新生儿早发型败血症并发的急性肾损伤危险因素分析

doi:10.12372/jcp.2024.23e1250

摘要/Abstract

摘要：

目的分析新生儿早发型败血症（EOS）临床资料，探索影响新生儿早发型败血症并发急性肾损伤（AKI）的危险因素。方法通过回顾分析2018年1月至2022年4月于新生儿科病房住院的EOS患儿的临床资料，将满足新生儿改良KDIGO AKI诊断标准的患儿设为AKI组，按照1∶2配对，纳入不合并AKI患儿设为NAKI组，比较临床资料，调查分析影响新生儿早发型败血症并发急性肾损伤（ESA-AKI）的危险因素。结果研究期间共纳入AKI组70例，NAKI组140例。单因素条件logstic回归分析发现，入院日龄大、母孕期高血压、窒息、入院时血尿素氮和肌酐水平高，合并中重度贫血、肺出血、动脉导管未闭、感染性休克，小剂量多巴胺、美罗培南暴露以及手术是AKI发病的危险因素，AKI组死亡或放弃治疗率高（P<0.05)。结论在早发型败血症群体中，对于入院日龄大、窒息、母孕期高血压，入院时血尿素氮和肌酐水平高，合并中重度贫血、肺出血、动脉导管未闭和感染性休克，使用多巴胺和美罗培南以及手术的EOS患儿，需警惕入院后AKI发生。

关键词: 急性肾损伤, 早发型败血症, 危险因素, 新生儿

Abstract:

Objective The clinical data of neonates with early-onset sepsis (EOS) were analyzed in order to explore the risk factors affecting neonatal early-onset sepsis associated acute kidney injury (AKI). Methods The clinical data of EOS neonates hospitalized in the neonatal ward from January 2018 to April 2022 were retrospectively analyzed. The neonates meeting the revised KDIGO AKI diagnostic criteria were assigned to AKI group, and the neonates without AKI were assigned to NAKI group according to 1:2 matching method. The clinical data between the two groups were compared to analyze the risk factors of neonatal early-onset sepsis complicated with acute kidney injury (ESA-AKI). Results A total of 70 neonates in the AKI group and 140 in the NAKI group were included in the study. A univariate conditional logistic regression analysis revealed that older admission age, maternal hypertension during pregnancy, asphyxia, high levels of serum urea nitrogen and creatinine at admission, coexisting with moderate to severe anemia, pulmonary hemorrhage, patent ductus arteriosus, septic shock, exposure to small doses of dopamine and meropenem, and surgery were risk factors for the development of AKI. The AKI group had a higher rate of death or abandonment (P<0.05). Conclusions AKI should be closely monitored in the group of neonates with EOS who were treated with dopamine, meropenem, and surgery and who had higher admission ages, asphyxia, maternal hypertension during pregnancy, high serum urea nitrogen and creatinine levels at admission, complicated by moderate to severe anemia, pulmonary hemorrhage, patent ductus arteriosus, and septic shock.

Key words: acute kidney injury, early-onset sepsis, risk factor, neonate

汪漫, 李禄全, 李晓文. 新生儿早发型败血症并发的急性肾损伤危险因素分析[J]. 临床儿科杂志, 2024, 42(6): 520-525.

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.

