stage-3 to stage-5. A total of 100 subjects were selected by purposive sampling. The age group was 18 to 70 years. Results: Among the 100 subjects mild, Moderate and Severe aneamia were found in 27%, 44% and 29% respectively. Maximum cases showed normocytic normochromic anaeamia (54%) and 7% cases showed macrocytic aneamia. Serum folic acid levels were found to have decreased in 1 (16.7%), 2 (8.33%) and 7 (10.0%) cases and increased in 2 (33.3%), 5 (20.83%) and 21 (30.0%) cases in stage-3, stage-4 and stage-5 respectively. Conclusion: Anemia is a frequent complication of chronic kidney disease. Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells. Folic acid deficiency may represent an influential factor in renal anemia. Eastern Med Coll J. July 2023; 8 (2): 13-18

A novel scenario in the therapeutic management of anemia of chronic kidney disease: placement and use of roxadustat.

Anemia is a frequent and early chronic kidney disease (CKD) complication. Its management is currently based on oral or intravenous iron supplements, erythropoiesis-stimulating agents, and red blood cell transfusions, when the benefits of transfusion outweigh the risks. Anemia in CKD patients is underdiagnosed and undertreated. Current standard of care is associated with challenges and therefore new treatment approacheshave been sought. Hypoxia-inducible factor-prolyl-hydroxylase enzyme inhibitors are a new class of orally administered drugs used to treat anemia associated with CKD. Small-molecule hypoxia-inducible factor-prolyl-hydroxylase inhibitors have a novel mechanism of action that activates the hypoxia-inducible factor (oxygen-sensing) pathway resulting in a coordinated erythropoietic response, leading to increased endogenous erythropoietin production, improved iron absorption and transport, and reduced hepcidin. Roxadustat is the first hypoxia-inducible factor-prolyl-hydroxylase inhibitor approved by the European Medicines Agency (EMA) and reimbursed in Italy by the Italian Medicines Agency (AIFA) for the treatment of adult patients with symptomatic CKD-related anemia. This authorization was based on the outcome of a globally-conducted phase 3 clinical trial program comprising eight pivotal multicenter randomized studies. In the absence of up-to-date guidelines, we performed a critical appraisal of the placement and use of roxadustat in this therapeutic context.

PENGARUH ERITROPOETIN TERHADAP TINGKAT KEBERHASILAN TERAPI ANEMIA PADA PASIEN ANEMIA PADA PASIEN CHRONIC KIDNEY DISEASE DI RSUD ULIN BANJARMASIN

Chronic kidney disease (CKD) is kidney damage for more than 3 months. The medical in hospital taken was hemodialysis. The aim of this study was to determine the success rate of anemia therapy, the incidence of anemia in CKD patients, and determine the effect of erythropoietin administration on the success rate of anemia therapy in CKD patients at Ulin Hospital, Banjarmasin. This research is a non-experimental research, observational in nature. Data collection was carried out prospectively. The sample used in this study was patient hemoglobin data in medical records that met the inclusion and exclusion criteria. The sample selection method used was total sampling. The measurement of therapeutic success used is the patient's hemoglobin data after being given erythropoietin. The research data obtained is displayed descriptively analytically. The research results of 90 patients with CKD (Chronic Kidney Disease). The results obtained were that 50 patients (55.55%) achieved success in anemia therapy and 40 patients (45.45%) did not achieve success in anemia therapy. The incidence of anemia was 90 patients (100%). Based on the analysis of data obtained, there is an influence of erythropoietin on the success of anemia therapy in Chronic Kidney Disease (CKD) at Ulin Regional Hospital, Banjarmasin.

LEFT VENTRICULAR GEOMETRY AMONG CHRONIC KIDNEY DISEASE PATIENTS: THE ROLE OF ANEMIA

BACKGROUND: Anaemia and abnormal left ventricular (LV) geometric pattern are common findings in Chronic Kidney disease (CKD) patients.&#x0D; OBJECTIVES: To assess LV geometric pattern and its relationship with anaemia among CKD patients.&#x0D; METHODS: A cross sectional study of 163 subjects (102 and 61 CKD subjects with and without anaemia respectively). Echocardiography determined the LV geometric pattern while packed cell volume (PCV) levels determined anaemia.&#x0D; RESULTS: The mean age of subjects with and without anaemia was 54.04 ± 14.47 and 54.92 ± 15.67 years respectively (p = 0.717) while the prevalence of LVH among the two groups was 68.8% and 57.9% respectively (p = 0.174). The most frequent LV geometry in both groups was concentric LVH (53.8% and 43.9% respectively). Prevalence of LV systolic dysfunction was 45%, higher among anaemic subjects (58(61.7%) vs 10(17.5%)) p &lt; 0.001. There was a strong negative correlation between PCV and left ventricular mass index (r = -0.345, p = 0.001) among anaemic subjects, but weak positive correlation among patients without anaemia (r = 0.001, p = 0.993).&#x0D; CONCLUSION: Anaemic CKD patients had a high prevalence of abnormal LV geometry with significant contribution from anaemia. Early management of anaemia may thus improve cardiovascular outcomes.

