title: Acute kidney injury following acute liver failure: potential role of systemic cadmium mobilization?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology, Brussels, Belgium.
authors.forename: Perrine
authors.initials: P
authors.lastname: Hoet
authors.forename: Vincent
authors.initials: V
authors.lastname: Haufroid
authors.forename: Gladys
authors.initials: G
authors.lastname: Deumer
authors.forename: Xavier
authors.initials: X
authors.lastname: Dumont
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantson
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology / Q000652:urine*; D000328:Adult; D000368:Aged; D001530:Belgium; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity / Q000652:urine*; D016022:Case-Control Studies; D015897:Comorbidity; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D007854:Lead / Q000652:urine; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000150:complications / Q000652:urine*; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D015032:Zinc / Q000652:urine
chemical_list: D004785:Environmental Pollutants; D002104:Cadmium; D007854:Lead; D015032:Zinc