FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3190502078> ?p ?o ?g. }

• W3190502078 endingPage "2762" @default.
• W3190502078 startingPage "2752" @default.
• W3190502078 abstract "The physiological role of iron extends well beyond hematopoiesis. Likewise, the pathophysiological effects of iron deficiency (ID) extend beyond anemia. Although inextricably interrelated, ID and anemia of chronic kidney disease (CKD) are distinct clinical entities. For more than 3 decades, however, nephrologists have focused primarily on the correction of anemia. The achievement of target hemoglobin (Hgb) concentrations is prioritized over repletion of iron stores, and iron status is generally a secondary consideration only assessed in those patients with anemia. Historically, the correction of ID independent of anemia has not been a primary focus in the management of CKD. In contrast, ID is a key therapeutic target in the setting of heart failure (HF) with reduced ejection fraction (HFrEF); correction of ID in this population improves functional status and quality of life and may improve cardiovascular (CV) outcomes. Given the strong interrelationships between HF and CKD, it is reasonable to consider whether iron therapy alone may benefit those with CKD and evidence of ID irrespective of Hgb concentration. In this review, we differentiate anemia from ID by considering both epidemiologic and pathophysiological perspectives and by reviewing the evidence linking correction of ID to outcomes in patients with HF and/or CKD. Furthermore, we discuss existing gaps in evidence and provide proposals for future research and practical considerations for clinicians. The physiological role of iron extends well beyond hematopoiesis. Likewise, the pathophysiological effects of iron deficiency (ID) extend beyond anemia. Although inextricably interrelated, ID and anemia of chronic kidney disease (CKD) are distinct clinical entities. For more than 3 decades, however, nephrologists have focused primarily on the correction of anemia. The achievement of target hemoglobin (Hgb) concentrations is prioritized over repletion of iron stores, and iron status is generally a secondary consideration only assessed in those patients with anemia. Historically, the correction of ID independent of anemia has not been a primary focus in the management of CKD. In contrast, ID is a key therapeutic target in the setting of heart failure (HF) with reduced ejection fraction (HFrEF); correction of ID in this population improves functional status and quality of life and may improve cardiovascular (CV) outcomes. Given the strong interrelationships between HF and CKD, it is reasonable to consider whether iron therapy alone may benefit those with CKD and evidence of ID irrespective of Hgb concentration. In this review, we differentiate anemia from ID by considering both epidemiologic and pathophysiological perspectives and by reviewing the evidence linking correction of ID to outcomes in patients with HF and/or CKD. Furthermore, we discuss existing gaps in evidence and provide proposals for future research and practical considerations for clinicians. The association between CKD and anemia has been recognized for nearly 2 centuries.1Cases and observations illustrative of renal disease, accompanied with the secretion of albuminous urine.Med Chir Rev. 1836; 25: 23-35PubMed Google Scholar,2Babitt J.L. Lin H.Y. Mechanisms of anemia in CKD.J Am Soc Nephrol. 2012; 23: 1631-1634https://doi.org/10.1681/ASN.2011111078Crossref PubMed Scopus (483) Google Scholar Contemporary research has revealed that anemia of CKD is independently associated with a range of adverse outcomes, including reduced quality of life, hospitalization, progression to kidney failure, major CV events, and death.3Kovesdy C.P. Trivedi B.K. Kalantar-Zadeh K. Anderson J.E. Association of anemia with outcomes in men with moderate and severe chronic kidney disease.Kidney Int. 2006; 69: 560-564https://doi.org/10.1038/sj.ki.5000105Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 4Jurkovitz C.T. Abramson J.L. Vaccarino L.V. Weintraub W.S. McClellan W.M. Association of high serum creatinine and anemia increases the risk of coronary events: results from the prospective community-based atherosclerosis risk in communities (ARIC) study.J Am Soc Nephrol. 