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Blood urea nitrogen, a marker for severe retinopathy of prematurity?

Journal of Perinatology volume 43, pages 830–832 (2023)Cite this article

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In addition to gestational age at birth and oxygen exposure, weight gain of premature infants is directly proportional to the risk of the severity of retinopathy of prematurity (ROP) implying that the metabolic state of the premature infant is associated with postnatal morbidities [1,2,3]. We and others have found that hyperoxia downregulates, and hypoxiamimesis upregulates, metabolites of the urea cycle, a fundamental mechanism for neutralizing ammonia to urea by the liver [4, 5]. These experimental findings in preclinical models of ROP and diabetes stimulated the idea if indeed ammonia metabolism is a marker of stress associated with prematurity and hypoxia, consequently, blood urea nitrogen (BUN) may be associated with oxygen-induced complications such as ROP. Although BUN concentration is affected by both ureagenesis and excretion, there is evidence that an ELBW infant’s kidney function stabilizes after the 3rd week, which coincides with the time when most ELBW infants have reached full feeds and are receiving the optimal amount of dietary protein, suggesting that a comparison of BUN between infants who have similar creatinine levels might primarily reflect differences in the synthesis of urea [6].

Pathological angiogenesis associated with severe ROP follows a two-step development: early hyperoxia (phase 1) causes retinovascular growth attenuation and vaso-obliteration that induces subsequent relative hypoxic ischemia (phase 2) that induces pathological angiogenesis, termed Stage 3 neovascularization [7]. Therefore, knowing that hypoxia correlates to an increase in urea cycle metabolites and that relative retinal hypoxia in phase 2 induces ROP beginning at 30 weeks corrected gestational age, we correlated the BUN to ROP severity at four weeks after birth to capture urea measurements at this most clinically relevant time point. In this investigation, we tested the hypothesis that increased BUN level in the 4th week of life in an ELBW infant are positively associated with the severity of ROP.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Neonatology, Cleveland Clinic Children’s Hospital, Cleveland, OH, USA

    Anirudha Das & Hany Aly

  2. Department of Neonatology, Tufts University school of medicine, Boston, MA, USA

    Indrani Bhattacharjee

  3. Department of Internal Medicine, Rutgers health/ Monmouth Medical Center, Long Branch, NJ, USA

    Farah Heis

  4. Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Jonathan E. Sears

  5. Cardiovascular and Metabolic Sciences, Cleveland Clinic Foundation, Cleveland, OH, USA

    Jonathan E. Sears

Authors
  1. Anirudha Das
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  4. Jonathan E. Sears
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Contributions

AD, HA and JES conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. IB and FH collected data, carried out the initial analyses, and reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Anirudha Das.

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The authors declare no competing interests.

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The need for consent was waived for this study by the IRB.

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Das, A., Bhattacharjee, I., Heis, F. et al. Blood urea nitrogen, a marker for severe retinopathy of prematurity?. J Perinatol 43, 830–832 (2023). https://doi.org/10.1038/s41372-023-01618-3

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  • DOI: https://doi.org/10.1038/s41372-023-01618-3

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