Urinary liver‐type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone‐induced acute kidney injury

Abstract

AimCirculated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L‐FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L‐FABP increase using a more severe mouse model with histone‐induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L‐FABP as a preliminary study.MethodsHuman L‐FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L‐FABP, we used heparin and rolipram.ResultsThe histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L‐FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L‐FABP levels significantly decreased.ConclusionHistone is one of the causative agents for the increase of urinary L‐FABP at an early stage of AKI. In addition, it suggested that urinary L‐FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L‐FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.

Comparative quantitation of liver-type fatty acid-binding protein localizations in liver injury and non-pathological liver tissue in dogs

“…At present, plasma L-FABP is used as a novel biomarker for injury in many organs, especially the kidneys and intestines, which are the main sources of L-FABP production. The study of L-FABP used as a biomarker of acute kidney injury (AKI) showed that urinary L-FABP elevation correlates with the severity of AKI, particularly in the early stages, and can be used for drug administration or tissue transplant monitoring [38,39]. Serum L-FABP and trefoil factor-3 levels decrease in the case of displaced abomasum (DA) in ruminants in contrast with increasing leptin levels.…”

Unravelling the role of urinary liver‐type fatty acid binding protein in histone‐induced AKI

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The recent work by Ohata et al, titled "Urinary liver-type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone-induced AKI," has piqued our interest. 1

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