合并急性肾损伤的危重症患者输注白蛋白后血清白蛋白水平与28 d死亡率的相关性

doi:10.12122/j.issn.1673-4254.2025.05.21

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (5): 1074-1081.doi: 10.12122/j.issn.1673-4254.2025.05.21

合并急性肾损伤的危重症患者输注白蛋白后血清白蛋白水平与28 d死亡率的相关性

张柳攀¹^,²(), 石晓彤³, 李露兰¹, 师瑞⁴, 安胜利³, 曾振华¹()

^1.南方医科大学第一临床医学院/南方医院重症医学科，广东广州 510515
^2.中山市神湾医院内科，广东中山 528400
^3.南方医科大学公共卫生学院（广东省热带病研究重点实验室）生物统计学系，广东广州 510515
^4.中山大学第一附属医院重症医学科，广东广州 510062

收稿日期:2025-02-06 出版日期:2025-05-20 发布日期:2025-05-23
通讯作者: 曾振华 E-mail:50804260@qq.com;zhenhuazeng.2008@163.com
作者简介:张柳攀，硕士，主治医师，E-mail: 50804260@qq.com
基金资助:
国家自然科学基金(82172175)

Association between serum albumin levels after albumin infusion and 28-day mortality in critically ill patients with acute kidney injury

Liupan ZHANG¹^,²(), Xiaotong SHI³, Lulan LI¹, Rui SHI⁴, Shengli AN³, Zhenhua ZENG¹()

^1.Department of Critical Care Medicine, First Clinical Medical College of Southern Medical University, Nanfang Hospital, Guangzhou 510515, China
^2.Department of Internal Medicine, Shenwan Hospital, Zhongshan 528400, China
^3.Department of Biostatistics, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou 510515, China
^4.Department of Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510062, China

Received:2025-02-06 Online:2025-05-20 Published:2025-05-23
Contact: Zhenhua ZENG E-mail:50804260@qq.com;zhenhuazeng.2008@163.com
Supported by:
National Natural Science Foundation of China(82172175)

摘要/Abstract

摘要：

目的探讨危重症急性肾损伤（AKI）患者输注人血白蛋白后不同血清白蛋白水平与28 d死亡率的关系及其对90 d死亡率、液体出入量、持续肾脏替代治疗、机械通气比例及时间等的影响。方法回顾性纳入MIMIC IV数据库（2008~2019年）5918例在ICU内接受白蛋白治疗的AKI患者的资料，根据输注后72 h内血清白蛋白水平将其分为低白蛋白组（LA，<30 g/L）、中等白蛋白组（MA，30~35 g/L）和高白蛋白组（HA，>35 g/L） 3组，采用限制性立方样条回归及多因素Logistic回归分析白蛋白水平与死亡率的关系。另纳入南方医科大学南方医院2017年1月~2022年2月的110例脓毒症AKI患者作为外部验证队列，通过生存分析和多因素校正验证结果。结果在MIMIC训练队列中，多因素Logistic回归分析显示不同白蛋白分组与危重症AKI患者28 d死亡率无相关性（P>0.05），但限制性立方样条分析提示白蛋白水平与28 d死亡率呈非线性剂量反应关系（阈值效应：>36 g/L时风险升高）。次要终点分析显示，与LA组相比，HA组机械通气时间更短（P<0.001），但ICU住院时间延长（P<0.001）。外部验证队列中，白蛋白水平≥30 g/L与28 d死亡率降低相关（P<0.05）。结论输注人血白蛋白以提高血清白蛋白水平与AKI危重患者28 d死亡率的关系存在队列依赖性，可能受疾病类型及严重程度、输注策略及统计方法等多因素影响。

关键词: 急性肾损伤, 危重症患者, 白蛋白输注, 血清白蛋白水平, 28 d死亡率

Abstract:

Objective To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. Methods We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. Results In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). Conclusion The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.

Key words: acute kidney injury, critically ill patients, albumin infusion, serum albumin level, 28-day mortality

张柳攀, 石晓彤, 李露兰, 师瑞, 安胜利, 曾振华. 合并急性肾损伤的危重症患者输注白蛋白后血清白蛋白水平与28 d死亡率的相关性[J]. 南方医科大学学报, 2025, 45(5): 1074-1081.

