Anemia Of Chronic Kidney Disease Research Articles

Efficacy of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Clinical Parameters in Patients with Heart Failure.

Background and Objectives: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been approved as an oral drug for treating anemia in chronic kidney disease (CKD). However, the clinical effect of HIF-PH inhibitors in patients with heart failure (HF) is unclear. Thus, this study investigated the effect of HIF-PH inhibitors in patients with HF and CKD. Materials and Methods: Thirteen patients with HF complicated by renal anemia who were started on vadadustat were enrolled. Clinical parameters were compared before and 1 month after vadadustat was started. Results: The mean left ventricular ejection fraction was 49.8 ± 13.9%, and the mean estimated glomerular filtration rate was 29.4 ± 10.6 mL/min/1.73 m2. The hemoglobin level was significantly increased (9.7 ± 1.3 mg/dL vs. 11.3 ± 1.3 mg/dL, p < 0.001), and the N-terminal prohormone of B-type natriuretic peptide was significantly decreased after the introduction of vadadustat [4357 (2651-15182) pg/mL vs. 2367 (1719-9347) pg/mL, p = 0.002]. Furthermore, the number of patients with New York Heart Association functional class ≥ 3 was also decreased after the introduction of vadadustat [8 (61.5%) vs. 1 (7.7%), p = 0.008]. No thromboembolic adverse events or new tumors were observed in any patient during the study period. Conclusions: The introduction of vadadustat in patients with HF complicated by renal anemia led to improvements in anemia and symptoms of HF.

Therapeutic Advancements in Anemia of Chronic Kidney Disease and End Stage Kidney Disease

Therapeutic Advancements in Anemia of Chronic Kidney Disease and End Stage Kidney Disease

Efficacy and safety of molidustat for the anemia of chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials

Objective: Anemia is a prevalent complication in chronic kidney disease (CKD) patients, necessitating effective management for improved clinical outcomes. This systematic review and meta-analysis aim to evaluate the efficacy and safety of molidustat for iron-deficient anemia in CKD patients. Methods: A comprehensive search of Ovid MEDLINE, Web of Science, PubMed, and Cochrane CENTRAL was conducted. The primary efficacy outcomes included changes in hemoglobin (Hb) levels during follow-up and at week 16. Inverse variance random effects models were used for main analysis. The overall risk of bias (RoB) was assessed using the Cochrane RoB2 tool. Results: Six randomized controlled trials (RCTs) involving 999 patients were included. The meta-analysis for Hb change during follow-up revealed a mean difference (MD) of 0.09 (95% CI, -0.49 to 0.67), p=0.071, with an I² of 81% whereas Hb change at week 16 showed an MD of 0.12 (95% CI, -0.40 to 0.64), p=0.65 with an I² of 85%. Notably, changes in hepcidin levels during follow-up (MD -16.55, 95% CI -29.54 to -3.56) favored molidustat but not changes in total iron binding capacity at week 16 (MD 2.89, 95% CI 1.74 to 4.04). However, the impact of molidustat on transferrin saturation, iron levels, and ferritin levels showed comparable results. Regarding safety outcomes, no significant differences were observed in treatment emergent adverse events (TEAE) leading to death, patients with ≥1 major adverse cardiovascular event (MACE), hyperkalemia, any TEAE, and any serious TEAE. The risk of CKD worsening was increased with molidustat (MD 1.79, 95% CI 1.03 to 3.10). Subgroup analyses for primary outcomes were consistent with main analyses. RoB for Hb change was found as high/some concerns in 5/1 RCTs, respectively. Conclusion: Molidustat exhibited noninferiority to ESAs in managing anemia in CKD patients. However, a concerning finding was the increased risk of CKD worsening associated with molidustat use. Well-designed RCTs are essential to enhance our understanding of molidustat's in CKD-related anemia.

Sodium-Glucose Transporter 2 (SGLT2) Inhibitors and Iron Deficiency in Heart Failure and Chronic Kidney Disease: A Literature Review.

