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

Abstract

OBJECTIVE\nTo 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 corrected gestational age (cGA) compared with those randomized to placebo.\n\n\nSTUDY DESIGN\nWe performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.\n\n\nRESULTS\nThe 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 [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22-26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73m2, 35.8% had urine albumin/creatinine ratio (ACR) > 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<0.04). This association remained even after controlling for gestational age, site and sibship (adjusted OR=0.6 [95% CI=0.39-0.92]). We did not find statistically significant differences between treatment groups in eGFR, ACR, rates of SBP >95th percentile or DBP >90th or >95th percentiles.\n\n\nCONCLUSIONS\nELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months cGA. Recombinant erythropoietin (rhEpo) 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 cGA.