RESUMO
BACKGROUND: The management of chemotherapy induced anemia (CIA) remains challenging. The potential risk and benefits in providing patient-centered care need to be balanced; the disease is multifactorial; and the major treatments including red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs) and intravenous injection (i.v.)iron supplementation have a unique set of strengths and limitations. Also, most previous survey based on the patient data could not reveal the process of evaluation and decision-making for CIA treatment from a physician's perspective. As the comparison of China Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines, the standard of CIA treatment in China will vary from United States and Europe, for example, the initial hemoglobin (Hb) for RBC transfusions. In order to understand the diagnosis, treatment, and unmet medical needs of CIA patients, the China Medical Education Association (CMEA), in conjunction with Cancer Hope Medium, initiated the first national survey of Chinese physicians regarding the diagnosis and treatment of CIA. METHODS: The CMEA sent an online, 12-item questionnaire (via wjx.cn) to physicians across China from September 1, 2022 to October 22, 2022. Two hundred and sixty-five samples were calculated usingsurveyplanet.com. The questionnaire evaluated the impact of anemia on chemotherapy interruption, initial treatment, the target Hb level of CIA in, and the current status of ESAs prescription in clinical practice. Respondents were asked to score their reasons for not using ESAs (including safety issues, drug access in practice or adherence) and the risk options of the current treatment including ESAs, RBC transfusion, and i.v.iron. RESULTS: A total of 331 questionnaires among 5,000 web visits were gathered, covering 247 hospitals in 29 provinces across China, of which 130 (53%) were tier IIIA hospitals, 50 (20%) were tier III B hospitals, 59 (24%) were tier IIA hospitals, and 8 (3%) were tier II B hospitals. The frequency of chemotherapy dose delay/reduction due to anemia was 24% [standard deviation (SD) 49%]. Most responding physicians rated an initial Hb level for ESAs treatment to be 80 g/L, with a favorable Hb level for chemotherapy being 100 g/L (60%), which would not limit treatment availability. The majority (67.6%, n=221) of physicians who responded indicated that they had used ESAs for anemia correction, while the others (32.4%, n=106) reported never using them. CONCLUSIONS: This is the first study in conducting a large-scale survey on the diagnosis and treatment of CIA in China from a physicians' perspective. We found that in China, nearly one-quarter of patients undergoing chemotherapy with concurrent anemia may experience interruption of chemotherapy and that the initiation of anemia treatment is not adequately timed. In treating CIA, most physicians prioritize the completion of chemotherapy via Hb level over treating the symptoms of anemia.
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Anemia , Antineoplásicos , Hematínicos , Neoplasias , Médicos , Humanos , Estados Unidos , Antineoplásicos/uso terapêutico , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Ferro/efeitos adversos , Hematínicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Inquéritos e Questionários , PercepçãoRESUMO
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 (p < 0.05), but no significant change was observed (p = 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.
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Anemia , Hematínicos , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Hematínicos/farmacologia , Hematínicos/uso terapêutico , Anemia/tratamento farmacológico , Inibidores de Prolil-Hidrolase/farmacologia , Inibidores de Prolil-Hidrolase/uso terapêutico , Zinco/farmacologia , Zinco/uso terapêutico , Eritropoese , Prolil Hidroxilases/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Darbepoetina alfa/farmacologia , Darbepoetina alfa/uso terapêutico , Estudos Retrospectivos , Glicina/farmacologia , Suplementos NutricionaisRESUMO
Anemia is the most common modifiable risk factor for postoperative morbidity and mortality. Early identification and optimal management are key to restore iron stores and ensure its resolution before surgery. Several therapies have been proposed to treat anemia in the perioperative period, such as iron supplementation and erythropoiesis-stimulating agents, though it remains unclear which is the most optimal to improve clinical outcomes. This article summarizes the most updated evidence on perioperative management of anemia and denotes differences among the international guidelines to reflect the conflicting evidence in this field and the need for further research in specific areas.
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Anemia , Hematínicos , Humanos , Anemia/terapia , Ferro/uso terapêutico , Hematínicos/uso terapêutico , Fatores de Risco , Período Pós-OperatórioRESUMO
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 approaches have 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.
