157P Queen Elizabeth II Conference Centre London
Pharmacology 2013

 

 

Reference Intervals For Urinary Kidney Injury Molecule-1 And Neutrophil Gelatinase-Associated Lipocalin In Children

SJ McWilliam*1, DJ Antoine1, RL Smyth2, M Pirmohamed1. 1University of Liverpool, UK, 2University College London, UK

There is increasing interest in a number of novel urinary biomarkers which are not only more sensitive than serum creatinine for the identification of drug induced kidney injury, but can also indicate the site of damage to different portions of the nephron. The aim of this study was to describe reference intervals in healthy children for two of these biomarkers, urinary Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL).

120 healthy children were recruited in Liverpool, UK, and provided at least one urine sample each. 39 provided multiple samples over several weeks (including a set of paired morning and evening samples). Urinary KIM-1 and NGAL were measured using Meso Scale Discovery analytical platforms. Biomarker values were normalised to urinary creatinine. Reference intervals are reported by partition (age and sex) where there exist significant differences (p<0.05) between groups. Whilst NGAL concentration was significantly associated with sex, KIM-1 concentration was not. Both showed significant variation with age.

Table 1. Biomarker reference intervals

Biomarker and partitions

95% RI (90% CI of UL), ng/mg Cr

KIM-1

0.09-2.07 (1.68-2.54)

 - Age 0-4 years

0.10-4.08 (2.42-6.87)

 - Age 5-16 years

0.09-1.59 (1.29-1.96)

NGAL

1.23-93.66 (70.40-124.59)

 - Female

2.75-133.98 (91.78-195.57)

 - Male

1.01-42.46 (30.40-59.31)

 - Female, age 0-4 years

3.40-128.76 (62.63-264.73)

 - Female, age 5-12 years

2.26-69.04 (43.85-108.68)

 - Female, age 13-16 years

14.02-172.13 (102.58-288.83)

 - Male, age 0-4 years

0.97-126.19 (48.05-331.42)

 - Male, age 5-12 years

1.48-17.32 (12.81-23.42)

 - Male, age 13-16 years

0.83-64.80 (30.46-137.83)

(RI, Reference Interval. CI, Confidence Interval. UL, Upper Limit. Cr, Urinary Creatinine)

KIM-1 was less variable within individuals than NGAL (KIM-1 Intra-individual standard deviation (SD); 0.16ng/mg Cr, 95% CI, 0.12-0.22ng/mg Cr. NGAL Intra-individual SD; 3.84ng/mg Cr, 95% CI, 2.57-5.74ng/mg Cr). KIM-1 showed significant diurnal variation (Mean morning KIM-1; 0.77ng/mg Cr, 95% CI, 0.61-0.97ng/mg Cr. Mean evening KIM-1; 0.47ng/mg Cr, 95% CI 0.36-0.62ng/mg Cr. p<0.001).

As an important step in their validation for use in children to identify drug induced kidney injury, we have reported reference intervals for urinary KIM-1 and NGAL in a healthy paediatric population.