0
selected
-
1.
When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?
Rostoker, G
Seminars in dialysis. 2019;(1):22-29
-
-
Free full text
-
Abstract
Parenteral iron is used to restore the body's iron pool before and during erythropoiesis-stimulating agent (ESA) therapy; together these agents form the backbone of anemia management in end-stage renal disease (ESRD) patients undergoing hemodialysis. ESRD patients receiving chronic intravenous iron products, which exceed their blood loss are exposed to an increased risk of positive iron balance. Measurement of the liver iron concentration (LIC) reflects total body iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Recent studies of LIC in hemodialysis patients, measured by quantitative MRI and magnetic susceptometry, have demonstrated a high risk of iron overload in dialysis patients treated with IV iron products at doses advocated by current anemia management guidelines for dialysis patients. Liver iron overload causes increased production of hepcidin and elevated plasma levels, which can activate macrophages of atherosclerotic plaques. This mechanism may explain the results of 3 long-term epidemiological studies which showed the association of excessive IV iron doses with increased risk of cardiovascular morbidity and mortality among hemodialysis patients. A more physiological approach of iron therapy in ESRD is needed. Peritoneal dialysis patients, hemodialysis patients infected with hepatitis C virus, and hemodialysis patients with ferritin above 1000 μg/L without a concomitant inflammatory state, all require specific and cautious iron management. Two recent studies have shown that most hemodialysis patients will benefit from lower maintenance IV iron dosages; their results are applicable to American hemodialysis patients. Novel pharmacometric and economic approaches to iron therapy and anemia management are emerging which are designed to lessen the potential side effects of excessive IV iron while maintaining hemoglobin stability without an increase in ESA dosing.
-
2.
Iron and Cancer.
Torti, SV, Manz, DH, Paul, BT, Blanchette-Farra, N, Torti, FM
Annual review of nutrition. 2018;:97-125
-
-
Free full text
-
Abstract
This review explores the multifaceted role that iron has in cancer biology. Epidemiological studies have demonstrated an association between excess iron and increased cancer incidence and risk, while experimental studies have implicated iron in cancer initiation, tumor growth, and metastasis. The roles of iron in proliferation, metabolism, and metastasis underpin the association of iron with tumor growth and progression. Cancer cells exhibit an iron-seeking phenotype achieved through dysregulation of iron metabolic proteins. These changes are mediated, at least in part, by oncogenes and tumor suppressors. The dependence of cancer cells on iron has implications in a number of cell death pathways, including ferroptosis, an iron-dependent form of cell death. Uniquely, both iron excess and iron depletion can be utilized in anticancer therapies. Investigating the efficacy of these therapeutic approaches is an area of active research that promises substantial clinical impact.
-
3.
Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
Sadaf, A, Hasan, B, Das, JK, Colan, S, Alvi, N
The Cochrane database of systematic reviews. 2018;(7):CD011626
-
-
Free full text
-
Abstract
BACKGROUND Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The most common cause of morbidity and mortality is cardiac dysfunction from iron overload. The use of iron chelation therapy has reduced the severity of systemic iron overload but specific, non-toxic treatment is required for removal of iron from the myocardium. OBJECTIVES To assess the effects of calcium channel blockers combined with standard iron chelation therapy in people with transfusion-dependent beta thalassaemia on the amount of iron deposited in the myocardium, on parameters of heart function, and on the incidence of severe heart failure or arrhythmias and related morbidity and mortality. SEARCH METHODS We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials databases, and the reference lists of relevant articles and reviews.Date of last search: 24 February 2018. SELECTION CRITERIA We included randomised controlled trials of calcium channel blockers combined with standard chelation therapy compared with standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS Two authors independently applied the inclusion criteria for the selection of trials. Two authors assessed the risk of bias of trials and extracted data and a third author verified these assessments. The authors used the GRADE system to assess the quality of the evidence. MAIN RESULTS Two randomised controlled trials (n = 74) were included