Liupan ZHANG, Xiaotong SHI, Lulan LI, Rui SHI, Shengli AN, Zhenhua ZENG. Association between serum albumin levels after albumin infusion and 28-day mortality in critically ill patients with acute kidney injury[J]. Journal of Southern Medical University, 2025, 45(5): 1074-1081.

图/表 7

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Variable	Total (n=7126)	NKD (n=1208)	AKI (n=5918)	P
Age [year, Median (P₂₅, P₇₅)]	68.05(58.97, 76.40)	66.11(58.17, 73.55)	68.49(59.21, 76.95)	<0.001
Female [n (%)]	2785(39.08)	403(33.36)	2382(40.25)	<0.001
Emergency [n (%)]	2148 (30.14)	210 (17.38)	1938 (32.75)	<0.001
Weight [kg, Median (P₂₅, P₇₅)]	80.25(68.50, 94.30)	74.80 (65.00, 85.40)	81.80 (69.60, 96.30)	<0.001
Height (cm, Mean±SD)	169.96±10.51	169.98±10.26	169.96±10.56	0.953
Comorbidity [n (%)]
Diabetes	1861 (26.12)	287 (23.76)	1574 (26.60)	0.044
Coronary atherosclerotic heart disease	3757 (52.72)	729 (60.35)	3028 (51.17)	<0.001
Hypertension	4346 (60.99)	742 (61.42)	3604 (60.90)	0.758
Cerebral Infarction	202 (2.83)	13 (1.08)	189 (3.19)	<0.001
Heart failure	1619 (22.72)	190 (15.73)	1429 (24.15)	<0.001
Cancer	680 (9.54)	91 (7.53)	589 (9.95)	0.011
Gastrointestinal related diseases	365 (5.12)	33 (2.73)	332 (5.61)	<0.001
Chronic obstructive pulmonary disease	1606 (22.54)	245 (20.28)	1361 (23.00)	0.043
Sepsis	4379 (61.45)	594 (49.17)	3785 (63.96)	<0.001
Burns	8 (0.11)	0 (0.00)	8 (0.14)	0.420
RR [min, Median (P₂₅, P₇₅)]	16.00 (14.00, 19.00)	16.00 (14.00, 17.00)	16.00 (14.00, 20.00)	<0.001
HR [b/min, Median (P₂₅, P₇₅)]	82.00 (76.00, 94.00)	80.00 (75.00, 88.00)	83.00 (77.00, 95.00)	<0.001
T [°C, Median (P₂₅, P₇₅)]	36.50 (36.00, 36.83)	36.44 (35.80, 36.72)	36.50 (36.10, 36.83)	<0.001
MAP [mmHg, Median (P₂₅, P₇₅)]	77.00 (69.00, 87.00)	78.00 (70.00, 86.00)	77.00 (68.00, 87.00)	0.633
SpO₂ [%, Median (P₂₅, P₇₅)]	100.00 (98.00, 100.00)	100.00 (99.00, 100.00)	100.00 (97.00, 100.00)	<0.001
Albumin level (g/dL, Mean±SD)	2.84±0.72	3.02±0.74	2.83±0.72	0.002
WBCs [×10⁹, Median (P₂₅, P₇₅)]	11.80 (8.40, 16.10)	11.50 (8.45, 15.45)	11.90 (8.40, 16.30)	0.105
Hemoglobin, [g/dL, Median (P₂₅, P₇₅)]	11.90 (10.10, 13.30)	12.50 (11.10, 13.60)	11.70 (10.00, 13.20)	<0.001
PLT [×10⁹, Median (P₂₅, P₇₅)]	157.00 (117.00, 216.00)	150.00 (116.00, 195.00)	159.00 (117.00, 222.00)	<0.001
Glucose [mg/dL, Median (P₂₅, P₇₅)]	114.00 (99.00, 146.00)	107.00 (96.00, 131.00)	115.00 (100.00, 149.00)	<0.001
Cr [mg/dL, Median (P₂₅, P₇₅)]	0.90 (0.70, 1.10)	0.80 (0.60, 0.90)	0.90 (0.70, 1.10)	<0.001
Lac [mmol/L, Median (P₂₅, P₇₅)]	1.50 (1.10, 2.10)	1.40 (1.10, 1.80)	1.50 (1.10, 2.20)	<0.001
SAPS II [Median (P₂₅, P₇₅)]	38.00 (31.00, 46.00)	33.00 (28.00, 40.00)	39.00 (32.00, 48.00)	<0.001
SOFA [Median (P₂₅, P₇₅)]	6.00 (4.00, 9.00)	5.00 (4.00, 7.00)	7.00 (5.00, 9.00)	<0.001
CCI [Median (P₂₅, P₇₅)]	4.00 (3.00, 5.00)	3.00 (2.00, 5.00)	4.00 (3.00, 6.00)	<0.001
GCS [Median (P₂₅, P₇₅)]	14.00 (11.00, 15.00)	15.00 (14.00, 15.00)	14.00 (11.00, 15.00)	<0.001
Fluid input within 24 h [mL, Median (P₂₅, P₇₅)]	11188.35 (8524.44, 14410.81)	10332.90 (8432.29, 12367.03)	11415.04 (8575.50, 15023.15)	<0.001
Fluid output within 24 h [mL, Median (P₂₅, P₇₅)]	2775.00 (1975.00, 3717.00)	3550.00 (2836.25, 4380.75)	2601.00 (1830.00, 3529.50)	<0.001

