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Transfusion and Apheresis Science :... Jun 2024Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management...
INTRODUCTION
Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia.
PROJECT AIM
The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation.
DESIGN
This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%).
RESULTS
Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection.
CONCLUSION
Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.
Topics: Humans; Kidney Transplantation; Anemia; Male; Female; Middle Aged; Erythrocyte Transfusion; Retrospective Studies; Graft Rejection; Adult
PubMed: 38365525
DOI: 10.1016/j.transci.2024.103896 -
Cureus Jan 2024Anemia is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). It presents multifaceted challenges that impact patients' quality of... (Review)
Review
Anemia is a prevalent and debilitating complication in patients with chronic kidney disease (CKD). It presents multifaceted challenges that impact patients' quality of life and overall well-being. The advent of darbepoetin alfa (DPO) as a therapeutic alternative to recombinant human erythropoietin alpha (EPO) has revolutionized the management of CKD-associated anemia. This review article presents a comprehensive comparative analysis highlighting the advantages of DPO over EPO in the effective management of anemia, in both predialysis and dialysis-dependent (DD) CKD patients. DPO's distinct pharmacokinetic advantages play a pivotal role in its efficacy and safety. With a significantly longer half-life and several-fold increased biological activity compared to EPO, DPO enables extended dosing intervals. Through an in-depth examination of diverse clinical trials, it becomes evident that DPO consistently demonstrates remarkable efficacy and safety in improving and maintaining hemoglobin (Hb) levels. Furthermore, its simplified dosage regimen, coupled with the convenience of less frequent administration, not only improves patient adherence but also translates to reduced healthcare costs and resource utilization. In conclusion, this review provides compelling evidence of the advantages of DPO over conventional recombinant human EPO for managing anemia in CKD patients, both in the predialysis and dialysis-dependent CKD patients. DPO's pharmacokinetic advantages, patient-centered advantages, enhanced compliance, and cost-effectiveness converge to establish DPO as a transformative therapeutic option. In both predialysis and dialysis settings, DPO's superior efficacy and patient-centric attributes collectively redefine the landscape of anemia management in CKD.
PubMed: 38313992
DOI: 10.7759/cureus.51613 -
Kidney Research and Clinical Practice May 2024For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than...
Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis.
BACKGROUND
For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis.
METHODS
In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs.
RESULTS
DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001).
CONCLUSION
Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.
PubMed: 38268126
DOI: 10.23876/j.krcp.23.074 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment...
PURPOSE
Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of glaucoma with the causative drugs using a spontaneous reporting system database.
METHODS
Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on reports of glaucoma caused by all drugs, we calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for glaucoma.
RESULTS
Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate. Among 207 reports involved in angle-closure glaucoma (86%, women), anticholinergic drug and antidepressants ranked high and showed signals. Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma.
CONCLUSION
A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it.
PubMed: 38050555
DOI: 10.2147/OPTH.S439255 -
The Lancet. Haematology Dec 2023Up to 88% of infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions require erythrocyte transfusions after birth. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Darbepoetin alfa to reduce transfusion episodes in infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions in the Netherlands: an open-label, single-centre, phase 2, randomised, controlled trial.
BACKGROUND
Up to 88% of infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions require erythrocyte transfusions after birth. We aimed to investigate the effect of darbepoetin alfa on the prevention of postnatal anaemia in infants with haemolytic disease of the fetus and newborn.
METHODS
We conducted an open-label, single-centre, phase 2 randomised controlled trial to evaluate the effect of darbepoetin alfa on the number of erythrocyte transfusions in infants with haemolytic disease of the fetus and newborn. All infants who were treated with intrauterine transfusion and born at 35 weeks of gestation or later at the Leiden University Medical Center, Leiden, Netherlands, were eligible for inclusion. Included infants were randomised by computer at birth to treatment with 10 μg/kg darbepoetin alfa subcutaneously once a week for 8 weeks or standard care (1:1 allocation, in varying blocks of four and six, with no stratification). Treating physicians and parents were not masked to treatment allocation, but the research team, data manager, and statistician were masked to treatment allocation during the process of data collection. The primary outcome was the number of erythrocyte transfusion episodes per infant from birth up to 3 months of life in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03104426) and has been completed.
