新生儿急性肾损伤危险因素及新型生物标志物研究进展

doi:10.12372/jcp.2026.25e0928

Abstract

Abstract:

Neonatal acute kidney injury (AKI) predominantly occurs in critically ill infants, with an incidence rate of approximately 30% in neonatal intensive care units. It is associated with a significantly increased risk of mortality and a high propensity to progress to chronic kidney disease. This review mainly summarizes recent advances in the risk factors and emerging biomarkers for neonatal AKI. Besides, this review summarizes the clinical characteristics associated with different risk factors and the sensitivity and specificity of corresponding biomarkers. The occurrence of neonatal acute kidney injury is characterized by multifactorial interactions, and the pathological mechanisms vary depending on the underlying risk factors. The use of specific biomarkers facilitates early diagnosis and precise intervention. Combined monitoring of risk factors and biomarker levels enables early identification of acute kidney injury, guiding individualized treatment and prognosis assessment.

Key words: acute kidney injury, risk factor, biomarker, neonate

CLC Number:

ZHANG Wenjing, WANG Fan, ZHANG Li, LI Lan. Advances in risk factors and novel biomarkers for neonatal acute kidney injury[J].Journal of Clinical Pediatrics, 2026, 44(1): 71-78.

Figures/Tables 1

References 58

[1]	Ronco C, Bellomo R, Kellum JA. Acute kidney injury[J]. Lancet, 2019, 394(10212): 1949-1964. doi: S0140-6736(19)32563-2 pmid: 31777389
[2]	Ramya K, Mukhopadhyay K, Kumar J. Predictive factors and risk scoring system for acute kidney injury (AKI) in sick neonates-a prospective cohort study[J]. Eur J Pediatr, 2024, 183(12): 5419-5424. doi: 10.1007/s00431-024-05816-9 pmid: 39407040
[3]	Charlton JR, Boohaker L, Askenazi D, et al. Incidence and risk factors of early onset neonatal AKI[J]. Clin J Am Soc Nephrol, 2019, 14(2): 184-195. doi: 10.2215/CJN.03670318
[4]	Starr MC, Charlton JR, Guillet R, et al. Advances in Neonatal Acute Kidney Injury[J]. Pediatrics, 2021, 148(5): e2021051220.
[5]	Askenazi D, Abitbol C, Boohaker L, et al. Optimizing the AKI definition during first postnatal week using Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) cohort[J]. Pediatr Res, 2019, 85(3): 329-338. doi: 10.1038/s41390-018-0249-8 pmid: 30643188
[6]	De Mul A, Parvex P, Héneau A, et al. Urine output monitoring for the diagnosis of early-onset acute kidney injury in very preterm infants[J]. Clin J Am Soc Nephrol, 2022, 17(7): 949-956. doi: 10.2215/CJN.15231121
[7]	Meena J, Kumar J, Kocharlakota JP, et al. Acute kidney injury in neonates: a meta-analysis[J]. Pediatrics, 2024, 154(1): e2023065182.
[8]	Wu Y, Wang H, Pei J, et al. Acute kidney injury in premature and low birth weight neonates: a systematic review and meta-analysis[J]. Pediatr Nephrol, 2022, 37(2): 275-287. doi: 10.1007/s00467-021-05251-0
[9]	Medina Muñoz M, Cantó Cerdán M, Matías Del Pozo V, et al. Progression of serum creatinine and glomerular filtration rate in neonatal critical care patients during the first seven days of life[J]. Pediatr Nephrol, 2025, 40(5): 1783-1793. doi: 10.1007/s00467-024-06631-y
[10]	Iacobelli S, Guignard JP. Maturation of glomerular filtration rate in neonates and infants: an overview[J]. Pediatr Nephrol, 2021, 36(6): 1439-1446. doi: 10.1007/s00467-020-04632-1
[11]	Carpenter J, Yarlagadda S, VandenHeuvel KA, et al. Human nephrogenesis can persist beyond 40 postnatal days in preterm infants[J]. Kidney Int Rep, 2024, 9(2): 436-450. doi: 10.1016/j.ekir.2023.10.032 pmid: 38344733
