Renal Precision Medicine in Neonates and Acute Kidney Injury: How to Convert a Cloud of Creatinine Observations to Support Clinical Decisions

Frontiers in Pediatrics

article

Karel Allegaert¹  Anne Smits¹  Tamara van Donge⁵  John van den Anker⁶  Kosmas Sarafidis⁸  Elena Levtchenko¹  Djalila Mekahli¹ 

[1] Department of Development and Regeneration;Department of Pharmacy and Pharmaceutical Sciences;Department of Clinical Pharmacy;Neonatal Intensive Care Unit, University Hospitals Leuven;University of Basel Children's Hospital (UKBB), University of Basel;Division of Clinical Pharmacology, Children's National Hospital, United States;Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital;First Department of Neonatology, School of Medicine, Aristotle University of Thessaloniki, Hippokrateion General Hospital;Department of Pediatric Nephrology and Organ Transplantation, Hospitals Leuven

关键词: creatinine;    Cystatin C;    precision medicine;    acute kidney injury;    newborn;    nephron number;   

DOI  :  10.3389/fped.2020.00366

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Renal precision medicine in neonates is useful to support decision making on pharmacotherapy, signal detection of adverse (drug) events, and individual prediction of short- and long-term prognosis. To estimate kidney function or glomerular filtration rate (GFR), the most commonly measured and readily accessible biomarker is serum creatinine (S cr ). However, there is extensive variability in S cr observations and GFR estimates within the neonatal population, because of developmental physiology and superimposed pathology. Furthermore, assay related differences still matter for S cr , but also exist for Cystatin C. Observations in extreme low birth weight (ELBW) and term asphyxiated neonates will illustrate how renal precision medicine contributes to neonatal precision medicine. When the Kidney Disease Improving Global Outcome (KDIGO) definition of acute kidney injury (AKI) is used, this results in an incidence up to 50% in ELBW neonates, associated with increased mortality and morbidity. However, urine output criteria needed adaptations to broader time intervals or weight trends, while S cr and its trends do not provide sufficient detail on kidney function between ELBW neonates. Instead, we suggest to use assay-specific centile S cr values to better describe postnatal trends and have illustrated its relevance by quantifying an adverse drug event (ibuprofen) and by explaining individual amikacin clearance. Term asphyxiated neonates also commonly display AKI. While oliguria is a specific AKI indicator, the majority of term asphyxiated cases are non-oliguric. Asphyxia results in a clinical significant—commonly transient—mean GFR decrease (−50%) with a lower renal drug elimination. But there is still major (unexplained) inter-individual variability in GFR and subsequent renal drug elimination between these asphyxiated neonates. Recently, the Baby-NINJA (nephrotoxic injury negated by just-in-time action) study provided evidence on the concept that a focus on nephrotoxic injury negation has a significant impact on AKI incidence and severity. It is hereby important to realize that follow-up should not be discontinued at discharge, as there are concerns about long-term renal outcome. These illustrations suggest that integration of renal (patho)physiology into neonatal precision medicine are an important tool to improve contemporary neonatal care, not only for the short-term but also with a positive health impact throughout life.

【 授权许可】

CC BY