Drug-induced renal injury in neonates: challenges in clinical practice and perspectives in drug development

ABSTRACT

Introduction: Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development.

Areas covered: We described the tools currently used to detect renal damage in neonatal settings, their limits and applicability, as well as the role of drugs on renal toxicity occurrence. Subsequently, we discuss current knowledge on new biomarkers for the detection of kidney injury and drug-induced kidney injury in neonates, and the qualification programs developed by regulatory agencies for biomarkers intended as tools in drug development.

Expert opinion: Some molecules are emerging as potential biomarkers for early detection of AKI: promising data has demonstrated higher sensitivity and accuracy compared with tools currently used in the clinical setting. In addition, novel techniques (e.g. high power magnetic resonance imaging) to assess long-term consequences of AKI in neonates are in early steps of development.

KEYWORDS:

• Acute kidney injury
• biomarkers
• drug-induced renal injury
• neonates

Article highlights

• Assessment of AKI in preterm neonates poses specific challenges, which relate to the maturational changes, the ‘black’ box of the first days of postnatal life, and the inaccuracy and variability in the assays at present used in the clinical setting (creatinine, cystatin C).

• Biomarkers, especially those detectable in urine samples, are increasingly studied in the neonatal population as new tools for the diagnosis of renal function alteration. For many of them, references values were published for term and preterm babies up to 3 months.

• So far, only few studies investigated the applicability of urinary biomarkers in drug-induced kidney injury in neonates and results are promising. Their utility and applicability were also recognized by regulatory agencies, which started to include biomarkers in drug development.

• Besides biomarkers to assess ‘short’ or ‘intermediate’ AKI, clinical researchers should also focus on late outcome biomarkers of renal function since disturbed postnatal glomerulogenesis and its risk factors (e.g. drugs, hypoxia, nutrition) in neonates may only become recognizable in later years.

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Declaration of interest

A Girardi, E Raschi, S Galletti, E Poluzzi and F De Ponti are supported by Institutional Research Funds (Ricerca Fondamentale Orientata) of the University of Bologna. K Allegaert has been supported by the Fund for Scientific Research, Flanders (fundamental clinical investigatorship 1800214N). The research activities are further facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033).

Additional information

Funding

This paper was not funded.