scholarly journals Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents

2021 ◽  
Vol 8 ◽  
Author(s):  
Jose Portolés ◽  
Leyre Martín ◽  
José Jesús Broseta ◽  
Aleix Cases
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Current Knowledge ◽  
Hypoxia Inducible Factor ◽  
Intravenous Iron ◽  
Great Expectations ◽  
Functional Iron Deficiency ◽  
Endogenous Erythropoietin ◽  
The One

Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and an increased morbidity and mortality. The mechanisms involved in anemia associated to CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Patients are most commonly managed with oral or intravenous iron supplements and with erythropoiesis stimulating agents (ESA). However, these treatments have associated risks, and sometimes are insufficiently effective. Nonetheless, in the last years, there have been some remarkable advances in the treatment of CKD-related anemia, which have raised great expectations. On the one hand, a novel family of drugs has been developed: the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). These agents induce, among other effects, an increase in the production of endogenous EPO, improve iron availability and reduce hepcidin levels. Some of them have already received marketing authorization. On the other hand, recent clinical trials have elucidated important aspects of iron supplementation, which may change the treatment targets in the future. This article reviews the current knowledge of the pathophysiology CKD-related anemia, current and future therapies, the trends in patient management and the unmet goals.

scholarly journals P0860INTRAVENOUS IRON ADMINISTRATION SUPPRESSES ENDOGENOUS ERYTHROPOIETIN SECRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Katarzyna Muras-Szwedziak ◽  
Ewa Pawlowicz ◽  
Michal Nowicki
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intravenous Iron ◽  
Bone Alkaline Phosphatase ◽  
Iron Therapy ◽  
Endogenous Erythropoietin ◽  
The Third ◽  
Iron Administration ◽  
Intravenous Iron Therapy ◽  
Fgf 23

Abstract Background and Aims Iron therapy may induce inflammatory response that may indirectly affect endogenous erythropoietin (EPO) production. We postulated that increased secretion of FGF-23 may provide a link between intravenous iron administration and suppression of endogenous EPO secretion. Evaluation of a short-term effect of intravenous iron sucrose administration on the secretion of endogenous EPO in patients with chronic kidney disease (CKD). Method 35 non-dialysed patients with G3b-5 CKD were included. All patients received 100 mg of intravenous iron infusion (iron (III)-hydroxide sucrose complex) daily for 5 days. Plasma concentration of EPO, iFGF-23, cFGF-23, PTH, bone alkaline phosphatase (BAP), phosphorus (PO4) and calcium (Ca) were measured before and two hours after the first and third iron infusion and at the end of iron therapy. Results EPO concentration at the end of iron treatment was significantly lower compared to 2 h after the first iron infusion (p<0.001) and before the third dose (p<0.001) (12.6 [31.2] mIU/mL, 30.9 [38.3] mIU/mL, 33.4 [41.3] mIU/mL and, respectively). Conversely, serum iFGF-23 increased significantly after the third dose (61.1 [401.5] pg/mL; p<0.05) and after the treatment (92.1 [849.7] pg/mL; p<0.01) compared to pre-treatment value (48.4 [403.8] pg/mL). cFGF-23 concentration decreased significantly after the first dose of iron (491.8 [828.6] vs. 339.2 [875.8] RU/mL; p<0.01) and after the completion of the therapy (398.7 [931.9]) vs. baseline (p<0.05). There was no linear correlation between EPO and FGF-23. Conclusion Intravenous iron therapy increases the secretion of FGF-23 and supresses endogenous EPO production but these two effects do not seem to be related.

scholarly journals A Multicenter Prospective Double Blinded Randomized Controlled Pilot Trial of Intravenous Iron (Ferric Derisomaltose (FDI)) in Iron Deficient but not Anemic Patients with Chronic Kidney Disease on Functional Status.

2020 ◽  
Author(s):  
Sunil Bhandari ◽  
Victoria Allgar ◽  
Archie Lamplugh ◽  
Iain Macdougall ◽  
Philip Kalra
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Exercise Capacity ◽  
Intravenous Iron ◽  
Iron Deficient ◽  
Iv Iron ◽  
Double Blinded

Abstract Background Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality of life measurements; however, data in patients with CKD are lacking.Methods The Iron and the Heart Study was a prospective double blinded randomized study in non-anemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI) ) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on hematinic profiles and hemoglobin, safety analysis and quality of life questionnaires (QoL).Results We randomly assigned 54 patients mean (SD) age for FDI (n=26) 61.6 (10.1) years vs placebo (n=28; 57.8 (12.9) years) and mean eGFR (32.1 (9.6) vs. 29.1 (9.6) ml/min/1.73m2) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p=0.736), or 3 months (p=0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Hemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p<0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron. Conclusion This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anemic non-dialysis CKD patients without heart failure to improve the 6MWT.Trial Registration: European Clinical Trials Database (EudraCT) No: 2014-004133-16https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004133-16/GBREC no: 14/YH/1209Date First Registered: 2015-02-17 and date of end of trail 2015-05-23Sponsor ref R1766 and Protocol No: IHI 141

scholarly journals A Phase 3 Study of Enarodustat (JTZ-951) in Japanese Hemodialysis Patients for Treatment of Anemia in Chronic Kidney Disease: SYMPHONY HD Study

2021 ◽  
pp. 1-9
Author(s):  
Tadao Akizawa ◽  
Masaomi Nangaku ◽  
Takuhiro Yamaguchi ◽  
Ryosuke Koretomo ◽  
Kazuo Maeda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Binding Capacity ◽  
Hypoxia Inducible Factor ◽  
Intravenous Iron ◽  
Target Range ◽  
Maintenance Hemodialysis ◽  
Phase 3 ◽  
Evaluation Period ◽  
The Mean

