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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia in chronic kidney disease is common and iron deficiency is an important cause. To repair iron-deficiency anemia, replacement of iron is needed. Iron can be replaced either by the oral route or by the intravenous route. In a meta-analysis, 5 of the 6 trials were short-term, 1 to 3 months, and compared to oral iron, the mean increase in hemoglobin with intravenous iron was only 0.31 g/dL. However, one of the studies included in this meta-analysis was 6 months long and had a mean decline in hemoglobin of 0.52 g/dL associated with intravenous iron administration. Given the short duration of most of the clinical trials comparing oral with intravenous administration of iron the long-term safety of these modes of administration of supplemental iron could not be assessed. Replacement of iron by the oral route is associated with mostly minor complications such as black stools, constipation, and abdominal discomfort. In contrast, intravenous administration of iron may lead to severe adverse events such as anaphylaxis and, as a more recent randomized trial has suggested, delayed complications such as infections and cardiovascular disease. Delayed complications of repeated intravenous iron use are difficult to recognize at an individual level therefore inpatients who have had recent cardiovascular events or are infected, intravenous iron should probably be avoided. Balancing safety and efficacy would require clinical judgment because 1 size may not fit all till we have better data to support the liberal use of parenteral iron.
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PMID:Iron deficiency anemia in chronic kidney disease: Uncertainties and cautions. 2840 61

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.
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PMID:Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver. 2940 11

Restless legs syndrome, also known as Willis-Ekbom disease, is a common neurological condition whose manifestation is affected by complex environmental and genetic interactions. Restless legs syndrome can occur on its own, mostly at a young age, or with comorbidities such as cardiovascular disease, diabetes, and arterial hypertension, making it a difficult condition to properly diagnose. However, the concept of restless legs syndrome as being two entities, primary or secondary to another condition, has been challenged with genetic data providing further insight into the pathophysiology of the condition. Although dopaminergic treatment was formerly the first-line therapy, prolonged use can result in a serious worsening of symptoms known as augmentation. Clinical studies on pregabalin, gabapentin enacarbil, oxycodone-naloxone, and iron preparations have provided new treatment options, but most patients still report inadequate long-term management of symptoms. Studies of the hypoxic pathway activation and iron deficiency have provided valuable information about the pathophysiology of restless legs syndrome that should now be translated into new, more effective treatments for restless legs syndrome.
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PMID:Comorbidities, treatment, and pathophysiology in restless legs syndrome. 3024 28

Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in globin synthesis and erythropoiesis and has also been implicated in the enhancement of iron absorption from human diets. Studies have found that L-histidine exhibits antioxidant capabilities, such as scavenging free radicals and chelating divalent metal ions, hence the advocacy for its use in improving oxidative stress in CKD. The current review advances and discusses evidence for iron-induced toxicity in CKD and the mechanisms by which histidine exerts cytoprotective functions.
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PMID:Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease. 3034 74

Iron deficiency is the most frequent deficiency disease and parameters of iron metabolism appear to be linked to major metabolic and cardiovascular diseases. We screened a large set of small molecules in plasma for associations with iron status among apparently healthy subjects to elucidate subclinical profiles which may provide a link between iron status and onset of diseases. Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined 613 plasma metabolites and lipoprotein subfractions among 820 apparently healthy individuals. Associations between ferritin, transferrin, haemoglobin and myoglobin and metabolite levels were tested by sex-specific linear regression analyses controlling for common confounders. Far more significant associations in women (82 out of 102) compared to men became obvious. The majority of the metabolites associated with serum ferritin and haemoglobin in women comprising fatty acid species, branched-chain amino acid catabolites and catabolites of heme. The latter was also obvious among men. Positive associations between serum transferrin and VLDL and IDL particle measures seen in women were observed in men with respect to serum ferritin. We observed a sexual-dimorphic fingerprint of surrogates of iron metabolism which may provide a link for the associations between those parameters and major metabolic and cardiovascular disease.
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PMID:Molecular Fingerprints of Iron Parameters among a Population-Based Sample. 3046 74

