Subject(s)
Flow Cytometry , Mutation , Myelodysplastic Syndromes , Humans , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/drug therapy , Female , Male , Aged , Middle Aged , Erythroid Precursor Cells/pathology , Erythroid Precursor Cells/metabolism , Hematinics/therapeutic use , Aged, 80 and over , AdultABSTRACT
We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (Pâ >â .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (Pâ <â .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (Pâ >â .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (Pâ >â .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.
Subject(s)
Anemia , Hemoglobins , Isoquinolines , Renal Dialysis , Humans , Male , Female , Renal Dialysis/adverse effects , Anemia/drug therapy , Anemia/etiology , Middle Aged , Prospective Studies , Isoquinolines/therapeutic use , Isoquinolines/adverse effects , Isoquinolines/administration & dosage , Hemoglobins/analysis , Hemoglobins/metabolism , Aged , Erythropoietin/therapeutic use , Hematinics/therapeutic use , Hematinics/adverse effects , Hematinics/administration & dosage , Glycine/analogs & derivatives , Glycine/therapeutic use , Ferritins/blood , Treatment OutcomeABSTRACT
Traditionally, the treatment of anemia associated with chronic kidney disease (CKD) involves prescribing erythropoiesis-stimulating agents (ESAs) or iron preparations. The effectiveness and safety of ESAs and iron have been established. However, several clinical issues, such as hyporesponsiveness to ESAs or defective iron utilization for erythropoiesis, have been demonstrated. Recently, a new class of therapeutics for renal anemia known as hypoxia-inducible factor (HIF)/proline hydroxylase (PH) inhibitors has been developed. Several studies have reported that HIF-PH inhibitors have unique characteristics compared with those of ESAs. In particular, the use of HIF-PH inhibitors may maintain target Hb concentration in patients treated with a high dose of ESAs without increasing the dose. Furthermore, several recent studies have demonstrated that patients with CKD with defective iron utilization for erythropoiesis had a high risk of cardiovascular events or premature death. HIF-PH inhibitors increase iron transport and absorption from the gastrointestinal tract; thus, they may ameliorate defective iron utilization for erythropoiesis in patients with CKD. Conversely, several clinical problems, such as aggravation of thrombotic and embolic complications, diabetic retinal disease, and cancer, have been noted at the time of HIF-PH inhibitor administration. Recently, several pooled analyses of phase III trials have reported the non-inferiority of HIF-PH inhibitors regarding these clinical concerns compared with ESAs. The advantages and issues of anemia treatment by ESAs, iron preparations, and HIF-PH inhibitors must be fully understood. Moreover, patients with anemia and CKD should be treated by providing a physiological erythropoiesis environment that is similar to that of healthy individuals.
Subject(s)
Anemia , Erythropoiesis , Hematinics , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Erythropoiesis/drug effects , Anemia/drug therapy , Anemia/etiology , Hematinics/therapeutic use , Iron/metabolismABSTRACT
Previous studies have demonstrated that erythropoiesis-stimulating agents (ESAs) can reduce anemia and improve quality of life in cancer patients, but ESAs may increase mortality. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) comparing the effect and risk of ESAs about the prevention or treatment of anemia in cancer patients. Four databases including PubMed, Embase, Web of science and Cochrane Library were searched for published RCTS on ESAs in the treatment of anemia in lung cancer patients from 2000 to 2023. Endpoints including mortality, incidence of thrombotic vascular events, blood transfusion requirement, and incidence of adverse events. Our meta-analysis included 8 studies, with a sample size of 4240 patients, including 2548 patients in the ESAs group and 1692 patients in the control group. The risk of mortality was lower in patients using ESAs than control group (RR 0.96, 95% CI 0.92-0.99, P = 0.02). But there was no significant difference in the risk of mortality between the patients using ESAs and controls (RR 0.99, 95% CI 0.92-1.06, P = 0.69) after removing Pere 2020. Subgroup analysis found that patients diagnosed with small cell lung cancer (SCLC) (RR 1.00, 95% CI 0.92-1.08, P = 0.16) or non-small cell lung cancer (NSCLC) (RR 1.01, 95% CI 0.87-1.17, P = 0.13) were no significant difference in mortality rate. The thrombotic vascular events increase in patients using ESAs than control group (RR 1.40, 95% CI 1.13-1.72, P = 0.002). The blood transfusion requirement of ESAs group was lower than control group (RR 0.56, 95% CI 0.44-0.72, P < 0.00001). And the subgroups of Darbepoetin alfa (RR 0.57, 95% CI 0.41-0.79, P = 0.003) and Epoetin alfa (RR 0.68, 95% CI 0.47-0.99, P = 0.01) had lower transfusion requirements than the control group. In the SCLC subgroup (RR 0.51, 95% CI 0.40-0.65, P = 0.34), blood transfusion requirements were lower in the ESAs group, but there was no significant difference between the subgroup of patients with NSCLC (RR 0.61, 95% CI 0.36-1.04, P = 0.009). There was no statistically significant difference between the two groups in the incidence of adverse reactions (RR 0.98, 95% CI 0.95-1.00, P = 0.10). In conclusion, ESAs does not increase the mortality of lung cancer patients or may reduce the risk of death, and can reduce the need for blood transfusion, although ESA can increase the incidence of thrombotic vascular adverse events.Registration PROSPERO CRD42023463582.