Heart failure (HF) and chronic kidney disease (CKD) are associated with high mortality. In both disorders, impaired iron homeostasis, mostly in the form of a functional iron deficiency, is a frequent co-morbidity. In HF, functional iron deficiency and management by i.v. iron supplementation have been proven to affect both prognosis and functional capacity. In the same context, iron supplementation is routine for the adequate management of renal anemia in CKD. In numerous recent studies in HF and in CKD, sodium-glucose transporter 2 (SGLT2) inhibitor treatment has been proven to significantly reduce mortality. Furthermore, the same trials showed that these drugs alleviate iron deficiency and anemia. These effects of SGLT2 inhibitors may be due to an amelioration of inflammation with reduced interleukin-6 (IL-6) and to an enhancement of autophagy with increased sirtuin 1 (SIRT1), both associated with modified production of hepcidin and enhanced ferritinophagy. However, the exact pathogenic basis of the beneficial SGLT2 inhibitor action is not fully elucidated. Nevertheless, effects on iron homeostasis might be a potential explanatory mechanism for the powerful SGLT2 inhibitors' cardiovascular and renal outcome benefits. In addition, the interaction between iron supplementation and SGLT2 inhibitors and its potential impact on prognosis remains to be clarified by future studies. This review represents a significant effort to explore the complex relationships involved, seeking to elucidate the intricate mechanisms by which SGLT2 inhibitors influence iron homeostasis.

Comparison of outcomes on hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in anaemia associated with chronic kidney disease: network meta-analyses in dialysis and non-dialysis dependent populations.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are oral alternatives to current standard-of-care treatments for anaemia in chronic kidney disease (CKD). We conducted network meta-analyses to indirectly compare clinical outcomes for three HIF-PHIs in dialysis and non-dialysis populations with anaemia in CKD. The evidence base comprised phase III, randomised, controlled trials evaluating daprodustat, roxadustat, or vadadustat. Three outcomes were evaluated: efficacy [change from baseline in haemoglobin (Hgb)], cardiovascular safety [time to first major adverse cardiovascular event (MACE)] and quality of life [change from baseline in 36-Item Short Form Health Survey (SF-36) Vitality score]. Analyses were performed separately for all patients and for erythropoiesis-stimulating agent (ESA) non-users at baseline (non-dialysis population) or prevalent dialysis patients (dialysis population). Bayesian Markov Chain Monte Carlo methods with non-informative priors were used to estimate the posterior probability distribution and generate pairwise treatment comparisons. Point estimates (medians of posterior distributions) and 95% credible intervals (CrI) were calculated. Seventeen trials were included. In non-dialysis patients, there were no clinically meaningful differences between the three HIF-PHIs with respect to Hgb change from baseline [all patients analysis (total n=7907): daprodustat vs. roxadustat, 0.09g/dL (95% CrI -0.14, 0.31); daprodustat vs. vadadustat, 0.09g/dL (-0.04, 0.21); roxadustat vs. vadadustat, 0.00g/dL (-0.22, 0.22)] or risk of MACE [all patients analysis (total n=7959): daprodustat vs. roxadustat, hazard ratio (HR) 1.16 (95% CrI 0.76, 1.77); daprodustat vs. vadadustat, 0.88 (0.71, 1.09); roxadustat vs. vadadustat, 0.76 (0.50, 1.16)]. Daprodustat showed a greater increase in SF-36 Vitality compared with roxadustat [total n=4880; treatment difference 4.70 points (95% CrI 0.08, 9.31)]. In dialysis patients, Hgb change from baseline was higher with daprodustat and roxadustat compared with vadadustat [all patients analysis (total n=11 124): daprodustat, 0.34g/dL (0.22, 0.45); roxadustat, 0.38g/dL (0.27, 0.49)], while there were no clinically meaningful differences in the risk of MACE between the HIF-PHIs [all patients analysis (total n=12 320): daprodustat vs. roxadustat, HR 0.89 (0.73, 1.08); daprodustat vs. vadadustat, HR 0.99 (0.82, 1.21); roxadustat vs. vadadustat, HR 1.12 (0.92, 1.37)]. Results were similar in analyses of ESA non-users and prevalent dialysis patients. In the setting of anaemia in CKD, indirect treatment comparisons suggest that daprodustat, roxadustat, and vadadustat are broadly clinically comparable in terms of efficacy and cardiovascular safety (precision was low for the latter), while daprodustat may be associated with reduction in fatigue to a greater extent than roxadustat.