in the review; there were 35 participants in the amlodipine arms and 39 in the control arms. The mean age of participants was 24.4 years with a standard deviation of 8.5 years. There was comparable participation from both genders. Overall, the risk of bias in included trials was low. The quality of the evidence ranged across outcomes from low to high, but the evidence for most outcomes was judged to be low quality.Cardiac iron assessment, as measured by heart T2*, did not significantly improve in the amlodipine groups compared to the control groups at six or 12 months (low-quality evidence). However, myocardial iron concentration decreased significantly in the amlodipine groups compared to the control groups at both six months, mean difference -0.23 mg/g (95% confidence interval -0.07 to -0.39), and 12 months, mean difference -0.25 mg/g (95% confidence interval -0.44 to -0.05) (low-quality evidence). There were no significant differences between treatment and control groups in serum ferritin (low-quality evidence), liver T2* (low-quality evidence), liver iron content (low-quality evidence) and left ventricular ejection fraction (low-quality evidence). There were no serious adverse events reported in either trial; however, one trial (n = 59) reported mild adverse events, with no statistically significant difference between groups (low-quality evidence). AUTHORS' CONCLUSIONS The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia, although a potential for this was seen. There is a need for more long-term, multicentre trials to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should be designed to compare commonly used iron chelation drugs with the addition of calcium channel blockers to investigate the potential interplay of these treatments. In addition, the role of baseline myocardial iron content in affecting the response to calcium channel blockers should be investigated. An analysis of the cost-effectiveness of the treatment is also required.
-
4.
[Myelodysplastic syndromes and iron metabolism].
Kawabata, H
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2018;(10):2042-2049
Abstract
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis in bone marrow and cytopenias in peripheral blood. In patients with MDS, iron overload is frequent due to red blood cell transfusions and ineffective erythropoiesis. Dysplastic erythroblasts in MDS secrete humoral factors such as erythroferrone, which suppress hepatic expression of hepcidin. Hepcidin is the key regulator of systemic iron homeostasis, and suppression of hepcidin expression leads to an increase in iron absorption from the intestines, exacerbating systemic iron overload. Patients with MDS with ring sideroblasts (MDS-RS) are prone to iron overload, with most harboring splicing factor 3B subunit 1 (SF3B1) mutations in hematopoietic cells. SF3B1 mutations may induce ring sideroblasts by downregulating ATP binding cassette subfamily B member 7, which exports iron-sulfur clusters from the mitochondria to the cytoplasm. Iron overload in MDS causes hepatic dysfunction, diabetes, cardiac failure, and atherosclerosis, whereas excess iron may suppress normal hematopoiesis. Though randomized control studies are lacking, results from retrospective and cohort studies indicate that iron chelation therapy is appropriate for lower-risk MSD patients with transfusion-related iron overload, although it is not recommended for higher-risk MSD patients with short life expectancy.
-
5.
Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease.
Daher, R, Manceau, H, Karim, Z
Presse medicale (Paris, France : 1983). 2017;(12 Pt 2):e272-e278
Abstract
Although iron is vital, its free form is likely to be involved in oxidation-reduction reactions, leading to the formation of free radicals and oxidative stress. Living organisms have developed protein systems to transport free iron through the cell membranes and biological fluids and store it in a non-toxic and readily mobilizable form to avoid iron toxicity. Hepcidin plays a crucial role in maintaining iron homeostasis. Hepcidin expression is directly regulated by variations in iron intake and its repression leads to an increase in bioavailable serum iron level. However, in pathological situations, prolonged repression often leads to pathological iron overload. In this review, we describe the different molecular mechanisms responsible for the maintenance of iron metabolism and the consequences of iron overload. Indeed, genetic hemochromatosis and post-transfusional siderosis are the two main conditions responsible for iron overload. Long-term iron overload is deleterious, and treatment relies on venesection therapy for genetic hemochromatosis and chelation therapy for iron overload resulting from multiple transfusions.
-
6.
