Sirolimus interferes with iron homeostasis in renal transplant recipients
Sirolimus interferes with iron homeostasis in renal transplant recipients
复制标题
DOI：
10.1097/01.tp.0000235545.49391.1b
复制
发表时间：
2006-10-15
期刊：
影响因子：
6.2
通讯作者：
Grandaliano, Giuseppe
中科院分区：
文献类型：
--
作者：
Maiorano, Annamaria;Stallone, Giovanni;Grandaliano, Giuseppe
背景资料。西罗莫司是一种免疫抑制药物，其使用经常与贫血有关。西罗莫司引起的贫血和炎症状态的出现之间的致病联系最近被提出。由于炎症性贫血的特征是功能性缺铁，我们调查了西罗莫司是否会影响铁的稳态和血清中的海普西丁水平，而海普西丁是炎症性贫血的关键介质。为此，42名经活检证实为慢性移植物肾病的连续移植患者被随机分为两组，一组接受40%环孢素减量(A组，14例)，另一组立即停用环孢素加西罗莫司(B组，28例)。在随机化前和随机化后6个月评估患者的血红蛋白水平和铁状态。两组在基线时的血红蛋白水平和铁状态相似。在随机分组后，我们没有观察到A组患者的血红蛋白和铁状态有任何显著变化。相反，我们观察到在引入西罗莫司后，血红蛋白显著减少，而红细胞计数没有任何变化，平均红细胞体积和平均红细胞血红蛋白显著减少。转换后血清铁和转铁蛋白饱和度(TSAT)水平显著降低，而血清铁蛋白浓度保持稳定。尽管西罗莫司引起的贫血最近被认为类似于炎症相关性贫血，但随机分组后，两组患者的血清海普西丁水平相似。A组和B组中的8例患者均未出现TSAT<；20，经随机分组后给予补铁治疗，所有患者的口服铁剂治疗均不影响血红蛋白和血清铁水平。我们证明，西罗莫司诱导的贫血不依赖于药物的抗增殖作用，并且不呈现炎症相关性贫血的特征。这一事件可能是由于西罗莫司对铁稳态的直接影响。
Background. Sirolimus is an immunosuppressive drug whose use is frequently associated with anemia. A pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we investigated whether sirolimus may influence iron homeostasis and serum levels of hepcidin, a key mediator of inflammation-related-anemia.Methods. To this purpose, 42 consecutive transplanted patients with biopsy-proven chronic allograft nephropathy were randomized (2:1 ratio) to receive either a 40% cyclosporine reduction (group A, 14 patients) or immediate cyclosporine withdrawal and sirolimus introduction (group B, 28 patients). Hemoglobin levels and iron status were evaluated 6 months before and after randomization.Results. The two groups had similar hemoglobin levels and iron status at baseline. We did not observe any significant change in hemoglobin and iron status in group A patients after randomization. On the contrary, we observed a significant reduction of hemoglobin without any change of red blood cell count after sirolimus introduction, with a significant reduction of mean corpuscular volume and mean corpuscular hemoglobin. Serum iron and transferrin saturation (TSAT) levels were markedly reduced after the switch, while ferritin serum concentrations remained stable. Although sirolimus-induced anemia was recently suggested to resemble inflammation-related anemia, hepcidin serum levels were similar in the two groups after randomization. None of group A and eight of group B patients presented a TSAT < 20 and were given iron supplementation after randomization, in all of them oral iron therapy did not influence either hemoglobin or serum iron levels.Conclusion. We demonstrated that sirolimus-induced anemia is independent of the drug antiproliferative effect and does not present the features of inflammation-related anemia. This event maybe due to the direct influence of sirolimus on iron homeostasis.