Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Biomarkers for the early detection of acute kidney injury
Acute kidney injury (AKI) is largely asymptomatic, and
establishing the diagnosis in this increasingly common
disorder currently hinges on functional biomarkers such
as serum creatinine. Unfortunately, serum creatinine is
a delayed and unreliable indicator of AKI for a variety
of reasons [1–4]. This is a problem, because animal
studies have identified several interventions that can
prevent and/or treat AKI if instituted early in the
disease course, well before the serum creatinine begins
to rise . The paucity of early structural injury bio-
markers has hampered our ability to translate these
promising therapies to human AKI, which now com-
plicates about 5% of all hospitalizations [2–6]. The
incidence of AKI in the pediatric intensive care unit
(PICU) is even higher, afflicting about 10% of all
children admitted to a PICU [7?] and 82% of the most
severely ill children . AKI on admission to the PICU
is associated with a greater than five-fold increased risk
of mortality, and development of AKI during a PICU
stay is associated with a nine-fold increase in mortality
and a four-fold increase in length of hospital stay [7?,9].
Biomarkers of AKI that are capable of early detection,
risk stratification, and prognostication would represent
a tremendous advance in the care of this highly vulner-
Clinically applicable AKI biomarkers should be nonin-
vasive, using easily accessible samples such as blood or
urine; rapidly measurable using standardized clinical
assay platforms; sensitive to facilitate early detection,
with a wide dynamic range and cut-off values that allow
risk stratification; specific for AKI, to differentiate intrin-
sic AKI from prerenal azotemia and chronic kidney
disease; predictive of clinical outcomes such as need
for dialysis, length of hospital stay, and mortality; able
to guide initiation of therapies; and should facilitate
monitoring the response to interventions [10–13]. For-
tunately, understanding the early stress response of the
that inform early pathophysiology, and, serendipitously,
represent potential biomarkers [14,15]. The current sta-
tus of the most promising of these novel AKI biomarkers,
(NGAL), kidney injury molecule-1 (KIM-1), liver-type
fatty acid binding protein (L-FABP) and interleukin
(IL)-18, is appraised in this review.
Center for Acute Care Nephrology, Cincinnati
Children’s Hospital Medical Center, University of
Cincinnati School of Medicine, Cincinnati, Ohio, USA
Correspondence to Prasad Devarajan, MLC 7022,
3333 Burnet Avenue, Cincinnati, OH 45229-3039,
Tel: +1 513 636 4531; fax: +1 513 636 7407;
Current Opinion in Pediatrics 2011, 23:194–200
Purpose of review
Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which
depends on serum creatinine, which is a delayed and unreliable indicator of AKI.
Fortunately, understanding the early stress response of the kidney to acute injuries has
revealed a number of potential biomarkers. The current status of the most promising of
these novel AKI biomarkers, including neutrophil gelatinase-associated lipocalin
(NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP),
and interleukin (IL)-18, is reviewed.
early prediction of AKI, for monitoring clinical trials in AKI, and for the prognosis of AKI in
several common clinical scenarios. However, biomarker combinations may be required
to improve our ability to predict AKI and its outcomes in a context-specific manner.
It is vital that additional large future studies demonstrate the association between
biomarkers and hard clinical outcomes independent of serum creatinine concentrations
and that randomization to a treatment for AKI based on high biomarker levels results in
an improvement in clinical outcomes.
acute kidney injury, acute renal failure, biomarker, interleukin-18, kidney injury
molecule-1, liver-type fatty acid binding protein, neutrophil gelatinase-associated
Curr Opin Pediatr 23:194–200
? 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
1040-8703 ? 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MOP.0b013e328343f4dd
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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