Search Results (6)

Background: Our study aimed to evaluate the differences in hemoglobin variability among patients undergoing hemodialysis (HD) treated with three types of erythropoiesis-stimulating agents (ESAs) and the association between hemoglobin variability and clinical outcomes. Methods: In this study, data from the 6th and 7th HD quality assessments were used, comprising 48,726 patients in South Korea. ESAs are categorized into short-acting (epoetin alfa/beta/delta, requiring more frequent administration), intermediate-acting (darbepoetin alfa), and long-acting agents (methoxy polyethylene glycol-epoetin beta, requiring extended dosing intervals), each with distinct pharmacokinetic properties and dosing schedules. Based on use of ESA types, participants were divided into the following groups: Short, Intermediate, and Long. Hemoglobin levels were measured monthly over a 6-month assessment period. Hemoglobin variability was defined as the residual standard deviation derived from a within-subject linear regression model with six hemoglobin values for each patient. Results: The Short, Intermediate, and Long groups comprised 36,420, 10,514, and 1792 patients, respectively. The hemoglobin variability (mean [95% confidence interval]) was 0.60 (0.60–0.60), 0.68 (0.67–0.68), and 0.64 (0.62–0.65) g/dL in the Short, Intermediate, and Long groups, respectively. Multivariate and subgroup analyses revealed that the hemoglobin variability was lower in the Short group than in the other two groups. Cox regression did not show a significant association between an increase in hemoglobin variability and all-cause mortality or cardiovascular events in univariate and multivariate analyses. Conclusions: Our cohort study found that the use of short-acting ESAs showed the lowest hemoglobin variability, whereas the use of intermediate-acting ESAs showed the highest variability. In the context of South Korea’s healthcare system, where frequent hemoglobin monitoring and strict ranges are emphasized, short-acting ESAs combined with regular laboratory follow-up appeared to support more stable hemoglobin levels. Full article

Background/Objectives: Peritoneal dialysis (PD) is a renal replacement therapy for patients with kidney failure. Managing PD patients often involves addressing a complex interplay of comorbidities and complications, necessitating the use of multiple medications. This study aimed to systematically characterize commonly co-prescribed drugs in PD and to identify novel drug combinations that may target dysregulated molecular mechanisms associated with PD’s pathophysiology. Methods: We analyzed clinical records from 702 PD patients spanning 30 years, encompassing over 5500 prescription points. Using network-based modeling techniques, we assessed drug co-prescription patterns, clinical outcomes, and longitudinal treatment trends. To explore potential drug repurposing opportunities, we constructed a molecular network model of PD based on a consolidated transcriptomics dataset and integrated this with drug–target interaction information. Results: We found commonly prescribed drugs such as furosemide, sucroferric oxyhydroxide, calcitriol, darbepoetin alfa, and aluminum hydroxide to be integral components of PD patient management, prescribed in over 30% of PD patients. The molecular-network-based approach found combinations of drugs like theophylline, fluoxetine, celecoxib, and amitriptyline to possibly have synergistic effects and to target dysregulated molecules of PD-related pathomechanisms. Two further distinct categories of drugs emerged as particularly interesting in our study: selective serotonin reuptake inhibitors (SSRIs), which were found to modulate molecules implicated in peritoneal fibrosis, and vascular endothelial growth factor (VEGF) inhibitors, which exhibit anti-fibrotic properties that are potentially useful for PD. Conclusions: This comprehensive exploration of drug co-prescriptions in the context of PD-related pathomechanisms provides valuable insights for opening future therapeutic strategies and identifying new targets for drug repurposing. Full article

Functional iron-deficiency anemia (FIDA) is a side effect of many cancer treatments, occurring when chemotherapy drugs damage bone marrow cells, which are responsible for producing red blood cells, due to the myelosuppressive effects of chemotherapy, or to the cancer itself. This study was performed to compare the effects of darbepoetin alfa alone, or in combination with ferric derisomaltose in cancer patients with FIDA, and to elucidate the mechanism underlying the effects in F36E cells. F36E cells treated with darbepoetin alfa showed increased cell viability. AML and GC cells treated with darbepoetin alfa, ferric derisomaltose, or ferric derisomaltose plus darbepoetin alfa showed no induction of apoptosis. The effects of these drugs on the anticancer efficacy of PTX chemotherapy were examined by analyzing cell viability and induction of apoptosis. Darbepoetin alfa, ferric derisomaltose, and ferric derisomaltose plus darbepoetin alfa showed no significant inhibitory effects on the apoptosis-inducing activity of PTX in GC cell lines. Patients with chemotherapy-induced FIDA in Group I receiving ferric derisomaltose plus darbepoetin alfa showed higher hemoglobin levels, transferrin saturation, and ferritin levels compared to those in Group II, treated with darbepoetin alfa alone. In cancer patients with FIDA, the prognosis of anemia treatment was better in the ferric derisomaltose plus darbepoetin alfa combination group than in the group receiving darbepoetin alfa monotherapy. Full article

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. Full article

The impact on health care of patients with myelodysplastic syndromes (MDS) is continuously rising. To investigate the perception of hemato-oncologists concerning the recommended MDS patient care in Switzerland, we conducted a web-based survey on diagnosis, risk-stratification and treatment. 43/309 physicians (13.9%) replied to 135 questions that were based on current guidelines between 3/2017 and 2/2018. Only questions with feedback-rates >50% were further analysed and ratios >90% defined “high agreement”, 70–90% “agreement”, 30–70% “insufficient agreement” and <30% “disagreement”. For diagnosis, we found insufficient agreement on using flow-cytometry, classifying MDS precursor conditions, performing treatment response assessment after hypomethylating agents (HMA) and evaluating patients with suspected germ-line predisposition. For risk-stratification, we identified agreement on using IPSS-R but insufficient agreement for IPSS and patient-based assessments. For treatment, we observed disagreement on performing primary infectious prophylaxis in neutropenia but agreement on using only darbepoetin alfa in anaemic, lower-risk MDS patients. For thrombopoietin receptor agonists, insufficient agreement was found for the indication, preferred agent and triggering platelet count. Insufficient agreement was also found for immunosuppressive treatment in hypoplastic MDS and HMA dose adjustments. In conclusion, we identified areas for improvement in MDS patient care, in need of further clinical trials, information, and guiding documents. Full article

Anemia, already common in cancer patients, is often exacerbated by chemotherapy. Cancer patients who are anemic have been shown to have a blunted response for production of endogenous erythropoietin growth factor. This anemia can be corrected with exogenous erythropoietin growth factors, of which three available are worldwide: epoetin alfa, epoetin beta, and darbepoetin alfa. Collectively, these drugs are known as erythropoiesis-stimulating agents (ESAS). Orders for ESAS have been used not only to reverse anemia so as to avoid blood transfusion, but also to improve quality of life. Guidelines have been developed for initiation, dosage titration, and termination of these agents. Since the late 1990s, trials have been conducted using esas in unapproved dosing regimens or to reach hemoglobin levels outside of approved guidelines, raising several safety concerns. The present article explores the risks and benefits of ESAS. Full article