Variable	Total (n=7126)	NKD (n=1208)	AKI (n=5918)	P
Age [year, Median (P₂₅, P₇₅)]	68.05(58.97, 76.40)	66.11(58.17, 73.55)	68.49(59.21, 76.95)	<0.001
Female [n (%)]	2785(39.08)	403(33.36)	2382(40.25)	<0.001
Emergency [n (%)]	2148 (30.14)	210 (17.38)	1938 (32.75)	<0.001
Weight [kg, Median (P₂₅, P₇₅)]	80.25(68.50, 94.30)	74.80 (65.00, 85.40)	81.80 (69.60, 96.30)	<0.001
Height (cm, Mean±SD)	169.96±10.51	169.98±10.26	169.96±10.56	0.953
Comorbidity [n (%)]
Diabetes	1861 (26.12)	287 (23.76)	1574 (26.60)	0.044
Coronary atherosclerotic heart disease	3757 (52.72)	729 (60.35)	3028 (51.17)	<0.001
Hypertension	4346 (60.99)	742 (61.42)	3604 (60.90)	0.758
Cerebral Infarction	202 (2.83)	13 (1.08)	189 (3.19)	<0.001
Heart failure	1619 (22.72)	190 (15.73)	1429 (24.15)	<0.001
Cancer	680 (9.54)	91 (7.53)	589 (9.95)	0.011
Gastrointestinal related diseases	365 (5.12)	33 (2.73)	332 (5.61)	<0.001
Chronic obstructive pulmonary disease	1606 (22.54)	245 (20.28)	1361 (23.00)	0.043
Sepsis	4379 (61.45)	594 (49.17)	3785 (63.96)	<0.001
Burns	8 (0.11)	0 (0.00)	8 (0.14)	0.420
RR [min, Median (P₂₅, P₇₅)]	16.00 (14.00, 19.00)	16.00 (14.00, 17.00)	16.00 (14.00, 20.00)	<0.001
HR [b/min, Median (P₂₅, P₇₅)]	82.00 (76.00, 94.00)	80.00 (75.00, 88.00)	83.00 (77.00, 95.00)	<0.001
T [°C, Median (P₂₅, P₇₅)]	36.50 (36.00, 36.83)	36.44 (35.80, 36.72)	36.50 (36.10, 36.83)	<0.001
MAP [mmHg, Median (P₂₅, P₇₅)]	77.00 (69.00, 87.00)	78.00 (70.00, 86.00)	77.00 (68.00, 87.00)	0.633
SpO₂ [%, Median (P₂₅, P₇₅)]	100.00 (98.00, 100.00)	100.00 (99.00, 100.00)	100.00 (97.00, 100.00)	<0.001
Albumin level (g/dL, Mean±SD)	2.84±0.72	3.02±0.74	2.83±0.72	0.002
WBCs [×10⁹, Median (P₂₅, P₇₅)]	11.80 (8.40, 16.10)	11.50 (8.45, 15.45)	11.90 (8.40, 16.30)	0.105
Hemoglobin, [g/dL, Median (P₂₅, P₇₅)]	11.90 (10.10, 13.30)	12.50 (11.10, 13.60)	11.70 (10.00, 13.20)	<0.001
PLT [×10⁹, Median (P₂₅, P₇₅)]	157.00 (117.00, 216.00)	150.00 (116.00, 195.00)	159.00 (117.00, 222.00)	<0.001
Glucose [mg/dL, Median (P₂₅, P₇₅)]	114.00 (99.00, 146.00)	107.00 (96.00, 131.00)	115.00 (100.00, 149.00)	<0.001
Cr [mg/dL, Median (P₂₅, P₇₅)]	0.90 (0.70, 1.10)	0.80 (0.60, 0.90)	0.90 (0.70, 1.10)	<0.001
Lac [mmol/L, Median (P₂₅, P₇₅)]	1.50 (1.10, 2.10)	1.40 (1.10, 1.80)	1.50 (1.10, 2.20)	<0.001
SAPS II [Median (P₂₅, P₇₅)]	38.00 (31.00, 46.00)	33.00 (28.00, 40.00)	39.00 (32.00, 48.00)	<0.001
SOFA [Median (P₂₅, P₇₅)]	6.00 (4.00, 9.00)	5.00 (4.00, 7.00)	7.00 (5.00, 9.00)	<0.001
CCI [Median (P₂₅, P₇₅)]	4.00 (3.00, 5.00)	3.00 (2.00, 5.00)	4.00 (3.00, 6.00)	<0.001
GCS [Median (P₂₅, P₇₅)]	14.00 (11.00, 15.00)	15.00 (14.00, 15.00)	14.00 (11.00, 15.00)	<0.001
Fluid input within 24 h [mL, Median (P₂₅, P₇₅)]	11188.35 (8524.44, 14410.81)	10332.90 (8432.29, 12367.03)	11415.04 (8575.50, 15023.15)	<0.001
Fluid output within 24 h [mL, Median (P₂₅, P₇₅)]	2775.00 (1975.00, 3717.00)	3550.00 (2836.25, 4380.75)	2601.00 (1830.00, 3529.50)	<0.001

