Iron overload as cardiovascular risk factor in children and adolescents with renal disease

Ruiz-Jaramillo, Ma de la Cruz; Guízar-Mendoza, Juan Manuel; Amador-Licona, Norma; Gutiérrez-Navarro, María; Hernández-González, Martha Alicia; Dubey-Ortega, Luis Antonio; Solorio-Meza, Sergio

doi:10.1093/ndt/gfr044

Cited by 14 publications

(14 citation statements)

References 41 publications

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“…Similar findings have been found in transfusion-dependent anemias, such as sickle-b-thalassemia and myelodysplastic syndromes (33,34). A recent study, however, reported that IO can be a cardiovascular risk factor in children and adults on LTH (35).…”

Section: Discussionsupporting

confidence: 77%

Evidence for tissue iron overload in long‐term hemodialysis patients and the impact of withdrawing parenteral iron

Ghoti

Rachmilewitz

Simon-Lopez³

et al. 2012

European J of Haematology

127

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Background/aims Erythropoiesis in long‐term hemodialyzed (LTH) patients is supported by erythropoietin (rHuEpo) and intravenous (IV) iron. This treatment may end up in iron overload (IO) in major organs. We studied such patients for the parameters of IO in the serum and in major organs. Methods Patients were treated with rHuEpo (6–8 x 103 units × 1–3/wk) and IV 100 mg ferric saccharate. Results Of 115 patients, 21 had serum ferritin (SF) > 1000 ng/mL. This group was further analyzed. Their SF and transferrin saturation (TSAT) were 2688 ± 1489 ng/mL and 54.2 ± 32.7%, respectively (vs. 125–360 ng/mL and 20–50% in normal controls). Serum hepcidin was 60.1 ± 29.5 nm (vs. 10.61 ± 6.44 nm in controls) (P < 0.001). Nineteen patients had increased malonyldialdehyde, a product of lipid peroxidation, indicating oxidative stress. T2* MRI disclosed in 19 of 21 patients moderate to severe IO in the liver and spleen, in three of eight patients in the pancreas, but in no patient in the heart. After stopping IV iron for a mean of 12 months, while continuing rHuEpo, the mean SF decreased in 11 patients to 1682 ng/mL and the mean TSAT decreased to 28%, whereas hemoglobin did not change indicating that tissue iron was utilized. Conclusion High SF correlates with IO in the liver and spleen, but not in the heart.

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Section: Discussionsupporting

confidence: 77%

Evidence for tissue iron overload in long‐term hemodialysis patients and the impact of withdrawing parenteral iron

Ghoti

Rachmilewitz

Simon-Lopez³

et al. 2012

European J of Haematology

127

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“…Due to confounding effects of the acute-phase response on the interpretation of most iron indicators, the assessment of iron status is challenging when concomitant inflammation is present. In fact, serum levels of ferritin were positively correlated with CRP, a measure of inflammation, in children and adults on HD [ 16 , 39 , 40 ]. Under minor inflammation, serum ferritin appears to be a most reliable biomarker of total body iron stores and ID is diagnosed below the cutoff serum ferritin levels of <15 ng/mL in individuals older than 5 years [ 1 ].…”

Section: Biomarkers Of Iron Status and Inflammation In Ckdmentioning

confidence: 99%

“…In support of this hypothesis, inflammation and hyperferritinemia (>500 ng/mL) were associated with cardiovascular and all-cause mortality in HD adults [ 90 ]. In addition, in dialysis children and adolescents with iron overload, ferritin levels showed a positive correlation with inflammation markers (CRP and IL-6) and left ventricular mass (LVM) [ 39 ].…”

Section: Ida In Ckdmentioning

confidence: 99%

“…Higher levels of serum ferritin induced by aggressive IIT may be a cause of increased incidence of atherosclerosis in HD patients [ 171 ]. In dialysis children and adolescents with iron overload, ferritin levels showed a positive correlation with CRP, IL-6 and LVM [ 39 ]. On the other hand, decreased levels of serum hepcidin were associated with a higher LVM index in ND-CKD patients [ 172 ].…”

Section: Role Of Ferritin Hepcidin and Inflammation For The Develmentioning

confidence: 99%

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Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

2018

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Iron deficiency anemia (IDA) is a major problem in chronic kidney disease (CKD), causing increased mortality. Ferritin stores iron, representing iron status. Hepcidin binds to ferroportin, thereby inhibiting iron absorption/efflux. Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability. While intravenous iron therapy (IIT) is superior to oral iron therapy (OIT) in CKD patients with inflammation, OIT is as effective as IIT in those without. Inflammation reduces predictive values of ferritin and hepcidin for iron status and responsiveness to iron therapy. Upper limit of ferritin to predict iron overload is higher in CKD patients with inflammation than in those without. However, magnetic resonance imaging studies show lower cutoff levels of serum ferritin to predict iron overload in dialysis patients with apparent inflammation than upper limit of ferritin proposed by international guidelines. Compared to CKD patients with inflammation, optimal ferritin levels for IDA are lower in those without, requiring reduced iron dose and leading to decreased mortality. The management of IDA should differ between CKD patients with and without inflammation and include minimization of inflammation. Further studies are needed to determine the impact of inflammation on ferritin, hepcidin and therapeutic strategy for IDA in CKD.

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“…Ferritin as an acute-phase reactant is frequently elevated in CKD patients irrespective of their iron stores [49]. Increased serum ferritin levels are the result of systemic inflammation and correlate positively with the severity of inflammation [50,51]. Thus, the interpretation of serum ferritin is complicated by concomitant inflammation [35,45].…”

Section: Assessment Of Iron Statusmentioning

confidence: 99%

Biomarkers of iron metabolism in chronic kidney disease

2020

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Iron is the most abundant transition metal in the human body and an essential element required for growth and survival. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 20 years due to the discovery of hepcidin, which regulates the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Anemia and iron deficiency are common in chronic kidney disease. The pathogenesis of anemia of chronic kidney disease is multifactorial. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. However, there are still many uncertainties in regard to iron metabolism in patients with chronic kidney disease and in renal replacement therapy. The aim of this review was to summarize the current knowledge on iron metabolism in this population, including new biomarkers of iron status. There is an area of uncertainty regarding diagnostic utility of both erythroferrone (ERFE) and hepcidin in end-stage renal disease (ESRD) patients. Higher concentration of hepcidin in oligoanuric patients may reflect decreased renal clearance. Furthermore, the hepcidin-lowering effect of ERFE in ESRD patients treated with erythropoiesis-stimulating agents (ESAs) may be blunted by underlying inflammation and concomitant iron treatment. Thus, future studies should validate the use of ERFE as a biomarker of erythropoiesis and predictor of response to iron and ESA therapy in dialysis-dependent patients.

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Iron overload as cardiovascular risk factor in children and adolescents with renal disease

Abstract: Children and adolescents with iron overload show more CVRFs, especially if they received replacement therapy with HD. Ferritin is related to CRP and IL-6 levels.

Cited by 14 publications

References 41 publications

Evidence for tissue iron overload in long‐term hemodialysis patients and the impact of withdrawing parenteral iron

Evidence for tissue iron overload in long‐term hemodialysis patients and the impact of withdrawing parenteral iron

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

Biomarkers of iron metabolism in chronic kidney disease

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