Urinary Biomarkers of Renal Injury KIM-1 and NGAL: Reference Intervals for Healthy Pediatric Population in Sri Lanka

Abstract

Emerging renal biomarkers (e.g., kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) are thought to be highly sensitive in diagnosing renal injury. However, global data on reference intervals for emerging biomarkers in younger populations are lacking. Here, we aimed to determine reference intervals for KIM-1 and NGAL across a pediatric population in Sri Lanka—a country significantly impacted by the emergence of chronic kidney disease of unexplained etiology (CKDu). Urine samples were collected from children (10–18 years) with no prior record of renal diseases from the dry climatic zone of Sri Lanka (N = 909). Urinary KIM-1 and NGAL concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) and adjusted to urinary creatinine. Biomarker levels were stratified by age and gender, and reference intervals derived with quantile regression (2.5th, 50th, and 97.5th quantiles) were expressed at 95% CI. The range of median reference intervals for urinary KIM-1 and NGAL in children were 0.081–0.426 ng/mg Cr, 2.966–4.850 ng/mg Cr for males, and 0.0780–0.5076 ng/mg Cr, 2.0850–3.4960 ng/mg Cr for females, respectively. Renal biomarkers showed weak correlations with age, gender, ACR, and BMI. Our findings provide reference intervals to facilitate screening to detect early renal damage, especially in rural communities that are impacted by CKDu.

Early indications on pediatric renal injury: Evidence from biomarkers; Kidney injury molecule-1 and Neutrophil gelatinase associated lipocalin.

“…Particularly in CKDu endemic regions, boys and girls in most of the age strata showed signi cantly higher incidence of elevated urinary KIM-1 levels above the reference intervals reported in the previous study 35 , compared to the children in CKDu non-endemic regions. When considering the entire age range, boys and girls in CKDu endemic regions reported signi cantly higher incidence of elevated KIM-1 levels.…”

“….Here we focused on renal function in a pediatric population in Sri Lanka and report the rst study to use KIM-1 and NGAL to assess renal health. This is an extension of our previous study for de ning reference intervals for urinary KIM-1 and NGAL for the pediatric population in Sri Lanka 35 . The main objective of the present study was to assess the utility of KIM-1 and NGAL to identify early renal injury or renal abnormalities in a pediatric population in CKDu endemic, emerging and non-endemic areas in Sri Lanka.…”

“…As per the reference intervals given in our previous study (50 th quantile at 95% CI) in school children of Sri Lanka 35 , the incidence of elevated biomarker levels above the given reference intervals in each age group is shown in tables 3 and 4.…”

“…Age is given to the date of sample collection. The number of children in each age stratum with urinary KIM-1 levels above the RI (50 th quantile at 90 % CI) given in the previous study 35 for that particular age group is given as N along with its percentage with respect to the total size of the respective study group, endemic, emerging or non-endemic. Similarly, the children with urinary KIM-1 levels above the 97.5 th quantile of RI are given as extreme elevations.…”

“…RI: reference intervals of biomarkers; N T : total number of children in an age stratum within the study group; KIM-1: Kidney injury molecule-1. The number of children in each age stratum with urinary NGAL levels above the RI (50 th quantile at 90 % CI) given in the previous study 35 for that particular age group is given as N along with its percentage with respect to the total size of the respective study group, endemic, emerging or non-endemic. Similarly, the children with urinary KIM-1 levels above the 97.…”