Abstract
Background
To study the influence of hyperbilirubinemia on indexes of neonatal kidney function.
Methods
A prospective cohort study was conducted September 2019 to March 2020 in Neonatology Department of Xuzhou Central Hospital. Neonates with gestational age ≥ 35 weeks and aged ≤ 7 days were included and divided into mild, moderate, and severe groups according to total serum bilirubin level. Epidemiologic and demographic data and daily urine output were recorded. Total serum bilirubin, serum creatinine, serum cystatin C, serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, and kidney injury molecule-1 were tested before and 12~18 h after phototherapy. Parameters of kidney function were compared between groups.
Results
Fifty-three, 52, and 49 neonates were included in the mild, moderate, and severe groups, respectively. Urine NGAL was higher in severe (1.36 ± 0.24 μg/L) compared to moderate (1.22 ± 0.19 μg/L) and mild groups (1.16 ± 0.19 μg/L), and differences were statistically significant (P = 0.004 and < 0.001, respectively). Urine NGAL was not significantly different between moderate and mild groups (P > 0.05). No significant differences in other kidney function indexes were observed between the three groups (all P > 0.05). Significant reduction in urine NGAL levels 12~18 h after stopping phototherapy was found in severe group ((1.17 ± 0.28) μg/L vs. (1.35 ± 0.23) μg/L, P < 0.001). Urine NGAL positively correlated with total serum bilirubin (r = 0.575, P < 0.001). Among all cases, neither serum creatinine nor daily urine output met neonatal acute kidney injury diagnostic criteria.
Conclusion
Severe hyperbilirubinemia may temporarily impair renal tubular reabsorption functions in full-term and near-term neonates, which is likely reversible. However, it has little effect on glomerular filtration function.
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Data availability
All the data used in this publication are available through contact with the corresponding author.
References
Rauti R, Qaisiya M, Tiribelli C, Ballerini L, Bellarosa C (2020) Bilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: a new pathway of neurotoxicity. Arch Toxicol 94:845–855. https://doi.org/10.1007/s00204-020-02659-9
Watchko JF (2018) 84 - Neonatal indirect hyperbilirubinemia and kernicterus. In: Gleason CA, Juul SE (eds) Avery’s Diseases of the Newborn, 10th edn. Elsevier, Philadelphia, pp 1198–1218
Cheng B, Jin Y, Liu G, Chen Z, Dai H, Liu M (2014) Urinary N-acetyl-beta-D-glucosaminidase as an early marker for acute kidney injury in full-term neonates with neonatal hyperbilirubinemia. Dis Markers 2014:315843. https://doi.org/10.1155/2014/315843
Perico N, Askenazi D, Cortinovis M, Remuzzi G (2018) Maternal and environmental risk factors for neonatal AKI and its long-term consequences. Nat Rev Nephrol 14:688–703. https://doi.org/10.1038/s41581-018-0054-y
Neonatology Group of Pediatrics Branch of Chinese Medical Association, Editorial committee of The Chinese Journal of Pediatrics (2014) Expert consensus on diagnosis and treatment of neonatal hyperbilirubinemia. Chin J Pediatr 52:745–748. https://doi.org/10.3760/cma.j.issn.0578-1310.2014.10.006
Ricci Z, Ronco C (2013) Neonatal RIFLE. Nephrol Dial Transplant 28:2211–2214. https://doi.org/10.1093/ndt/gft074
Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D (2011) Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res 69:354–358. https://doi.org/10.1203/PDR.0b013e31820b95ca
Kandasamy Y, Rudd D, Smith R (2017) The relationship between body weight, cystatin C and serum creatinine in neonates. J Neonatal-Perinatal Med 10:419–423. https://doi.org/10.3233/NPM-171719
Nakashima T, Inoue H, Fujiyoshi J, Matsumoto N (2016) Longitudinal analysis of serum cystatin C for estimating the glomerular filtration rate in preterm infants. Pediatr Nephrol 31:983–989. https://doi.org/10.1007/s00467-015-3309-x
Axelsen RA, Burry AF (1976) Bilirubin-associated renal papillary necrosis in the homozygous Gunn rat: light-and electron-microscopic observations. J Pathol 120:165–175. https://doi.org/10.1002/path.1711200306