Subject(s)
Anemia , Hematinics , Lung Neoplasms , Randomized Controlled Trials as Topic , Humans , Anemia/drug therapy , Blood Transfusion , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/complications , Hematinics/therapeutic use , Hematinics/adverse effects , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Quality of Life , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/mortality , Treatment OutcomeABSTRACT
Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.
Subject(s)
Anemia , Erythropoietin , Glycine , Hematinics , Isoquinolines , Renal Dialysis , Humans , Male , Female , Anemia/drug therapy , Anemia/etiology , Hematinics/therapeutic use , Hematinics/administration & dosage , Retrospective Studies , Middle Aged , Isoquinolines/therapeutic use , Isoquinolines/administration & dosage , Aged , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/administration & dosage , Drug Therapy, Combination , Hemoglobins/metabolism , Hemoglobins/analysis , Drug Resistance/drug effects , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/blood , Adult , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic useABSTRACT
OBJECTIVE: To evaluate the effects of darbepoetin on platelet population and reactivity in healthy cats (HCs) and azotemic cats with remnant kidney (RK) model-induced chronic kidney disease. ANIMALS: 12 purpose-bred domestic shorthair cats (n = 6 HCs and n = 6 RK). METHODS: In this pilot study, all cats received darbepoetin (1 µg/kg, SC) on days 0, 7, and 14. Blood was sampled at baseline and on days 3, 10, 15, 17, 20, and 21. At each time point, a CBC was performed, platelet aggregometry was assessed by impedance and optical methods, and platelet P-selectin (CD62P) was quantified before and after thrombin stimulation. Additionally, reticulated platelets were quantified using both thiazole orange staining and proprietary analysis by the CBC analyzer. For RK cats, systemic blood pressure (BP) was serially measured. RESULTS: No adverse effects of darbepoetin were seen. There was no statistically significant change in platelet count between or within groups at any time point. Hematocrit increased significantly over time in the RK but not the HC group. RBC reticulocyte numbers in both groups increased over time. Reticulated platelet percentage did not increase in either group. Differences in platelet reactivity within or between groups were not seen in the aggregometry or flow cytometric assessments. In RK cats, indirect BP did not significantly change during the study. CLINICAL RELEVANCE: This preliminary investigation did not find evidence that darbepoetin administration impacted platelet number, reactivity, nor reticulated platelet count. Anemic RK cats experienced increased hematocrit and RBC reticulocytes as expected with darbepoetin therapy.
Subject(s)
Cat Diseases , Darbepoetin alfa , Hematinics , Renal Insufficiency, Chronic , Animals , Cats , Darbepoetin alfa/pharmacology , Darbepoetin alfa/therapeutic use , Cat Diseases/drug therapy , Renal Insufficiency, Chronic/veterinary , Renal Insufficiency, Chronic/blood , Platelet Count/veterinary , Pilot Projects , Male , Hematinics/pharmacology , Hematinics/therapeutic use , Female , Blood Platelets/drug effects , Hematocrit/veterinaryABSTRACT
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 (PRO2TECT) 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 (INNO2VATE) 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.