Effect of Recommended Dietary Intake versus Higher Doses of Supplemental Zinc on Iron and Copper Deficiency Anemia Among Patients with Chronic Kidney Diseases, A Double-Blinded, Randomized Clinical Trial

Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P&lt;0.001) compared to their baseline values. Conclusion: Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.

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.

Prevalence and treatment of anemia in chronic kidney disease patients based on regional medical big data

Objective: To assess the prevalence, risk factors and treatment of anemia in patients with chronic kidney disease (CKD). Methods: A descriptive method was used to analyze the prevalence and treatment of anemia in CKD patients based on regional health data in Yinzhou District of Ningbo during 2012-2018. The multivariate logistic regression analysis was used to identify independent influence factors of anemia in the CKD patients. Results: In 52 619 CKD patients, 15 639 suffered from by anemia (29.72%), in whom 5 461 were men (26.41%) and 10 178 were women (31.87%), and anemia prevalence was higher in women than in men, the difference was significant (P<0.001). The prevalence of anemia increased with stage of CKD (24.77% in stage 1 vs. 69.42% in stage 5, trend χ2 test P<0.001). Multivariate logistic regression analysis revealed that being women (aOR=1.57, 95%CI: 1.50-1.63), CKD stage (stage 2: aOR=1.10, 95%CI: 1.04-1.16;stage 3: aOR=2.28,95%CI: 2.12-2.44;stage 4: aOR=4.49,95%CI :3.79-5.32;stage 5: aOR=6.31,95%CI: 4.74-8.39), age (18-30 years old: aOR=2.40,95%CI: 2.24-2.57, 61-75 years old: aOR=1.35,95%CI:1.28-1.42, ≥76 years old: aOR=2.37,95%CI:2.20-2.55), BMI (<18.5 kg/m2:aOR=1.29,95%CI: 1.18-1.41;23.0-24.9 kg/m2:aOR=0.79,95%CI: 0.75-0.83;≥25.0 kg/m2:aOR=0.70,95%CI: 0.66-0.74), abdominal obesity (aOR=0.91, 95%CI: 0.86-0.96), chronic obstructive pulmonary disease (aOR=1.15, 95%CI: 1.09-1.22), cancer (aOR=3.03, 95%CI: 2.84-3.23), heart failure (aOR=1.44, 95%CI: 1.35-1.54) and myocardial infarction (aOR=1.54, 95%CI:1.16-2.04) were independent risk factors of anemia in CKD patients. Among stage 3-5 CKD patients with anemia, 12.03% received iron therapy, and 4.78% received treatment with erythropoiesis-stimulating agent (ESA) within 12 months after anemia was diagnosed. Conclusions: The prevalence of anemia in CKD patients was high in Yinzhou. However, the treatment rate of iron therapy and ESA were low. More attention should be paid to the anemia management and treatment in CKD patients.

#4993 EFFECT OF ETELCALCETIDE TREATMENT ON ERYTHROPOIESIS-STIMULATING AGENTS (ESAS) REQUIREMENT IN HEMODIALYSIS PATIENTS: A SINGLE CENTER STUDY