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Anemia , Glicina , Prolina Dioxigenases do Fator Induzível por Hipóxia , Isoquinolinas , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anemia/tratamento farmacológico , Anemia/etiologia , Glicina/análogos & derivados , Glicina/uso terapêutico , Isoquinolinas/uso terapêutico , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Inibidores de Prolil-Hidrolase/uso terapêutico , Resultado do Tratamento , Hematínicos/uso terapêuticoRESUMO
BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have played an important role in the treatment of renal anemia in children, but cannot improve hemoglobin to target level in some cases. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate endogenous erythropoietin production and regulate iron metabolism even in patients with kidney failure. However, roxadustat has not yet been approved for use in children. CASE-DIAGNOSIS/TREATMENT: We report a case of refractory renal anemia in an 80-day-old boy, who was hyporesponsive to ESAs even in combination with iron supplementation and transfusion. Compassionate use of roxadustat successfully corrected the intractable anemia. Hyperkalemia is a manageable adverse event of concern during follow-up. CONCLUSION: The successful experience in this case may inform the clinical utility of roxadustat for refractory renal anemia in children, which should be further confirmed by well-designed prospective clinical trials.
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Anemia , Hematínicos , Insuficiência Renal Crônica , Masculino , Criança , Humanos , Ensaios de Uso Compassivo , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Anemia/etiologia , Anemia/induzido quimicamente , Hematínicos/efeitos adversos , Doença Crônica , Glicina/uso terapêutico , Glicina/farmacologia , Isoquinolinas/efeitos adversos , Ferro/uso terapêuticoRESUMO
PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.
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Anemia , Antineoplásicos , Eritropoetina , Hematínicos , Neoplasias , Adulto , Humanos , Epoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Eritropoetina/efeitos adversos , Qualidade de Vida , Estudos Prospectivos , Escala Visual Analógica , Hematínicos/uso terapêutico , Hematínicos/efeitos adversos , Antineoplásicos/efeitos adversos , Resultado do Tratamento , Anemia/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Fadiga/induzido quimicamenteRESUMO
Natural resources have recently received considerable attention as complementary or alternative hematinic agents. In this regard, olive leaf extract, which is rich in bioactive phenolic compounds, has been reported to induce erythroid differentiation in human hematopoietic stem cells. Therefore, in the present study, we aimed to explore the potential hematinic properties of aqueous olive leaf extract (WOL) in vivo. After 24 days of administering WOL to healthy mice orally, red blood cell (RBC), hematocrit, reticulocyte, and reticulocyte hemoglobin content (CHr) showed a significant increase. Additionally, WOL promoted plasma iron levels and the expression of splenic ferroportin (Fpn), an iron transporter. Additionally, a single-arm pilot study involving a limited number of healthy volunteers was conducted to assess WOL's feasibility, compliance, and potential benefits. Following an 8-week intervention with WOL, RBC count and hemoglobin level were significantly increased. Notably, there were no significant changes in the safety measures related to liver and kidney functions. Furthermore, we identified oleuropein and oleuroside as the active components in WOL to induce erythroid differentiation in the K562 cell line. Altogether, our study presents evidence of the hematinic potential of WOL in the in vivo studies, opening up exciting possibilities for future applications in preventing or treating anemia.
Assuntos
Hematínicos , Olea , Humanos , Camundongos , Animais , Voluntários Saudáveis , Projetos Piloto , Ferro , HemoglobinasRESUMO
BACKGROUND: Treatment for anemia of chronic kidney disease (CKD) largely consists of erythropoiesis-stimulating agents (ESAs) with iron supplementation. Although ESAs are well-established and efficacious, their use has been associated with considerable economic and humanistic burdens. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that targets multiple causes of CKD and has a similar efficacy and safety profile to ESAs. The cost-effectiveness of this treatment, however, has yet to be investigated. OBJECTIVE: The study objective was to develop a health economic model to evaluate the cost-effectiveness of roxadustat compared with ESAs for treating anemia of non-dialysis-dependent (NDD) CKD. METHODS: A cohort-based model was developed for a hypothetical cohort of 1,000 patients with anemia of NDD CKD, incorporating eight health states, representing the hemoglobin level of each patient. The model was informed by individual patient-level data from the roxadustat global phase 3 clinical trial program. Total and incremental costs as well as quality-adjusted life-years (QALYs) associated with roxadustat versus ESAs were estimated from the perspective of the UK National Health Service. Sensitivity analyses were performed to assess the robustness of the model. Analyses exploring alternative scenarios were also conducted. RESULTS: On a per-person basis, over 1,000 simulations, roxadustat was found to be on average less costly (-£32) and more effective (+0.01 QALYs) than ESAs, with a dominant incremental cost-effectiveness ratio. The probability of cost-effectiveness at a £20,000 per QALY willingness-to-pay threshold from the UK perspective was 67%. CONCLUSION: The model developed may be a useful instrument that, alongside expert clinical opinion, can inform clinical and policy decision-making regarding treatment of anemia of NDD CKD. The model highlights the cost-effectiveness of roxadustat, as well as its potential to have a meaningful impact in reducing the burden of anemia of NDD CKD.
