van Landeghem G F, D'Haese P C, Lamberts L V, Djukanovic L, Pejanovic S, Goodman W G, De Broe M E
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
Clin Nephrol. 1998 Aug;50(2):69-76.
Using an HPLC/ETAAS hybrid speciation technique we previously demonstrated iron to have a multifold effect on the binding of aluminum to transferrin by limiting the number of available binding sites and decreasing the affinity of transferrin for aluminum. Theoretically, at a 60% iron-transferrin saturation the aluminum-transferrin fraction in serum should not exceed 30 microg/l. In the present study previous experimental data were confronted with recent clinical observations in patients with either normal iron status or iron overload.
Serum aluminum levels and iron overload: In 38 dialysis patients with a normal iron status and of whom 63% received Al(OH)3 for phosphate binding 26 (68%) had a serum aluminum level >30 microg/l. On the other hand out of 28 transfusional iron overloaded patients; 68% of them taking Al(OH)3, only 1 subject (4%) had a serum aluminum value in excess of 30 microg/l. Taking patients of both groups receiving Al(OH)3 together a significant (p = 0.001) negative correlation (r = -0.5017) was found between the iron-transferrin saturation and the serum aluminum levels. Iron status and parenteral aluminum loading: Also could a significant (p = 0.001) negative correlation (r = -0.6383) between these parameters be found in an independent group of 44 patients which were acutely intoxicated by the use of aluminum-contaminated dialysis fluids. Since in this population aluminum loading occurred parenterally and not via the gastrointestinal tract, a direct effect of iron on the transferrin binding of aluminum rather than on the element's gastrointestinal absorption must have been responsible for the inverse relationship. Bone aluminum and iron overload: Out of 22 patients with a normal iron status (mean + SD serum ferritin: 216 +/- 245 microg/l; iron-transferrin saturation 20.4 +/- 9.6%), all of them having aluminum overload (bone aluminum level >15 microg/g and/or positive Aluminon staining) none of them presented with a serum aluminum <30 microg/l (mean +/- SD: 82.2 +/- 51.6 microg/l). On the other hand out of 13 iron overloaded patients (serum ferritin >800 microg/l; iron-transferrin saturation 61.4 +/- 17.6%) 10 (77%) presented the proposed criteria of aluminum overload in the presence of a serum aluminum level <30 microg/l.
Our data indicate that in dialysis patients with iron overload (iron-transferrin saturation >60%; serum ferritin >800 microg/l) serum aluminum levels are low (<30 microg/l) despite exposure to aluminum by the intake of Al(OH)3 or the use of aluminum-contaminated dialysis fluids. Low serum aluminum nevertheless may be associated with aluminum overload and even aluminum-related bone disease. An effect of iron on the serum aluminum speciation may at least in part explain our observations. Our findings allow a more accurate interpretation of baseline serum aluminum values.
我们之前使用高效液相色谱/电热原子吸收光谱联用的形态分析技术证明，铁通过限制可用结合位点的数量并降低转铁蛋白对铝的亲和力，对铝与转铁蛋白的结合具有多重影响。理论上，当铁-转铁蛋白饱和度为60%时，血清中铝-转铁蛋白部分不应超过30微克/升。在本研究中，将先前的实验数据与近期对铁状态正常或铁过载患者的临床观察结果进行了对比。
血清铝水平与铁过载：在38名铁状态正常的透析患者中，63%接受氢氧化铝用于结合磷酸盐，其中26名（68%）患者的血清铝水平>30微克/升。另一方面，在28名输血性铁过载患者中，68%服用氢氧化铝，只有1名患者（4%）的血清铝值超过30微克/升。将两组接受氢氧化铝的患者合并在一起，发现铁-转铁蛋白饱和度与血清铝水平之间存在显著的（p = 0.001）负相关（r = -0.5017）。铁状态与胃肠外铝负荷：在另一组44名因使用受铝污染的透析液而急性中毒的患者中，也发现这些参数之间存在显著的（p = 0.001）负相关（r = -0.6383）。由于在该人群中铝负荷是通过胃肠外途径而非胃肠道发生的，铁对铝与转铁蛋白结合的直接作用而非对元素胃肠道吸收的作用必定是导致这种负相关关系的原因。骨铝与铁过载：在22名铁状态正常的患者中（血清铁蛋白均值±标准差：216±245微克/升；铁-转铁蛋白饱和度20.4±9.6%），所有患者均存在铝过载（骨铝水平>15微克/克和/或铝试剂染色阳性），他们的血清铝均≥30微克/升（均值±标准差：82.2±51.6微克/升）。另一方面，在13名铁过载患者中（血清铁蛋白>800微克/升；铁-转铁蛋白饱和度61.4±17.6%），10名（77%）患者在血清铝水平<30微克/升时符合铝过载的既定标准。
我们的数据表明，在铁过载（铁-转铁蛋白饱和度>60%；血清铁蛋白>800微克/升）的透析患者中，尽管通过摄入氢氧化铝或使用受铝污染的透析液接触了铝，但血清铝水平仍较低（<30微克/升）。血清铝水平低仍可能与铝过载甚至铝相关骨病有关。铁对血清铝形态的影响可能至少部分解释了我们的观察结果。我们的发现有助于更准确地解读基线血清铝值。