KRONİK BÖBREK HASTALIĞI VARLIĞINDA HASTANEDE EDİNİLMİŞ ANEMİ GELİŞİMİNE ETKİ EDEN FAKTÖRLERİN DEĞERLENDİRİLMESİ

Kronik böbrek hastalığı (KBH) 3 aydan uzun süren, böbrekte işlevsel ya da yapısal bozukluk ve/veya glomerüler filtrasyon hızında azalma olmasıdır. Hastanede edinilmiş anemi (HEA), hastaneye yatış sonrası hastalarda etyolojik bir neden olmaksızın anemi gelişmesidir. İyatrojenik geliştiği düşünülmektedir. Çalışmamızda KBH tanısıyla hasta-neye yatırılan hastalarda HEA prevalansını ve etki eden faktörleri saptamayı amaçladık. Mart- Eylül 2014 arasında, 18 yaş ve üzerine, KBH tanılı, nefroloji servisine yatışı yapılan hastalar çalışmaya alındı. Hipervolemi, kanama, hemoliz, sepsis, hematolojik malignite varlığı, antikoagülan kullanımı olan hastalar, sıvı replasmanı planlanan ve renal replasman tedavisi alan hastalar çalışmaya dahil edilmedi. Hastaneye yatış sonrasında hemoglobin düzeyinde 0,5 g/dl ve üzerinde düşme olması HEA olarak tanımlandı. Çalışmamızda KBH hastalarında HEA sıklığı %70 saptanmıştır. HEA gelişimi, KBH evresi ve hipotiroidi varlığı ile istatiksel anlamlı olarak ilişkili saptanmıştır (KBH p=0.021, hipotiroidi p=0.002). Günlük flebotomi miktarınin (p=0,203) ve hastanede yatış süresinin (p=0,180) HEA gelişimi ile ilişkisi saptanmamıştır. HEA’nın tanınması ve gelişimi açısından risk faktörlerinin saptanarak, önlenmesinin hastaların sağlık durumuna olumlu etki edeceği düşüncesindeyiz.

Efficacy and safety of hypoxia-inducible factor-prolyl hydroxylase inhibitor treatment for anemia in chronic kidney disease: an umbrella review of meta-analyses

The objective was to provide a comprehensive summary of existing evidence on the efficacy and safety of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for the treatment of anemia in chronic kidney disease (CKD). A systematic search was conducted in the Medline, Embase, and Cochrane databases. Only meta-analyses that evaluated the efficacy and safety of HIF-PHI treatment for anemia in CKD were included. The efficacy outcomes included hemoglobin levels and iron metabolism indices, while the safety outcomes were assessed by examining adverse events. The qualities of methodologies and evidence were assessed using the AMSTAR 2 system and the NutriGrade tool, respectively. Fourteen meta-analyses, comprising 105 distinct comparisons, were included. The comparisons were backed by evidence of high, moderate, and low levels, distributed in approximately equal proportions. None of the studies were deemed to possess a high level of confidence. In both the overall and individual treatment groups of HIF-PHI, there was an increase in the levels of hemoglobin, transferrin, and transferrin saturation, while the levels of hepcidin and total iron binding capacity decreased. Serum ferritin exhibited a reduction to some extent, while serum iron did not show significant alterations following HIF-PHI treatments. There were no notable disparities in safety outcomes between the HIF-PHI and erythropoietin stimulating agents or placebo groups. This umbrella review suggests that HIF-PHI treatment can effectively increase hemoglobin levels in CKD patients and enhance iron metabolism by decreasing hepcidin levels and improving iron transport. The safety profiles of HIF-PHIs were generally comparable to those of ESA therapies or placebos.

The Heparinoid Sevuparin Improves Anemia and Kidney Status in a Mouse Model of Chronic Kidney Disease