FINDINGS
Between Oct 31, 2017, and April 31, 2022, we recruited 76 infants, of whom 44 (58%) were randomly assigned to a treatment group (20 [45%] were allocated to receive darbepoetin alfa and 24 [55%] were allocated to receive standard care). Follow-up lasted 3 months and one infant dropped out of the trial before commencement of treatment. A significant reduction in erythrocyte transfusion episodes was identified with darbepoetin alfa treatment compared with standard care (median 1·0 [IQR 1·0-2·0] transfusion episodes vs 2·0 [1·3-3·0] transfusion episodes; p=0·0082). No adverse events were reported and no infants died during the study.
INTERPRETATION
Darbepoetin alfa reduced the transfusion episodes after intrauterine transfusion treatment for haemolytic disease of the fetus and newborn. Treatment with darbepoetin alfa or other types of erythropoietin should be considered as part of the postnatal treatment of severe haemolytic disease of the fetus and newborn.
FUNDING
Sanquin Blood Supply.
TRANSLATION
For the Dutch translation of the abstract see Supplementary Materials section.
Topics: Infant, Newborn; Female; Pregnancy; Infant; Humans; Darbepoetin alfa; Blood Transfusion, Intrauterine; Hematinics; Netherlands; Hemolysis; Fetus
PubMed: 38030319
DOI: 10.1016/S2352-3026(23)00285-5 -
The Lancet. Haematology Dec 2023
Topics: Humans; Infant, Newborn; Anemia; Darbepoetin alfa; Erythropoietin; Fetus; Hematologic Diseases; Hemolysis
PubMed: 38030313
DOI: 10.1016/S2352-3026(23)00316-2 -
Frontiers in Pharmacology 2023: The comparative benefits and acceptability of HIF-PHIs for treating anemia have not been well researched to date. We sought to compare the effectiveness of 6 HIF-PHIs...
Comparative effectiveness and acceptability of HIF prolyl-hydroxylase inhibitors for anemia patients with chronic kidney disease undergoing dialysis: a systematic review and network meta-analysis.
: The comparative benefits and acceptability of HIF-PHIs for treating anemia have not been well researched to date. We sought to compare the effectiveness of 6 HIF-PHIs and 3 ESAs for the treatment of renal anemia patients undergoing dialysis. Cochrane Central Register of Controlled Trials, PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, and clinicaltrials.gov databases. Twenty-five RCTs (involving 17,204 participants) were included, all of which were designed to achieve target Hb levels by adjusting thee dose of HIF-PHIs. Regarding the efficacy in achieving target Hb levels, no significant differences were found between HIF-PHIs and ESAs in Hb response at the dose-adjusted designed RCTs selected for comparison. Intervention with roxadustat showed a significantly lower risk of RBC transfusion than rhEPO, with an OR and 95% CI of 0.76 (0.56-0.93). Roxadustat and vadadustat had higher risks of increasing the discontinuation rate than ESAs; the former had ORs and 95% CIs of 1.58 (95% CI: 1.21-2.06) for rhEPO, 1.66 (1.16-2.38) for DPO (darbepoetin alfa), and 1.76 (1.70-4.49) for MPG-EPO, and the latter had ORs and 95% CIs of 1.71 (1.09-2.67) for rhEPO, 1.79 (1.29-2.49) for DPO, and 2.97 (1.62-5.46) for MPG-EPO. No differences were observed in the AEs and SAEs among patients who received the studied drugs. Results of a meta-analysis of gastrointestinal disorders among AEs revealed that vadadustat was less effect on causing diarrea than DPO, with an OR of 0.97 (95% CI, 0.9-0.99). Included HIF-PHIs, were proven to be more effective than ESAs in reducing hepcidin levels and increasing TIBC and serum iron level with OR of -0.17 (95% CI, -0.21 to -0.12), OR of 0.79 (95% CI, 0.63-0.95), and OR of 0.39 (95% CI, 0.33-0.45), respectively. HIF-PHIs and ESAs have their characteristics and advantages in treating anemia undergoing dialysis. With the selected dose-adjusted mode, some HIF-PHIs appeared to be a potential treatment for DD-CKD patients when ompared with rhEPO, due to its effectiveness in decreasing the risk of RBC transfusion rate or regulating iron or lipid metabolism while achieving target Hb levels. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306511; Identifier: CRD42022306511.
