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Cureus Jun 2022Glycogen storage disease type Ⅰa (GSDIa), also known as von Gierke disease, is a rare inherited metabolic disorder caused by defective glucose 6-phosphatase (G6Pase)...
Glycogen storage disease type Ⅰa (GSDIa), also known as von Gierke disease, is a rare inherited metabolic disorder caused by defective glucose 6-phosphatase (G6Pase) activity. Although anemia, renal failure, and hepatic adenoma are the major clinical manifestations of GSDIa, there has been no report of refractory anemia in GSDIa patients on maintenance hemodialysis (HD) concomitant with multiple liver adenomas. Herein, we present a case of refractory anemia in a patient with GSDIa undergoing HD with multiple hepatic adenomas, successfully managed through aggressive treatment for renal anemia and intravenous iron therapy (IIT). A 26-year-old man with GSDIa who had been on HD for a year suffered from refractory anemia. He had experienced hypoglycemia and hyperlactic acidemia repeatedly and unusual hypertriglyceridemia had been observed for a long time. In addition, multiple hepatic adenomas developed and his renal function gradually declined, eventually progressing to end-stage kidney disease, and HD was started. Despite 120 µg/week of darbepoetin alfa (DA), 200 mg/day of oral sodium ferrous citrate, and 600 mg/week of roxadustat, the anemia persisted and iron deficiency gradually progressed. We considered that renal anemia, blood loss by each HD session, and decreased intestinal iron absorption due to inappropriately increased hepcidin from hepatic adenomas were the main etiology of the anemia; hence, we changed oral sodium ferrous citrate to intravenous saccharated ferric oxide along with continuous aggressive treatment of renal anemia, and the anemia resolved quickly within three months. We believe that refractory anemia was mainly induced by renal anemia and chronic iron deficiency due to blood loss during HD and inappropriately elevated hepcidin levels in hepatic adenomas. Aggressive treatment of renal anemia, along with IIT, may be a promising treatment option. Strict monitoring of iron overload is essential for safe treatment.
PubMed: 35891878
DOI: 10.7759/cureus.26213 -
Qatar Medical Journal 2024Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating...
BACKGROUND
Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex) and long-acting (Aranesp) ESAs.
METHOD
This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared.
RESULTS
Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference ( < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp was considered the cost-saving protocol.
CONCLUSION
In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex.
TRIAL REGISTRATION
The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).
PubMed: 38567102
DOI: 10.5339/qmj.2024.16 -
Case Reports in Nephrology and Dialysis 2022Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl...
Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel approach for renal anemia management. Many intestinal genes, including , and copper transporter ATPase7A, related to iron absorption are transactivated by HlF-α, during iron deficiency. We first report 4 cases of patients with renal anemia who showed excess in serum copper level during roxadustat or daprodustat treatment, which were decreased to the normal level after discontinuing HIF-PHIs and changing the drug to darbepoetin alfa, suggesting that HIF-PHI is associated with serum copper excess. HIF-PHI modulates iron metabolism, such as iron absorption, sequestration, and mobilization, and may increase serum copper levels by increasing copper absorption and/or redistribution of copper in tissues. Therefore, it is urgent to examine the correlation between HIF-PHI use and serum copper levels because copper excess might be involved in several acute or chronic adverse events.
PubMed: 36160635
DOI: 10.1159/000525735 -
Nutrients Feb 2024Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing...
Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient's dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI ( < 0.05), but no significant change was observed ( = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.
Topics: Humans; Hematinics; Anemia; Prolyl-Hydroxylase Inhibitors; Zinc; Erythropoiesis; Prolyl Hydroxylases; Renal Insufficiency, Chronic; Darbepoetin alfa; Retrospective Studies; Glycine; Dietary Supplements
PubMed: 38398842
DOI: 10.3390/nu16040520 -
Hospital Pharmacy Jun 2022Dialysis patients are often iron deficient due to a multiple factors. Ferric pyrophosphate citrate is a complex iron salt that can be given via dialysate allowing...
