Nenatal Drug Induced Nephrotoxicity: Old and Next Generation Biomarkers for Early Detection and Management of Neonatal Drug-Induced Nephrotoxicity, with Special Emphasis on uNGAL and on Metabolomics

For a long time, nephrotoxicity has been definitively defined as renal injury or dysfunction that arises as a direct or indirect result of exposure to drugs and industrial or environmental chemicals. There are a number of inherent difficulties in diagnostic procedures for toxic nephropathy, which include the absence of standard diagnostic criteria and the inability to relate exposure to a given agent and the observed effect. Critically ill newborns represent a high risk population for developing toxic nephropathy because of incomplete maturation of the kidney; furthermore, they are often treated with a combination of various therapeutic agents, each of them potentially inducing renal tissue injury. Antibiotics, antifungals, and non-steroidal antiiflammatory drugs (NSAIDs) can induce nephrotoxic damage by several, concomitant mechanisms of action on different segments of the nephron. The most common clinical feature following a nephrotoxic effect is acute kidney injury (AKI) which, in turn, comprises a spectrum of severe tissue damages along the nephron, leading to an abrupt decline in renal function. Because early stages of toxic nephropathy are characterized by very few specific clinical signs and symptoms, there is the urgent need to investigate new biomarkers for predicting nephrotoxicity and localizing the injury to a specific nephron site, in order to reduce the risk of acute renal injury and/or acute tubular necrosis. The most promising biomarker for the early assessment of kidney injury and damage is neutrophil gelatinase-associated lipocalin (NGAL). NGAL can be easily measured in urine by an automated analytical method, allowing its clinical use in emergency likewise creatinine. Considerable expectations in terms of improvement of the management of newborns developing drug-induced nephropaties derive from the clinical application of metabolomics.