Abstract
Objectives
The 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.
Methods
A 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).
Results
ALB 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.
Conclusions
This 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.
Acknowledgments
We like to thank all patients and parents, physicians, nurses and other medical staff from the short stay units and the hospital wards together with the Departments of Surgery, Anesthesia, ENT and Orthopedics for facilitating blood sample collections and participant recruitment. Thomas Erlanger (Clinical Trial Unit, Department of Clinical Research) is acknowledged for his assistance concerning the sample size calculation. Additionally, we want to thank Mrs. Hillmann for her assistance regarding the lab measurements. We also like to thank the study nurses from the Ambulatory Study Center for their assistance with participant recruitment and sample preparation.
Research funding: This project has been supported by the Eckenstein-Geigy Foundation and was part of the national SwissPedNet and SwissPedPha consortia. This funding organizations played no role in the study design; in the collection, analysis and interpretation of the data or in the writing of the manuscript.
Author contributions: TVD, ES, JVDA, TW and MP conceived and designed the study. TVD and TW collected the data and were responsible for data management. LR provided the means for the analysis for the samples. TVD, VG and AA performed the statistical analysis. TVD, ES, VG, JVDA, TW and MP contributed to the interpretation of the results. TVD and TW wrote the draft of the manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Study protocol was approved by the local Ethics Committee (EKNZ BASEC 2016-00884).
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0781).
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