Dialysis patients are often iron deficient due to a multiple factors. Ferric pyrophosphate citrate is a complex iron salt that can be given via dialysate allowing maintenance of hemoglobin (Hgb) concentration and iron balance while reducing the need for IV iron. The purpose of this study is to perform a cost evaluation of FPC and the effect it has on lowering the dose/use of ESAs and IV iron therapy. This study reviewed the same 100 hemodialysis patient's charts before and after the use of FPC. The data points that were collected and analyzed are as follows: hemoglobin, ferritin levels, average weekly ESA dosing, and IV iron replacement therapy dose. Out of 100 patients, there was no statistical difference in the average hemoglobin, ferritin, and iron saturation levels observed in the patients before and after FPC use. The average weekly dose of darbepoetin alfa per patient was 52.74 μg before the FPC group compared to 39.27 μg in the post FPC group ( < .0001). The total dose of ferric gluconate per patient was 3290.01 mg in the before FPC group and 585.60 mg in the post FPC group ( < .0001). The average total iron sucrose dose per patient in the before FPC group was 3097.92 mg versus 1216.67 mg in the post FPC group ( < .1563). When comparing FPC's cost and implementation into both of our outpatient dialysis centers, this yielded a net savings of $296 751.49.
PubMed: 35615489
DOI: 10.1177/00185787211032363 -
BMC Nephrology Jun 2023Appropriate management of anemia in patients with hemodialysis (HD) involves the administration of iron supplementation and erythropoietin-stimulating agents (ESAs), in...
BACKGROUND
Appropriate management of anemia in patients with hemodialysis (HD) involves the administration of iron supplementation and erythropoietin-stimulating agents (ESAs), in addition to monitoring the response. This study aimed to evaluate the treatment of anemia in patients with HD and describe the factors associated with it and its effect on health-related quality of life (HRQOL).
METHODS
The study was cross-sectional in design. The patients were included from three dialysis centers in Palestine from June to September 2018. The data collection instrument consisted of two portions; the initial portion contained demographic and clinical information on the patients, while the second consisted of the European Quality of Life 5-Dimension Scale (EQ-5D-5 L) and the visual analog scale EQ (EQ-VAS).
RESULTS
The study included 226 patients. Their mean age (± SD) was 57 ± 13.9 years. The mean level of hemoglobin (Hb) (± SD) was 10.63 ± 1.71 g/dl, and 34.1% of the patients had a Hb level of 10-11.5 g/dl. All patients who required iron supplementation received it intravenously with a dose of 100 mg of iron sucrose. Almost 86.7% of the patients received darbepoetin alfa intravenously at 0.45 mcg/kg a week, and 24% had a Hb level > 11.5 g/dl. There were significant associations between the level of Hb and the number of comorbid diseases and the ESA that was received. However, other demographics and clinical factors did not significantly affect Hb levels. Certain variables, such as exercise, were a predictor of a higher quality of life. It should be noted that there is a significant impact of a low Hb value on the EQ-VAS scale.
CONCLUSIONS
Our study found that more than half of the patients had a Hb level below the recommended goal of Kidney Disease Improving Global Outcomes (KDIGO). Furthermore, a significant association was found between patients' Hb level and HRQOL. Therefore, the appropriate treatment of anemia in patients with HD should be followed by adherence to the guideline recommendations, which consequently improves the HRQOL of HD patients, in addition to obtaining optimal therapy.
Topics: Humans; Adult; Middle Aged; Aged; Quality of Life; Cross-Sectional Studies; Anemia; Renal Dialysis; Iron
PubMed: 37391687
DOI: 10.1186/s12882-023-03254-7 -
Nephrology, Dialysis, Transplantation :... Nov 2021Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral... (Randomized Controlled Trial)
Randomized Controlled Trial
Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials.
BACKGROUND
Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics.
METHODS
Two Phase 3, open-label, sponsor-blind, active-controlled trials enrolled adults with anaemia of CKD who recently initiated dialysis and had limited ESA exposure (incident DD-CKD trial) or were receiving maintenance dialysis with ESA treatment (prevalent DD-CKD trial). Study periods include correction/conversion (Weeks 0-23), maintenance (Weeks 24-52), long-term treatment (Weeks 53 to end of treatment) and safety follow-up. The primary safety endpoint is the time to the first major adverse cardiovascular event and the primary efficacy endpoint is the change in haemoglobin (baseline to Weeks 24-36).
RESULTS
A total of 369 and 3554 patients were randomized in the incident DD-CKD and prevalent DD-CKD trials, respectively. Demographics and baseline characteristics were similar among patients in both trials and comparable to those typically observed in DD-CKD.
CONCLUSIONS
The two INNO2VATE trials will provide important information on the safety and efficacy of a novel approach for anaemia management in a diverse DD-CKD population. Demographics and baseline characteristics of enrolled patients suggest that study results will be representative for a large proportion of the DD-CKD population.
