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

Abstract

on behalf of the PENUT Trial Consortium* 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 designWe performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. ResultsThe 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 m 2 , 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.

Effects of prematurity on long-term renal health: a systematic review

“…15 16 22 25 42 43 45 Askenazi et al found that at 22-26 months, approximately 330 (35.8%) of their 923 participants had a urine albumin/creatinine ratio greater than 30 mg/g. 45 Bacchetta et al found that 2 out of their 50 participants had moderate microalbuminuria at approximately 7 years of age. 25 Jones et al found that 2 out of their cohort of 28 premature had microalbuminuria at 4-5 years of age.…”

“…Studies that found a significant difference in GFR between groups Studies that did not find a significant difference in GFR between groups Askenazi et al 45 Open access…”

“…43 Askenazi et al found that of their 923 extremely premature study participants, 16% had a GFR <90 mL/ min/1.73 m 2 at 22-26 months of age. 45…”

“…42 Askenazi et al found that of their 923 extremely low gestational age participants at 22-26 months of age, approximately 212 (23%) have a systolic BP >95th percentile for their age and approximately 369 (40%) had a diastolic BP >95th percentile. 45 Proteinuria/albuminuria Nineteen studies commented on proteinuria or albuminuria. 15-22 24-26 31 33 36 38 41-43 45 Of these, 11 studies found no significant difference between study and control groups.…”

“…Randomisation of study subjects was only done in 1 of the 31 included studies which was a randomised control trial where all study participants were premature. 45 All other studies were observational, and randomisation was not possible as birth weight and gestational age are not variables that can be ethically influenced. Furthermore, 17 studies did not have term born controls.…”