The control of systemic iron availability is essential to sustain the different needs of the body, without causing iron overload disease or deficiency (anemia) meaning that iron is highly regulated and the master regulator is hepcidin. High levels of hepcidin induce ferroportin degradation, inhibiting iron release from enterocytes and macrophages resulting in an internal iron deficiency, which underlies anemia of chronic diseases (ACD). Patients with chronic kidney disease (CKD) often have ACD due to a combination of inflammation, erythropoietin (EPO) insufficiency/unresponsiveness, elevated hepcidin levels, reduced kidney function and decreased iron availability. Treatments involve erythropoiesis-stimulating agents, that in a longer perspective often fail to ameliorate the anemia, highlighting the need for new therapeutic tools. Interestingly, it has been reported that hepcidin suppression improves anemia in rodent models of CKD, suggesting that normalising hepcidin levels may be a means to treat anemia in CKD and in general in ACD. It is known that heparins are potent hepcidin suppressors; sevuparin, a novel, clinical stage, low-molecular weight heparinoid compound with substantially reduced anticoagulant activity is a promising candidate drug to control hepcidin expression in patients with CKD. The authors previously found that sevuparin strongly suppressed basal, BMP6- and IL6-dependent hepcidin expression in vitro with a maximum effect after 6h (90% reduction) persisting for at least 16h. The hepcidin lowering effect of sevuparin was confirmed also in healthy mice. Furthermore, in healthy volunteers, a single dose of subcutaneous sevuparin caused a significant reduction of about 50% (3 mg/kg) and 80% (9 mg/kg) of serum hepcidin after 12 and 24h, respectively, providing a robust translational context to the sevuparin effects on hepcidin levels. The aim of the present work was to investigate the effect of sevuparin on hepcidin, hemoglobin and the kidney status in a CKD mouse model of high hepcidin anemia. Mice fed with “adenine rich diet” (ARD) (0.2% adenine; 0.9% phosphorus; 0.6% calcium; 20% casein) developed moderate or severe signs of kidney damage as manifested by weight loss, increased serum creatinine, high hepcidin levels, low serum iron and anemia (hemoglobin ≤ 12.5 g/dL) after 7-9 weeks. After the onset of CKD, the mice were chronically treated with PBS or sevuparin (10 mg/kg/daily) subcutaneously for 3 or 6 weeks alone or in combination with erythropoietin (EPO) administered intraperitoneally (50 U/mouse twice a week in the first 3 weeks followed by 3 weeks and then 25 U/mouse once a week to simulate EPO hypo-responsiveness). Sevuparin was provided by Modus Therapeutics AB, Sweden, whereas EPO was used in the form of the commercially available darbapoietin alfa (ARANESP ®). Sevuparin treatment alone increased hemoglobin, hematocrit and weight (Hb 11-12 g/dL; Ht 20%; 22 g vs baseline values of Hb 9-10 g/dL; Ht 18%; 14.5 g PBS) with adjoining modest decreases of serum hepcidin and creatinine. The reduction of creatinine was supported by a concomitant improvement of the kidney status visible as a reduction of collagen deposits indicative of reduced fibrosis compared to the mice treated with PBS only. The EPO/sevuparin combination showed a strong reduction from control of serum hepcidin levels (292 ng/mL vs 1382 ng/mL) after 3 weeks of treatment whereas after 6 weeks levels were increased up to 2000 ng/mL suggesting that the chronic treatment with EPO is not optimal, as observed in patients. Interestingly the concomitant benefit on anemia at 3w (about Hb 18 g/dL, Ht 54%) for the combination remained stable at 6w, further supported by the maintained high Ret-He (about 15.62 pg); suggesting a phased dependency on hepcidin in the development of CKD anemia. Furthermore, the improvement of the kidney status (histology and function) was also maintained throughout combination treatment. Our data in this mouse CKD model add new insights to the role of hepcidin in the development of CKD anemia over time. Furthermore, the results are promising and support further mechanistic and clinical studies to elucidate the therapeutic role for sevuparin as a treatment in anemia of inflammatory and/or chronic diseases in monotherapy or in combination with EPO and to explore its role in kidney protection.

Addressing Chronic Anemia in Sickle Cell Disease: Characterizing Erythropoiesis-Stimulating Agent (ESA) Utilization and Practice Patterns Among Providers