Topics: Adult; Anemia; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Picolinic Acids; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 33188693
DOI: 10.1093/ndt/gfaa204 -
Kidney Diseases (Basel, Switzerland) Nov 2021Enarodustat (JTZ-951) is a new oral hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). We conducted a...
INTRODUCTION
Enarodustat (JTZ-951) is a new oral hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). We conducted a phase 3 study to compare the efficacy and safety of enarodustat with darbepoetin alfa (DA) in Japanese anemic patients with CKD receiving maintenance hemodialysis.
METHODS
Subjects receiving maintenance hemodialysis were randomly assigned at a 1:1 ratio to receive oral enarodustat once daily or intravenous DA every week for 24 weeks with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within a target range (≥10.0 to <12.0 g/dL). The primary efficacy endpoint was difference in mean Hb level between arms during the evaluation period defined as weeks 20-24 (noninferiority margin: -1.0 g/dL). Intravenous iron preparations were prohibited during the screening period and during weeks 0-4.
RESULTS
The mean Hb level of each arm during the evaluation period was 10.73 g/dL (95% confidence interval [CI]: 10.56, 10.91) in the enarodustat arm and 10.85 g/dL (95% CI: 10.72, 10.98) in the DA arm. The difference in the mean Hb level between arms was -0.12 g/dL (95% CI: -0.33, 0.10), confirming the noninferiority of enarodustat to DA. The mean Hb level of each arm was maintained within the target range during the treatment period. Increased total iron-binding capacity and serum iron and decreased hepcidin were observed through week 4 in the enarodustat arm albeit after switching from erythropoiesis-stimulating agents. No apparent safety concerns of enarodustat were observed compared with DA.
DISCUSSION/CONCLUSION
Enarodustat was noninferior to DA for the treatment of anemia in CKD patients receiving maintenance hemodialysis and was generally well tolerated over 24 weeks.
PubMed: 34901195
DOI: 10.1159/000517053 -
Acta Diabetologica Aug 2020The minimal-invasive transplantation of pancreatic islets is a promising approach to treat diabetes mellitus type 1. However, islet transplantation is still hampered by...
AIMS
The minimal-invasive transplantation of pancreatic islets is a promising approach to treat diabetes mellitus type 1. However, islet transplantation is still hampered by the insufficient process of graft revascularization, leading to a poor clinical outcome. Accordingly, the identification of novel compounds, which accelerate and improve the revascularization of transplanted islets, is of great clinical interest. Previous studies have shown that darbepoetin (DPO)-α, a long lasting analogue of erythropoietin, is capable of promoting angiogenesis. Hence, we investigated in this study whether DPO improves the revascularization of transplanted islets.
METHODS
Islets were isolated from green fluorescent protein-positive FVB/N donor mice and transplanted into dorsal skinfold chambers of FVB/N wild-type animals, which were treated with DPO low dose (2.5 µg/kg), DPO high dose (10 µg/kg) or vehicle (control). The revascularization was assessed by repetitive intravital fluorescence microscopy over an observation period of 14 days. Subsequently, the cellular composition of the grafts was analyzed by immunohistochemistry.
RESULTS
The present study shows that neither low- nor high-dose DPO treatment accelerates the revascularization of free pancreatic islet grafts. However, high-dose DPO treatment increased the blood volume flow of the transplanted islet.
CONCLUSIONS
These findings demonstrated that DPO treatment does not affect the revascularization of transplanted islets. However, the glycoprotein increases the blood volume flow of the grafts, which results in an improved microvascular function and may facilitate successful transplantation.
Topics: Animals; Darbepoetin alfa; Islets of Langerhans; Islets of Langerhans Transplantation; Mice; Mice, Transgenic; Neovascularization, Physiologic; Regional Blood Flow; Transplants; Up-Regulation
PubMed: 32221724
DOI: 10.1007/s00592-020-01512-w -
Indian Journal of Nephrology 2020Acquired pure red cell aplasia (PRCA) following use of recombinant erythropoietin (rEPO) is distinctly rare and sporadically reported in the literature. We discuss a...
Acquired pure red cell aplasia (PRCA) following use of recombinant erythropoietin (rEPO) is distinctly rare and sporadically reported in the literature. We discuss a case of PRCA following the usage of rEPO (darbepoetin-α) during the management of anemia of chronic kidney disease in an elderly male subject with review of literature and a brief insight into proposed pathophysiologic mechanism, diagnosis, and management.
PubMed: 32269436
DOI: 10.4103/ijn.IJN_129_19