Subject(s)
Anemia , Hematinics , Renal Insufficiency, Chronic , Humans , Anemia/drug therapy , Anemia/etiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Hematinics/therapeutic use , Hematinics/adverse effects , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/adverse effects , Prolyl-Hydroxylase Inhibitors/therapeutic use , Prolyl-Hydroxylase Inhibitors/adverse effects , Prolyl-Hydroxylase Inhibitors/pharmacology , Prolyl-Hydroxylase Inhibitors/administration & dosage , Randomized Controlled Trials as Topic , Erythropoietin/therapeutic use , Erythropoietin/adverse effects , Picolinic Acids/therapeutic use , Picolinic Acids/adverse effects , Picolinic Acids/pharmacologyABSTRACT
El síndrome de Parsonage-Turner o plexopatía braquial idiopática es una inflamación total o parcial del plexo braquial cuya presentación típica es una omalgia intensa y súbita, seguida de debilidad braquial y amiotrofia precoz. La etiología es desconocida, aunque se propone un mecanismo inmunomediado.El trasplante de progenitores hematopoyéticos es un tratamiento bien establecido de las neoplasias hematológicas y tiene un papel creciente en el tratamiento de enfermedades autoinmunes. Los efectos adversos neurológicos son probablemente infradiagnosticados.La asociación del síndrome de Parsonage-Turner y el trasplante de progenitores hematopoyéticos es muy poco conocida. Describimos dos casos clínicos de plexopatía braquial idiopática tras trasplante de células stem (progenitores) hematopoyéticas (TPH).La reconstitución del sistema inmune tras un trasplante de progenitores hematopoyéticos puede ser un desencadenante de plexopatía braquial, aunque se necesitan más estudios para entender la fisiopatología de esta entidad y establecer su relación causal con el trasplante. (AU)
Parsonage-Turner syndrome or idiopathic brachial neuritis is a total or partial inflammation of the brachial plexus, with a typical presentation as a sudden and very intense pain in the shoulder, followed by weakness and early amyotrophy. The etiology is still unknown, although an immune mediated mechanism is thought to be involved.Hematopoietic stem cell transplantation is a well-established treatment for hematological malignancies, but with a growing implication in the treatment of autoimmune diseases. The neurological side effects are probably underdiagnosed.The association of the Parsonage-Turner syndrome and the hematopoietic stem cell transplantation is scarce. We describe two clinical cases of idiopathic brachial plexopathy after hematopoietic stem cell transplantation.The reconstruction of the immune system after a transplant may be the trigger of a brachial plexopathy, but more studies are necessary for the etiology of this disease to be understood and to establish a cause-effect relation with the transplant. (AU)
Subject(s)
Humans , Male , Adult , Transplantation , Brachial Plexus Neuropathies , Brachial Plexus Neuritis , Hematinics , Immune System , Brachial PlexusABSTRACT
INTRODUCTION: The incidence of anaemia and its consequences are often underestimated during cancer management. We propose to evaluate the situation before and after the recommendations were updated in order to assess their impact on the day-to-day practice. METHODS: In this single-centre retrospective study, eligible patients were treated for cancer and warranted overnight hospitalization over two periods (n = 206 in 2011, n = 143 in 2018). The diagnosis of anaemia was defined by a haemoglobin level below 12 and 13 g/dL for women and men, respectively. RESULTS: The prevalence of anaemia was 26% in 2011 and 16% in 2018 (p < 0.001). Biological assessment had changed between the two periods, with more tests of iron metabolism and measurements of inflammatory parameters. Patients hospitalized in 2018 had more advanced cancer and more severe anaemia (8.2 g/dL [±1.07] in 2011 vs. 7.9 g/dL [±1.18] in 2018). Rate of transfusion therapy did not change, but patients with mild and moderate anaemia were transfused less in 2018 (57% in 2011 vs. 44% in 2018). Intravenous iron and erythropoiesis-stimulating agent were used more frequently in 2018 (1 and 5 and 13 and 23% in 2011 and 2018, respectively), mainly for mild anaemia and life-threatening anaemia, respectively. Overall survival was poor in both cohorts at 24 months (15.4% in 2011 and 6.5% in 2018, p = 0.048). CONCLUSION: Practices have changed in the diagnosis of anaemia and prescriptions for erythropoiesis-stimulating agents and intravenous iron have increased. Efforts must continue to explore the causes of anaemia, optimize patients' quality of life, and reduce transfusions.
