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Randomized Controlled Trial
. 2025 Mar 19;26(1):138.
doi: 10.1186/s12882-025-04065-8.

Association of patent ductus arteriosus treatment in extremely low gestational age neonates with two year kidney outcomes: a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT)

Paige E Condit  1   2 , Ronnie Guillet  3 , Dinushan Kaluarachchi  4 , Russell L Griffin  5 , Shina Menon  6 , David J Askenazi  7 , Matthew W Harer  4
Affiliations
Randomized Controlled Trial

Association of patent ductus arteriosus treatment in extremely low gestational age neonates with two year kidney outcomes: a secondary analysis of the preterm erythropoietin neuroprotection trial (PENUT)

Paige E Condit et al. BMC Nephrol. .

Abstract

Background: Management of patent ductus arteriosus (PDA) is variable and includes expectant, medical, and procedural options. Both the hemodynamic effects of a PDA and its treatment put neonates at risk for acute kidney injury (AKI). Little is known about how different management approaches to a PDA, either conservative management or active management and either medical or surgical treatment, in preterm neonates impact kidney function over the longer term. The objective of this study is to evaluate rates of kidney dysfunction at two years of age in extremely low gestational age neonates (ELGANs) with treated compared to untreated PDAs.

Methods: Secondary analysis of prospectively collected data from the PENUT trial. Kidney dysfunction defined by: eGFR < 90 mL/min/1.73 m2, systolic or diastolic blood pressures (SBP or DBP) > 90th percentile, or proteinuria measured by albumin to creatinine ratio (ACR) > 30 mg/g. Between-group, variables were compared using chi-square or t-test statistics. General estimating equations and multivariable logistic regression was used to evaluate the association with outcomes.

Results: Of 780 ELGANs, 261 (43%) were treated for PDA. Of those treated, 168 (64.4%) received pharmacologic treatment, 12 (4.6%) received surgical treatment, 57 (21.8%) received both, and 24 (9.2%) were listed as having a treated PDA without specification of management. After adjusting for confounding factors, those actively treated for a PDA were less likely to have SBP > 90th percentile at two years (29.5% treated vs. 34.3% control, adjusted OR 0.59, CI 0.36-0.99). The adjusted odds-ratios for differences in other 2-year kidney outcomes did not differ. Among those medically treated, indomethacin was used more commonly than either ibuprofen or acetaminophen.

Conclusions: ELGANs receiving treatment for a PDA were less likely to have elevated SBP at two years. Prospective studies are needed to examine the effects of a hemodynamically significant PDA and its management on long-term kidney outcomes.

Keywords: Acetaminophen; Chronic kidney disease; Hypertension; Ibuprofen; Indomethacin; Kidney dysfunction.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This is a retrospective observational study using existing data. There were no study intervention and the existing data was received and used in a de-identified manner to protect subject privacy. The original PENUT trial received ethics approvals from all participating centers with the University of Washington institutional review board (IRB) serving as the central institutional review board. Consent for publication: Not applicable. Disclosure: For full disclosure, we provide here an additional list of other author’s commitments and funding sources that are not directly related to this study: In the last 24 months, David J Askenazi has consulted with Nuwellis, Seastar, and Abbott. Over the last 24 months, his institution has received funding for education and research that is not related to this project from Nuwellis, Bioporto, Leadiant and Seastar. He has financial interests in patent/innovations pending in the area of kidney support therapies and urine collection devices. He is the Founder and Chief Scientific Officer for Zorro-Flow Inc. Ronnie Guillet: Ronnie Guillet is a stockholder in Zorro-Flow Inc. Dinushan Kaluarachchi: Dinushan Kaluarachchi serves as a consultant for ONY Biotech. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Forest plot of odds ratios for the association between patent ductus arteriosus and two-year outcomes. Odds ratios estimated from generalized estimating equation logistic regression and adjusted for gestational age, birthweight, intubation, bronchopulmonary dysplasia at 36 weeks gestational age, vasopressor administration, indomethacin administration, vancomycin administration, severe sepsis, and 5-minute Apgar
See this image and copyright information in PMC

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