Tamara van Donge

Kidney injury biomarkers in pediatrics 169 9 Serum creatinine is the most widely used marker for monitoring KI, whereas glomerular filtration rate is established as a standard measure of KI. The most accurate determination of measured glomerular filtration rate requires injection of an exogenous marker, such as inulin or iohexol and their measurement of elimination over time. This cumbersome method is often not feasible in clinical practice, especially not in pediatric patients. Therefore, in children the Schwartz formula is used more often. 10 It provides the estimated glomerular filtration rate and is based on the child`s height and serum creatinine values, a by-product of muscle metabolism eliminated through glomerular filtration. 10 Unfortunately, estimated glomerular filtration rate and serum creatinine are both unreliable and inaccurate markers for monitoring of kidney function and detecting KI in pediatric populations for the following reasons; (i) approximately 50% of renal parenchymal loss must occur before serum creatinine changes can be detected, (ii) serum creatinine can be influenced by muscle mass variation, nutrition, age and sex, (iii) during the first days of life serum creatinine rather reflects the maternal kidney function instead of the kidney function of the neonate, (iv) overestimation of kidney function is possible in patients with cachexia, and (v) serum creatinine does not allow the exact localization, nor the extent of KI. 11-23 Understanding age-dependent changes in pediatrics Kidney function comprises three main processes. First, glomerular filtration is responsible for the filtration of the plasma across the glomerular membrane into the renal tubule. Second, tubular excretion transporters can increase the excretion of drug molecules by more actively transport from the plasma into the tubule. Third, tubular reabsorption ensures the reabsorption of small molecules (e.g. glucose, sodium) and water by passive diffusion back into the plasma. Each of these three processes is affected by different rates of development and maturation in pediatrics. 24,25 Although in term neonates, the kidney contains the full collection of nephrons at birth, many developmental changes occur during the first weeks and months of life, which influence the glomerular filtration rate, tubular excretion and reabsorption. 25 Kidney function relies on high renal blood flow across a large glomerular endothelial surface area followed by extremely active tubular reabsorption and secretion, therefore kidney cells are at a high risk for drug-related injury. 26 A biomarker is usually developed in an adult population and over time validated in the pediatric population. These validation studies, where appropriate references ranges are obtained for neonates, infants and children, can take many years. Up to now KI biomarker research shows much less efforts in investigating KI biomarkers in pediatrics and developing age-adjusted references ranges as well as threshold cut-off values as compared to adults. 2 Extrapolation of KI biomarkers established in adults to the pediatric population incorrectly assumes that adult and pediatric kidney diseases are identical, and that maturational and physiological changes can be neglected. 24 One of the reasons for