MRI for the measurement of liver iron content, and for the diagnosis and follow-up of iron overload disorders.
Paisant, A, d'Assignies, G, Bannier, E, Bardou-Jacquet, E, Gandon, Y
Presse medicale (Paris, France : 1983). 2017;(12 Pt 2):e279-e287
Abstract
MRI is now the reference method for detecting and quantifying hepatic and extrahepatic iron overload, regardless of its cause. The decrease of the hepatic signal is proportional to the amount of iron in the tissues. It is more pronounced with T2*-weighted gradient echo sequences. It increases proportionally with the strength of the magnetic field. Thus a 3-T MRI is be more sensitive and probably more accurate to detect a slight iron overload, as seen in dysmetabolic hepatosiderosis. Conversely, a 1.5-T MRI better estimates a high overload. Quantification can be done with the calculation of T2* (or R2*) or by using the liver to muscle signal intensity ratio (SIR). Today with a single multi-echo gradient-echo sequence, obtained in a unique apnea, the two methods can be used simultaneously. An associated quantification of steatosis is also obtained. This same type of sequence is proposed for quantification of iron in other tissues and in particular for the myocardium.
-
7.
Diagnosis and quantification of the iron overload through Magnetic resonance.
Alústiza Echeverría, JM, Barrera Portillo, MC, Guisasola Iñiguiz, A, Ugarte Muño, A
Radiologia. 2017;(6):487-495
-
-
Free full text
-
Abstract
There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and can not assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when Magnetic Resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the aplication of the technique and to be it included in the clinical guidelines.
-
8.
Impact of iatrogenic iron overload on the course of hepatitis C in the dialysis population: A plea for caution.
Rostoker, G, Vaziri, ND
Hemodialysis international. International Symposium on Home Hemodialysis. 2017;:S68-S77
Abstract
About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population. Regular loss of blood in the hemodialysis circuit, in routine blood sampling for laboratory tests (for uremia monitoring), and in gut due to uremic enteropathy, invariably results in iron deficiency for which patients are commonly treated with intravenous (IV) iron preparations. Data on the effects of IV iron in hemodialysis patients with hepatitis C are limited (2 studies) and strongly suggest that parenteral iron may contribute to hepatocellular injury. Iatrogenic iron overload is extremely prevalent among hemodialysis population worldwide. Iron overload and toxicity has emerged as one of the most controversial topic in the management of anemia in dialysis patients. Given the known impact of iron in promoting growth and virulence of HCV and the associated liver disease, it is necessary to use iron therapy cautiously and closely monitor plasma markers of iron metabolism and liver iron stores non-invasively by means of MRI to avoid iron overload in this vulnerable population.
-
9.
QUESTION 1: Are paediatric oncology patients at risk of transfusional iron overload?
Rompola, M
Archives of disease in childhood. 2016;(6):586-590
-
10.
Safety Issues in Iron Treatment in CKD.
Vaziri, ND
Seminars in nephrology. 2016;(2):112-8
Abstract
Intravenous iron products are essential for the treatment of anemia in end-stage renal disease patients maintained on hemodialysis. Although proper use of these compounds is necessary for the prevention of iron deficiency, their indiscriminate use could potentially cause insidious adverse consequences. Iron overload can intensify the chronic kidney disease-associated oxidative stress, inflammation, and cardiovascular disease; increase the risk of infections; worsen the severity of type 2 diabetes; and exacerbate neurologic and cognitive dysfunction. These and other adverse effects largely are mediated by iron-catalyzed generation of reactive oxygen species. Unlike conventional oral iron products, the newly released iron-containing phosphate binder ferric citrate has been shown to increase iron stores in end-stage renal disease patients. Therefore, iron indices should be monitored in patients receiving this product. Two published studies have shown a high prevalence of hepatic iron loading among hemodialysis patients treated with erythropoiesis-stimulating agents and intravenous iron compounds. Given the potential risks related to iron treatment in this vulnerable population, studies to better understand safety are needed.