PubMed: 37521459
DOI: 10.3389/fphar.2023.1050412 -
American Journal of Health-system... Oct 2023Post-transplantation anemia (PTA) is common in kidney transplant recipients, with patients frequently treated with erythropoietin-stimulating agents such as darbepoetin...
PURPOSE
Post-transplantation anemia (PTA) is common in kidney transplant recipients, with patients frequently treated with erythropoietin-stimulating agents such as darbepoetin alfa. The optimal dosing for darbepoetin alfa remains controversial.
METHODS
This retrospective cohort study involved kidney transplant recipients who received darbepoetin alfa at 2 clinics. Patients were stratified into 2 groups: those who received a fixed dose of 200 μg and those who received a weight-based dose of 0.45 μg/kg. The dosing interval varied depending on clinical response, clinic visit timing, and frequency allowed by insurance. The primary outcome was achieving a hemoglobin concentration of at least 10 g/dL without blood transfusion by 12 weeks after darbepoetin alfa initiation.
RESULTS
Of the 110 patients in the study, 45% received weight-based dosing and 55% received fixed dosing. Darbepoetin alfa was initiated significantly earlier after transplantation in the fixed-dose group (median of 14 vs 20 days; P = 0.003). The weight-based group received more doses of darbepoetin alfa (median of 4 vs 2 doses; P = 0.002) and had a significantly lower cumulative exposure to darbepoetin alfa (125 vs 590 μg; P < 0.001). The median time between doses was 9 days (interquartile range, 7-14 days) in the weight-based group and 12 days (7-32 days) in the fixed-dose group (P = 0.04). Patients in the weight-based group more frequently achieved the primary outcome (67.3% vs 47.5%; P = 0.059). There was no significant difference in secondary or safety outcomes between the groups.
CONCLUSION
Weight-based and fixed dosing approaches for darbepoetin alfa were not different in the achievement of a hemoglobin concentration of at least 10 g/dL without blood transfusion at 12 weeks after darbepoetin alfa initiation, with significantly lower cumulative darbepoetin alfa utilization in the weight-based group. Weight-based dosing of darbepoetin alfa in PTA appears to be safe and effective, with the potential for significant patient and health-system cost savings.
Topics: Humans; Darbepoetin alfa; Kidney Transplantation; Retrospective Studies; Anemia; Hemoglobins; Hematinics; Treatment Outcome
PubMed: 37471466
DOI: 10.1093/ajhp/zxad163 -
Kidney Medicine Jul 2023Prespecified analyses of the PROTECT trials comparing the safety of the oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in...
Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PROTECT Randomized Clinical Trial of ESA-Naïve Patients.
RATIONALE & OBJECTIVE
Prespecified analyses of the PROTECT trials comparing the safety of the oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) found no difference in major adverse cardiovascular events (MACE; death from any cause or nonfatal myocardial infarction or stroke) among US patients and a higher risk among patients treated with vadadustat outside the United States. We investigated regional differences in MACE in the PROTECT trial that enrolled 1,751 patients previously untreated with erythropoiesis-stimulating agents.
STUDY DESIGN
Phase 3, global, open-label, randomized, active-controlled clinical trial.
SETTING AND PARTICIPANTS
Erythropoiesis-stimulating agent-untreated patients with anemia and NDD-CKD.
INTERVENTION
Eligible patients were randomized 1:1 to receive vadadustat or darbepoetin alfa.