[12]	Romejko K, Markowska M, Niemczyk S. The review of current knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL)[J]. Int J Mol Sci, 2023, 24(13): 10470. doi: 10.3390/ijms241310470
[13]	Renganathan A, Warner BB, Tarr PI, et al. The progression of serum cystatin C concentrations within the first month of life after preterm birth-a worldwide systematic review[J]. Pediatr Nephrol, 2021, 36(7): 1709-1718. doi: 10.1007/s00467-020-04543-1
[14]	Kuo J, Akison LK, Chatfield MD, et al. Serum and urinary biomarkers to predict acute kidney injury in premature infants: a systematic review and meta-analysis of diagnostic accuracy[J]. J Nephrol, 2022, 35(8): 2001-2014. doi: 10.1007/s40620-022-01307-y pmid: 35384606
[15]	Albert C, Zapf A, Haase M, et al. Neutrophil gelatinase-associated lipocalin measured on clinical laboratory platforms for the prediction of acute kidney injury and the associated need for dialysis therapy: a systematic review and meta-analysis[J]. Am J Kidney Dis, 2020, 76(6): 826-841. doi: 10.1053/j.ajkd.2020.05.015 pmid: 32679151
[16]	Ziegelasch N, Vogel M, Müller E, et al. Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage[J]. Pediatr Nephrol, 2019, 34(3): 449-457. doi: 10.1007/s00467-018-4087-z pmid: 30460495
[17]	Humphreys JD, Jain A, Khan AM, et al. Urinary biomarkers of acute kidney injury in neonates < 25 weeks' gestation: a pilot study[J]. Pediatr Nephrol, 2025, Epub ahead of print. DOI: 10.1007/s00467-025-06968-y.
[18]	Lakat T, Fekete A, Demeter K, et al. Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthoods[J]. Am J Physiol Renal Physiol, 2024, 327(2): F314-F326.
[19]	Bozkurt O, Yucesoy E. Acute kidney injury in neonates with perinatal asphyxia receiving therapeutic hypothermia[J]. Am J Perinatol, 2021, 38(9): 922-929. doi: 10.1055/s-0039-1701024
[20]	李玲, 管亚飞, 张存, 等. 窒息相关新生儿急性肾损伤危险因素及临床特征分析[J]. 实用临床医药杂志, 2024, 28(18): 81-85.
	Li L, Guan YF, Zhang C, et al. Prediction of risk factors and clinical features of asphyxia-related neonatal acute kidney injury[J]. Shiyong Linchuang Yiyao Zazhi, 2024, 28(18): 81-85.
[21]	Abdullah, Kadam P, Yachha M, et al. Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia[J]. Eur J Pediatr, 2022, 181(1): 281-286. doi: 10.1007/s00431-021-04205-w
[22]	Oso BI, Oseni SBA, Aladekomo TA, et al. Predictive ability of 2-h serum neutrophil gelatinase-associated lipocalin for perinatal asphyxia-induced acute kidney injury[J]. Pediatr Nephrol, 2024, 39(1): 283-289. doi: 10.1007/s00467-023-06054-1
[23]	Ostermann M, Cennamo A, Meersch M, et al. A narrative review of the impact of surgery and anaesthesia on acute kidney injury[J]. Anaesthesia, 2020, 75(Suppl 1): e121-e133.
[24]	Alten JA, Cooper DS, Blinder JJ, et al. Epidemiology of acute kidney injury after neonatal cardiac surgery: a report from the multicenter neonatal and pediatric heart and renal outcomes network[J]. Crit Care Med, 2021, 49(10): e941-e951.
[25]	Wu Y, Hua X, Yang G, et al. Incidence, risk factors, and outcomes of acute kidney injury in neonates after surgical procedures[J]. Pediatr Nephrol, 2020, 35(7): 1341-1346. doi: 10.1007/s00467-020-04532-4 pmid: 32232634
[26]	Cui Y, Fang X, Li J, et al. Evaluation of neonatal acute kidney injury (AKI) after emergency gastrointestinal surgery[J]. Asian J Surg, 2023, 46(5): 1924-1930. doi: 10.1016/j.asjsur.2022.08.086
[27]	Luan J, Fu J, Jiao C, et al. IL-18 deficiency ameliorates the progression from AKI to CKD[J]. Cell Death Dis, 2022, 13(11): 957. doi: 10.1038/s41419-022-05394-4 pmid: 36379914
