Progression of the estimated glomerular filtration rate in asphyxiated neonates undergoing therapeutic hypothermia during the first 10 days of life.

Abstract

Background: Serum creatinine (Scr) centile values were recently described in a cohort of 1136 (near)-term neonates that underwent therapeutic hypothermia (TH) because of moderate to severe hypoxic-ischemic encephalopathy. Recent methodological progress enables conversion of these Scr centiles to estimated glomerular filtration rate (eGFR) values.

Methods: Scr centiles in the TH dataset during the first 10 days of life were converted to eGFR values, using the Schwartz formula, with the Smeets k-value (0.31) and fixed body length (50 cm) to generate postnatal reference eGFR values, centiles, and an equation for median eGFRs. These findings were compared to published eGFR data in term controls.

Results: A polynomial function was estimated: $\mathrm{eGFR}\left(\frac{\mathrm{mL}}{\min },\bullet ,1.73,m^2\right)=9.1667+7.1173-0.3439x^2,(x=\mathrm{days})$ for eGFR in TH neonates. The median eGFR increases 2- to threefold over the first week (day 1: 16.1; day 2: 19.4; day 7: 41.2 mL/min∙1.73 m²), while the polynomial function does not fully reflect the interindividual variability in eGFR values (intra-day variability is also 2- to threefold). Patterns in acute kidney injury (AKI) TH cases differ significantly from non-AKI TH cases. Based on pooling of published eGFR data, this was compared to a function in healthy term neonates: $\mathrm{eGFR}\left(\frac{\mathrm{mL}}{\min },\bullet ,1.73,m^2\right)=14.2167+6.7644-0.3901x^2(x=\mathrm{days})$ (day 1: 20; day 2: 26; day 7: 42 mL/min/1.73 m²).

Conclusions: Based on a pooled dataset in TH cases, we converted Scr centiles to eGFR centiles. Based on median values, this resulted in a polynomial function in TH cases, compared to healthy term neonates. This eGFR function enables precision pharmacotherapy for GFR-cleared drugs in this vulnerable population.