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

the PENUT Trial Consortium

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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.

Original languageEnglish (US)
JournalJournal of Pediatrics
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
Recombinant Erythropoietin for Protection of Infant Renal Disease (REPaIReD) Study is a National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases –funded (R01 DK103608) ancillary study designed to look at kidney outcomes in patients enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT), which is an NIH National Institute of Neurological Disorders and Stroke –funded (U01 NS077953, U01 NS077955) trial. The clinicaltrials.gov identifier is NCT01378273 . Funding sources for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. D.A. is consultant for Baxter, CHF Solutions Inc, Medtronic, Bioporto, and AKI Foundation; and receives external grant funding for research and education for projects not related to this report from Baxter , CHF Solutions Inc , Medtronic and NIH . S.G. reports personal fees from and a position as a consultant to CHF Solutions Inc, Renibus, ExThera, Reata, and Medtronic Inc; receives grant funding from and serves as a consultant and on a Speaker's Bureau for Baxter Healthcare, Inc ; receives grant funding and serves as a consultant for BioPorto, Inc ; and serves on a Speaker's Bureau for Fresenius Medical Corporation. R.S. receives grant funding for studies not related to this project from National Heart, Lung, and Blood Institute and Patient-Centered Outcomes Research Institute . The other authors declare no conflicts of interest.

Funding Information:
Recombinant Erythropoietin for Protection of Infant Renal Disease (REPaIReD) Study is a National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases?funded (R01 DK103608) ancillary study designed to look at kidney outcomes in patients enrolled in the Preterm Erythropoietin Neuroprotection Trial (PENUT), which is an NIH National Institute of Neurological Disorders and Stroke?funded (U01 NS077953, U01 NS077955) trial. The clinicaltrials.gov identifier is NCT01378273. Funding sources for this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. D.A. is consultant for Baxter, CHF Solutions Inc, Medtronic, Bioporto, and AKI Foundation; and receives external grant funding for research and education for projects not related to this report from Baxter, CHF Solutions Inc, Medtronic and NIH. S.G. reports personal fees from and a position as a consultant to CHF Solutions Inc, Renibus, ExThera, Reata, and Medtronic Inc; receives grant funding from and serves as a consultant and on a Speaker's Bureau for Baxter Healthcare, Inc; receives grant funding and serves as a consultant for BioPorto, Inc; and serves on a Speaker's Bureau for Fresenius Medical Corporation. R.S. receives grant funding for studies not related to this project from National Heart, Lung, and Blood Institute and Patient-Centered Outcomes Research Institute. The other authors declare no conflicts of interest. Funding and conflicts of interest statement available at www.jpeds.com.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • acute kidney injury
  • acute renal failure
  • chronic kidney disease
  • hypertension
  • proteinuria

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