2003; 14: 2919-2925https://doi.org/10.1097/01.asn.0000092138.65211.71Crossref PubMed Scopus (0) Google Scholar, 5Abramson J.L. Jurkovitz C.T. Vaccarino V. Weintraub W.S. McClellan W. Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study.Kidney Int. 2003; 64: 610-615https://doi.org/10.1046/j.1523-1755.2003.00109.xAbstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar, 6Palaka E. Grandy S. van Haalen H. McEwan P. Darlington O. The impact of CKD anaemia on patients: incidence, risk factors, and clinical outcomes—a systematic literature review.Int J Nephrol. 2020; 2020: 7692376https://doi.org/10.1155/2020/7692376Crossref PubMed Scopus (11) Google Scholar, 7Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work GroupKDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (625) Google Scholar The burden of CKD anemia increases with declining kidney function. International studies reveal that the prevalence of anemia—defined as a Hgb concentration <12.0 g/dl—is substantial, at 30%, 46%, and 72% in patients with stage 3b CKD, stage 4 CKD, and stage 5 CKD without kidney replacement therapy, respectively.8Wong M.M.Y. Tu C. Li Y. et al.Anemia and iron deficiency among chronic kidney disease stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.Clin Kidney J. 2019; 13: 613-624https://doi.org/10.1093/ckj/sfz091Crossref PubMed Google Scholar Moreover, nearly 85% of patients with stage 5 CKD treated with hemodialysis in the United States have Hgb levels <12.0 g/dl.9Hemoglobin (most recent), categories. US-DOPPS practice monitor.https://www.dopps.org/DPM/Files/hgbgdl_c_overallTAB.htmGoogle Scholar ID, whether resulting from a lack of iron stores (absolute ID) or the inability to use existing iron stores (functional ID), is a major contributor to the development of anemia in patients with CKD.2Babitt J.L. Lin H.Y. Mechanisms of anemia in CKD.J Am Soc Nephrol. 2012; 23: 1631-1634https://doi.org/10.1681/ASN.2011111078Crossref PubMed Scopus (483) Google Scholar,7Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work GroupKDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (625) Google Scholar ID, however, is not the sole cause of CKD anemia; other contributory mechanisms include relative erythropoietin deficiency and the shortened life span of red blood cells.2Babitt J.L. Lin H.Y. Mechanisms of anemia in CKD.J Am Soc Nephrol. 2012; 23: 1631-1634https://doi.org/10.1681/ASN.2011111078Crossref PubMed Scopus (483) Google Scholar,7Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work GroupKDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (625) Google Scholar Naturally, patients with CKD can also experience non–CKD-associated causes of ID and anemia, including infection, gastrointestinal bleeding, and hemoglobinopathies. Many patients with CKD meet criteria for ID without clinical evidence of anemia.8Wong M.M.Y. Tu C. Li Y. et al.Anemia and iron deficiency among chronic kidney disease stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.Clin Kidney J. 2019; 13: 613-624https://doi.org/10.1093/ckj/sfz091Crossref PubMed Google Scholar,10Guedes M. Robinson B.M. Obrador G. et al.Management of anemia in non-dialysis chronic kidney disease: current recommendations, real-world practice, and patient perspectives.Kidney 360. 2020; 1: 855-862https://doi.org/10.34067/KID.0001442020Crossref Google Scholar, 11Klip I.T. Jankowska E.A. Enjuanes C. et al.The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.Eur J Heart Fail. 2014; 16: 655-662https://doi.org/10.1002/ejhf.84Crossref PubMed Scopus (51) Google Scholar, 12Fishbane S. Pollack S. Feldman H.I. Joffe M.M. Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988-2004.Clin J Am Soc Nephrol. 