Serum Creatinine Patterns in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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%, <i>p</i> < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (<i>p</i> < 0.01) or AKI neonates (<i>p</i> < 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). <b><i>Conclusions:</i></b> 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.

Rescaling Creatinine Centiles in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy

“…Using the published TH ( caling SCr biomarker approach," described by Pottel et al [5]. In essence, we calculated the SCr TH /Scr controls ratio (TH to controls) for 10th-25th-50th-75th-90th centiles as published in the Neonatology paper and its supplement [2]. In the event of "similar SCr values,ˮ the centiles for this ratio should be straight lines around 1.…”

“…Fig.1. Based on the centiles (10th, 25th, 50th, 75th, and 90th) SCr values over PNA (day 1-day 7) previously reported in the TH (1,136 cases, 4,724 SCr values) and the control (801 cases, 2,779 SCr values) group, the SCr TH / SCr controls ratio has been calculated[2,5]. Black continuous lines: P10, P50, and P90; grey discontinuous lines: P25 and P75; black discontinuous line: line of "equal" ratio.…”

Editorial: The developing kidney: Perinatal aspects and relevance throughout life

“…This resulted in better identification of risk groups (“precision medicine”), development of prediction models (like urinary neutrophil gelatinase-associated lipocalin (NGAL) after cardiac surgery) ( 7 ). Alternatively, a suggestion to consider a centile approach (somewhat similar to commonly used growth charts) over postnatal age has been applied to extreme low birth weight (ELBW) infants, and more recently, to neonates treated with therapeutic hypothermia for neonatal encephalopathy ( 6 , 8 ).…”

Serum Creatinine in Neonates Treated with Therapeutic Hypothermia

“…When we look at their data (Table 2; Fig. 1a–d) [1], we see a downward trend in SCr level among all cases. For example, neonates with acute kidney injury (AKI) and with no AKI had a downward trending pattern irrespective of the initial value.…”

“…Dear Editor, I read with interest the article by Keles et al [1], describing serum creatinine (SCr) centiles in neonates treated with therapeutic hypothermia (TH). They suggested that a centile-based approach could guide pharmacotherapy, fluid management, and kidney-supportive therapies.…”