Subject(s)
Anemia , Hospitalization , Neoplasms , Practice Guidelines as Topic , Humans , Female , Retrospective Studies , Male , Neoplasms/complications , Neoplasms/therapy , Anemia/therapy , Anemia/epidemiology , Aged , Middle Aged , Hospitalization/statistics & numerical data , Prevalence , Blood Transfusion/statistics & numerical data , Hematinics/therapeutic use , Aged, 80 and over , Incidence , Iron/therapeutic use , AdultABSTRACT
BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).
Subject(s)
Ferric Compounds , Gastrointestinal Hemorrhage , Hemoglobins , Maltose , Maltose/analogs & derivatives , Quality of Life , Humans , Ferric Compounds/adverse effects , Ferric Compounds/administration & dosage , Ferric Compounds/therapeutic use , Male , Maltose/administration & dosage , Maltose/adverse effects , Maltose/therapeutic use , Female , Aged , Hemoglobins/metabolism , Hemoglobins/analysis , Gastrointestinal Hemorrhage/drug therapy , Aged, 80 and over , Double-Blind Method , Treatment Outcome , Prospective Studies , Hematinics/adverse effects , Hematinics/administration & dosage , Hematinics/therapeutic use , France , Injections, Intravenous , Age FactorsABSTRACT
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.
Subject(s)
Anemia, Sickle Cell , Darbepoetin alfa , Erythropoietin , Hemoglobins , Humans , Darbepoetin alfa/therapeutic use , Darbepoetin alfa/administration & dosage , Male , Erythropoietin/therapeutic use , Erythropoietin/analogs & derivatives , Female , Retrospective Studies , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/blood , Hemoglobins/analysis , Adult , Hematinics/therapeutic use , Middle Aged , Treatment Outcome , Adolescent , Young Adult , Benzaldehydes/therapeutic use , Benzaldehydes/administration & dosage , Benzaldehydes/pharmacology , Pyrazines , PyrazolesABSTRACT
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are new drugs developed for the treatment of anemia associated with chronic kidney disease (CKD). This class of drugs stimulates endogenous erythropoietin production and, at the same time, improves iron absorption and mobilization of iron stores (less evident with daprodustat, vadadustat and enarodustat). Several studies have been published in the last few years showing that these agents are not inferior to standard therapy in correcting anemia associated with CKD. The efficacy of HIF-PHIs is coupled with a safety profile comparable to that of standard erythropoiesis stimulating agent (ESA) treatment. However, studies with HIF-PHIs were not long enough to definitively exclude the impact of new drugs on adverse events, such as cancer, death and possibly cardiovascular events, that usually occur after a long follow-up period. Kidney Disease: Improving Global Outcomes (KDIGO) recently reported the conclusions of the Controversies Conference on HIF-PHIs held in 2021. The goal of the present position paper endorsed by the Italian Society of Nephrology is to better adapt the conclusions of the latest KDIGO Conference on HIF-PHIs to the Italian context by reviewing the efficacy and safety of HIF-PHIs as well as their use in subpopulations of interest as emerged from more recent publications not discussed during the KDIGO Conference.
