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Journal of Nephrology Jun 2024Although the widespread use of long-acting erythropoiesis-stimulating agents (ESAs) has facilitated the improvement of anemia in patients with chronic kidney disease...
BACKGROUND
Although the widespread use of long-acting erythropoiesis-stimulating agents (ESAs) has facilitated the improvement of anemia in patients with chronic kidney disease (CKD), the improvement in prognosis has not been fully demonstrated. Iron deficiency is associated with the development of cardiovascular diseases (CVDs), and the relative iron deficiency induced by erythropoiesis-stimulating agents may prevent the improvement of prognosis. Therefore, we investigated the association between iron deficiency and cardiovascular events during long-acting erythropoiesis-stimulating agent therapy using transferrin saturation (TSAT), which is less susceptible to inflammation than ferritin.
METHODS
This study included 1040 patients with non-dialysis-dependent CKD, aged ≥ 20 years, with a glomerular filtration rate < 60 mL/min/1.73 m and hemoglobin < 11 g/dL, who were treated with darbepoetin alfa for 96 weeks. The patients were recruited in the BRIGHTEN Trial, a multicenter, prospective, observational study conducted to evaluate erythropoiesis-stimulating agent resistance to darbepoetin alfa in treating anemia in non-dialysis-dependent CKD in a clinical setting. The association between transferrin saturation and the cumulative incidence of cardiovascular events was evaluated using the Kaplan-Meier method. To calculate the hazard ratio (HR), 95% confidence intervals (CI) and the Cox proportional hazards model were used.
RESULTS
Survival curve analysis for cardiovascular events indicated that patients with transferrin saturation ≥ 30% had a significantly better prognosis, with an adjusted hazard ratio of 0.34 (95% confidence interval 0.22-0.52). Stratified analysis revealed that patients with transferrin saturation of 30-40% had a significantly lower risk of cardiovascular events than those with transferrin saturation of 20-30%, even after a multivariate-adjusted hazard ratio of 0.33 (95% confidence interval 0.21-0.54).
CONCLUSION
Patients with CKD and transferrin saturation of 30-40% had significantly fewer cardiovascular events than those with transferrin saturation of 20-30% among patients treated with long-acting erythropoiesis-stimulating agents. Therefore, it may be useful to maintain higher transferrin saturation from the viewpoint of erythropoiesis-stimulating agent responsiveness and the reduction of cardiovascular events.
PubMed: 38941000
DOI: 10.1007/s40620-024-02000-y -
Expert Opinion on Pharmacotherapy Jun 2024The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal... (Review)
Review
INTRODUCTION
The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under hypoxic conditions has led to the development of oral drugs, HIF-Prolyl Hydroxylase inhibitors (HIF-PHIs), that constantly activate erythropoietin by inhibiting prolyl hydroxylase. HIF-PHIs have gained rapid approval in Asian countries, including Japan, with six distinct types entering clinical application.
AREAS COVERED
This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat.
EXPERT OPINION
A phase 3, randomized, open-label, clinical trial (PROTECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNOVATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies.
PubMed: 38896547
DOI: 10.1080/14656566.2024.2370896 -
Clinical Lymphoma, Myeloma & Leukemia May 2024Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization...
INTRODUCTION
Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States.
PATIENTS AND METHODS
This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary ESA failure by SF3B1 mutational status, per recently updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines©).
RESULTS
A total of 142 patients were included with a median follow-up time of 17 months (interquartile range [IQR], 7-33). Median age at ESA initiation was 79 years (IQR, 73-85). Patients were predominantly male (54%), overweight or obese (32% and 23%, respectively), of White race (96%) and non-Hispanic ethnicity (89%). Overall, 57% patients were initially treated with darbepoetin alfa and 43% with epoetin alfa. Clinical outcomes were poor, and there was a significant burden on both the health system and individual patients treated with ESA therapies. Hematologic improvement- erythroid was only seen in 26% of 142 patients treated with ESAs, and 65% of 82 retreated patients experienced primary ESA failure.
CONCLUSION
Our results indicate that primary ESA failure is largely unrecognized and that many patients should be considered for alternative treatments.
PubMed: 38871557
DOI: 10.1016/j.clml.2024.05.007 -
Expert Review of Hematology Jun 2024To date, there is limited evidence on patients utilizing both voxelotor and darbepoetin alfa and its impact on hemoglobin levels. The objective is to evaluate the effect...
BACKGROUND
To date, there is limited evidence on patients utilizing both voxelotor and darbepoetin alfa and its impact on hemoglobin levels. The objective is to evaluate the effect of voxelotor and darbepoetin alfa on hemoglobin levels in patients with SCD.
RESEARCH DESIGN AND METHODS
This was a retrospective chart review study that assessed the primary independent variable as the utilization of either voxelotor alone, darbepoetin alfa alone, or the concurrent administration of voxelotor and darbepoetin alfa. Descriptive statistics were utilized to obtain the mean standard deviation for numerical variables and proportions for categorical variables.