Abstract Background and Aims Anemia is a common consequence of advanced chronic kidney disease (CKD). There are various causes of renal anemia like decreased production of and resistance to Erythropoietin, shortened survival of red blood cells and chronic blood loss. Secondary hyperparathyroidism is a potential cause of renal anemia in CKD patients due to direct effect on Erythropoietin synthesis, red cell survival and bone marrow fibrosis [1]. There are several reports of the beneficial effect of treatment of hyperparathyroidism on hemoglobin (Hb) levels. Etelcalcetide is a novel intravenous calcimimetic used for the treatment of secondary hyperparathyroidism in hemodialysis patients. However, there are very few reports of Etelcalcetide's effect on anemia management in hemodialysis patients. We aimed to study the effect of Etelcalcitide on ESAs requirement in our hemodialysis cohort. Method This is a retrospective study in Al Wakra Hospital hemodialysis unit conducted on patients with uncontrolled secondary hyperparathyroidism who needed to be started on Etelcalcetide. Mean Hb and mean ESAs dose were calculated for a period of 6 months before and 6 months after starting Etelcalcetide, while iPTH levels were measured at the beginning and 6 months after starting Etelcalcetide. Inclusion criteria: hemodialysis patients who are on Etelcalcetide for at least 6 months. Exclusion criteria: Patients’ age &amp;lt; 18 years, hemodialysis duration &amp;lt; 12 months and patients with acute blood loss. Results Out of 94 hemodialysis patients, 26 (27.6%) were on Etelcalcetide. 2 patients were excluded, one for acute hematuria and the other for erosive gastritis. 24 patients were included (13 females and 11 males). Mean age of the patients was 58.7 years. 15 patients were on Darbepoetin, 8 on Erythropoietin and 1 patient was switched from Darbepoetin to Erythropoietin due to poor response. There was no significant difference in mean Hb levels for all the patients before and after starting Etelcalcetide (10.6 g/dl and 10.8 g/dl, respectively). Out of 24 patients, 19 had reduction while 5 had increase in ESAs dose requirement. In total, the mean reduction of ESAs dose for all the patients was 17.3%. There was a mean of 33.4% reduction in ESAs requirement for the 19 patients while a mean of 44% increase in the requirement for the 5 patients. Mean iPTH for the cohort at the time of starting Etelcalcetide and 6 months after was 1036 pg/ml and 473 pg/ml respectively. The mean reduction of iPTH for those who had decreased ESAs requirement was 58% while it was 38.8% for those who had increased ESA requirement. Conclusion This study showed that control of severe secondary hyperparathyroidism with Etelcalcetide was associated with reduction in ESAs requirement in hemodialysis patients. The more the control of hyperparathyroidism, the more the reduction of ESAs requirement. These findings were observed also in a one case report [2]. We believe that our study has one of the largest number of patients to show such an observation, however larger controlled studies are needed to confirm these preliminary findings in the improvement of anemia after treatment of hyperparathyroidism by Etelcalcetide.

Relationships between blood bone metabolic biomarkers and anemia in patients with chronic kidney disease

Introduction Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices. Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested. Results The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased. Conclusions Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment.

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.

The role of folic acid supplementation on lowering homocysteine level in chronic kidney disease

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD) patients. Elevated homocysteine levels in CKD patients were thought to be one of the causes. Folic acid supplementation, which was known to improve anemia in CKD patients, can also reduce homocysteine levels, which would reduce cardiovascular events. In this review we will discuss the pathophysiology of hyperhomocysteinemia in CKD patients and studies that explain the role of folic acid to lower homocysteine levels that can also lower the risk of CVD in CKD patients. There are some conflicting results among available studies, but folic acid still seems reasonable to be considered as a suitable supplementary therapy in individuals with CKD after a thorough evaluation of the patient's folate status.

The impacts of hypoxia-inducible factor stabilizers on laboratory parameters and clinical outcomes in chronic kidney disease patients with renal anemia: a systematic review and meta-analysis.

Renal anemia in chronic kidney disease (CKD) is associated with poor outcomes. Hypoxia-inducible factor (HIF) stabilizer, which induces endogenous erythropoietin synthesis and enhances iron mobilization, is a novel treatment for anemia in CKD. We conducted a systematic review and meta-analysis to analyze the effect of HIF stabilizers in anemic CKD patients. This meta-analysis included 43 officially published articles and 3 unpublished studies (27 338 patients). HIF stabilizer treatment significantly increased hemoglobin (Hb) level when compared with placebo (mean difference 1.19g/dL; 95% confidence interval 0.94 to 1.44g/dL; P<.001). There was no significant difference in Hb level when compared with erythropoiesis-stimulating agents (ESAs). Significant reductions of ferritin and transferrin saturation (TSAT) were observed, while total iron-binding capacity was increased in the HIF stabilizer group compared with placebo or ESAs. HIF stabilizers significantly reduced hepcidin, high-density lipoprotein, low-density lipoprotein and triglyceride levels. Acute kidney injury and thrombotic events were significantly observed in patients receiving HIF stabilizers. There were no significant differences in myocardial infarction, stroke, dialysis initiation, pulmonary hypertension and mortality between HIF stabilizer and control groups. The present meta-analysis provided evidence that HIF stabilizers increased Hb and TIBC levels and reduced hepcidin, ferritin and TSAT in CKD patients with renal anemia. Long-term follow-up studies on clinical outcomes of HIF stabilizers are still needed.