Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents

Abstract

ObjectivesThe use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents.MethodsA single center prospective observational study was conducted between December 2018 and June 2019. Serum samples from 142 healthy infants, children and adolescents aged between 0 and ≤15 years were collected. Statistical analyses for eight markers (albumin (ALB), β2-microglobulin (B2M), β-trace protein (BTP), creatinine (SCR), cystatin C (CYSC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (URO)) were performed to obtain reference intervals and associations with age, sex and weight were investigated (Pearson correlation, linear and piecewise regression).ResultsALB and SCR increased with age (p<0.01), whereas B2M, BTP and KIM-1 values decreased with advancing age (p<0.05) in this healthy pediatric study population. CYSC showed dependency on sex (lower concentration in females) and decreased with age until reaching approximately 1.8 years; thereafter an increase with age was seen. NGAL and URO did not show any age-dependency.ConclusionsThis study provides age appropriate reference intervals for key serum kidney function and injury markers determined in healthy infants, children and adolescents. Such reference intervals facilitate the interpretation of changes in kidney function and injury markers in daily practice, and allow early detection of glomerular and tubular injury in infancy, childhood and adolescence.

The Predicted Value of Kidney Injury Molecule-1 (KIM-1) in Healthy People

“…Some researchers established reference intervals in particular sections or populations in recent years. 14 , 15 In our research, including KIM-1, biomarkers of 176 participants’ age distributed evenly and considered healthily were detected for correlation analysis with age. It had a moderate correlation with age ( r =0.41), independent with gender, suggesting it is a common phenomenon in the population.…”

The Assessment of the Usefulness of Selected Markers in the Diagnosis of Chronic Kidney Disease in Children

“…Similarly, van Donge et al did not show significant differences in the serum values of UMOD, NGAL, and KIM-1 between healthy boys and girls. 53 In contrast, Bennett et al 54 reported statistically significant higher values of uNGAL in girls than boys. A similar relationship was not observed for KIM-1 level.…”

“…This study did not show any NGAL and UMOD age-dependency. 53 Scherberich et al 22 showed similarity of uromodulin serum levels in adults and children. In the group of 190 healthy adult patients, the mean sUMOD level was 207 ng/ml, whereas in pediatric population of 443 patients it was 193 ng/ml, and the difference was statistically insignificant.…”

Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper

“…210 Recognition and quantification of adverse events of the kidney necessitate age-appropriate reference intervals of kidney function and injury markers. 211,212 Besides these preclinical models might offer add-on benefit (e.g. to separate the impact of asphyxia vs. hypothermia on PK).…”