Tamara van Donge

Abstract Currently used creatinine-based parameters for monitoring kidney function are not reliable for early detection of kidney injury (KI), particularly tubular damage. Several KI biomarkers allow for early detection of glomerular and tubular damage and may help to prevent drug-related chronic kidney diseases in pediatrics. This literature review describes the state of current research, and investigates reference values for these KI biomarkers in neonates, infants and children to better understand age-related changes. A total of 12 out of 237 screened studies fulfilled predefined criteria including 219 preterm neonates, 70 neonates, 596 infants and 1726 children. KI biomarkers were analyzed in urine (6 studies), in serum/plasma (5 studies) and in serum and urine (1 study). Four studies (n=555) measured urinary kidney injury molecule-1 (KIM-1), whereas urinary neutrophil gelatinase-associated lipocalin (NGAL) was assessed in five studies (n=888) and two studies (n=203) investigated serum cystatin C. This review of KI biomarkers in different pediatric age groups indicates that (i) the majority of KI biomarkers are measured in urine, (ii) the three most commonly analyzed KI biomarkers are urinary NGAL, urinary KIM-1 and serum cystatin C, (iii) values of KI biomarkers appear to decrease from prematurity to infancy, and (iv) there is an unmet need to further enhance knowledge on age-dependent changes of KI biomarkers in pediatrics. Studies are needed to better characterize reference values for these key KI biomarkers in healthy pediatric populations and to evaluate the value of these markers in the early detection of drug-related kidney injury in neonates, infants and children. Key words: age-effect, biomarkers, kidney injury, pediatrics, reference values