2009; 4: 57-61https://doi.org/10.2215/CJN.01670408Crossref PubMed Scopus (122) Google Scholar, 13Hsu C.Y. McCulloch C.E. Curhan G.C. Iron status and hemoglobin level in chronic renal insufficiency.J Am Soc Nephrol. 2002; 13: 2783-2786https://doi.org/10.1097/01.asn.0000034200.82278.dcCrossref PubMed Scopus (0) Google Scholar For more than 3 decades, nephrologists have focused primarily on the correction of anemia in patients with CKD using erythropoiesis-stimulating agents (ESAs) and supplemental iron. Historically, the main objective of therapy has been achievement of a specific Hgb target, based on the premise that this alone is the principal determinant of clinical outcomes. The correction of iron stores and functional iron reserves ensuring an adequate supply of iron to the bone marrow has traditionally been viewed as a secondary objective, and one that is only targeted in patients with evidence of anemia. A central question surrounding the management of anemia in CKD posed in this review is whether ID should be considered, and treated, as an entity distinct from anemia defined by Hgb targets. The assertion that ID per se is a distinct entity and should be treated independently of anemia should be supported by strong biological plausibility, epidemiologic data, and robust evidence from clinical trials.14Tong S. Vichinsky E. Iron deficiency: implications before anemia.Pediatr Rev. 2021; 42: 11-20https://doi.org/10.1542/pir.2018-0134Crossref PubMed Google Scholar, 15Anand I.S. Gupta P. Anemia and iron deficiency in heart failure: current concepts and emerging therapies.Circulation. 2018; 138: 80-98https://doi.org/10.1161/CIRCULATIONAHA.118.030099Crossref PubMed Scopus (158) Google Scholar, 16Schrage B. Rübsamen N. Schulz A. et al.Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study.Clin Res Cardiol. 2020; 109: 1352-1357https://doi.org/10.1007/s00392-020-01631-yCrossref PubMed Scopus (12) Google Scholar, 17Pratt J.J. Khan K.S. Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review.Eur J Haematol. 2016; 96: 618-628https://doi.org/10.1111/ejh.12645Crossref PubMed Scopus (65) Google Scholar The use of iron supplementation by nephrologists is quite different from the approach used by cardiologists in the setting of HF. In cardiology, iron is administered with the primary goal of correcting ID, improving functional status and quality of life, and potentially reducing CV events (notably hospitalizations for HF), not correcting anemia and increasing Hgb levels.18Yancy C.W. Jessup M. Bozkurt B. et al.2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.Circulation. 2017; 136: e137-e161https://doi.org/10.1161/CIR.0000000000000509Crossref PubMed Scopus (1484) Google Scholar, 19Ponikowski P. Voors A.A. Anker S.D. et al.2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC [published correction appears in Eur Heart J. 2018;39:860.Eur Heart J. 2016; 37: 2129-2200https://doi.org/10.1093/eurheartj/ehw128Crossref PubMed Scopus (8171) Google Scholar, 20Anker S.D. Kirwan B.A. van Veldhuisen D.J. et al.Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis.Eur J Heart Fail. 2018; 20: 125-133https://doi.org/10.1002/ejhf.823Crossref PubMed Scopus (202) Google Scholar, 21Ponikowski P. Kirwan B.A. Anker S.D. et al.Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.Lancet. 2020; 396: 1895-1904https://doi.org/10.1016/S0140-6736(20)32339-4Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar In contrast, in nephrology, management of ID is primarily a means to correct anemia of CKD and to achieve a specific Hgb target. Thus, the correction of ID independent of anemia is not a primary consideration. By limiting the use of iron to patients with CKD with evidence of anemia and ID, it is possible that nephrologists are excluding a relatively large population of patients who would otherwise benefit from the therapy. This review will evaluate whether nephrologists should consider iron therapy for patients with CKD and evidence of ID irrespective of Hgb concentration. Such an approach