[28]	Shi S, Fan J, Shu Q. Early prediction of acute kidney injury in neonates with cardiac surgery[J]. World J Pediatr Surg, 2020, 3(2): e000107.
[29]	Slagle CL, Goldstein SL, Gavigan HW, et al. Association between elevated urine neutrophil gelatinase-associated lipocalin and postoperative acute kidney injury in neonates[J]. J Pediatr. 2021, 238: 193-201. doi: 10.1016/j.jpeds.2021.07.041
[30]	Peerapornratana S, Manrique-Caballero CL, Gómez H, et al. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment[J]. Kidney Int, 2019, 96(5): 1083-1099. doi: S0085-2538(19)30601-5 pmid: 31443997
[31]	Coggins SA, Laskin B, Harris MC, et al. Acute kidney injury associated with late-onset neonatal sepsis: a matched cohort study[J]. J Pediatr, 2021, 231: 185-92. doi: 10.1016/j.jpeds.2020.12.023
[32]	Al Gharaibeh FN, Mohan S, Santoro MA, et al. Acute kidney injury and early fluid load in a retrospective cohort of neonatal sepsis[J]. Pediatr Nephrol, 2023, 38(6): 1971-1977. doi: 10.1007/s00467-022-05840-7
[33]	Abdelsattar S, Al-Amodi HS, Nazih M, et al. Genotype-phenotype correlation of TNF-α (-238, rs361525) and cystatin C for early detection of sepsis-associated aki and its severity in critically Ill neonates[J]. Int J Mol Sci, 2025, 26(14): 6738. doi: 10.3390/ijms26146738
[34]	Ganda IJ, Kasri Y, Susanti M, et al. Kidney injury molecule type-1, interleukin-18, and insulin-like growth factor binding protein 7 levels in urine to predict acute kidney injury in pediatric sepsis[J]. Front Pediatr, 2022, 10: 1024713. doi: 10.3389/fped.2022.1024713
[35]	Garg PM, Tatum R, Ravisankar S, et al. Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins[J]. Pediatric research, 2015, 78(5): 527-532. doi: 10.1038/pr.2015.146 pmid: 26270572
[36]	Garg PM, Pittman IA, Ansari MAY, et al. Gestational age-specific clinical correlates of acute kidney injury in preterm infants with necrotizing enterocolitis[J]. Pediatr Res, 2023, 94(6): 2016-2025. doi: 10.1038/s41390-023-02736-6 pmid: 37454184
[37]	杨霄, 张诗雨, 刘一帆, 等. 早产儿坏死性小肠结肠炎合并急性肾损伤的临床研究[J]. 中华新生儿科杂志(中英文), 2024, 39(11): 669-673.
	Yang X, Zhang SY, Liu YF, et al. A clinical investigation on acute kidney injury among premature infants diagnosed with necrotizing enterocolitis[J]. Zhonghua Xinshengerke Zazhi, 2024, 39(11): 669-673.
[38]	Ting JY, McDougal K, De Mello A, et al. Acute kidney injury among preterm infants receiving nonsteroidal anti-inflammatory drugs: a pilot study[J]. Pediatr Neonatol. 2023, 64(3): 313-318. doi: 10.1016/j.pedneo.2022.06.018
[39]	McWilliam SJ, Antoine DJ, Smyth RL, et al. Aminoglycoside-induced nephrotoxicity in children[J]. Pediatr Nephrol. 2017, 32(11): 2015-2025. doi: 10.1007/s00467-016-3533-z pmid: 27848094
[40]	Murphy HJ, Thomas B, Van Wyk B, et al. Nephrotoxic medications and acute kidney injury risk factors in the neonatal intensive care unit: clinical challenges for neonatologists and nephrologists[J]. Pediatr Nephrol, 2020, 35(11): 2077-2088. doi: 10.1007/s00467-019-04350-3 pmid: 31605211
[41]	万隽, 赖昕, 陈权耀, 等. 万古霉素血清谷浓度与药时曲线下面积预测新生儿肾毒性的临床应用价值[J]. 中国感染与化疗杂志, 2024, 24(6): 645-651. doi: 10.16718/j.1009-7708.2024.06.003
	Wan J, Lai X, Chen QY, et al. Clinical utility of vancomycin serum trough concentrations and area under the curve in predicting nephrotoxicity in neonates[J]. Zhongguo Gan ran Yu Hualiao Zazhi, 2024, 24(6): 645-651.
