7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Cooling for newborns with hypoxic ischaemic encephalopathy.

          Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae without adverse effects. To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68 to 0.83); typical RD -0.15, 95% CI -0.20 to -0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5 to 10) (8 studies, 1344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64 to 0.88), typical RD -0.09 (95% CI -0.13 to -0.04); NNTB 11 (95% CI 8 to 25) (11 studies, 1468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63 to 0.94), typical RD -0.13 (95% CI -0.19 to -0.07); NNTB 8 (95% CI 5 to 14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia. There is evidence from the 11 randomised controlled trials included in this systematic review (N = 1505 infants) that therapeutic hypothermia is beneficial in term and late preterm newborns with hypoxic ischaemic encephalopathy. Cooling reduces mortality without increasing major disability in survivors. The benefits of cooling on survival and neurodevelopment outweigh the short-term adverse effects. Hypothermia should be instituted in term and late preterm infants with moderate-to-severe hypoxic ischaemic encephalopathy if identified before six hours of age. Further trials to determine the appropriate techniques of cooling, including refinement of patient selection, duration of cooling and method of providing therapeutic hypothermia, will refine our understanding of this intervention.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia.

              To test the hypothesis that acute kidney injury (AKI) would be independently associated with increased morbidity and mortality.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                28 July 2020
                2020
                : 8
                : 366
                Affiliations
                [1] 1Department of Development and Regeneration, KU Leuven , Leuven, Belgium
                [2] 2Department of Pharmacy and Pharmaceutical Sciences, KU Leuven , Leuven, Belgium
                [3] 3Department of Clinical Pharmacy, Erasmus MC , Rotterdam, Netherlands
                [4] 4Neonatal Intensive Care Unit, University Hospitals Leuven , Leuven, Belgium
                [5] 5Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital (UKBB), University of Basel , Basel, Switzerland
                [6] 6Division of Clinical Pharmacology, Children's National Hospital , Washington, DC, United States
                [7] 7Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital , Rotterdam, Netherlands
                [8] 8First Department of Neonatology, School of Medicine, Aristotle University of Thessaloniki, Hippokrateion General Hospital , Thessaloniki, Greece
                [9] 9Department of Pediatric Nephrology and Organ Transplantation, Hospitals Leuven , Leuven, Belgium
                Author notes

                Edited by: Yogen Singh, Cambridge University Hospitals NHS Foundation Trust, United Kingdom

                Reviewed by: Sajeev Job, Cambridge University Hospitals, United Kingdom; Ömer Erdeve, Ankara University, Turkey

                *Correspondence: Karel Allegaert karel.allegaert@ 123456uzleuven.be

                This article was submitted to Neonatology, a section of the journal Frontiers in Pediatrics

                Article
                10.3389/fped.2020.00366
                7399072
                eef0fa51-4e68-423f-93ed-54cc4ef6bee3
                Copyright © 2020 Allegaert, Smits, van Donge, van den Anker, Sarafidis, Levtchenko and Mekahli.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 May 2020
                : 02 June 2020
                Page count
                Figures: 6, Tables: 3, Equations: 0, References: 64, Pages: 10, Words: 8205
                Categories
                Pediatrics
                Review

                creatinine,cystatin c,precision medicine,acute kidney injury,newborn,nephron number

                Comments

                Comment on this article