The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial

J Pediatr. 2021 May:232:65-72.e7. doi: 10.1016/j.jpeds.2021.01.031. Epub 2021 Jan 20.

Abstract

Objective: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.

Study design: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.

Results: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2, 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.

Conclusions: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.

Keywords: acute kidney injury; acute renal failure; chronic kidney disease; hypertension; proteinuria.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / classification
  • Acute Kidney Injury / epidemiology*
  • Albuminuria / epidemiology
  • Double-Blind Method
  • Erythropoietin / therapeutic use*
  • Female
  • Gestational Age
  • Glomerular Filtration Rate
  • Humans
  • Hypertension / epidemiology
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Infant, Premature, Diseases / epidemiology
  • Male
  • Recombinant Proteins / therapeutic use*
  • Renal Insufficiency, Chronic / epidemiology

Substances

  • Recombinant Proteins
  • Erythropoietin