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Abstract: TH-PO012

Theophylline Use to Mitigate AKI in Infants Undergoing Total Body Cooling for Perinatal Asphyxia

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention


  • Merrill, Kyle, University of Iowa, Iowa City, Iowa, United States
  • Jetton, Jennifer G., University of Iowa, Iowa City, Iowa, United States
  • Klein, Jonathan M., University of Iowa, Iowa City, Iowa, United States
  • Misurac, Jason, University of Iowa, Iowa City, Iowa, United States

Perinatal asphyxia is a common cause of acute kidney injury (AKI) and hypoxic ischemic encephalopathy (HIE). Theophylline is protective against AKI in infants with HIE who are not treated with total body cooling. However, there is a paucity of information on the effect of theophylline to protect against AKI in infants with HIE treated with total body cooling.


Single-center retrospective cohort analysis of infants diagnosed with HIE treated with total body cooling from 1/2007 to 12/2017. Inclusion criteria were: moderate or severe HIE, gestational age > 36 weeks, measurement of at least two serum creatinine (SCr) values at least 12h apart, and absence of prenatally diagnosed renal disease. Included infants were stratified based on receipt of theophylline and theophylline dose strategy: either a single dose of 5-8 mg/kg on day of life (DOL) 0 (standardized) or multiple doses (non-standardized). AKI was defined according to a Kidney Disease: Improving Global Outcomes (KDIGO) definition modified for neonates: SCr >50% above the lowest previous baseline; increase in SCr of >0.3 mg/dL within 48h; or urine output (UOP) ≤1 ml/kg/h for 24h.


There were 116 infants who met the inclusion criteria. Among included infants, SCr was missing on 374/812 days (46%) from DOL 0-6, limiting the detection of AKI by SCr. AKI incidence was 63/116 (54%). There was no significant difference in AKI incidence between groups (χ2=0.18, p=0.91). AKI severity was higher in the no theophylline group but the difference was not significant (χ2=3.9, p=0.42). UOP was different between groups on DOL 1 (p=0.008) but not on DOL 2-6.


In this cohort of infants with HIE treated with total body cooling, theophylline administration was not associated with a significant difference in the incidence or severity of AKI.

 No Theophylline (n=58)Standardized Theophylline (n=46)Non-standardized Theophylline (n=12)
AKI (UOP or SCr)32/58 (55%)24/46 (52%)7/12 (58%)
AKI (SCr only)6/58 (10%)8/46 (17%)2/12 (17%)
AKI StageStage 1 -- 17/58 (29%)
Stage 2 -- 7/58 (12%)
Stage 3 -- 8/58 (14%)
Stage 1 -- 17/46 (37%)
Stage 2 -- 3/46 (7%)
Stage 3 -- 4/46 (9%)
Stage 1 -- 6/12 (50%)
Stage 2 -- 0/12 (0%)
Stage 3 -- 1/12 (8%)
UOP DOL 1 (ml/kg/hr)*1.3 (0.8-2.1)1.9 (1.3-2.7)1.5 (0.6-2)
Nephrotoxins Received**1 - 72%
≥2 - 25%
1 - 25%
≥2 - 3%
1 - 58%
≥2 - 8%
HIE SeverityMod. - 78%
Severe - 22%
Mod. - 70%
Severe - 30%
Mod. 50%
Severe 50%
Mortality (DOL 0-6)2/58 (3.4%)4/46 (8.6%)1/12 (8.3%)

*Median (IQR) **Gentamicin, vancomycin, piperacillin/tazobactam, acyclovir, and captopril