could be contrasted with current guidelines that “only” recommend consideration of iron therapy for adults with anemia (defined as Hgb <13.0 g/dl in men and <12.0 g/dl in women) and evidence of ID.7Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work GroupKDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (625) Google Scholar We will evaluate the differences between anemia and ID from epidemiologic and pathophysiological perspectives before reviewing the current evidence from published clinical trials in HF and CKD. We will further explore gaps in our knowledge before concluding with recommendations for future research and practical considerations for clinicians. Although this review aims to evaluate the implications of considering, for the purposes of management, ID as a clinical entity distinct from anemia of CKD, we acknowledge that ID is a key contributor to the anemia of CKD, and thus both are inextricably interrelated. Depletion of iron stores will, if left untreated, progress to impaired erythropoiesis and reduced Hgb concentrations.22Beard J.L. Iron biology in immune function, muscle metabolism and neuronal functioning.J Nutr. 2001; 131: 568S-580Shttps://doi.org/10.1093/jn/131.2.568SCrossref PubMed Google Scholar In the setting of CKD, ID results from blood loss, reduced iron intake/absorption, and reduced mobilization of iron from storage cells secondary to increased hepcidin concentrations.23Wish J.B. Aronoff G.R. Bacon B.R. et al.Positive iron balance in chronic kidney disease: how much is too much and how to tell?.Am J Nephrol. 2018; 47: 72-83https://doi.org/10.1159/000486968Crossref PubMed Scopus (46) Google Scholar There are limited data on the concurrent prevalence of ID and anemia within the same population of patients with CKD. In a cohort of 700 kidney transplant recipients with a mean (SD) estimated glomerular filtration rate (eGFR) of 52.3 (20.2) ml/min per 1.73 m2, 30% of the patients had ID (transferrin saturation [TSAT] <20% and ferritin <300 ng/ml) without anemia (World Health Organization criteria: Hgb <13.0 g/dl for men and <12.0 g/dl for women) and 34% had anemia without ID.24Eisenga M.F. Minović I. Berger S.P. et al.Iron deficiency, anemia, and mortality in renal transplant recipients.Transpl Int. 2016; 29: 1176-1183https://doi.org/10.1111/tri.12821Crossref PubMed Scopus (24) Google Scholar Wong et al.8Wong M.M.Y. Tu C. Li Y. et al.Anemia and iron deficiency among chronic kidney disease stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.Clin Kidney J. 2019; 13: 613-624https://doi.org/10.1093/ckj/sfz091Crossref PubMed Google Scholar found the prevalence of ID among patients with CKD varied across countries, but not appreciably across stages of CKD. In contrast, the prevalence of anemia increased substantially with advancing stage of CKD. The lack of additional data on ID among patients with CKD is not unexpected, given that assessment of iron parameters (i.e., TSAT and ferritin) is generally prompted by the presence of anemia, and typically restricted to patients with CKD and anemia.7Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work GroupKDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (625) Google Scholar Even when indicated, real-world assessment of iron parameters occurs at suboptimal rates. For example, in the United States, only 47% of patients with CKD stages 3 to 5 and Hgb <10.0 g/dl had iron indices measured.8Wong M.M.Y. Tu C. Li Y. et al.Anemia and iron deficiency among chronic kidney disease stages 3-5ND patients in the Chronic Kidney Disease Outcomes and Practice Patterns Study: often unmeasured, variably treated.Clin Kidney J. 2019; 13: 613-624https://doi.org/10.1093/ckj/sfz091Crossref PubMed Google Scholar Although impractical for routine assessment, bone marrow staining is the gold standard for assessment of iron status. In clinical practice, reliance on laboratory assessments—particularly, TSAT <20%—has been recommended for both HF and CKD populations.25Grote Beverborg N. Klip I.T. Meijers W.C. et al.Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients.Circ Heart Fail. 2018; 11e004519https://doi.org/10.1161/CIRCHEARTFAILURE.117.004519Crossref PubMed Scopus (82) Google Scholar,26Batchelor E.K. Kapitsinou P. Pergola P.E. Kovesdy C.P. Jalal D.I. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment.J Am Soc Nephrol. 2020; 31: 456-468https://doi.org/10.1681/ASN.2019020213Crossref PubMed Scopus (42) Google Scholar Data on the prevalence of ID in the setting of HF are more readily available than those observed for CKD. Reduced intracellular iron in the setting of HF is thought to result from inhibition of transferrin receptor protein 1 secondary to a combination of systemic inflammation, overactivity of the renin-angiotensin-aldosterone system, and increased sympathetic nervous activity.27Rocha B.M.L. Cunha G.J.L. Menezes Falcão L.F. The burden of iron deficiency in heart failure: therapeutic approach.J Am Coll Cardiol. 2018; 71: 782-793https://doi.org/10.1016/j.jacc.2017.12.027Crossref PubMed Scopus (64) Google Scholar As reviewed by Rocha et al.,27Rocha B.M.L. Cunha G.J.L. Menezes Falcão L.F. The burden of iron deficiency in heart failure: therapeutic approach.J Am Coll Cardiol. 2018; 71: 782-793https://doi.org/10.1016/j.jacc.2017.12.027Crossref PubMed Scopus (64) Google Scholar the prevalence of ID was 30% to 50% among patients with stable HF and between 50% and 80% among patients with acute HF. In an international cohort of >1500 patients with HF, the prevalence of ID, CKD, and anemia was 50%, 28%, and 28%, respectively.11Klip I.T. Jankowska E.A. Enjuanes C. et al.The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.Eur J Heart Fail. 2014; 16: 655-662https://doi.org/10.1002/ejhf.84Crossref PubMed Scopus (51) Google Scholar,28Klip I.T. Comin-Colet J. Voors A.A. et al.Iron deficiency in chronic heart failure: an international pooled analysis.Am Heart J. 2013; 165: 575-582.e3https://doi.org/10.1016/j.ahj.2013.01.017Crossref PubMed Scopus (393) Google Scholar Among those patients with CKD and ID (in addition to HF), 58% did not have concomitant anemia. Conversely, among patients with CKD and anemia (in addition to HF), 38% did not have concomitant ID. The burden of ID generally increases with worsening HF (as determined by the New York Heart Association classification).28Klip I.T. Comin-Colet J. Voors A.A. et al.Iron deficiency in chronic heart failure: an international pooled analysis.Am Heart J. 2013; 165: 575-582.e3https://doi.org/10.1016/j.ahj.2013.01.017Crossref PubMed Scopus (393) Google Scholar,29Martens P. Nijst P. Verbrugge F.H. Smeets K. Dupont M. Mullens W. Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction.Acta Cardiol. 2018; 73: 115-123https://doi.org/10.1080/00015385.2017.1351239Crossref PubMed Scopus (61) Google Scholar ID is a common comorbidity of HF regardless of whether left ventricular ejection fraction is reduced or preserved. Given that iron is necessary for multiple cellular processes, including energy production, DNA synthesis, drug metabolism, steroid synthesis, immune function, drug metabolism, and oxygen transport,30Pantopoulos K. Porwal S.K. Tartakoff A. Devireddy L. Mechanisms of mammalian iron homeostasis.Biochemistry. 2012; 51: 5705-5724https://doi.org/10.1021/bi300752rCrossref PubMed Scopus (341) Google Scholar,31Muckenthaler M.U. Lill R. Cellular iron physiology.in: Anderson G.A. McLaren G.D. Iron Physiology and Pathophysiology in Humans. Springer, 2012: 27-50Crossref Scopus (11) Google Scholar it is not surprising that the effects of ID are wide ranging. These effects can be broadly classified as those resulting from either hematopoietic or nonhematopoietic pathway (Figure 1).32Ponikowski P. Kirwan B.A. Anker S.D. et al.Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.Eur J Heart Fail. 2019; 21: 1651-1658https://doi.org/10.1002/ejhf.1710Crossref PubMed Scopus (28) Google Scholar From a temporal perspective, impairment in muscle function, immunologic defense, neuronal functioning, and exercise tolerance seems to occur long before reductions in Hgb concentrations.22Beard J.L. Iron biology in immune function, muscle metabolism and neuronal functioning.J Nutr. 2001; 131: 568S-580Shttps://doi.org/10.1093/jn/131.2.568SCrossref PubMed Google Scholar In the setting of HF, dysfunctional mitochondrial energy production (a potential consequence of ID) in the heart, skeletal muscle, and kidneys is associated with reduced systolic function, exercise intolerance and fatigue, and kidney impairment, respectively.33Brown D.A. Perry J.B. Allen M.E. et al.Expert consensus document: mitochondrial function as a therapeutic target in heart failure.Nat Rev Cardiol. 2017; 14: 238-250https://doi.org/10.1038/nrcardio.2016.203Crossref PubMed Scopus (331) Google Scholar, 34Martens P. Verbrugge F.H. Nijst P. Dupont M. Mullens W. Limited contractile reserve contributes to poor peak exercise capacity in iron-deficient heart failure.Eur J Heart Fail. 2018; 20: 806-808https://doi.org/10.1002/ejhf.938Crossref PubMed Scopus (14) Google Scholar, 35Melenovsky V. Petrak J. Mracek T. et al.Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis.Eur J Heart Fail. 2017; 19: 522-530https://doi.org/10.1002/ejhf.640Crossref PubMed Scopus (125) Google Scholar The impact of mitochondrial dysfunction on the heart, skeletal muscle, and kidneys is strongly aligned with the high metabolic demands and energy consumption of these organ systems and tissues.36Boyman L. Karbowski M. Lederer W.J. Regulation of mitochondrial ATP production: Ca2+ signaling and quality control.Trends Mol Med. 2020; 26: 21-39https://doi.org/10.1016/j.molmed.2019.10.007Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar The impact of ID on functional outcomes in HF has been well documented. In a study of 443 patients with HFrEF, ID was an independent predictor of reduced exercise capacity as assessed by peak oxygen consumption and ventilatory response to exercise.37Jankowska E.A. Rozentryt P. Witkowska A. et al.Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.J Card Fail. 2011; 17: 899-906https://doi.org/10.1016/j.cardfail.2011.08.003Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar The impact of ID alone (i.e., in the absence of anemia) was greater than that observed with anemia alone (i.e., in the absence of ID). Similarly, Comín-Colet et al.38Comín-Colet J. Enjuanes C. González G. et al.Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status.Eur J Heart Fail. 2013; 15: 1164-1172https://doi.org/10.1093/eurjhf/hft083Crossref PubMed Scopus (129) Google Scholar found that ID, and not anemia, was independently associated with reduced health-related quality of life among patients with HF. Observed declines in quality of life were largely driven by reductions in physical domain components (e.g., walking or climbing stairs, appetite, fatigue). The observed impact of ID on quality of life is substantial and has been replicated by other investigators.39Enjuanes C. Klip I.T. Bruguera J. et al.Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study.Int J Cardiol. 2014; 174: 268-275https://doi.org/10.1016/j.ijcard.2014.03.169Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar Several studies have identified strong independent associations of ID with mortality in patients with HF. Klip et al.11Klip I.T. Jankowska E.A. Enjuanes C. et al.The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.Eur J Heart Fail. 2014; 16: 655-662https://doi.org/10.1002/ejhf.84Crossref PubMed Scopus (51) Google Scholar reported a 42% increased risk of death for patients with ID in a cohort study of 1506 patients with HF. This association persisted regardless of CKD and/or anemia.11Klip I.T. Jankowska E.A. Enjuanes C. et al.The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences.Eur J Heart Fail. 2014; 16: 655-662https://doi.org/10.1002/ejhf.84Crossref PubMed Scopus (51) Google Scholar Similarly, in a Belgian cohort, Martens et al.29Martens P. Nijst P. Verbrugge F.H. Smeets K. Dupont M. Mullens W. Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction.Acta Cardiol. 2018; 73: 115-123https://doi.org/10.1080/00015385.2017.1351239Crossref PubMed Scopus (61) Google Scholar found that ID, in the absence of anemia, was also an independent risk factor for death and hospitalization in patients with HF. In contrast, they found that anemia, in the absence of ID, did not predict HF hospitalization and was a weaker predictor of mortality. Notably, the independent association between ID and adverse outcomes was not affected by left ventricular ejection fraction. In contrast to HF—in which the presence of ID has independently been associated with impaired exercise tolerance37Jankowska E.A. Rozentryt P. Witkowska A. et al.Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.J Card Fail. 2011; 17: 899-906https://doi.org/10.1016/j.cardfail.2011.08.003Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar and increased mortality19Ponikowski P. Voors A.A. Anker S.D. et al.2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC [published correction appears in Eur Heart J. 2018;39:860.Eur Heart J. 2016; 37: 2129-2200https://doi.org/10.1093/eurheartj/ehw128Crossref PubMed Scopus (8171) Google Scholar—there are limited outcome studies of ID in the absence of anemia in the general population and patients with CKD. In an analysis of data from almost 16,000 adults in the Third National Health and Nutrition Examination Survey (1988–1994), Stack et al.40Stack A.G. Mutwali A.I. Nguyen H.T. Cronin C.J. Casserly L.F. Ferguson J. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.QJM. 2014; 107: 623-633https://doi.org/10.1093/qjmed/hcu045Crossref PubMed Scopus (24) Google Scholar found that TSAT levels <23.7% were independently associated with increased CV and all-cause mortality (relative to the reference group; TSAT 23.7%–31.3%) after adjustment for multiple confounders, including kidney function and Hgb. Recent data from Germany also reveal that >50% of healthy adults without anemia met criteria for functional ID (i.e., ferritin ≤100 ng/ml or ferritin 100–299 ng/ml with TSAT <20%).16Schrage B. Rübsamen N. Schulz A. et al.Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study.Clin Res Cardiol. 2020; 109: 1352-1357https://doi.org/10.1007/s00392-020-01631-yCrossref PubMed Scopus (12) Google Scholar In multivariate analyses adjusting for Hgb and CV risk factors, functional and absolute ID were associated with 30% and 90% increases in all-cause mortality, respectively, in a median follow-up of approximately 10 years. In a large cohort of patients with CKD not requiring dialysis, functional ID was more strongly predictive of 1-year mortality than absolute ID (relative to a reference group of patients without ID) despite similar Hgb levels across all groups (mean ~12.0 g/dl).41Cho M.E. Hansen J.L. Peters C.B. Cheung A.K. Greene T. Sauer B.C. An increased mortality risk is associated with abnormal iron status in diabetic and non-diabetic veterans with predialysis chronic kidney disease.Kidney Int. 2019; 96: 750-760https://doi.org/10.1016/j." @default.
• W3190502078 created "2021-08-16" @default.
• W3190502078 creator A5005351139 @default.
• W3190502078 creator A5021273139 @default.
• W3190502078 creator A5054496507 @default.
• W3190502078 creator A5064592202 @default.
• W3190502078 creator A5079420772 @default.
• W3190502078 creator A5091066764 @default.
• W3190502078 date "2021-11-01" @default.
• W3190502078 modified "2023-10-16" @default.
• W3190502078 title "Iron Deficiency in CKD Without Concomitant Anemia" @default.
• W3190502078 cites W1520619906 @default.
• W3190502078 cites W162181629 @default.
• W3190502078 cites W1711653832 @default.
• W3190502078 cites W1900257882 @default.
• W3190502078 cites W1968364422 @default.
• W3190502078 cites W1998943227 @default.
• W3190502078 cites W2017704094 @default.
• W3190502078 cites W2020198029 @default.
• W3190502078 cites W2028265881 @default.
• W3190502078 cites W2033465391 @default.
• W3190502078 cites W2040029744 @default.