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Anemia , Hematínicos , Insuficiência Renal Crônica , Humanos , Análise Custo-Benefício , Medicina Estatal , Anemia/tratamento farmacológico , Anemia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Hematínicos/uso terapêutico , Glicina/uso terapêutico , Isoquinolinas/uso terapêutico , Isoquinolinas/farmacologia , Modelos EconômicosRESUMO
Anemia is a common complication of kidney disease and the prevalence increases as the disease progresses. It worsens the quality of life of patients and increases morbidity and mortality. The current rationale for treating renal anemia is based on the use of erythropoiesis-stimulating agents, iron supplementation and, to a lesser extent, the use of transfusions. Stimulation of endogenous erythropoietin synthesis and improvement of iron availability, through inhibition of prolil-hydroxilase-hypoxia-inducible factor (PH-HIF), represents a new oral alternative for renal anemia treatment. Clinical trials with PH-HIF inhibitors have demonstrated their efficacy in maintaining target hemoglobin levels. However, aspects concerning long-term safety are pending a clarification. In conclusion, advances in the pathogenesis of renal anemia make it possible to have current treatments to treat renal anemia. The development of new molecules, based on the inhibition of PH-HIF, represents a new effective alternative for anemia associated with kidney disease, especially in patients with resistance to erythropoiesis-stimulating agents.
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Anemia , Hematínicos , Insuficiência Renal Crônica , Humanos , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anemia/tratamento farmacológico , Anemia/etiologia , Ferro/uso terapêutico , Hematínicos/uso terapêutico , Doença CrônicaAssuntos
Anemia Ferropriva , Insuficiência Cardíaca , Hematínicos , Humanos , Ferro/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Administração Intravenosa , Hematínicos/uso terapêutico , Suplementos Nutricionais , Anemia Ferropriva/tratamento farmacológicoRESUMO
Evidence-based medicine is considered 1 of the 15 great inventions in medicine. It aims to remove bias in medical decision-making as much as possible through a rigorous process. In this article, the principles of evidence-based medicine are illustrated using the case of patient blood management (PBM). Acute or chronic bleeding, iron deficiency, and renal and oncological diseases may lead to preoperative anemia. To compensate for severe and life-threatening blood loss during surgery, doctors transfuse red blood cells (RBCs). PBM is an approach to take care of patients at risk for anemia, which includes detecting and treating anemia before surgery. Alternative interventions to treat preoperative anemia are the use of iron supplementation with or without erythro-stimulating agents (ESAs). The best available scientific evidence today indicates that preoperative intravenous (IV) or oral iron monotherapy may not be effective to reduce RBC utilization (low-certainty evidence). Preoperative IV iron supplementation in addition to ESAs is probably effective to reduce RBC utilization (moderate-certainty evidence), whereas oral iron supplementation in addition to ESAs may be effective to reduce RBC utilization (low-certainty evidence). The adverse events of preoperative oral/IV iron and/or ESAs and their impact on patient-important outcomes (morbidity, mortality, quality of life) remain unclear (very low-certainty evidence). Since PBM is a patient-centered approach, emphasis on monitoring and evaluation of patient-important outcomes in future research is urgently needed. Finally, the cost-effectiveness of preoperative oral/IV iron monotherapy is unproven, whereas preoperative oral/IV iron in addition to ESAs is extremely cost-ineffective.
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Anemia , Hematínicos , Humanos , Qualidade de Vida , Ferro , Transfusão de Sangue , Medicina Baseada em EvidênciasRESUMO
In patients on chronic hemodialysis, there is no standard protocol for maintenance iron supplementation. This study aimed to compare two fixed-dose intravenous (IV) iron protocols to reduce erythropoiesis-stimulating agents (ESA). We conducted a double-blinded, randomized controlled study on hemodialysis patients having ferritin levels between 200 and 700 ng/dl and transferrin saturation values between 20 and 40%. Patients were assigned to receive either 100 or 200 mg of IV iron each month. ESA was adjusted every month to keep Hb between 10 and 12 g/dl. ESA dose at 12 months was the primary outcome. The secondary outcomes were all-cause mortality, cardiovascular events, absolute iron deficiency anemia (IDA), blood transfusion, adverse events, and iron withholding rate. Of the 79 eligible patients, 40 received 100 mg of IV iron, while 39 received 200 mg. At month 12, the mean monthly ESA dose in the 100-mg IV iron group was 35,706 ± 21,637 IU, compared to 26,382 ± 14,983 IU in the 200-mg group (P = 0.03). IDA was found in twelve patients (30%) in the 100-mg group and four patients (10.5%) in the 200-mg group (P = 0.05). In each group, three patients died (P = 0.9). Hospitalization, venous access thrombosis, and infection rates were similar in both groups. The withholding rate of IV iron was higher in 200-mg group (25% vs. 64.1%), but the protocol compliance was found more in 100-mg group (50% vs. 28.2%) (P = 0.001). In conclusion, monthly 200-mg IV iron infusions significantly reduce ESA doses but have a higher withholding rate. (Funded by the Kidney Foundation of Thailand and the Research Group in Nephrology and Renal Replacement Therapy from the Faculty of Medicine, Thammasat University).Thai Clinical Trials Registry number, TCTR20190707001.
