Urinarni biomarkeri kao rani indikatori akutnog bubrežnog oštećenja kod neonatusa sa perinatalnom asfiksijom
Biomarkeri akutnog bubrežnog oštećenja
Ključne reči:
perinatalna asfiksija, akutna bubrežna insuficijencija, urinarni biomarkeri
Sažetak
Perinatalna asfiksija (PA) je stanje u kojem je neposredno pre, u toku ili neposredno nakon porođaja smanjen ili prekinut dotok krvi i kiseonika tkivima fetusa, tj. novorođenčeta. Predstavlja značajan uzrok mortaliteta i čini 23-24% svih letalnih ishoda u neonatalnom periodu. Procenjena incidencija perinatalne hipoksije na globalnom nivou iznosi oko 0,5% od ukupnog broja živorođene dece gestacijske starosti preko 36 nedelja. PA ima negativan uticaj na čitav organizam, a posebno na metabolički vrlo zahtevna tkiva. Kako su bubrezi veoma osetljivi na deprivaciju kiseonika, akutna bubrežna insuficijencija (ABI) se može razviti već u prva 24 sata od početka ishemične epizode. Ukoliko se ishemija prolongira, može doći i do ireverzibilne kortikalne nekroze. Rano prepoznavanje ABI je veoma važno radi adekvatne nadoknade tečnosti i elektrolita, jer delovanje prerenalnih etioloških faktora predstavlja dinamičan proces čiji je početak reverzibilan. Ipak, ABI predstavlja loš prognostički znak. Mortalitet je veći kod neonatusa koji nakon perinatalne asfiksije razviju i ABI, a čak do 40% preživelih može imati trajno oštećenje bubrega. Imajući u vidu specifičnosti kako populacije tako i samog kliničkog entiteta, jasna je potreba za novijim, senzitivnijim i specifičnijim biomarkerima bubrežne fukcije. Kada se razmatra potencijalni biohemijski marker, vrsta biološkog uzorka u kojem se isti kvantifikuje je jedna od glavnih karakteristika koja se mora uzeti u obzir. Za novorođenčad je od izuzetnog značaja da dobijanje uzorka bude neinvazivno. Imajući to u vidu, analiza urina se nameće kao dobar izbor. Metaboliti u urinu pacijenata s PA su dokazano značajni za praćenje renalne funkcije.
Reference
1. Moshiro R, Mdoe P, Perlman JM. A Global View of Neonatal Asphyxia and Resuscitation. Front Pediatr. 2019;7:489.
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.
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.
Objavljeno
2025/11/19
Broj časopisa
Rubrika
Pregledni rad / Review article