• W3190502078 cites W2046551865 @default.
• W3190502078 cites W2049258517 @default.
• W3190502078 cites W2055583487 @default.
• W3190502078 cites W2098124630 @default.
• W3190502078 cites W2118281989 @default.
• W3190502078 cites W2120601666 @default.
• W3190502078 cites W2134487085 @default.
• W3190502078 cites W2136542175 @default.
• W3190502078 cites W2138920166 @default.
• W3190502078 cites W2139318112 @default.
• W3190502078 cites W2148669301 @default.
• W3190502078 cites W2165232064 @default.
• W3190502078 cites W2179358297 @default.
• W3190502078 cites W2276227009 @default.
• W3190502078 cites W2427094903 @default.
• W3190502078 cites W2514795156 @default.
• W3190502078 cites W2525452034 @default.
• W3190502078 cites W2565443325 @default.
• W3190502078 cites W2609879055 @default.
• W3190502078 cites W2614710189 @default.
• W3190502078 cites W2734960411 @default.
• W3190502078 cites W2739352460 @default.
• W3190502078 cites W2755484298 @default.
• W3190502078 cites W2786908448 @default.
• W3190502078 cites W2790152587 @default.
• W3190502078 cites W2790235460 @default.
• W3190502078 cites W2790601563 @default.
• W3190502078 cites W2809850559 @default.
• W3190502078 cites W2897539802 @default.
• W3190502078 cites W2898498137 @default.
• W3190502078 cites W2899658840 @default.
• W3190502078 cites W2946654824 @default.
• W3190502078 cites W2964863420 @default.
• W3190502078 cites W2978791123 @default.
• W3190502078 cites W2990822273 @default.
• W3190502078 cites W2998657350 @default.
• W3190502078 cites W3006132236 @default.
• W3190502078 cites W3013073300 @default.
• W3190502078 cites W3013802100 @default.
• W3190502078 cites W3014160396 @default.
• W3190502078 cites W3014325832 @default.
• W3190502078 cites W3028348581 @default.
• W3190502078 cites W3038356324 @default.
• W3190502078 cites W3039785915 @default.
• W3190502078 cites W3092208366 @default.
• W3190502078 cites W3106240111 @default.
• W3190502078 cites W3106816916 @default.
• W3190502078 cites W3117400963 @default.
• W3190502078 cites W3118697061 @default.
• W3190502078 cites W3120042682 @default.
• W3190502078 cites W3122060261 @default.
• W3190502078 cites W3146111338 @default.
• W3190502078 cites W3160031138 @default.
• W3190502078 cites W4238907867 @default.
• W3190502078 cites W3149132779 @default.
• W3190502078 doi "https://doi.org/10.1016/j.ekir.2021.07.032" @default.
• W3190502078 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8589703" @default.
• W3190502078 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34805628" @default.
• W3190502078 hasPublicationYear "2021" @default.
• W3190502078 type Work @default.
• W3190502078 sameAs 3190502078 @default.
• W3190502078 citedByCount "8" @default.
• W3190502078 countsByYear W31905020782022 @default.
• W3190502078 countsByYear W31905020782023 @default.
• W3190502078 crossrefType "journal-article" @default.
• W3190502078 hasAuthorship W3190502078A5005351139 @default.
• W3190502078 hasAuthorship W3190502078A5021273139 @default.
• W3190502078 hasAuthorship W3190502078A5054496507 @default.
• W3190502078 hasAuthorship W3190502078A5064592202 @default.
• W3190502078 hasAuthorship W3190502078A5079420772 @default.
• W3190502078 hasAuthorship W3190502078A5091066764 @default.
• W3190502078 hasBestOaLocation W31905020781 @default.
• W3190502078 hasConcept C126322002 @default.
• W3190502078 hasConcept C177713679 @default.
• W3190502078 hasConcept C187212893 @default.
• W3190502078 hasConcept C2777417653 @default.

• next