Rawat V, Bortolussi G, Gazzin S, Tiribelli C, Muro AF (2018) Bilirubin-induced oxidative stress leads to DNA damage in the cerebellum of hyperbilirubinemic neonatal mice and activates DNA double-strand break repair pathways in human cells. Oxidative Med Cell Longev 2018:1801243. https://doi.org/10.1155/2018/1801243
Wallner M, Antl N, Rittmannsberger B, Schreidl S, Najafi K, Müllner E, Mölzer C, Ferk F, Knasmüller S, Marculescu R, Doberer D, Poulsen HE, Vitek L, Bulmer AC, Wagner KH (2013) Anti-genotoxic potential of bilirubin in vivo: damage to DNA in hyperbilirubinemic human and animal models. Cancer Prev Res (Phila) 6:1056–1063. https://doi.org/10.1158/1940-6207.CAPR-13-0125
Lv L (2017) Hyperbilirubinemia aggravates renal ischemia reperfusion injury and the potential mechanism. Peking Union Medical College Chinese Academy of Medical Sciences
Zhang Y, Zhang B, Wang D, Shi W, Zheng A (2020) Evaluation of novel biomarkers for early diagnosis of acute kidney injury in asphyxiated full-term neonates: a case-control study. Med Princ Pract 29:285–291. https://doi.org/10.1159/000503555
Bellos I, Fitrou G, Daskalakis G, Perrea DN, Pergialiotis V (2018) Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis. Eur J Pediatr 177:1425–1434. https://doi.org/10.1007/s00431-018-3221-z
Kamianowska M, Wasilewska A, Szczepański M, Kulikowska E, Bebko B, Koput A (2016) Health term-born girls had higher levels of urine neutrophil gelatinase-associated lipocalin than boys during the first postnatal days. Acta Paediatr 105:1105–1108. https://doi.org/10.1111/apa.13508
Zwiers AJ, de Wildt SN, van Rosmalen J, de Rijke YB, Buijs EA, Tibboel D, Cransberg K (2015) Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study. Crit Care 19:181. https://doi.org/10.1186/s13054-015-0910-0
OuYang XD, Peng HB, Kuang XM, Tang RK, Zeng Q, Zhu JM (2016) Analysis of serum and urine cystatin C level in neonates with unconjugated hyperbilirubinemia. Chin J Neonatol 31:168–172. https://doi.org/10.3969/j.issn.1673-6710.2016.03.002
Yang Y, Li SJ, Pan JJ, Hu YH, Zhou XY, Cheng R, Chen XQ (2018) Reference values for serum cystatin C in very low-birthweight infants: from two centres of China. J Paediatr Child Health 54:284–288. https://doi.org/10.1111/jpc.13732
Zhang D, Gao L, Ye H, Chi R, Wang L, Hu L, Ouyang X, Hou Y, Deng Y, Long Y, Xiong W, Chen C (2019) Impact of thyroid function on cystatin C in detecting acute kidney injury: a prospective, observational study. BMC Nephrol 20:41. https://doi.org/10.1186/s12882-019-1201-9
Deng Y, Wang L, Hou Y, Ma J, Chi R, Ye H, Zhai Y, Zhang D, Gao L, Hu L, Hou T, Li J, Tan N, Chen C (2019) The influence of glycemic status on the performance of cystatin C for acute kidney injury detection in the critically ill. Ren Fail 41:139–149. https://doi.org/10.1080/0886022X.2019.1586722
Muhari-Stark E, Burckart GJ (2018) Glomerular filtration rate estimation formulas for pediatric and neonatal use. J Pediatr Pharmacol Ther 23:424–431. https://doi.org/10.5863/1551-6776-23.6.424
Sweetman DU (2017) Neonatal acute kidney injury-severity and recovery prediction and the role of serum and urinary biomarkers. Early Hum Dev 105:57–61. https://doi.org/10.1016/j.earlhumdev.2016.12.006
Stojanović VD, Barišić NA, Vučković NM, Doronjski AD, Peco Antić AE (2015) Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates. Pediatr Res 78:430–435. https://doi.org/10.1038/pr.2015.125
Elmas AT, Karadag A, Tabel Y, Ozdemir R, Otlu G (2017) Analysis of urine biomarkers for early determination of acute kidney injury in non-septic and non-asphyxiated critically ill preterm neonates. J Matern Fetal Neonatal Med 30:302–308. https://doi.org/10.3109/14767058.2016.1171311
Velazquez DM, Reidy KJ, Sharma M, Kim M, Vega M, Havranek T (2019) The effect of hemodynamically significant patent ductus arteriosus on acute kidney injury and systemic hypertension in extremely low gestational age neonates. J Matern Fetal Neonatal Med 32:3209–3214. https://doi.org/10.1080/14767058.2018.1460349
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Wang, H., Su, M., Yang, B. et al. The influence of hyperbilirubinemia on indexes of kidney function in neonates. Pediatr Nephrol 36, 3711–3716 (2021). https://doi.org/10.1007/s00467-021-05151-3
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DOI: https://doi.org/10.1007/s00467-021-05151-3