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

doi:10.12122/j.issn.1673-4254.2025.05.21

Abstract

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

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.

Figures/Tables 7

References 30

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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