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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 &#x3c;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. <b><i>Results:</i></b> 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. <b><i>Discussion/Conclusion:</i></b> Enarodustat was noninferior to DA for the treatment of anemia in CKD patients receiving maintenance hemodialysis and was generally well tolerated over 24 weeks.

scholarly journals A multicentre prospective double blinded randomised controlled trial of intravenous iron (ferric Derisomaltose (FDI)) in Iron deficient but not anaemic patients with chronic kidney disease on functional status

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
S. Bhandari ◽  
V. Allgar ◽  
A. Lamplugh ◽  
I. Macdougall ◽  
P. A. Kalra
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Exercise Capacity ◽  
Intravenous Iron ◽  
Iron Deficient ◽  
Iv Iron ◽  
Double Blinded

Abstract Background Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality-of-life measurements; however, data in patients with CKD are lacking. Methods The Iron and the Heart Study was a prospective double blinded randomised study in non-anaemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI)) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on haematinic profiles and haemoglobin, safety analysis and quality of life questionnaires (QoL). Results We randomly assigned 54 patients mean (SD) age for FDI (n = 26) 61.6 (10.1) years vs placebo (n = 28; 57.8 (12.9) years) and mean eGFR (33.2 (9.3) vs. 29.1 (9.6) ml/min/1.73m2) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p = 0.736), or 3 months (p = 0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Haemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p < 0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron. Conclusion This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anaemic non-dialysis CKD patients without heart failure to improve the 6MWT. Trial registration European Clinical Trials Database (EudraCT) No: 2014-004133-16 REC no: 14/YH/1209 Date First Registered: 2015-02-17 and date of end of trail 2015-05-23 Sponsor ref R1766 and Protocol No: IHI 141

scholarly journals Anemia in Chronic Kidney Disease : Role of Hypoxia Inducible Factor Stabilizer

2021 ◽  
Vol 5 (5) ◽  
pp. 462-467
Author(s):  
Emilia ◽  
Zulkhair Ali
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Randomized Clinical Trials ◽  
Hypoxia Inducible Factor ◽  
Standard Of Care ◽  
Current Standard ◽  
Endogenous Erythropoietin ◽  
Red Blood Cell Transfusions ◽  
Erythropoietin Deficiency

Anemia contributes to increased morbidity and mortality in chronic kidney disease patients. The pathogenesis of anemia in these patients is multifactorial, but the contribution of erythropoietin deficiency becomes greater as glomerular filtration rate declines which related to decreased nephron mass. The current standard of care includes supplemental iron, erythropoiesis-stimulating agents (ESA), and red blood cell transfusions, although each has drawbacks. Lately, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm including increasing cardiovascular and thrombotic events, and even death. Recent experimental and clinical studies show the promising efficacy of hypoxia inducible factor (HIF) stabilizer which stimulates endogenous erythropoietin production and enhance iron availability.

Are prolyl-hydroxylase inhibitors potential alternative treatments for anaemia in patients with chronic kidney disease?

2019 ◽  
Vol 35 (6) ◽  
pp. 926-932 ◽  
Author(s):  
Francesco Locatelli ◽  
Lucia Del Vecchio
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Adverse Outcomes ◽  
The Body ◽  
Phase Iii ◽  
Endogenous Erythropoietin ◽  
Potential Alternative

Abstract Prolyl-hydroxylase (PHD) inhibitors (PHD-I) are the most appealing drugs undergoing clinical development for the treatment of anaemia in patients with chronic kidney disease. PHD inhibition mimics the exposure of the body to hypoxia and activates the hypoxia-inducible factor system. Among many other pathways, this activation promotes the production of endogenous erythropoietin (EPO) and the absorption and mobilization of iron. PHD-I are given orally and, differing from erythropoiesis-stimulating agents (ESAs), they correct and maintain haemoglobin levels by stimulating endogenous EPO production. Their efficacy and safety are supported by several Phases I and II studies with relatively short follow-up. This class of drugs has the potential to have a better safety profile than ESAs and there may be additional advantages for cardiovascular disease (CVD), osteoporosis and metabolism. However, possible adverse outcomes are feared. These span from the worsening or occurrence of new cancer, to eye complications or pulmonary hypertension. The data from the ongoing Phase III studies are awaited to better clarify the long-term safety and possible advantages of PHD-I.

HUBUNGAN EFIKASI DIRI DENGAN KUALITAS HIDUP PASIEN GAGAL GINJAL KRONIK YANG MENJALANI HEMODIALISIS

2018 ◽  
Vol 5 (2) ◽  
pp. 56-63
Author(s):  
Abdul Wakhid ◽  
Estri Linda Wijayanti ◽  
Liyanovitasari Liyanovitasari
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Self Efficacy ◽  
Healing Process ◽  
Sampling Technique ◽  
P Value ◽  
Cross Sectional ◽  
Kolmogorov Smirnov

Background: Self efficacy can optimize the quality of life of clients who undergo the healing process due to chronic diseases. Individuals with higher self-efficacy move their personal and social resources proactively to maintain and improve the quality and length of their lives so that they experience a better quality of life. Objectives: the purpose of this study was to find the correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency. Metode: This type of research was descriptive correlation with cross sectional approach. The samples in this study more 76 people with total sampling technique. The data collection tool for self efficacy was measured by General Self-Efficacy scale, for quality of life with WHOQoL-BREF. Statistical test used Kolmogorov-smirnov. Result: The result showed that self efficacy in patients with chronic kidney disease was mostly in moderate category (53,9%), quality of life in patients with chronic kidney disease was mostly in good category (68,4%). There was a correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency, the result obtained p-value of 0.000 <α (0,05). Suggestion: Patients with chronic kidney disease can maintain good quality of life by helping to generate positive self-esteem and high self efficacy.

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