RESULTS
A total of 23 participants were included in this study. When comparing baseline to 2 months and 3 months, participants on voxelotor alone experienced a 3% decrease and a 6.6% increase in hemoglobin, darbepoetin alfa alone group a 4.3% decrease and a 0.6% increase in hemoglobin and voxelotor and darbepoetin group a 4.4% decrease and a 0.5% decrease in hemoglobin levels. Fifty percent of the participants in the voxelotor group and 6 (66.7%) participants in the voxelotor plus darbepoetin alfa group experienced adverse drug events.
CONCLUSIONS
Voxelotor resulted in a clinically significant difference in the percent change of hemoglobin from baseline to 3 months.
Topics: Humans; Darbepoetin alfa; Male; Erythropoietin; Female; Retrospective Studies; Anemia, Sickle Cell; Hemoglobins; Adult; Hematinics; Middle Aged; Treatment Outcome; Adolescent; Young Adult; Benzaldehydes; Pyrazines; Pyrazoles
PubMed: 38753522
DOI: 10.1080/17474086.2024.2352497 -
Clinical Pharmacology and Therapeutics Jul 2024Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients... (Comparative Study)
Comparative Study
Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.
Topics: Humans; Renal Dialysis; Hematinics; Female; Male; Retrospective Studies; Aged; Middle Aged; Darbepoetin alfa; United States; Cardiovascular Diseases; Epoetin Alfa; Kidney Failure, Chronic; Anemia; Medicare; Delayed-Action Preparations; Aged, 80 and over; Erythropoietin; Recombinant Proteins
PubMed: 38629679
DOI: 10.1002/cpt.3271 -
Qatar Medical Journal 2024Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating...
BACKGROUND
Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex) and long-acting (Aranesp) ESAs.
METHOD
This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared.
RESULTS
Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference ( < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp was considered the cost-saving protocol.
CONCLUSION
In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex.
TRIAL REGISTRATION
The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).
PubMed: 38567102
DOI: 10.5339/qmj.2024.16 -
Case Reports in Ophthalmology 2024Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, used in the treatment of renal anemia, hold the potential to increase the production of vascular...
INTRODUCTION
Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, used in the treatment of renal anemia, hold the potential to increase the production of vascular endothelial growth factors. Therefore, HIF-PH inhibitors may exacerbate retinal hemorrhage in diseases such as diabetic retinopathy. Here, we present a case involving the administration of an HIF-PH inhibitor, resulting in the exacerbation of retinal hemorrhage in a patient with diabetic retinopathy.
CASE PRESENTATION
A 32-year-old man with diabetes mellitus and renal anemia caused by diabetic nephropathy was referred to our department for ophthalmic examination, revealing diabetic retinopathy with scattered retinal hemorrhages, exudates, and diabetic maculopathy in both eyes. Darbepoetin alfa was initially administered and switched to the HIF-PH inhibitor roxadustat on day 74. By day 88, fresh retinal hemorrhage was observed in the right eye. On day 132, the retinal hemorrhage had further worsened, with new preretinal hemorrhage in both eyes. Roxadustat was discontinued, replaced with darbepoetin alfa, resulting in retinal hemorrhage improvement by day 181 (49 days post-roxadustat cessation). On day 201, fundus hemorrhage further improved, optical coherence tomography showed no macular edema or subretinal fluid, and the retina was thinning. Fluorescein angiography showed neovascular vessels, active fluorescein leakage, and extensive avascular areas in both eyes, prompting pan-retinal photocoagulation. Visual acuity remained stable throughout treatment.
CONCLUSION
Patients with advanced diabetic retinopathy taking HIF-PH inhibitors should be aware of retinal hemorrhage exacerbations. If observed, the treatment plan, including discontinuation of the HIF-PH inhibitor or switching to another agent, should be discussed with a diabetologist, nephrologist, and ophthalmologist.
PubMed: 38529001
DOI: 10.1159/000537913 -
Chronic Diseases and Translational... Mar 2024[This corrects the article DOI: 10.1002/cdt3.13.].
Corrigendum: Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: A randomized, open-label, parallel-group, non-inferiority phase III trail.
[This corrects the article DOI: 10.1002/cdt3.13.].
PubMed: 38450310
DOI: 10.1002/cdt3.93 -
The Medical Letter on Drugs and... Feb 2024
Topics: Humans; Anemia; Barbiturates; Renal Insufficiency, Chronic; Glycine; Recombinant Proteins
PubMed: 38412265
DOI: 10.58347/tml.2024.1696a -
Nutrients Feb 2024Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing...
Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient's dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI ( < 0.05), but no significant change was observed ( = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.
Topics: Humans; Hematinics; Anemia; Prolyl-Hydroxylase Inhibitors; Zinc; Erythropoiesis; Prolyl Hydroxylases; Renal Insufficiency, Chronic; Darbepoetin alfa; Retrospective Studies; Glycine; Dietary Supplements
PubMed: 38398842
DOI: 10.3390/nu16040520