[42]	Zhang M, Huang L, Zhu Y, et al. Epidemiology of vancomycin in combination with piperacillin/tazobactam-associated acute kidney injury in children: a systematic review and meta-analysis[J]. Ann Pharmacother, 2024, 58(10): 1034-1044. doi: 10.1177/10600280231220379
[43]	Downes KJ, Hayes M, Fitzgerald JC, et al. Mechanisms of antimicrobial-induced nephrotoxicity in children[J]. J Antimicrob Chemother, 2020, 75(1): 1-13. doi: 10.1093/jac/dkz325 pmid: 31369087
[44]	Downes KJ, Boge CLK, Baro E, et al. Acute kidney injury during treatment with intravenous acyclovir for suspected or confirmed neonatal herpes simplex virus infection[J]. J Pediatr, 2020, 219: 126-132. doi: 10.1016/j.jpeds.2019.12.056
[45]	王天有, 申昆玲, 沈颖. 诸福棠实用儿科学(第9版)[M]. 北京: 人民卫生出版社, 2022: 353-354.
	Wang TY, Shen KL, Shen Y. Zhu Futang's Practical Pediatrics (9^th ed.)[M]. Beijing: People's Medical Publishing House, 2022: 353-354.
[46]	Stoops C, Stone S, Evans E, et al. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): Reduction of nephrotoxic medication-associated acute kidney injury in the neonatal intensive care unit[J]. J Pediatr, 2019, 215: 223-228. doi: 10.1016/j.jpeds.2019.08.046
[47]	Yang C, Xu H, Yang D, et al. A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury[J]. Nat Commun, 2023, 14(1): 4261. doi: 10.1038/s41467-023-40036-z pmid: 37460623
[48]	Sridharan K, Al Jufairi M, Al Segai O, et al. Biomarkers in neonates receiving potential nephrotoxic drugs[J]. Eur Rev Med Pharmacol Sci, 2021, 25(22): 7078-7088.
[49]	Raina R, Chakraborty R, Tibrewal A, et al. Advances in pediatric acute kidney injury[J]. Pediatr Res, 2022, 91(1): 44-55. doi: 10.1038/s41390-021-01452-3
[50]	Prideaux MA, Guillet R. The use of low-dose dopamine in the neonatal intensive care unit[J]. NeoReviews, 2024, 25(4): e207-e215.
[51]	Bhatt GC, Gogia P, Bitzan M, et al. Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review[J]. Arch Dis Child, 2019, 104(7): 670-679. doi: 10.1136/archdischild-2018-315805 pmid: 30798259
[52]	Harer MW, Askenazi DJ, Boohaker LJ, et al. Association between early caffeine citrate administration and risk of acute kidney injury in preterm neonates: results from the AWAKEN study[J]. JAMA Pediatr, 2018, 172(6): e180322.
[53]	Tzvi-Behr S, Schlesinger N, Ben-Shalom E, et al. The incidence of acute kidney injury in very-low-birth-weight infants treated early with caffeine[J]. Pediatr Nephrol, 2025, 40(6): 2091-2096. doi: 10.1007/s00467-025-06694-5
[54]	Devaranavadagi RA, Thomas J, Vishwanath S, et al. Successful initiation of continuous kidney replacement therapy in an extremely premature infant[J]. Pediatr Nephrol, 2025, 40(9):2811-2813. doi: 10.1007/s00467-025-06763-9
[55]	Robinson CH, Jeyakumar N, Luo B, et al. Long-term kidney outcomes after pediatric acute kidney injury[J]. J Am Soc Nephrol, 2024, 35(11): 1520-1532. doi: 10.1681/ASN.0000000000000445 pmid: 39018120
[56]	Kimberly J Reidy, Ronnie Guillet, David T Selewski, et al. Advocating for the inclusion of kidney health outcomes in neonatal research: best practice recommendations by the Neonatal Kidney Collaborative[J]. J Perinatol, 2024, 44(12): 1863-1873. doi: 10.1038/s41372-024-02030-1 pmid: 38969825
[57]	Akkoc G, Duzova A, Korkmaz A, et al. Long-term follow-up of patients after acute kidney injury in the neonatal period: abnormal ambulatory blood pressure findings[J]. BMC Nephrol, 2022, 23(1): 116. doi: 10.1186/s12882-022-02735-5 pmid: 35321692
[58]	Chen CC, Chu CH, Lin YC, et al. Neurodevelopment after neonatal acute kidney injury in very preterm-birth children[J]. Kidney Int Rep. 2023, 8(9): 1784-1791.