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Anemia Ferropriva , Eritropoetina , Hematínicos , Humanos , Hematínicos/uso terapêutico , Diálise Renal/efeitos adversos , Administração Intravenosa , Anemia Ferropriva/tratamento farmacológico , Hemoglobinas/uso terapêuticoRESUMO
All neonates experience a downtrend in their hematocrit values immediately following the birth through normal falls in erythropoietin (Epo) production, transition to adult hemoglobin, and hemodilution with somatic growth. However, this drop is more pronounced in critically ill and preterm neonates and can lead to potentially pathologic anemia that impairs tissue oxygen delivery. In this review, we highlight the mechanisms underlying physiologic anemia and anemia of prematurity and briefly review the evidence for the treatment of anemia in the neonatal population, including the use of red blood cell transfusions, erythropoietic stimulating agents, and iron supplementation.
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Anemia Neonatal , Eritropoetina , Hematínicos , Recém-Nascido , Humanos , Recém-Nascido de Baixo Peso , Fatores Etários , Recém-Nascido Prematuro , Eritropoetina/uso terapêutico , Anemia Neonatal/diagnóstico , Anemia Neonatal/terapiaRESUMO
BACKGROUND: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. METHODS: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st-5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. RESULTS: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (- 0.75, 95% CI - 1.36, - 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (ß = - 0.98; 95% CI - 1.78, - 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (ß = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (ß = - 1.33, 95% CI - 2.16, - 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (ß = - 1.09, 95% CI - 2.09, - 0.10, p = 0.03). CONCLUSIONS: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Anemia , Hematínicos , Insuficiência Renal Crônica , Humanos , Criança , Função Executiva , Anemia/epidemiologia , Anemia/etiologia , Insuficiência Renal Crônica/complicações , Hemoglobinas/análise , Hematínicos/uso terapêuticoRESUMO
Both preoperative anemia and the transfusion of red blood cells have been associated with increased morbidity and mortality after cardiac surgery. To reduce the need for blood transfusion during surgery and improve patient outcomes, patient blood management programs have been developed. A primary focus of patient blood management in the preoperative period is the identification, diagnosis, and treatment of preoperative anemia, as anemia is associated with an increased risk of preoperative blood transfusion. In this narrative review, the authors focus on the laboratory screening of anemia before surgery and the evidence and limitations of different treatment strategies in anemic patients scheduled for cardiac surgery. To accurately correct preoperative anemia, the timely detection and definition of the etiology of anemia before elective cardiac surgery are crucial. Multiple randomized studies have been performed using preoperative iron supplementation and/or administration of erythropoiesis-stimulating agents in patients undergoing cardiac surgery. Although preoperative iron substitution in patients with iron deficiency is recommended, the evidence of its effectiveness is limited. In patients with nonpure iron deficiency anemia, combined therapy with erythropoiesis-stimulating agents and intravenous iron is recommended. Combined therapy might effectively reduce the need for red blood cell transfusion, even if applied shortly before cardiac surgery. The therapeutic effect on morbidity and mortality remains unclear. Nonetheless, the timely preoperative assessment of anemia and determination of iron status, eventually leading to targeted therapy, should become a standard of care and might potentially improve patient outcomes.
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Anemia Ferropriva , Anemia , Procedimentos Cirúrgicos Cardíacos , Hematínicos , Humanos , Cuidados Pré-Operatórios , Anemia/diagnóstico , Anemia/terapia , Ferro/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hematínicos/uso terapêuticoRESUMO
Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.
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Anemia Ferropriva , Hematínicos , Deficiências de Ferro , Humanos , Anemia Ferropriva/tratamento farmacológico , Ferro/uso terapêutico , MaltoseRESUMO
Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.
