Iron, oxidative stress, and clinical outcomes

It is well known that iron is pro-oxidant. Chronic kidney disease (CKD) is a pro-oxidant state, and intravenous administration of iron is frequently used to correct anemia. On one hand, there is little doubt that iron causes oxidative stress. On the other, it is far from clear whether oxidative stress, so generated, leads to poor clinical outcomes. Iron has benefits that may be independent of the correction of anemia. Furthermore, concerns surround the use of high doses of erythropoietin in causing excess heart failure and death in patients with CKD. Thus, it would be prudent if iron were to continue to be used judiciously in patients who require erythropoietin. Iron, given orally, would be the preferred first-line agent in patients not on hemodialysis. In patients with sepsis, intravenous treatment with iron should be avoided, because, in animal experiments, intravenous administration of iron can compound the inflammatory response and increase mortality. Clinical trials are needed to ascertain the risk and benefits of the intravenous administration of iron in patients with CKD.     

Iron, hepcidin and chronic kidney disease

Iron deficiency is commonly observed in chronic kidney disease. Blood loss and iron consumption under erythropiesis activating agents (ESA) induce absolute deficiency whereas defect of iron intestinal absorption and storage release account for functional deficiency. High hepcidin plasma levels are probably induced by inflammatory process and can explain functional deficiency. However, hepcidin is negatively correlated with ESA needs and hepcidin expression is influenced by other factors as degree of renal insufficiency, iron pool, treatments (iron IV and ESA). IV iron is the common therapeutic approach of iron deficiency and only normalized iron marrow supply cannot account for his efficiency. New IV iron products allow us to conceive new therapeutic schemes. Hepcidin inhibition is another therapeutic alternative.     

Iron deficiency,anemia, and mortality in renal transplant recipients

Anemia, iron deficiency anemia (IDA), and iron deficiency (ID) are highly prevalent in renal transplant recipients (RTR). Anemia is associated with poor outcome, but the role of ID is unknown. Therefore, we aimed to investigate the association of ID, irrespective of anemia, with all‐cause mortality in RTR. Cox regression analyses were used to investigate prospective associations. In 700 RTR, prevalences of anemia, IDA, and ID were 34%, 13%, and 30%, respectively. During follow‐up for 3.1 (2.7–3.9) years, 81 (12%) RTR died. In univariable analysis, anemia [HR, 1.72 (95%CI: 1.11–2.66), P = 0.02], IDA [2.44 (1.48–4.01), P < 0.001], and ID [2.04 (1.31–3.16), P = 0.001] were all associated with all‐cause mortality. In multivariable analysis, the association of anemia with mortality became weaker after adjustment for ID [1.52 (0.97–2.39), P = 0.07] and disappeared after adjustment for proteinuria and eGFR [1.09 (0.67–1.78), P = 0.73]. The association of IDA with mortality attenuated after adjustment for potential confounders. In contrast, the association of ID with mortality remained independent of potential confounders, including anemia [1.77 (1.13–2.78), P = 0.01]. In conclusion, ID is highly prevalent among RTR and is associated with an increased risk of mortality, independent of anemia. As ID is a modifiable factor, correction of ID could be a target to improve survival.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

Successful Treatment of Severe Iron Intoxication with Gastrointestinal Decontamination,Deferoxamine, and Hemodialysis

Acute iron poisoning is a common and potentially serious problem in the pediatric population. Early recognition and treatment is crucial for a better outcome and to prevent morbidity and mortality. An 18-year-old female, who had accidental ingestion of 50 tablets of ferrous sulfate (100 mg of elemental iron per 335 mg tablet), 100 mg/kg of elemental iron, developed acute gastrointestinal and neurologic signs of toxicity and severe anion gap metabolic acidosis. The patient had received gastrointestinal decontamination, deferoxamine (DFO) infusion, and hemodialysis (HD) resulting in a decrease in serum iron concentration from 2150 to 160 mcg/dL at 24-h post-ingestion and improved mental status. Our cases demonstrate that HD may assist in decreasing serum iron concentration and improving clinical status in patients with massive overdose and life-threatening toxicity.     

铁稳态与骨质疏松

铁在机体正常的生理活动中扮演着重要角色，铁稳态调节机制已成为目前铁代谢领域研究的热点。近年研究表明，铁稳态失调（铁过载或铁缺乏）与骨代谢异常密切相关，可导致骨质疏松的发生。因此，将近年“铁介导的骨代谢异常”相关文献进行梳理综述，以期为铁代谢与骨代谢的研究提供一定的参考。     

Obesity Alters Adipose Tissue Macrophage Iron Content and Tissue Iron Distribution

Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe^hi, and the remaining ATMs are referred to as MFe^lo. In lean mice, ~25% of the ATMs are MFe^hi; this percentage decreases in obesity owing to the recruitment of MFe^lo macrophages. Similar to MFe^lo cells, MFe^hi ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe^hi ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe^hi iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe^hi ATM phenotype and their reduced capacity to handle iron.     

再灌注兔脑皮层中Ca^2＋,Mg^2＋和Fe^3＋的变化

为深入认识离子失衡在神经元再灌注损害中的作用，我们测定了兔脑完全性缺血２０ｍｉｎ后再灌注时ＢＣＴ中Ｃａ＾２＋，Ｍｇ＾２＋，和Ｆｅ＾３＋总量的改变。实验动物随机分成未缺血、缺血、再灌注和尼非的平（１０μｇ．ｋｇ＾－１）治疗组。结果显示，与未缺血动物比，Ｃａ＾２＋在再灌注时均升高，以再灌注１２０ｍｉｎ最高，尼非的平可影响Ｃａ＾２＋和Ｆｅ＾３＋可能是早期的主要始动因子之一，而Ｍｇ＾２＋则可能主要始动因子     

Iron metabolism

Iron is a key micronutrient and has a vital role in oxygen transport through its presence in haemoglobin and a key part in oxidative phosphorylation via electron transfer in cytochromes. Total body iron is approximately 4000 mg in a 70-kg man. This goes through a continual cycle of conservation and re-utilization. Syndromes of iron deficiency and overload arise from aberrancy within the steps of iron metabolism.