分期	sCr	尿量（24 h）/ mL·kg^-1·h^-1
1期	48小时内sCr较基线值上升≥0.3 mg·dL^-1或7天内sCr较基线值上升1.5~1.9倍	<1
2期	7天内sCr较基线值上升2.0~2.9倍	<0.5
3期	7天内sCr较基线值上升3倍或sCr≥2.5 mg·dL^-1或需肾脏替代治疗	<0.3

Advances in risk factors and novel biomarkers for neonatal acute kidney injury

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 1

References 58

Related Articles 15

Metrics

Comments

Recommended 0

[1]	LI Shanshan, HU Dandan. Analysis of risk factors for death from influenza A (H1N1)-associated encephalopathy in children [J]. Journal of Clinical Pediatrics, 2025, 43(3): 177-183.
[2]	HUANG Jing, LIU Xiaochen, GAO Xiong, LI Xiaowen, LI Guanghong, LI Luquan. The value of measuring trace elements and oxidative/antioxidant factors in umbilical blood in predicting the onset and evaluation of neonatal respiratory distress syndrome [J]. Journal of Clinical Pediatrics, 2025, 43(3): 204-210.
[3]	HE Ying, LIU Zhiyong, YANG Hansong, CAI Yali, XU Jinglin, CHEN Dongmei. Clinical analysis of 153 neonatal enterovirus infections and antibiotic management improvement study [J]. Journal of Clinical Pediatrics, 2025, 43(2): 128-134.
[4]	CHEN Chao. Significance of introducing the concept of “small vulnerable newborns” [J]. Journal of Clinical Pediatrics, 2025, 43(11): 803-806.
[5]	LI Jing, LIANG Xuxia, ZHANG Jihong, ZHANG Chun, LU Yanqun, WU Hua. Parental factors associated with singleton small vulnerable neonates: a 5-year retrospective cohort study [J]. Journal of Clinical Pediatrics, 2025, 43(11): 807-815.
[6]	YANG Mengyuan, CHEN Yanshan, PEI Wanjun, LI Jing, DONG Huifang. A single - center study on extrauterine growth retardation in preterm infants after surgery for necrotizing enterocolitis [J]. Journal of Clinical Pediatrics, 2025, 43(11): 823-829.
[7]	ZHENG Ruixue, SUN Xiaodong, WU Guilan, SHEN Leilei. Neonatal refractory congenital chylothorax: two case reports and literature review [J]. Journal of Clinical Pediatrics, 2025, 43(10): 775-781.
[8]	JIANG Weiqin, WANG Jing, CHENG Anna, CHEN Tingting, HUANG Yujuan. Predictors of recurrent febrile seizures during the same febrile illness in children with febrile seizures [J]. Journal of Clinical Pediatrics, 2025, 43(1): 8-13.
[9]	DING Yaping, XIA Shanshan, ZHANG Chenmei. Interpretation of “2023 Children’s Renal Nutrition Working Group Clinical Practice Recommendations: Nutritional Management of Children with Acute Kidney Injury” [J]. Journal of Clinical Pediatrics, 2024, 42(8): 667-672.
[10]	WANG Dan, SHAO Jingbo, LI Hong, ZHANG Na, ZHU Jiashi, FU Pan, WANG Zhen. Clinical analysis of 38 cases of hematological malignancies complicated with tumor lysis syndrome in children [J]. Journal of Clinical Pediatrics, 2024, 42(8): 684-690.
[11]	ZHANG Ruijie, XI Guannan, WANG Xuefeng, LIN Xin’ao, DAI Jiale, FAN Xiaobo, WANG Jimei. Application of simplified lung ultrasound performed shortly after birth in the respiratory support needs of late preterm and term infants [J]. Journal of Clinical Pediatrics, 2024, 42(8): 714-721.
[12]	WANG Man, LI Luquan, LI Xiaowen. Analysis of risk factors for early-onset sepsis associated acute kidney injury in neonates [J]. Journal of Clinical Pediatrics, 2024, 42(6): 520-525.
[13]	LI Zhijuan, BAO Ying, HUANG Huimei, ZHANG Min, WANG Ying, NIU Yunhe, YANG Nan, SUO Lei, LIANG Nan. Clinical features and factors associated with diabetes mellitus in children-onset systemic lupus erythematosus [J]. Journal of Clinical Pediatrics, 2024, 42(5): 419-424.
[14]	DAI Nini, GAO Yajuan, SUN Jinbo, ZHANG Juan, LI Zailing. The dynamic changes and application value of MUC2 and sIgA in intestinal mucus layer of infants with food allergy [J]. Journal of Clinical Pediatrics, 2024, 42(4): 297-304.
[15]	CHEN Mengxue, LI Jingyang, YANG Fen, TIAN Ye, LI Jing, DING Guodong. Clinical features and risk factors of macrolide-resistant severe Mycoplasma pneumoniae pneumonia in children [J]. Journal of Clinical Pediatrics, 2024, 42(3): 187-192.