Louvain Centre for Toxicology and Applied Pharmacology, Brussels, Belgium.
Intensive Care Med. 2012 Mar;38(3):467-73. doi: 10.1007/s00134-011-2449-0. Epub 2012 Jan 12.
A significant fraction of patients with acute liver failure (ALF) suffer from a concomitant acute kidney injury (AKI), the mechanism of which is probably multifactorial. Cadmium (Cd) is a widespread environmental pollutant and a tubulotoxic metal that accumulates in the liver. We tested the hypothesis that a release of Cd during ALF may cause a redistribution of Cd from the liver to the kidneys and play a role in the occurrence of ALF-associated AKI.
Twenty patients with ALF (ALF-patients), 20 patients from the ICU with no liver damage at admission (ICU-controls) and 20 healthy controls were recruited to compare the 24-h urinary excretion rate of Cd with that of lead (Pb), a nephrotoxic metal that does not accumulate in the liver, and zinc (Zn), a non-nephrotoxic element found in high amounts in the liver. The excretion rates of the low-molecular-weight proteins (LMWPs) were monitored.
ALF-patients excreted markedly more Cd than the healthy controls and ICU-controls. In ALF-patients, the four urinary LMWPs (RBP, β2-MG, CC16 and α1-MG) increased as a function of Cd excretion, with high correlation coefficients. The prevalence of patients excreting a high amount of LMWPs also increased with increasing Cd excretion. No relationship was found between the other elements investigated and the LMWPs, with the exception of copper, which shares close toxicokinetic similarities with Cd.
This study shows a strong association between urinary Cd levels and the excretion rates of LMWPs in patients with ALF. A causal relationship is possible but could not be fully demonstrated in this study.
急性肝衰竭（ALF）患者中有相当一部分伴有急性肾损伤（AKI），其发病机制可能是多因素的。镉（Cd）是一种广泛存在的环境污染物和肾小管毒性金属，在肝脏中蓄积。我们检验了这样一个假设，即在 ALF 期间释放的 Cd 可能导致 Cd 从肝脏重新分布到肾脏，并在 ALF 相关 AKI 的发生中发挥作用。
招募了 20 名 ALF 患者（ALF 患者）、20 名入院时无肝损伤的 ICU 患者（ICU 对照组）和 20 名健康对照者，以比较 24 小时尿镉排泄率与铅（Pb）和锌（Zn）的排泄率。Pb 是一种肾毒性金属，不会在肝脏中蓄积，而 Zn 是一种大量存在于肝脏中的非肾毒性元素。监测了低分子量蛋白（LMWP）的排泄率。
ALF 患者的 Cd 排泄量明显高于健康对照组和 ICU 对照组。在 ALF 患者中，四种尿 LMWP（RBP、β2-MG、CC16 和 α1-MG）随 Cd 排泄量的增加而增加，相关性很高。排泄大量 LMWP 的患者的患病率也随 Cd 排泄量的增加而增加。除了与 Cd 具有密切毒代动力学相似性的铜之外，未发现其他元素与 LMWP 之间存在关系。
本研究表明 ALF 患者尿 Cd 水平与 LMWP 排泄率之间存在很强的相关性。因果关系是可能的，但在本研究中无法完全证明。