Subject(s)
Anemia , Hypoxia-Inducible Factor-Proline Dioxygenases , Nephrology , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/complications , Anemia/drug therapy , Anemia/etiology , Nephrology/standards , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Consensus , Hematinics/therapeutic use , Italy , Prolyl-Hydroxylase Inhibitors/therapeutic use , Societies, MedicalABSTRACT
Importance: The consequences of low levels of environmental lead exposure, as found commonly in US household water, have not been established. Objective: To examine whether commonly encountered levels of lead in household water are associated with hematologic toxicity among individuals with advanced kidney disease, a group known to have disproportionate susceptibility to environmental toxicants. Design, Setting, and Participants: Cross-sectional analysis of household water lead concentrations and hematologic outcomes was performed among patients beginning dialysis at a Fresenius Medical Care outpatient facility between January 1, 2017, and December 20, 2021. Data analysis was performed from April 1 to August 15, 2023. Exposure: Concentrations of lead in household water were examined in categorical proportions of the Environmental Protection Agency's allowable threshold (15 µg/L) and continuously. Main Outcomes and Measures: Hematologic toxic effects were defined by monthly erythropoiesis-stimulating agent (ESA) dosing during the first 90 days of incident kidney failure care and examined as 3 primary outcomes: a proportion receiving maximum or higher dosing, continuously, and by a resistance index that normalized to body weight and hemoglobin concentrations. Secondarily, hemoglobin concentrations for patients with data prior to kidney failure onset were examined, overall and among those with concurrent iron deficiency, thought to increase gastrointestinal absorption of ingested lead. Results: Among 6404 patients with incident kidney failure (male, 4182 [65%]; mean [SD] age, 57 [14] years) followed up for the first 90 days of dialysis therapy, 12% (n = 742) had measurable lead in household drinking water. A higher category of household lead contamination was associated with 15% (odds ratio [OR], 1.15 [95% CI, 1.04-1.27]) higher risk of maximum monthly ESA dosing, 4.5 (95% CI, 0.8-8.2) µg higher monthly ESA dose, and a 0.48% (95% CI, 0.002%-0.96%) higher monthly resistance index. Among patients with pre-kidney failure hemoglobin measures (n = 2648), a higher household lead categorization was associated with a 0.12 (95% CI, -0.23 to -0.002) g/dL lower hemoglobin concentration, particularly among those with concurrent iron deficiency (multiplicative interaction, P = .07), among whom hemoglobin concentrations were 0.25 (95% CI, -0.47 to -0.04) g/dL lower. Conclusion: The findings of this study suggest that levels of lead found commonly in US drinking water may be associated with lead poisoning among susceptible individuals.
Subject(s)
Lead , Renal Insufficiency, Chronic , Humans , Male , Female , Cross-Sectional Studies , Middle Aged , Lead/blood , Renal Insufficiency, Chronic/epidemiology , Aged , Environmental Exposure/adverse effects , Hematinics/administration & dosage , Hematinics/adverse effects , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/adverse effects , Renal DialysisABSTRACT
BACKGROUND AND PURPOSE: Our previous study reported that erythroferrone (ERFE), a newly identified hormone produced by erythroblasts, responded to recombinant human erythropoietin (rHuEPO) sensitively but its dynamics was complicated by double peaks and circadian rhythm. This study intends to elucidate the underlying mechanisms for the double peaks of ERFE dynamics and further determine whether early ERFE measurements can predict haemoglobin responses to rHuEPO. EXPERIMENTAL APPROACH: By using the purified recombinant rat ERFE protein and investigating its deposition in rats, the production of ERFE was deconvoluted. To explore the role of iron in ERFE production, we monitored short-term changes of iron status after injection of rHuEPO or deferiprone. Pharmacokinetic/pharmacodynamic (PK/PD) modelling was used to confirm the mechanisms and examine the predictive ability of ERFE for long-term haemoglobin responses. KEY RESULTS: The rRatERFE protein was successfully purified. The production of ERFE was deconvoluted and showed two independent peaks (2 and 8 h). Transient iron decrease was observed at 4 h after rHuEPO injection and deferiprone induced significant increases of ERFE. Based on this mechanism, the PK/PD model could characterize the complex dynamics of ERFE. In addition, the model predictions further revealed a stronger correlation between ERFE and haemoglobin peak values than that for observed values. CONCLUSIONS AND IMPLICATIONS: The complex dynamics of ERFE should be composited by an immediate release and transient iron deficiency-mediated secondary production of ERFE. The early peak values of ERFE, which occur within a few hours, can predict haemoglobin responses several weeks after ESA treatment.