Outcome	Total (n=7126)	NKD (n=1208)	AKI (n=5918)	P
Ventilation [n (%)]	5506 (77.27)	877 (72.60)	4629 (78.22)	<0.001
Duration of ventilation [h, Median (P₂₅, P₇₅)]	9.38 (3.00, 26.00)	5.73 (0.00, 11.00)	11.05 (3.50, 35.30)	<0.001
CRRT [n (%)]	286 (4.01)	0 (0.00)	286 (4.83)	<0.001
Length of ICU [day, Median (P₂₅, P₇₅)]	2.53 (1.46, 4.85)	1.35 (1.20, 2.17)	3.05 (1.91, 5.40)	<0.001
Length of hospital stay [day, Median (P₂₅, P₇₅)]	8.23 (5.77, 13.75)	6.31 (4.99, 8.88)	8.93 (6.06, 15.03)	<0.001
28 d mortality [n (%)]	682 (9.57)	16 (1.32)	666 (11.25)	<0.001
90 d mortality [n (%)]	932 (13.08)	37 (3.06)	895 (15.12)	<0.001

Outcome	Total (n=7126)	NKD (n=1208)	AKI (n=5918)	P
Ventilation [n (%)]	5506 (77.27)	877 (72.60)	4629 (78.22)	<0.001
Duration of ventilation [h, Median (P₂₅, P₇₅)]	9.38 (3.00, 26.00)	5.73 (0.00, 11.00)	11.05 (3.50, 35.30)	<0.001
CRRT [n (%)]	286 (4.01)	0 (0.00)	286 (4.83)	<0.001
Length of ICU [day, Median (P₂₅, P₇₅)]	2.53 (1.46, 4.85)	1.35 (1.20, 2.17)	3.05 (1.91, 5.40)	<0.001
Length of hospital stay [day, Median (P₂₅, P₇₅)]	8.23 (5.77, 13.75)	6.31 (4.99, 8.88)	8.93 (6.06, 15.03)	<0.001
28 d mortality [n (%)]	682 (9.57)	16 (1.32)	666 (11.25)	<0.001
90 d mortality [n (%)]	932 (13.08)	37 (3.06)	895 (15.12)	<0.001

