P12
Biological variation of neutrophil gelatinase-associated lipocalin (NGAL) and kidney
injury molecule 1 (KIM-1) in chronic kidney disease (CKD) patients
Carter JL1, Stevens PE2, Knight S2, Eaglestone G2, Farmer CKT2, Lamb EJ1
1
Clinical Biochemistry and 2Kent and Kidney Care Centre, East Kent Hopsitals University
NHS Foundation Trust, Canterbury, Kent, UK.
Introduction: Several novel candidate biomarkers, including neutrophil gelatinase-associated
lipocalin (NGAL) and kidney injury molecule 1 (KIM-1), have been proposed as aids in the
early identification of acute kidney injury (AKI). There are currently no available data
describing the biological variation of these markers in chronic kidney disease (CKD) patients, a
group at increased risk of AKI. We evaluated the individual biological variation (CVi) of KIM1 and NGAL in CKD patients to derive the reference change value (RCV, critical difference)
required to be 95% certain that a change in an individual has occurred.
Methods: Random urine and blood samples were collected weekly for six consecutive weeks
from 40 CKD patients. Whole blood NGAL (wbNGAL) was measured on the same day as
collection using a point of care testing device. Aliquots of plasma and urine were stored at 80oC within four hours of collection. Urinary KIM-1 (uKIM-1), urinary NGAL (uNGAL), and
plasma NGAL (pNGAL) were analysed using commercial immunoassays. Urinary biomarker
data were analysed both as concentrations and as ratios to urinary creatinine. Intraindividual and
analytical (CVA) coefficients of variance and RCV were calculated.
Results: pNGAL exhibited lower CVi than urinary biomarkers (Table 1). The concentration of
serial pNGAL measurements would need to change by 43% between any two measurements
before it can be considered a signifcant change: serial changes in other markers would need to
be greater than this (Table 1). Adjusting urinary biomarker concentrations for urinary creatinine
reduced their biological variability, and consequently their RCV. The analytical variance (CVA)
was acceptable (<6.5%) for all biomarkers except for wbNGAL (18.2%).
Table 1. Estimation of variance components for CKD patients
Biomarker
pNGAL
wbNGAL
uKIM-1
uNGAL
uKIM-1/creatinine
uNGAL1/creatinine
CVI (%)
14.7
20.0
66.0
80.2
28.0
59.2
CVA (%)
5.2
18.2
4.2
5.2
6.4
5.4
RCV (%)
43
75
183
223
80
165
Conclusion: pNGAL exhibits lower CVi compared with urinary biomarker measurements and
may be a more favourable marker for AKI in terms of biological variation: plasma may also be
a more readily available sample than urine in many cases. In comparison, uNGAL and uKIM-1
vary considerably within an individual, even when corrected for creatinine concentration: large
changes are required to confirm a clinical change has occurred. However, the RCV needs to be
interpreted in the light of typical changes observed in clinical studies. It has been reported that
pNGAL and uNGAL increase up to 4-fold and 15-fold respectively in children with AKI after
cardiac surgery: such changes would be detectable against background biological variation.