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参考文献 29

[1]	中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257.
[2]	Flannery DD, Puopolo KM. Neonatal early-onset sepsis[J]. Neoreviews, 2022, 23(11): 756-770. doi: 10.1542/neo.23-10-e756 pmid: 36316253
[3]	Deep A, Sagar H, Goonasekera C, et al. Evolution of acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock[J]. Crit Care Med, 2018, 46(7): 677-683. doi: 10.1097/CCM.0000000000003156 pmid: 29677008
[4]	Fitzgerald JC, Ross ME, Thomas NJ, et al. Risk factors and inpatient outcomes associated with acute kidney injury at pediatric severe sepsis presentation[J]. Pediatr Nephrol, 2018, 33(10): 1781-1790. doi: 10.1007/s00467-018-3981-8 pmid: 29948309
[5]	Ozkaya PY, Taner S, Ersayoğlu I, et al. Sepsis associated acute kidney injury in pediatric intensive care unit[J]. Ther Apher Dial, 2023, 27(1): 73-82.
[6]	Zhang W, Qi R, Li T, et al. Kidney organoids as a novel platform to evaluate lipopolysaccharide-induced oxidative stress and apoptosis in acute kidney injury[J]. Front Med (Lausanne), 2021, 8: 766073.
[7]	Hua T, Wu X, Wang W, et al. Micro- and macrocirculatory changes during sepsis and septic shock in a rat model[J]. Shock, 2018, 49(5): 591-595. doi: 10.1097/SHK.0000000000000954 pmid: 28731900
[8]	Flannery AH, Ortiz-Soriano V, Li X, et al. Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study[J]. Crit Care, 2021, 25(1): 294.
[9]	van der Slikke EC, Star BS, van Meurs M, et al. Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI[J]. Crit Care, 2021, 25(1): 36.
[10]	Fitzgerald JC, Ross ME, Thomas NJ, et al. Association of early hypotension in pediatric sepsis with development of new or persistent acute kidney injury[J]. Pediatr Nephrol, 2021, 36(2): 451-461.
[11]	Jetton JG, Boohaker LJ, Sethi SK, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study[J]. Lancet Child Adolesc Health, 2017, 1(3): 184-194. doi: 10.1016/S2352-4642(17)30069-X pmid: 29732396
[12]	Durkan AM, Alexander RT. Acute kidney injury post neonatal asphyxia[J]. J Pediatr, 2011, 158(2 Suppl): e29-e33.
[13]	Saikumar P, Venkatachalam MA. Role of apoptosis in hypoxic/ischemic damage in the kidney[J]. Semin Nephrol, 2003, 23(6): 511-521. pmid: 14631559
[14]	Chan EG, Pan G, Clifford S, et al. Postoperative acute kidney injury and long-term outcomes after lung transplantation[J]. Ann Thorac Surg, 2023, 116(5): 1056-1062.
[15]	Kuo G, Chen JJ, Yen CL, et al. Association between early, small creatinine elevation and severe acute kidney injury in critically ill adult patients[J]. J Crit Care, 2022, 72: 154142.
[16]	潘益匆, 王大化, 郑俊虎, 等. 妊娠期高血压疾病对新生儿肾功能及脐血胆红素水平的影响[J]. 中国优生与遗传杂志, 2018, 26(11): 80-82.
[17]	Yuan T, Zhang T, Han Z. Placental vascularization alterations in hypertensive disorders complicating pregnancy (HDCP) and small for gestational age with HDCP using three-dimensional power doppler in a prospective case control study[J]. BMC Pregnancy Childbirth, 2015, 15: 240.
[18]	Yang Y, Xie Y, Li M, et al. Characteristics and fetal outcomes of pregnant women with hypertensive disorders in China: a 9-year national hospital-based cohort study[J]. BMC Pregnancy Childbirth, 2022, 22(1): 924.
[19]	陈子衿, 阳海平, 张高福, 等. 极低出生体质量儿急性肾损伤的危险因素及结局分析[J]. 临床儿科杂志, 2018, 36(6): 406-410.
[20]	Teixeira JP, Ambruso S, Griffin BR, et al. Pulmonary consequences of acute kidney injury[J]. Semin Nephrol, 2019, 39(1): 3-16. doi: S0270-9295(18)30152-9 pmid: 30606405
[21]	Iribarren I, Hilario E, Álvarez A, et al. Neonatal multiple organ failure after perinatal asphyxia[J]. An Pediatr (Engl Ed), 2022, 97(4): 280.
[22]	Gul R, Anwar Z, Sheikh M, et al. Neonatal AKI profile using KDIGO guidelines: a cohort study in tertiary care hospital ICU of Lahore, Pakistan[J]. Front Pediatr, 2022, 10: 1040077.
[23]	Majed B, Bateman DA, Uy N, et al. Patent ductus arteriosus is associated with acute kidney injury in the preterm infant[J]. Pediatr Nephrol, 2019, 34(6): 1129-1139. doi: 10.1007/s00467-019-4194-5 pmid: 30706125
[24]	Stanski NL, Pode Shakked N, Zhang B, et al. Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock[J]. Pediatr Nephrol, 2023, 38(9): 3099-3108. doi: 10.1007/s00467-023-05930-0 pmid: 36939916
[25]	Bellomo R, Forni LG, Busse LW, et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A Clinical Trial[J]. Am J Respir Crit Care Med, 2020, 202(9): 1253-1261.
[26]	Tumlin JA, Murugan R, Deane AM, et al. Angiotensin II for the treatment of high-output shock 3 (ATHOS-3) investigators. outcomes in patients with vasodilatory shock and renal replacement therapy[J]. Crit Care Med, 2018, 46(6): 949-957. doi: 10.1097/CCM.0000000000003092 pmid: 29509568
[27]	Zhang P, Tong Y, Yuan D, et al. Association of high-sensitivity C-reactive protein and anemia with acute kidney injury in neonates[J]. Front Pediatr, 2022, 10: 882739.
[28]	王彦娥, 丁伶清, 宋洪涛, 等. 非ICU患者肾毒性药物与急性肾损伤关系的病例对照研究[J]. 中国医院药学杂志, 2018, 38(8): 869-873.
[29]	Gorham J, Taccone FS, Hites M. Drug regimens of novel antibiotics in critically ill patients with varying renal functions: a rapid review[J]. Antibiotics (Basel), 2022, 11(5): 546.