Background: Chronic anemia exerts profound impacts on the morbidity, mortality, and quality of life in individuals with sickle cell disease (SCD), but therapeutic options are limited. Erythropoietin-stimulating agents (ESAs) are the standard of care for managing anemia in chronic kidney disease (CKD). However, their utilization in SCD remains ad hoc, with limited literature and no guidelines supporting the use of ESAs in SCD. To address this knowledge gap, we present preliminary findings from a survey designed to evaluate provider practices and identify factors influencing the use of ESAs in SCD. Methods: We conducted a cross-sectional web-based survey from March-July 2023 among providers taking care of patients with SCD in the United States (US) and internationally. Survey items were developed to assess provider demographic characteristics, practice environments, and provider practices around ESA use in SCD. The data was collected and managed using REDCap electronic data capture tools hosted at the University of Pittsburgh. Descriptive statistics were used to report the data. Results: The survey has been completed by 33 providers as of a cut date of July 23, 2023. Most providers were hematologists who practiced in an academic setting (23/33, 69.7%), with an equal gender distribution (Table 1). The number of patients with SCD seen annually varied, with 101-300 patients being the most common cohort size (13/33, 39.4%). In the 12 months prior to survey completion, 15/33 (45.5%) providers treated at least 1 patient with SCD with ESAs, usually outpatient (Table 2). Commonly reported barriers to outpatient ESA therapy included lack of insurance approval/coverage or cost concerns, lack of provider experience, and patient tolerability/adherence or inability to perform self-injections. Fewer respondents reported no barriers to prescribing ESAs in the outpatient setting, compared to in the acute/inpatient setting (18.2% vs. 48.5%). The most commonly reported indications for starting ESAs in the outpatient setting were chronic anemia from end-stage renal disease or CKD, reduction of blood transfusion requirement, and chronic anemia in patients refractory to approved therapies. Less commonly reported indications include severe or symptomatic anemia alone and chronic anemia in the setting of cardiopulmonary disease. Respondents reported several contraindications to starting ESAs, including a history of venous thromboembolism (VTE), malignancy, stroke, coronary artery disease, hypertension, and frequent vaso-occlusive crises. Respondents also expressed concerns about the cost/insurance coverage, efficacy, safety, patient burden, and appropriate dosing of ESAs in patients with SCD. Only 18/33 (54.5%) respondents reported ever treating outpatients with SCD with ESAs; nearly all of them used 1 st generation ESAs, and a majority used 2 nd generation ESAs. For 1 st generation ESAs, the most common starting dose was 3500-7000 units (U) (50-100 U/kg; 22.2%) or 7001-14000 U (101-200 U/kg; 22.2 %). Once weekly was the most common dosing interval (50%), followed by three times a week (TIW; 27.8%) and twice a week (16.7%). The maximum dose used was 56001-70000 U (801-1000 U/kg) TIW. For 2 nd generation ESAs, the most common starting dose was 141-210 mcg (2.1-3.0 mcg/kg) (22.2%), and administration often occurred once every 2 weeks (44.4%) or weekly (27.8%). The maximum dose used was 211-315 mcg (3.1-4.5 mcg/kg) weekly. Outpatient ESAs were most often initiated for hemoglobin (Hb) &amp;lt; 6 g/dL (8/18, 44.4%), and Hb &amp;gt; 9 g/dL was the most common treatment target (6/18, 33.3%). ESAs were often combined with hydroxyurea, voxelotor, and simple transfusions (Table 2). Conclusion: These preliminary survey results show considerable variability in how ESAs are currently being used in people with SCD. These variations in clinical practice highlight both significant ambiguity about what works in this setting and the need for further research into the optimal use of ESAs for the management of chronic anemia in SCD (ongoing clinical trial: ACHiEvE-SCD, NCT05451940). Future directions include evaluating differences in practice patterns among adult vs. pediatric and US-based vs. non-US-based providers.

Anaemia in CKD-treatment standard.

Anaemia is one of the most common complications of chronic kidney disease (CKD), having a significant impact on quality of life, and is also associated with a number of adverse clinical outcomes. Its pathogenesis is multifactorial, caused largely by an inadequate production of erythropoietin from the diseased kidneys, with iron deficiency, inflammation, shortened red cell lifespan and enhanced blood loss also being contributory factors. The management of this condition was transformed in the late 1980s by the advent of recombinant human erythropoietin (epoetin), and treatment paradigms have developed over the last three decades, largely focusing on a combination of epoetin or its analogues (erythropoiesis-stimulating agents; ESAs) along with iron supplementation, often administered intravenously due to increased hepcidin levels limiting iron absorption from the gut. Indeed, in patients with early CKD and iron deficiency, iron per se may be sufficient to improve the anaemia, delaying the need for ESA therapy. Other causes of anaemia should be excluded and corrected (if possible) before resorting to treatment with ESAs and iron. More recently, the hypoxia-inducible factor-prolyl hydroxylase inhibitors have entered the therapeutic arena; these are orally active agents that upregulate endogenous erythropoietin production as well as a number of iron-regulatory genes which may also enhance erythropoiesis. The latter drugs are highly efficacious, and may have advantages in inflammatory conditions causing resistance to conventional ESA therapy, but concerns exist regarding their safety, particularly in the longer term. This article reviews the current standards of treatment, as well as recent novel developments in the management of anaemia in CKD.