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Doenças Cardiovasculares , Hematínicos , Insuficiência Renal Crônica , Adulto , Humanos , Hematínicos/uso terapêutico , Diálise Renal , Eritropoese , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Darbepoetina alfa/uso terapêuticoRESUMO
INTRODUCTION AND AIMS: This study examined whether zinc supplementation with zinc acetate hydrate improved renal anemia with hypozincemia in patients undergoing hemodialysis. METHODS: The study participants included 21 patients undergoing hemodialysis who presented with a serum zinc level < 60 mg/dL and who were administered zinc acetate hydrate at 50 mg (reduced to 25 mg, as appropriate) for 6 months. Patients with a hemorrhagic lesion, acute-phase disease (pneumonia or cardiac failure), or hematologic disease and those whose treatment was switched from peritoneal dialysis to hemodialysis were excluded. The changes in the erythropoietin resistance index (ERI) before and after zinc acetate hydrate administration were examined. ERI was defined as the dose (IU) of erythropoiesis-stimulating agent (ESA)/week/body weight (kg)/hemoglobin content (g/dL). The differences between the two groups were analyzed using the Wilcoxon signed rank sum test, and p < 0.05 was considered statistically significant. RESULTS: The study participants included 19 men and 2 women aged 41-95 years (mean ± standard deviation (SD): 67.1 ± 13.6). The changes in the values of parameters measured before and after zinc acetate hydrate administration were as follows: Blood Hb did not change significantly, from 10.0-13.6 g/dL (11.5 ± 1.0 g/dL) to 10.2-12.4 g/dL (11.4 ± 0.7 g/dL); serum zinc concentration significantly increased, from 33.0-59.0 mg/dL µg/dL (52.4 ± 7.6 mg/dL µg/dL) to 57.0-124.0 mg/dL µg/dL (84.1 ± 16.3 mg/dL µg/dL; p < 0.01); the ESA dose significantly decreased, from 0-12,000 IU/week (5630 ± 3351 IU/week) to 0-9000 IU/week (4428 ± 2779; p = 0.04); and ERI significantly decreased, from 0.0-18.2 (8.1 ± 5.1) to 0.0-16.0 (6.3 ± 4.3; p = 0.04). CONCLUSIONS: Zinc supplementation increased the serum zinc concentration and significantly reduced the ESA dose and ERI, suggesting that a correction of hypozincemia contributes to lessening renal anemia in these patients.
Assuntos
Anemia , Hematínicos , Nefropatias , Falência Renal Crônica , Masculino , Humanos , Feminino , Acetato de Zinco/efeitos adversos , Anemia/tratamento farmacológico , Anemia/etiologia , Diálise Renal/efeitos adversos , Hematínicos/farmacologia , Hematínicos/uso terapêutico , Hemoglobinas , Falência Renal Crônica/terapia , Zinco/uso terapêutico , Doença Crônica , Suplementos NutricionaisRESUMO
BACKGROUND: The detection and correction of iron deficiency are essential for the treatment of anemia in chronic hemodialysis patients. The aim of our study was to assess the ability of serum iron to predict hemoglobin response to intravenous iron supplementation in hemodialysis patients. METHODS: It is a retrospective study in 91 hemodialysis patients during 2016 at Clermont-Ferrand University Hospital for whom intravenous iron supplementation had been started. A responder patient was defined as an increase in hemoglobin greater than or equal to 1 g/dL/month and/or a decrease in the dose of erythropoiesis stimulating agent after two months of iron supplementation. RESULTS: In responding patients, serum iron was significantly lower (6.7 ± 2.7 µmol/L) compared to non-responding patients (8.9±2.9 µmol/L; P<0.001). The positive response to iron supplementation was significantly associated with low serum iron (odds ratio = 0.58 [0.42-0.81]; P=0.002) in a logistic regression model taking into account ferritin, transferrin saturation coefficient, dose variation monthly iron and erythropoiesis stimulating agent and the duration of dialysis. The area under the receiver operating characteristic curve of serum iron, ferritin and transferrin saturation coefficient to predict the response to iron supplementation were 0.72, 0.51 and 0.64, respectively (serum iron versus ferritin [P=0.006] and serum iron versus transferrin saturation coefficient [P=0.04]). The sensitivity for serum iron below 7.5 µmol/L was better than that for ferritin below 86 ng/mL (P<0.001) and the specificity for serum iron below 7.5 µmol/L was better than that for TSC less than 19% (P=0.02). CONCLUSION: Serum iron below 7.5 µmol/L can predict the success of the response to iron supplementation in chronic hemodialysis patients.