Children with chronic kidney disease (CKD) are at high risk of anemia, an important risk factor for cardiovascular disease and poor quality of life. The present study used baseline data from the Korean cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-PedCKD). A Total of 437 patients was included in the analyses excluding missing data. The characteristics of patients with and without anemia and those of patients with and without iron deficiency were compared. Logistic regression analysis and Pearson correlation were conducted to evaluate associated risk factors and correlations in children with CKD. Anemia in children with CKD was associated with older age, low body weight and body mass index (BMI) z-score, birth age, preceding glomerulonephritis, decreased estimated glomerular filtration rate (eGFR), low levels of serum albumin and calcium, high levels of serum intact parathyroid hormone (iPTH), and serum phosphorus. Anemia was correlated positively with changes in the BMI z-score, body weight, and serum albumin and cholesterol levels, but correlated negatively with serum calcium, iPTH, ferritin levels, and transferrin saturation. Iron deficiency in children with CKD was associated with young age, low hemoglobin and serum ferritin levels, high BMI z-scores, and low levels of serum iPTH. This is the first nationwide cohort study of anemia in Korean children with CKD and the first prospective pediatric CKD cohort study in Asia. The study results demonstrated that anemia and iron deficiency are affected by various factors, including age, BMI, and levels of serum iPTH. To improve the retrospective outcome of affected children, it is important to understand the effect of each of these factors and to attempt an early intervention to prevent anemia and iron deficiency by regular measurement of these parameters in children at risk.
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PMID:Anemia and Iron Deficiency in Children with Chronic Kidney Disease (CKD): Data from the Know-Ped CKD Study. 3070 16

As the adverse effects of iron deficiency are better recognized, the use of oral and intravenous iron has increased dramatically. Oral iron is often poorly tolerated, with up to 70% or more of patients noting gastrointestinal issues; this may affect adherence to therapy. In addition, many patients will not respond to oral iron due to their underlying illness. Intravenous iron is being used more frequently to replete iron stores. True anaphylaxis is very rare, but complement-mediated infusion reactions may be seen in up to 1 in every 200 patients. Previous concerns about intravenous iron increasing the risk of infection or cardiovascular disease are unfounded.
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PMID:Safety of Oral and Intravenous Iron. 3097 Mar 54

Iron deficiency or overload poses an increasingly complex issue in cardiovascular disease, especially heart failure. The potential benefits and side effects of iron supplementation are still a matter of concern, even though current guidelines suggest therapeutic management of iron deficiency. In this review, we sought to examine the iron metabolism and to identify the rationale behind iron supplementation and iron chelation. Cardiovascular disease is increasingly linked with iron dysmetabolism, with an increased proportion of heart failure patients being affected by decreased plasma iron levels and in turn, by the decreased quality of life. Multiple studies have concluded on a benefit of iron administration, even if just for symptomatic relief. However, new studies field evidence for negative effects of dysregulated non-bound iron and its reactive oxygen species production, with concern to heart diseases. The molecular targets of iron usage, such as the mitochondria, are prone to deleterious effects of the polyvalent metal, added by the scarcely described processes of iron elimination. Iron supplementation and iron chelation show promise of therapeutic benefit in heart failure, with the extent and mechanisms of both prospects not being entirely understood. It may be that a state of decreased systemic and increased mitochondrial iron levels proves to be a useful frame for future advancements in understanding the interconnection of heart failure and iron metabolism.
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PMID:Influence of mitochondrial and systemic iron levels in heart failure pathology. 3101 25

Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P <0.05) and high-sensitivity C-reactive protein (hsCRP) (P <0.05) in FID as compared to AID as well as normal iron level. We also found other inflammatory markers such as albumin, transferrin, and ferritin to be significantly associated with FID. In univariate analysis, hemoglobin (Hb) varied significantly with serum total iron-binding capacity (r = 0.40, P <0.001), log hsCRP (r = -0.32, P <0.01), and log ferritin (r = -0.23, P <0.05); however, Hb was not affected significantly with log hepcidin (r = -0.07, P >0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.
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PMID:Association of hepcidin and anemia in early chronic kidney disease. 3103 67

Iron deficiency is the most common nutritional disorder in the world. It is prevalent amongst patients with cardiovascular disease, in whom it is associated with worse clinical outcomes. The benefits of iron supplementation have been established in chronic heart failure, but data on their effectiveness in other cardiovascular diseases are lacking or conflicting. Realising the potential of iron therapies in cardiovascular disease requires understanding of the mechanisms through which iron deficiency affects cardiovascular function, and the cell types in which such mechanisms operate. That understanding has been enhanced by recent insights into the roles of hepcidin and iron regulatory proteins (IRPs) in cellular iron homeostasis within cardiovascular cells. These studies identify intracellular iron deficiency within the cardiovascular tissue as an important contributor to the disease process, and present novel therapeutic strategies based on targeting the machinery of cellular iron homeostasis rather than direct iron supplementation. This review discusses these new insights and their wider implications for the treatment of cardiovascular diseases, focusing on two disease conditions: chronic heart failure and pulmonary arterial hypertension.
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PMID:Iron Deficiency as a Therapeutic Target in Cardiovascular Disease. 3146 21


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