Evaluation of bone marrow findings in hemodialysis patients with erythropoietin-resistant anemia.

Treatment with erythropoietin-stimulating agents (ESAs) is widely used in anemia of chronic kidney disease (CKD). Acquired ESA resistance is an important problem. The aim of this study is to examine the bone marrow findings in hemodialysis patients with ESA-resistant anemia. The data of 210 patients with acquired ESA resistance were reviewed retrospectively. The patients were divided into groups according to having diagnosis of dysplasia and hematological disease, and survival analysis was performed. A total of 26 patients were included in the study. While dysplasia was present in 10 (38.5%) patients, five of them were diagnosed hematologically. When survival analysis was performed between those with and without a hematological diagnosis, a difference in survival was observed against the group with the diagnosis (24.4 vs. 72 months, p = 0.045). Unresponsiveness to ESA treatment in CKD patients or a decrease in one of the other cell lines along with hemoglobin, it would be appropriate to perform early bone marrow examination.

Effect of the Phosphate Binder Sevelamer Carbonate on the Bioavailability of Enarodustat, an Oral Erythropoiesis Stimulating Agent.

Enarodustat is an orally available hypoxia-inducible factor-prolyl hydroxylase inhibitor which can correct the erythropoietic capacity and improve anemia in chronic kidney disease. Sevelamer carbonate, a non-calcium-based polymeric resin, is one of the commonly prescribed agents for the management of hyperphosphatemia in patients undergoing hemodialysis. This was an open-label, crossover study in healthy male subjects (N=12) that evaluated the effect of sevelamer carbonate (2400mg) on the bioavailability of enarodustat (25mg) when the 2 drugs were administered together (Treatment B) or when enarodustat was administered 3hours after (Treatment C) or 1hour before (Treatment D) sevelamer carbonate compared to enarodustat alone (Treatment A). With coadministration of the 2 drugs (Treatment B), enarodustat Cmax and AUCinf reductions were 53% and 45%, respectively. For Treatment C, Cmax and AUCinf reductions were 11% and 6%, respectively, and for Treatment D the corresponding values were 8% and 20%. Thus, coadministration of enarodustat and sevelamer carbonate resulted in a substantial reduction (≈50%) in the oral bioavailability of enarodustat. However, the interaction was substantially mitigated by staggering the administration of enarodustat and sevelamer carbonate. Administration of 4 single oral doses of enarodustat 25mg, with or without sevelamer carbonate, were safe and well tolerated in this study.

Morphological Patterns Of Anemia In Patients With Chronic Kidney Disease In A Tertiary Care Hospital, Nepal

Introduction: Anemia is the major health issue that is causing the most disability worldwide amongst the patients with chronic kidney disease (CKD). Anemia in CKD is defined as an Hemoglobin level &lt;13.5 g/dl and 12.0 g/dl in men and women respectively as demarcated by National Kidney Foundation. This study provides insights about the subtypes of anemia in patients with chronic kidney disease patients. We aim to determine the morphological Patterns of anemia in a patient with chronic kidney disease, the differential diagnosis of renal anemia. Methods: A descriptive cross-sectional study was conducted among diagnosed CKD patients presented to the Nephrology Out patient department of a tertiary level hospital in Kathmandu over a six months period, from September 15, 2022 to March 15, 2023. Etiology of anemia were worked out. All adults (&gt;18 years of age) with chronic kidney disease patients with an estimated glomerular filtration rate (eGFR) below 60 ml/min, and who were not started on dialysis were recruited. The study proposal was approved by Institutional review committee (IRC) of Nepalese army institute of health sciences (NAIHS) prior of conducting the study. Convenience Sampling was done. Result: Anemia was seen in 96.8% of patients among which 58.9% of the patients presented with severe anemia. Among all patients, mean hemoglobin value was 9.45±1.60 g/dl. Moderate anemia was the commonest (50.50%) degree of anemia. Microcytic hypochromic was the commonest (44.7%) finding in peripheral blood film study followed by normocytic normochromic type (43.7%) and plasmacytoma (5.3%). Conclusion: We found a high prevalence of anemia among chronic kidney disease as compared to other studies conducted in similar settings. The higher percentage of anemia found in the study may be attributed to NKF criteria for anemia diagnosis, the cutoff of which is higher than that for general population. Also, the patients not having received renal replacement therapy in the past were taken in the study, causing higher incidence of anemia in CKD. Treatment of anemia may somewhat improves quality of life. Thus, early recognition and effective treatment in patients with CKD is highly recommended.