Outcome	LA (<30 g/L)	MA (30-35 g/L)	HA (>35 g/L)	P
CRRT [n (%)]	139 (17.96)	50 (16.89)	32 (24.06)	0.184
Ventilation [n (%)]	678 (87.60)	263 (88.85)	115 (86.47)	0.758
Duration of ventilation [h, Median (P₂₅, P₇₅)]	120.42 (33.07, 254.00)	68.21 (15.00, 158.76)	59.00 (15.00, 178.00)	<0.001
Fluid input within 72 h [mL, Median (P₂₅, P₇₅)]	28821.47 (18874.31, 43478.88)	24942.46 (17068.04, 37728.76)	20563.86 (14194.31, 32221.87)	<0.001
Amount of albumin infusion within 72 h [g, Median (P₂₅, P₇₅)]	37.50 (25.00, 75.00)	50.00 (25.00, 102.48)	100.00 (62.50, 187.50)	<0.001
Serum albumin level at 72 h after albumin infusion [g/dL, Median (P₂₅, P₇₅)]	2.50 (2.10, 2.90)	2.90 (2.40, 3.40)	3.30 (2.70, 3.80)	<0.001
Length of ICU stay [d, Median (P₂₅, P₇₅)]	10.78 (6.17, 17.16)	8.21 (5.18, 14.39)	8.84 (5.56, 14.09)	<0.001
Length of hospital stay [d, Median (P₂₅, P₇₅)]	20.82 (13.82, 30.68)	15.98 (10.86, 24.36)	17.78 (11.89, 27.58)	<0.001
28 d mortality [n (%)]	176 (22.74)	63 (21.28)	33 (24.81)	0.714
90 d mortality [n (%)]	258 (33.33)	84 (28.38)	47 (35.34)	0.221

合并急性肾损伤的危重症患者输注白蛋白后血清白蛋白水平与28 d死亡率的相关性

Association between serum albumin levels after albumin infusion and 28-day mortality in critically ill patients with acute kidney injury

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Variable	Model 1		Model 2		Model 3
Variable	OR (95% CI)	P	OR(95% CI)	P	OR (95% CI)	P
28-day mortality	1203		1203		855
All	1.03 (0.84, 1.27)	0.768	1.04 (0.84, 1.28)	0.741	0.74 (0.51, 1.06)	0.768
LA	Ref		Ref		Ref
MA	0.92 (0.66, 1.27)	0.609	0.93 (0.67, 1.28)	0.653	0.82 (0.48, 1.38)	0.457
HA	1.12 (0.72, 1.70)	0.600	1.14 (0.73, 1.73)	0.562	0.91 (0.43, 1.88)	0.810
90-day mortality	1203		1203		915
All	0.99 (0.82, 1.19)	0.908	0.99 (0.82, 1.20)	0.946	0.89 (0.68, 1.19)	0.366
LA	Ref		Ref		Ref
MA	0.79 (0.59, 1.06)	0.120	0.80 (0.59, 1.07)	0.133	1.21 (0.51, 1.81)	0.345
HA	1.09 (0.74, 1.60)	0.651	1.11 (0.75, 1.63)	0.602	0.99 (0.55, 1.73)	0.964

Variable	OR (95%CI)	P	aOR (95% CI)	^aP
Female	0.35 (0.60, 3.75)	<0.001
Diabetes	0.37(0.45,3.96)	<0.001
Hypertension	0.43(0.32,1.95)	0.001
History of gastrointestinal tumors	0.36(0.55,5.03)	<0.001
History of other gastrointestinal tumors	0.35(0.67,6.74)	<0.001
Albumin level	0.93 (0.87, 1.00)	0.035
Cr	0.37(0.99,1.00)	0.012
Lactate	1.20 (1.04, 1.38)	0.014
APACHE II group	10.17 (1.30, 79.46)	0.027
MA	5.99 (1.63, 22.04)	0.007	4.24 (1.09, 16.52)	0.037
HA	15.00 (3.22, 69.84)	0.001	13.22(2.33, 75.10)	0.004

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