Does high protein intake cause tubular injury in very preterm neonates?

Abstract

Background: Very preterm birth rate was 10.8% of all preterm in Asia. Early aggressive nutritional strategies in very preterm neonates is important for catching up growth; however, preterm kidneys have fewer, immature functional nephrons. Studies have showed that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis through single nephron glomerular hyperfiltration (SNGHF), which leads to glomerulotubular injury. Aim: to analyse the correlation between protein intake and glomerulotubular injury in very preterm neonates. Method: A prospective cohort study was conducted in neonatal units of two hospitals in Jakarta. Urine samples were taken three times at post-natal ages 0-48 hours (T1), 72 hours (T2), and 21 days (T3) for determining the urinary neutrophil gelatinase-associated lipocalin to creatinine (uNGAL/Cr) ratio. Protein intake were given in accordance with local guideline while considering the clinical condition of participants. Protein levels from formula milk were recorded daily from 14-21 days of age, while breastmilk protein was measured twice by using a human milk analyser. Urinary NGAL (uNGAL) was tested with an ELISA. Glomerulotubular injury was defined as a uNGAL/Cr ratio ≥1 SD (22.74 ng/mg) at post-natal age 21 days. High protein intake was defined as average protein intake ≥ 3 g/kg/day. Results: Fifty-nine very preterm neonates were recruited, of which 39 completed the study. Glomerulotubular injury was found in 9 of 39 participants (23%). The proportion of glomerulotubular injury in very preterm neonates who had received high protein intake vs low protein intake was 5 of 29 vs 4 of 10 participants, respectively. The median of uNGAL/Cr ratio was not significantly different in the high vs low protein intake group (3.54 (range: 0.69-89.16) ng/mg vs (6.88 (range: 0.32-66.64)) ng/mg, respectively. The uNGAL/C ratio was not correlated with protein intake. However, it was inversely correlated with gestational age and birth weight. Conclusions: The proportion of glomerulotubular injury in very preterm neonates given high protein diet was 5 of 29. The uNGAL/Cr ratio was increased at the post-natal age of 72 hours and decreased in 21 days in both high and low protein intake groups. High protein intake was not correlated with glomerulotubular injury.

Point-of-Care (POC) Urinary L-Type Fatty Acid-Binding Protein (u-LFABP) Use in Critically Ill, Very Preterm Neonates

“…This study was a retrospective cohort study conducted at the neonatal intensive care unit (NICU), Cipto Mangunkusumo General Hospital from November to December 2020. Participants were very preterm neonates born between 28 and 32 weeks of gestational age, recruited consecutively for a previous study entitled “Does High Protein Intake Cause Tubular Injury in Very Preterm Neonates?” [ 13 ]. Exclusion criteria included any major congenital abnormalities (e.g., complex congenital heart disease, congenital anomalies of the kidney and urinary tract (CAKUT), craniofacial and cerebral anomalies, and congenital abdominal anomalies), intrauterine growth restriction (IUGR), nephrotoxic agent exposure during pregnancy, urine collection difficulties, and consent refusal.…”

“…Frozen urine samples from the previous study [ 13 ] were thawed for u-LFABP examination. Those frozen urine samples were previously collected at three different time points: 0–48 hours, 72 hours, and 21 days using a urine collector or urethral catheter.…”