Cardiac surgery-associated acute kidney injury (AKI) is common and carries a poor
prognosis. Hemodynamic and inflammatory factors and the release of labile iron, contributing
to oxidation from reactive oxygen species are among the major determinants of cardiac
surgery-associated AKI. The diagnosis of AKI is typically delayed because of the limitations
of currently used clinical biomarkers indicating loss of renal function. However,
several novel renal biomarkers, which predict AKI or protection from AKI after cardiopulmonary
bypass (CPB), have been identified as early markers of kidney injury. In this state-of-the-art
review, the authors analyze the pathophysiological implications of recent findings
regarding novel renal biomarkers in relation to CPB-associated AKI. Neutrophil gelatinase-associated
lipocalin, liver-type fatty acid-binding protein, and alpha-1 microglobulin predict
the development of CPB-associated AKI, while hepcidin isoforms appear to predict protection
from it, and these biomarkers are involved in iron metabolism. Neutrophil gelatinase-associated
lipocalin participates in local iron transport. Liver-type fatty acid-binding protein
and alpha-1 microglobulin function as high-affinity heme-binding proteins in different
species, while hepcidin is central to iron sequestration and when increased in the
urine appears to protect from CPB-associated AKI. Free iron-related, reactive oxygen
species-mediated kidney injury appears to be the unifying pathophysiological connection
for these biomarkers. Such novel findings on renal tubular biomarkers were further
combined with other lines of evidence related to hemolysis during CPB, the associated
excess of free heme and iron, knowledge of the effect of free iron on renal tubular
cells, and recent trial evidence targeting free iron-mediated mechanisms of AKI. Novel
biomarkers point toward free iron-mediated toxicity to be an important mechanism of
AKI in patients receiving cardiac surgery with CPB.
Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc.
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