Elif Keles1, Pia Wintermark2, Floris Groenendaal3,4, Noor Borloo5, Anne Smits5,6, Annouschka Laenen7, Djalila Mekahli6,8, Pieter Annaert9, Suzan Şahin10, Mehmet Yekta Öncel11, Valerie Chock12, Didem Armangil13, Esin Koc1, Malcolm R Battin14, Adam Frymoyer12, Karel Allegaert6,9,15. 1. Department of Neonatology, Gazi University, Faculty of Medicine, Ankara, Turkey. 2. Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal Children's Hospital, Research Institute of the McGill University Health Centre, Montreal, Québec, Canada. 3. Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Utrecht University, Utrecht, The Netherlands. 4. Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands. 5. Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. 6. Department of Development and Regeneration, KU Leuven, Leuven, Belgium. 7. Leuven Biostatistics and Statistical Bioinformatics Center (L-BioStat), KU Leuven, Leuven, Belgium. 8. Department of Pediatric Nephrology, University Hospitals of Leuven, Leuven, Belgium. 9. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. 10. Department of Neonatology, Izmir Demokrasi University, Faculty of Medicine, Izmir, Turkey. 11. Department of Neonatology, İzmir Katip Çelebi University, Faculty of Medicine, İzmir, Turkey. 12. Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California, USA. 13. Neonatal Intensive Care Unit, Koru Hospital, Ankara, Turkey. 14. Newborn Service, Auckland District Health Board, Auckland, New Zealand. 15. Department of Clinical Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
Abstract
INTRODUCTION: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. METHODS: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. RESULTS: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). CONCLUSIONS: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.
INTRODUCTION: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. METHODS: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. RESULTS: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). CONCLUSIONS: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.