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New lab test
predicts risk of Kidney Injury after surgery
Newswise — A simple
laboratory test may provide a new way for
doctors to identify patients at risk of
developing potentially severe acute kidney
injury (AKI) after surgery—up to three days
before the problem would otherwise be
detected, reports a pilot study in the May
2008 issue of the Clinical Journal of the
American Society of Nephrology.
The test, which
measures a biomarker called "neutrophil
gelatinase-associated lipocalin" (NGAL), may
permit earlier treatment, giving a chance to
prevent or improve outcomes of postoperative
AKI.
"Urine NGAL represents a powerful early
predictive marker of AKI, preceding the
increase in serum creatinine—the current
gold standard—by several hours to days,"
comments Dr. Prasad Devarajan of Cincinnati
Children's Hospital Medical Center, one of
the study authors.
The researchers
measured NGAL in urine samples from 196
children undergoing cardiopulmonary bypass (CPB)
during surgery to repair congenital heart
defects. Cardiopulmonary bypass is a major
risk factor for AKI, a serious complication
that can cause death or permanent loss of
kidney function.
Fifty-one percent of
the children in the study developed AKI.
This diagnosis was based on increased levels
of the breakdown product creatinine, which
did not occur until two or three days after
CPB.
In contrast, urine NGAL
levels began to increase within a few hours
in children who developed AKI. For this
group, NGAL increased 15 times higher than
normal within two hours after CPB, and 25
times higher by four hours.
Increases in urine NGAL
were highly accurate in predicting risk of
AKI. The NGAL level at two hours identified
90 percent of children who later developed
AKI. Urine NGAL also predicted the severity
of AKI—children with higher NGAL levels were
at higher risk of death, were more likely to
require dialysis, and had a longer time to
recovery of kidney function.
An important part of
the study was the incorporation of urine
NGAL measurement into a standard system for
monitoring patients during surgery. Previous
studies had linked NGAL levels to AKI risk,
but the NGAL test used was not practical for
routine clinical use.
The standardized
laboratory platform for measuring NGAL
levels in this study (ARCHITECT® assay,
Abbott, under development) requires only a
few drops of urine and provides results in
35 minutes.
The new test could be a
major advance in identifying patients at
risk of developing AKI after surgery or
trauma, and in other situations commonly
seen in critically ill patients.
"An early
elevation in urine NGAL would trigger an
immediate shift in clinical management,
making caregivers aware of the high
potential for development of clinical AKI,"
says Dr. Devarajan.
With close
monitoring—including treatments to ensure
good blood flow to the kidneys and avoidance
of potentially toxic drugs—it might be
possible to prevent AKI from developing.
"The availability of an
early biomarker like NGAL might also enable
the timely initiation of interventions such
as atrial natriuretic peptide and
insulin-like growth factor," adds Dr.
Devarajan.
Previous studies have yielded
mixed results as to whether these treatments
can improve kidney function in patients with
AKI—Dr. Devarajan speculates that they might
be more effective if started at the onset of
AKI.
The early information provided by NGAL
might also promote testing of other
promising treatments for AKI. NGAL
measurements may also provide predictive
kidney safety biomarker in future drug
development processes.
Confirmatory research
is needed, including studies of adults and
patients with certain characteristics
putting them at high risk of AKI, such as
pre-existing kidney dysfunction, diabetes,
and potentially toxic drugs.
Dr. Devarajan is
supported by grants from the National
Institutes of Health’s National Institute of
Diabetes and Digestive and Kidney Diseases,
a Grant-in-Aid from the American Heart
Association Ohio Valley Affiliate, and a
Translational Research Initiative Grant from
Cincinnati Children’s Hospital Medical
Center.
This work was supported in part by a
restricted research grant from Abbott.
The study was conducted
by researchers at Cincinnati Children’s
Hospital Medical Center, the University of
Cincinnati College of Medicine, Abbott
(Abbott Park, Ill.), and the College of
Physicians and Surgeons, Columbia University
(New York, N.Y.).
The American Society of
Nephrology (ASN) is a not-for-profit
organization of 10,500 physicians and
scientists dedicated to the study of
nephrology and committed to providing a
forum for the promulgation of information
regarding the latest research and clinical
findings on kidney diseases.
ASN publishes
the Journal of the American Society of
Nephrology (JASN), the Clinical
Journal of the American Society of
Nephrology (CJASN), and the Nephrology
Self-Assessment Program (NephSAP).
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