Hemoglobin Response to Zinc Supplementation in Chronic Kidney Disease in Patients with Zinc Deficiency and Anemia

Background: Chronic anemia has an estimated prevalence of 5.6% within the US, where 25.3% of patients with chronic kidney disease (CKD) 3-5 have anemia of chronic kidney disease according to NHANES. Anemia in CKD has long been attributed to a decrease in EPO production due to their kidney disease. While iron deficiency is treated in anemia of chronic kidney disease, other micronutrients are less commonly tested or supplemented. Zinc may be an additional micronutrient of interest in anemia of chronic kidney disease as zinc has numerous proposed mechanisms in erythropoeisis including acting as a catalyst in the iron metabolism and heme synthesis through the activity of alpha-aminolevulinic acid dehydratase enzyme. Zinc is found in the structure of the growth factor independent 1B (Gfi-1B) Zinc finger protein and GATA-1 Zinz finger transcription factor, which functions as a regulator in erythroid cell growth by modulating gene expression specific to erythroid series including the SMAD pathways and TGF-β signaling. The interaction with zinc in signaling cascades such as the growth hormone and insulin-like growth factor-1 pathways also result in increased erythropoietin transcription and therefore increased erythropoiesis. In addition, zinc is regarded as an important erythroid differentiation factor which progress maturation of erythrocytes. Zinc has also shown to stimulate EPO production in nephrectomized rats and Zinc supplementation increased reticulocyte production in human subjects. This descriptive, retrospective study describes zinc deficient patients with CKD 3-5 and chronic anemia; who underwent oral zinc supplementation, and their changes in hemoglobin (HGB) over a 12 month period in an academic outpatient hematology clinic in California, United States of America. Objectives: Primary endpoints: determine the rate of anemia resolution over 12 months following supplementation of zinc in patients with zinc deficiency, CKD, and anemia of chronic kidney disease. Secondary endpoints: determine if zinc supplementation in zinc deficient patients with chronic anemia and CKD 3-5 will improve HGB by at least 1.0 g.dL by 1, 3, 6, and 12 month time points. Methods: Hematology patients from Loma Linda University Cancer Center over the age of 18 who had CKD 3 or above (GFR &amp;lt;59 ml/min) with chronic anemia (HGB &amp;lt;12 for women, HGB &amp;lt;13 for men for &amp;gt;3 months) were identified to have zinc deficiency (plasma zinc concentration &amp;lt;65 ug/dL). Patients did not start new treatment for their anemia, including initiating new treatments for malignancy 3 months preceding, and within the data collection period. Patients were supplemented with Zinc Sulfate 50 mg daily and their HGB was followed over 12 months. A retrospective analysis was completed for prior medical history, lab data, and hemoglobin was tabulated at the time markers of 1, 3, 6, and 12 months following initiation of zinc supplementation. ANOVA, Wilcoxon rank-sum, and unpaired Students and t tests were performed to determine significant differences. p &amp;lt;0.05 is considered statistically significant. Results Thirty-Four patients were identified to have CKD 3-5 with chronic anemia and zinc deficiency. They were found to have no statistically significant baseline characteristics, hematologic values at time of diagnosis, or micronutrient and hormonal etiologies for anemia. HGB prior to supplementation averaged 9.96 g/dL, WBC averaged 5.8, and PLTS averaged 149. Following supplementation HGB at 1 month average was 10.47 g/dL (p=0.19 n=30), at 3 months average of 10.49 (p=0.12 n=31), at 6 months average of 11.03 (p=0.011 n=27), at 1 year 10.93 (p=0.03, n=17). Primary endpoint of HGB resolution was found in 12 of the 34 patients (35%). Secondary endpoint of HGB improvement by at least 1.0 g/dL was reached in 27% of patients at 1 month, 32% of patients at 3 months, 59% of patients at 6 months and 64% of patients at 12 months. Conclusions: Zinc supplementation improved patients' anemia with resolution of anemia in 35% of patients with incremental improvement in HGB over a 1 year time frame. There was statistically significant improvement from baseline HGB at the 6 and 12 month time markers. Further study is warranted to determine the specific mechanism of zinc deficiency in anemia with chronic kidney disease, as well as clinical studies determining zinc supplementation doses, monitoring, and toxicity.

