Przybylowski P, Malyszko J S, Macdougall I C, Malyszko J
Cardiovascular Surgery and Transplantology, Jagiellonian University, Krakow, Poland.
Transplant Proc. 2013 Jan-Feb;45(1):387-90. doi: 10.1016/j.transproceed.2012.02.040.
Functional iron deficiency is characterized by the presence of adequate stores as defined by conventional criteria, but with the inability to sufficiently mobilize iron for erythropoiesis. Hepcidin, produced by hepatocytes in response to anemia, hypoxia, or inflammation, is a key regulator of iron homeostasis. Anemia is relatively common among patients treated with mammalian target of rapamycin (mTOR) antagonists. We tested hypothesis that hepcidin was related to the functional iron deficiency, defined as a ferritin value above 200 ng/mL with transform saturation (TSAT) below 20% among orthotopic heart transplant recipients (OHT) treated (n = 35) versus not treated (n = 134) with mTOR.
Using standard laboratory methods we assessed iron status: serum iron, total iron binding capacity, ferritin, TSAT, complete blood count and creatinine. Soluble transferrin receptor (sTFR), high sensitivity C-reactive protein (hSCRP), interleukin-6 (IL-6) hepcidin, and cystatin C were measured using commercially available kits.
According to the World Health Organization definition, the prevalence of anemia was 51% among mTOR treated whereas in the rest of the OHT the prevalence of anemia 30% among the other OHT patients. Functional iron deficiency was present in 80% of mTOR-treated patients. Serum hepcidin, IL-6, hsCRP, serum creatinine, cystatin C, NT-proBNP were significantly higher among mTOR treated patients; whereas sTFR, estimated glomerular filtration rate, hemoglobin, and erythrocyte count were significantly lower.
Functional iron deficiency which is common among OHT patients treated with mTOR, was associated with high hepcidin levels and inflammatory markers. This form of anemia in mTOR-treated OHT resembles the disorder of chronic disease, suggesting that OHT patients show low-grade inflammation, which should be investigated for underlying, potentially reversible causes. Iron treatment should also be considered.
功能性缺铁的特征是按照传统标准有充足的铁储备，但无法充分动员铁用于红细胞生成。肝细胞在贫血、缺氧或炎症反应时产生的铁调素是铁稳态的关键调节因子。贫血在接受雷帕霉素靶蛋白（mTOR）拮抗剂治疗的患者中相对常见。我们检验了以下假设：在接受（n = 35）和未接受（n = 134）mTOR治疗的原位心脏移植受者（OHT）中，铁调素与功能性缺铁有关，功能性缺铁定义为铁蛋白值高于200 ng/mL且转铁蛋白饱和度（TSAT）低于20%。
我们使用标准实验室方法评估铁状态：血清铁、总铁结合力、铁蛋白、TSAT、全血细胞计数和肌酐。使用市售试剂盒检测可溶性转铁蛋白受体（sTFR）、高敏C反应蛋白（hSCRP）、白细胞介素-6（IL-6）、铁调素和胱抑素C。
根据世界卫生组织的定义，mTOR治疗组贫血患病率为51%，而其他OHT患者中贫血患病率为30%。80%接受mTOR治疗的患者存在功能性缺铁。mTOR治疗组患者的血清铁调素水平、IL-6、hsCRP、血清肌酐、胱抑素C、N末端脑钠肽前体（NT-proBNP）显著更高；而sTFR、估计肾小球滤过率、血红蛋白和红细胞计数显著更低。
在接受mTOR治疗的OHT患者中常见的功能性缺铁与高铁调素水平和炎症标志物有关。mTOR治疗的OHT患者中的这种贫血形式类似于慢性病紊乱，提示OHT患者存在低度炎症，应调查其潜在的、可能可逆的病因。还应考虑铁治疗。
