Urinary biomarkers as early indicators of acute kidney injury in neonates with perinatal asphyxia
Biomarkers of acute kidney injury
Keywords:
perinatal asphyxia, acute kidney injury, urinary biomarkers
Abstract
Perinatal asphyxia (PA) is a condition in which there is a decreased or interrupted blood and oxygen supply to the tissues of the fetus, i.e., the newborn, immediately before, during, or immediately after delivery. It constitutes a significant cause of mortality, accounting for 23-24% of all neonatal deaths. The estimated global incidence of perinatal hypoxia is approximately 0.5% of the total number of live births at gestational age over 36 weeks. PA negatively impacts the entire organism, especially metabolically demanding tissues. Due to the sensitivity of the kidneys to oxygen deprivation, acute kidney injury (AKI) can develop within the first 24 hours of the ischemic episode. Prolonged ischemia may lead to irreversible cortical necrosis. Early recognition of AKI is crucial for adequate fluid and electrolyte replacement, as the initiation of pre-renal etiological factors is a reversible process. However, AKI represents a poor prognostic sign, with higher mortality in neonates who develop AKI after perinatal asphyxia, and up to 40% of survivors may have permanent kidney damage. Given the specificity of both the population and the clinical entity, there is a clear need for newer, more sensitive, and specific biomarkers of renal function. The type of biological sample in which it is quantified is a crucial characteristic that must be taken into account. For newborns, obtaining a sample non-invasively is of utmost importance. In this context, urine analysis emerges as a good choice. Metabolites in the urine of PA patients have been proven significant for monitoring renal function.
References
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35. El-Gendy FM, El-mo'men KA, Badr HS, Mohammed AE. β2 -Microglobulin predicts renal injury in asphyxiated neonates. Menoufia Med J. 2014;27:316-21.
36. Abdullah, Kadam P, Yachha M, Srivastava G, Pillai A, Pandita A. Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia. Eur J Pediatr. 2022;181(1):281-6.
37. Mehrkash M, Gheissari A, Barekatain B, Ziabi F, Tabatabaei S. Investigation of Urinary Beta-2 Microglobulin Level in Neonates with Asphyxia Admitted in Alzahra Hospitals in Isfahan, 1396-1397. Iran J Neonatol. 2021;12(1):61-5.
2. Herrera CA, Silver RM. Perinatal Asphyxia from the Obstetric Standpoint: Diagnosis and Interventions. Clin Perinatol. 2016;43(3):423-38.
3. Rainaldi MA, Perlman JM. Pathophysiology of Birth Asphyxia. Clin Perinatol. 2016;43(3):409-22.
4. Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, et al. Neonatal Acute Kidney Injury. Pediatrics. 2015;136(2):e463-73.
5. Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal. 2004;89:152-5.
6. Starr MC, Charlton JR, Guillet R, Reidy K, Tipple TE, Jetton JG, et al. Advances in Neonatal Acute Kidney Injury. Pediatrics. 2021;148(5):e2021051220.
7. Yanga H, Linb C, Zhuang C, Chen J, Jia Y, Shi H, et al. Serum Cystatin C as a predictor of acute kidney injury in neonates: a meta-analysis. J Pediatr. 2022;98(3):230-40.
8. Hidayati EL, Utami MD, Rohsiswatmo R, Tridjaja B. Cystatin C compared to serum creatinine as a marker of acute kidney injury in critically ill neonates. Pediatr Nephrol. 2021;36(1):181-6.
9. Li Y, Fu C, Zhou X, Xiao Z, Zhu X, Jin M, et al. Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates. Pediatr Nephrol. 2012;27(5):851-60.
10. Sarafidis K, Tsepkentzi E, Agakidou E, Diamanti E, Taparkou A, Soubasi V, et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol. 2012;27:1575-82.
11. Khosravi N, Zadkarami M, Chobdar F, Hoseini R, Khalesi N, Panahi P, et al. The Value of Urinary Cystatin C Level to Predict Neonatal Kidney Injury. Curr Pharm Des. 2018;24(25):3002-4.
12. Libório AB, Branco KM, Torres de Melo Bezerra C. Acute kidney injury in neonates: from urine output to new biomarkers. Biomed Res Int. 2014;2014:601568.
13. Buonafine M, Martinez-Martinez E, Jaisser F. More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases. Clin Sci (Lond). 2018;132(9):909-23.
14. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinaseassociated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14(10):2534-43.
15. Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, et al. Neutrophil gelatinaseassociated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens. 2006;15(4):442-9.
16. Ortega LM, Heung M. The use of cell cycle arrest biomarkers in the early detection of acute kidney injury. Is this the new renal troponin? Nefrologia (Engl Ed). 2018;38(4):361-7.