因素	β	χ²值	P	OR(95%CI)
女性	－0.27	1.08	0.298	0.76(0.45~1.27)
窒息	0.75	5.81	0.016	2.12(1.15~3.90)
小于胎龄儿	0.22	0.26	0.607	1.25(0.54~2.91)
入院日龄^1）	0.01	0.52	0.047	1.01(0.99~1.03)
多胎或双胎	0.47	2.46	0.117	1.59(0.89~2.85)
剖宫产	－0.15	0.19	0.659	0.87(0.45~1.65)
绒毛膜羊膜炎	－0.84	1.56	0.210	0.43(0.12~1.61)
胎膜早破≥18 h	－0.28	0.52	0.472	0.76(0.35~1.62)
羊水污染	0.54	1.66	0.199	1.71(0.75~3.87)
妊娠期高血压	0.87	5.15	0.023	2.38(1.12~5.03)
妊娠期糖尿病	0.48	2.07	0.149	1.61(0.84~3.07)
产前激素暴露	0.33	1.10	0.292	1.40(0.75~2.60)

因素	β	χ²值	P	OR(95%CI)
入院血肌酐值^1）	0.04	28.94	<0.001	1.05(1.03~1.06)
入院血尿素氮^1）	0.27	18.06	<0.001	1.32(1.16~1.49)
K^+1）	－0.23	1.56	0.212	0.80(0.56~1.14)
入院时血糖^1）	0.10	2.40	0.122	1.11(0.97~1.26)
I/T比值^1）	0.47	0.08	0.783	1.60(0.06~45.77)
血小板值^1）	－0.01	3.42	0.065	0.10(0.10~1.00)
CRP≥10 mg/L	－0.57	3.35	0.067	0.57(0.31~1.04)
血培养阳性	0.40	1.12	0.288	1.49(0.71~3.11)
革兰阴性菌	0.61	1.54	0.216	1.84(0.70~4.86)

因素	β	χ²值	P	OR(95%CI)
颅内感染	0.06	0.02	0.885	1.06(0.46~2.47)
新生儿呼吸窘迫综合征	0.23	0.40	0.531	1.25(0.62~2.54)
新生儿坏死性小肠结肠炎	0.26	0.37	0.539	1.30(0.56~2.99)
颅内出血	0.45	1.77	0.182	1.57(0.81~3.04)
缺氧缺血性脑病	0.69	0.24	0.624	2.00(0.13~31.98)
低白蛋白血症	0.48	1.82	0.179	1.61(0.80~3.24)
中重度贫血	1.28	7.34	0.007	3.59(1.43~9.02)
高钾血症	0.28	0.56	0.454	1.32(0.64~2.71)
肺出血	1.26	12.53	<0.001	3.52(1.75~7.06)
动脉导管未闭	0.80	5.20	0.023	2.22(1.12~4.43)
感染性休克	1.38	11.83	<0.001	3.97(1.81~8.76)
胃肠穿孔	0.76	1.80	0.179	2.13(0.71~6.43)
住院天数	0.01	0.05	0.816	1.00(0.99~1.02)
死亡/放弃治疗	0.98	3.92	0.048	2.67(1.01~7.05)

因素	β	χ²值	P	OR(95%CI)
小剂量多巴胺	1.03	9.30	0.002	2.79(1.44~5.41)
布洛芬	0.53	1.82	0.178	1.69(0.79~3.64)
咖啡因	－0.14	0.10	0.758	0.87(0.35~2.14)
肺泡表面活性物质	0.37	1.59	0.210	1.45(0.81~2.58)
替考拉宁	－0.67	3.57	0.060	0.51(0.26~1.03)
万古霉素	0.57	0.77	0.377	1.77(0.50~6.24)
氨基糖苷类	－0.55	0.66	0.419	0.58(0.15~2.19)
美罗培南	1.17	10.76	0.001	3.23(1.60~6.51)
亚胺培南	－0.05	0.01	0.908	0.95(0.38~2.36)
青霉素类	－0.58	2.46	0.117	0.56(0.27~1.16)
抗真菌类	－0.75	3.06	0.081	0.47(0.20~1.10)
呋塞米	0.52	2.19	0.140	1.68(0.84~3.35)
机械通气	0.55	1.66	0.196	1.73(0.75~4.00)
中心静脉置管	0.71	2.59	0.108	2.04(0.86~4.86)
手术	1.24	6.92	0.009	3.44(1.37~8.65)