OUTCOMES
The primary safety end point was time to first MACE. Secondary safety end points included time to first expanded MACE (MACE plus hospitalization for heart failure or thromboembolic event, excluding vascular access thrombosis).
RESULTS
In the non-US/non-Europe region, there was a higher proportion of patients with baseline estimated glomerular filtration rate (eGFR) level of ≤10 mL/min/1.73 m in the vadadustat group [96 (34.7%)] than in the darbepoetin alfa group [66 (24.0%)]. In this region, there were 21 excess MACEs reported in the vadadustat group [78 events (n=276)] versus the darbepoetin alfa [57 events (n=275)], including 13 excess noncardiovascular deaths, largely from kidney failure. Noncardiovascular deaths were concentrated in Brazil and South Africa, which enrolled higher proportions of patients with an eGFR of ≤10 mL/min/1.73 m and who may not have had access to dialysis.
LIMITATIONS
Different regional treatment patterns of patients with NDD-CKD.
CONCLUSIONS
The higher MACE rate in the non-US/non-Europe vadadustat group may have been partly because of imbalances in the baseline eGFR level in countries where dialysis was not uniformly available resulting in many kidney-related deaths.
PubMed: 37427293
DOI: 10.1016/j.xkme.2023.100666 -
Kidney Medicine Jul 2023In the PROTECT trials, vadadustat was found to be noninferior to darbepoetin alfa in hematologic efficacy but not for major adverse cardiovascular events (MACE;...
Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With NonDialysis-Dependent CKD: A Post Hoc Regional Analysis of the PROTECT Randomized Clinical Trial of ESA-Treated Patients.
RATIONALE & OBJECTIVE
In the PROTECT trials, vadadustat was found to be noninferior to darbepoetin alfa in hematologic efficacy but not for major adverse cardiovascular events (MACE; all-cause death or nonfatal myocardial infarction or stroke) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). We investigated the regional differences in MACE in the PROTECT trials.
STUDY DESIGN
Phase 3, global, open-label, randomized, active-controlled clinical trial.
SETTING & PARTICIPANTS
A total of 1,725 erythropoiesis-stimulating agent (ESA)-treated patients with anemia and NDD-CKD.
INTERVENTION
1:1 randomization to receive vadadustat or darbepoetin alfa.
OUTCOMES
The primary safety end point was the time to first MACE.
RESULTS
At baseline, patients in Europe (n=444) were primarily treated with darbepoetin alfa, showed higher proportions on low ESA doses (<90 U/kg/wk epoetin alfa equivalents) with a hemoglobin concentration of ≥10 g/dL compared with patients in the US (n=665) and non-US/non-Europe (n=614) regions. The MACE rates per 100 person-years in the 3 vadadustat groups across regions were 14.5 in the US, 11.6 in Europe, and 10.0 in the non-US/non-Europe groups, whereas event rates in the darbepoetin alfa group were considerably lower in Europe than in the US and non-US/non-Europe groups (6.7 vs 13.3 and 10.5, respectively). The overall hazard ratio for MACE for vadadustat vs darbepoetin alpha was 1.16; 95% CI, 0.93-1.45, but varied by geographical region, with a greater hazard ratio seen in Europe (US, 1.07; 95% CI, 0.78-1.46; Europe, 2.05; 95% CI, 1.24-3.39; non-US/non-Europe, 0.91; 95% CI, 0.60-1.37); interaction between study treatment and geographical region, = 0.07). In Europe, ESA rescue was associated with a higher risk of MACE in both groups.
LIMITATIONS
Several analyses are exploratory.
CONCLUSIONS
In this trial, there was a low risk of MACE in the darbepoetin alfa group in Europe. Patients in Europe were generally on low doses of ESA, with hemoglobin already within target range. The low risk of MACE may have been related to a limited need to switch and titrate darbepoetin alfa compared with the non-US/non-Europe group.
FUNDING
Akebia Therapeutics, Inc.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02680574.
PubMed: 37427292
DOI: 10.1016/j.xkme.2023.100667