17. Kari JA, Shalaby MA, Sofyani K, Sanad AS, Ossra AF, Halabi RS, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU. World J Pediatr. 2018;14(2):134-42.
18. Zhang Y, Zhang B, Wang D, Shi W, Zheng A. Evaluation of Novel Biomarkers for Early Diagnosis of Acute Kidney Injury in Asphyxiated Full-Term Newborns: A Case-Control Study. Med Princ Pract. 2020;29(3):285-91.
19. Bellos I, Fitrou G, Daskalakis G, Perrea DN, Pergialiotis V. Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis. Eur J Pediatr. 2018;177(10):1425-34.
20. Moresco RN, Bochi GV, Stein CS, De Carvalho JAM, Cembranel BM, Bollick YS. Urinary kidney injury molecule-1 in renal disease. Clin Chim Acta. 2018;487:15-21.
21. Song J, Yu J, Prayogo GW, Cao W, Wu Y, Jia Z, et al. Understanding kidney injury molecule 1: a novel immune factor in kidney pathophysiology. Am J Transl Res. 2019;11(3):1219-29.
22. Samardžić Lukić M, Bosanac M, Dobrijević D, Kovač N, Ćuk D, Milanović B. et al. KIM-1 – A new biomarker of kidney injury. Medical Data. 2021;13(3-4):157-61.
23. Rumpel J, Spray BJ, Chock VY, Kirkley MJ, Slagle CL, Frymoyer A, et al. Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic
Ischemic Encephalopathy Receiving Therapeutic Hypothermia. J Pediatr. 2022;241:133-40.
24. Assadi F, Sharbaf FG. Urine KIM-1 as a Potential Biomarker of Acute Renal Injury After Circulatory Collapse in Children. Pediatr Emerg Care. 2019;35(2):104-7.
25. Yin C, Wang N. Kidney injury molecule-1 in kidney disease. Ren Fail. 2016;38(10):1567-73.
26. Miao N, Yin F, Xie H, Wang Y, Xu Y, Shen Y, et al. The cleavage of gasdermin D by caspase-11 promotes tubular epithelial cell pyroptosis and urinary IL-18 excretion in acute kidney injury. Kidney Int. 2019;96(5):1105-20.
27. Dyson A, Kent AL. Diagnosis of Acute Kidney Injury in Neonates: Can Urinary Biomarkers Help? Curr Treat Options Pediatr. 2018;4:425-37.
28. Marin T, DeRossett B, Bhatia J. Urinary Biomarkers to Predict Neonatal Acute Kidney Injury: A Review of the Science. J Perinat Neonatal Nurs. 2018;32(3):266-74.
29. Oncel MY, Canpolat FE, Arayici S, Alyamac Dizdar E, Uras N, Oguz SS. Urinary markers of acute kidney injury in newborns with perinatal asphyxia. Ren Fail. 2016;38(6):882-8.
30. Essajee F, Were F, Admani B. Urine neutrophil gelatinaseassociated lipocalin in asphyxiated neonates: a prospective cohort study. Pediatr Nephrol. 2015;30(7):1189-96.
31. Perrone S, Weiss MD, Proietti F, Rossignol C, Cornacchione S, Bazzini F, et al. Identification of a panel of cytokines in neonates with hypoxic ischemic encephalopathy treated with hypothermia. Cytokine. 2018;111:119-24.
32. Durkan AM, Alexander RT. Acute kidney injury post neonatal asphyxia. J Pediatr. 2011;158(2):29-33.
33. Sweetman DU, Riordan M, Molloy EJ. Management of renal dysfunction following term perinatal hypoxia-ischaemia. Acta Paediatr. 2013;102(3):233-41.
34. Franch H, McClellan W, Mitch W. Chronic Kidney Disease: Pathophysiology and Influence of Dietary Protein. In: Alpern R, Hebert S, editors. Seldin and Giebisch's The Kidney. Cambridge: Academic Press; 2008. p. 2615-69.
35. El-Gendy FM, El-mo'men KA, Badr HS, Mohammed AE. β2 -Microglobulin predicts renal injury in asphyxiated neonates. Menoufia Med J. 2014;27:316-21.
36. Abdullah, Kadam P, Yachha M, Srivastava G, Pillai A, Pandita A. Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia. Eur J Pediatr. 2022;181(1):281-6.
37. Mehrkash M, Gheissari A, Barekatain B, Ziabi F, Tabatabaei S. Investigation of Urinary Beta-2 Microglobulin Level in Neonates with Asphyxia Admitted in Alzahra Hospitals in Isfahan, 1396-1397. Iran J Neonatol. 2021;12(1):61-5.
Published
2025/11/19
Section
Pregledni rad / Review article