Does protein intake correlate with tubular function in very preterm neonates?

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Background High protein intake in very preterm neonates (VPN) is important for growth. However, preterm kidneys have fewer functional nephrons and many of the ones present may be imma-ture. Studies have shown that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis, which lead to tubular injury. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker that is released during proximal tubular cell injury. The uNGAL to creatinine (uNGAL/Cr) ratio is com-monly performed for normalization. Objective To assess for a possible association between protein intake and uNGAL/Cr ratio in VPN. Methods A prospective cohort study was conducted in two NICUs in Jakarta. Subjects’ urine specimens were collected at 0-48 hours, 72 hours, and 21 days after birth to determine uNGAL/Cr ratio as a biomarker of tubular injury. Protein was administered according to study sites NICU guidelines. Protein intake was recorded daily from 14-21 days of age for formula and measured twice with a human milk analyzer for breast milk. ELISA was used to mea-sure uNGAL concentration. Low protein intake was defined as <3g/kg/day and high protein intake was defined as ≥3g/kg/day. Maternal and perinatal variables were recorded from medical records. Results Fifty-nine VPN were recruited, of whom 39 completed the study. Median uNGAL/Cr ratio ranged from 0.32-104.11 ng/ mg. The uNGAL/Cr ratio was not correlated with protein intake but was inversely correlated with gestational age and birth weight [r=-0.320, P=0.019 for the 72-hr (T2) urinary collection]. Higher uNGAL/Cr levels were associated with maternal infection [14.4 (range 4.4-104.1) vs. 7.2 (range 0.5-32.4) ng/mg, P=0.004 at the 0-48-hr (T1)], maternal anemia [6.9 (range 1.2-66.6) vs. 1.7 (range 0.3-89.2) ng/mg, P=0.001 at the 21-day (T3)] and nephrotoxic medication [15.9 (range 1.3-63.8) vs. 1.0 (range 0.4-8.6) ng/mg, P=0.026 at the 72-hr]. Conclusion Protein intake according to current nutritional guidelines does not correlate with tubular injury in VPN, as measured by uNGAL/Cr ratio. Maternal infection, maternal anemia, lower birth weight, and nephrotoxic medication, are associated with higher uNGAL/Cr levels in VPN.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalPaediatrica Indonesiana(Paediatrica Indonesiana)
Issue number4
Publication statusPublished - 28 Aug 2023


  • protein
  • tubular injury
  • urinary neutrophil gelatinase-associated lipocalin
  • very preterm neonates


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