A Phase 1b Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Anemia

Hepcidin, a central regulator of iron homeostasis, is pathologically elevated in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and anemia. Elevations in hepcidin contribute to the onset, maintenance, and severity of anemia. DISC-0974 is an investigational, first-in-class, monoclonal antibody that blocks hemojuvelin (HJV), a co-receptor in the bone morphogenetic protein-signaling pathway regulating hepcidin expression. In a healthy volunteer study, DISC-0974 demonstrated dose-dependent reductions in serum hepcidin, increases in serum iron with doses up to 56 mg administered subcutaneously (SC), and increasing trends in reticulocyte count, reticulocyte hemoglobin, mean corpuscular hemoglobin, total hemoglobin (Hgb), and red blood cell count. In a rat model of anemia in CKD, DISC-0974 decreased hepcidin, increased serum iron, and normalized hemoglobin (Wu et al., ASH 2022). DISC-0974-103 is a Phase 1b, double-blind, placebo-controlled, single-ascending dose study (NCT05745883) to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DISC-0974 in patients with NDD-CKD and anemia. Eligible participants include patients over 18 years of age with NDD-CKD, stages 2-5, hemoglobin (Hgb) &amp;lt;10.5 g/dL in women and &amp;lt;11.0 g/dL in men, serum ferritin ≥100 μg/L, and transferrin saturation (TSAT) ≤30%. Major exclusionary criteria include: concomitant treatment with therapeutic oral iron, intravenous iron, erythropoietin-stimulating agents, or blood transfusions; splenectomy; and nutritional, genetic, infectious, or autoimmune causes of anemia. Approximately 32 participants will be enrolled. On Day 1, participants will receive a single dose of DISC-0974 SC with evaluations for safety, PK, and PD through 57 days of follow-up. Dose escalation is planned across 4 cohorts consisting of 8 participants each, randomized 3:1 active treatment to placebo, treated at single doses of 28, 40, 60, and 90 mg SC DISC-0974. Safety Review Committee assessments are planned to gate escalation decisions. Primary endpoints include adverse events (AEs), clinical laboratory assessments, vital signs, physical examinations, and electrocardiograms. Secondary endpoints include changes in serum hepcidin-25, iron, TSAT, ferritin, Hgb, and other hematology biomarkers. Enrollment is currently ongoing, and available study results will be presented at the meeting.

Red Blood Cell Transfusion Use in Dialysis-Dependent Patients with Anemia of CKD in the United States: A Systematic Literature Review

Red Blood Cell Transfusion Use in Dialysis-Dependent Patients with Anemia of CKD in the United States: A Systematic Literature Review

Real-World Clinical Use of Roxadustat in Patients with Anemia of CKD: Interim Results from a Post-Marketing Surveillance Study in Japan

Real-World Clinical Use of Roxadustat in Patients with Anemia of CKD: Interim Results from a Post-Marketing Surveillance Study in Japan

Evaluating the Outcomes of Roxadustat Treatment for Anemia in Dialysis-Dependent CKD: A Systematic Review and Meta-Analysis

Evaluating the Outcomes of Roxadustat Treatment for Anemia in Dialysis-Dependent CKD: A Systematic Review and Meta-Analysis

A Retrospective View of the Relationship of Soluble Fas with Anemia and Outcomes in CKD

A Retrospective View of the Relationship of Soluble Fas with Anemia and Outcomes in CKD

Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study.

Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD). In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks. A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level. Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.