Tamara van Donge

Kidney injury biomarkers in pediatrics 167 9 Introduction Early detection of drug-related glomerular and tubular kidney injury (KI) is only possible by optimized monitoring of the kidney function. Early KI detection during the reversible stage of kidney damage can avoid chronic kidney diseases. Current clinical established parameters (such as creatinine, estimated glomerular function rate or urine dipstick) used for monitoring of the kidney function are not sensitive enough to detect early tubular damage. As a consequence, there is a considerable risk of delayed diagnosis of drug- related tubular kidney damage. Furthermore, localization of KI with the above-mentioned parameters remains challenging. Over the last decade, the emerging field of clinical proteomics has modernized the identification of novel urine and serum biomarkers to characterize the cause and development of KI. 1 Multiple key markers for KI have been investigated in the adult population and different phases of clinical biomarker evaluation have been established. 1 The first phase includes proof of concept studies (10 markers investigated in 131 studies), demonstrating discrepancies in biomarker concentrations between patients with and without the condition of interest. Phase 2 comprises prospective validation studies to determine the association between the biomarker concentrations and the risk of hard outcomes (9 markers examined in 58 studies). The third phase considers the investigation of the additional predictive value of a key marker (9 markers measured in 64 studies). The subsequent three phases comprise the aspects of clinical incorporation (does the biomarker changes the therapy for at-risk patients, improves outcomes and is cost-effective?). In these final phases, only two studies have been performed in adults on two KI biomarkers, namely neutrophil gelatinase-associated lipocalin (NGAL) and γ-glutamyl transpeptidase. This highlights the need for more randomized clinical trials, not only in adults, but especially in pediatric patients. 1,2 A great advantage of these novel KI biomarkers is the possibility to identify the specific location of KI (Table 1). 3-8 In the pediatric population validated adequate KI biomarkers to early and easily detect KI are lacking in clinical practice. Therefore, biomarker research for the optimized monitoring of the kidney function in neonates, infants, children and adolescents remains an ongoing challenge. A biomarker is defined as a parameter of biochemical, genetic or physiologic change that indicates the presence, severity or progress of a disease. 9 Generally, a biomarker can be measured in urine, serum, plasma or other bodily fluids. An ideal pediatric KI biomarker should meet the following requirements; noninvasive, highly specific and sensitive, early and precise detection of KI, monitor kidney function dependent of age, identify the location of KI, and should have no