Subject(s)
Deferiprone , Erythropoietin , Hematinics , Hemoglobins , Rats, Sprague-Dawley , Recombinant Proteins , Hemoglobins/metabolism , Animals , Erythropoietin/pharmacology , Erythropoietin/administration & dosage , Rats , Recombinant Proteins/administration & dosage , Male , Deferiprone/pharmacology , Deferiprone/administration & dosage , Hematinics/pharmacology , Hematinics/administration & dosage , Humans , Pyridones/pharmacology , Pyridones/administration & dosage , Iron/metabolism , Erythropoiesis/drug effects , Models, Biological , Peptide Hormones/pharmacology , Peptide Hormones/administration & dosageABSTRACT
This updated British Society for Haematology guideline provides an up-to-date literature review and recommendations regarding the identification and management of preoperative anaemia. This includes guidance on thresholds for the diagnosis of anaemia and the diagnosis and management of iron deficiency in the preoperative context. Guidance on the appropriate use of erythropoiesis-stimulating agents and preoperative transfusion is also provided.
Subject(s)
Anemia , Hematinics , Preoperative Care , Humans , Anemia/therapy , Anemia/diagnosis , Anemia/etiology , Preoperative Care/standards , Hematinics/therapeutic use , Adult , Blood Transfusion , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/therapy , Anemia, Iron-Deficiency/etiology , United KingdomABSTRACT
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.
Subject(s)
Darbepoetin alfa , Hematinics , Renal Dialysis , Humans , Renal Dialysis/adverse effects , Hematinics/adverse effects , Hematinics/therapeutic use , Hematinics/administration & dosage , Female , Male , Retrospective Studies , Aged , Middle Aged , Darbepoetin alfa/therapeutic use , Darbepoetin alfa/adverse effects , Darbepoetin alfa/administration & dosage , United States/epidemiology , Cardiovascular Diseases/mortality , Epoetin Alfa/therapeutic use , Epoetin Alfa/adverse effects , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/complications , Anemia/drug therapy , Medicare , Delayed-Action Preparations , Aged, 80 and over , Erythropoietin , Recombinant ProteinsSubject(s)
Hematinics , Kidney Failure, Chronic , Lead , Humans , Hematinics/therapeutic use , Lead/blood , Male , Female , Middle Aged , AgedABSTRACT
BACKGROUND/AIMS: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. METHODS: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. RESULTS: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. CONCLUSION: For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
Subject(s)
Anemia , Erythropoietin , Glycine , Hematinics , Hemoglobins , Isoquinolines , Peritoneal Dialysis , Humans , Male , Retrospective Studies , Female , Middle Aged , Anemia/drug therapy , Anemia/etiology , Anemia/blood , Erythropoietin/therapeutic use , Erythropoietin/adverse effects , Treatment Outcome , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/adverse effects , Aged , Isoquinolines/therapeutic use , Isoquinolines/adverse effects , Peritoneal Dialysis/adverse effects , Hematinics/therapeutic use , Hematinics/adverse effects , Hemoglobins/metabolism , Adult , Time Factors , Biomarkers/blood , Prolyl-Hydroxylase Inhibitors/therapeutic use , Prolyl-Hydroxylase Inhibitors/adverse effectsABSTRACT
In the present study, a first validated and green spectrofluorimetric approach for its assessment and evaluation in different matrices was investigated. After using an excitation wavelength of 345 nm, Roxadustat (ROX) demonstrates a highly native fluorescence at an emission of 410 nm. The influences of experimental factors such as pH, diluting solvents, and different organized media were tested, and the most appropriate solvent choice was ethanol. It was confirmed that there was a linear relationship between the concentration of ROX and the relative fluorescence intensity in the range 60.0-1000.0 ng ml-1, with the limit of detection and limit of quantitation, respectively, being 17.0 and 53.0 ng ml-1. The mean recoveries % [±standard deviation (SD), n = 5] for pharmaceutical preparations were 100.11% ± 2.24%, whereas for plasma samples, they were 100.08 ± 1.08% (±SD, n = 5). The results obtained after the application of four greenness criteria, Analytical Eco-Scale metric, NEMI, GAPI, and AGREE metric, confirmed its eco-friendliness. In addition, the whiteness meter (RGB12) confirmed its level of sustainability. The International Council for Harmonisation (ICH) criteria were used to verify the developed method through the study in both spiked plasma samples and content uniformity evaluation. An appropriate standard for various applications in industry and quality control laboratories was developed.