The association between lactate dehydrogenase to serum albumin ratio and the 28-day mortality in patients with sepsis-associated acute kidney injury in intensive care: a retrospective cohort study

Figures & data

Figure 1. Flowchart of study patients.

Table 1. Baseline characteristics of participants and outcome parameters.

Variable	Lactate dehydrogenase to albumin ratio
		T1	T2	T3
	Total	LAR <8.59	8.59 ≤ LAR <14.66	LAR ≥14.66
	(n = 6453)	(n = 2150)	(n = 2151)	(n = 2152)	p Value
Age (years)	63.9 ± 16.1	65.4 ± 15.6	65.2 ± 15.8	61.3 ± 16.6	<0.001
Male (%)	3745 (58.0)	1273 (59.2)	1233 (57.3)	1239 (57.6)	0.396
Ethnicity, white (%)	4100 (63.5)	1441 (67)	1376 (64)	1283 (59.6)	<0.001
Weight (kg)	85.1 ± 26.7	84.9 ± 28.9	84.7 ± 25.4	85.8 ± 25.7	0.366
Medicare	2908 (45.1)	1029 (47.9)	1002 (46.6)	877 (40.8)	<0.001
UO (ml)	1310.0 (775.0, 2100.0)	1420.0 (857.0, 2175.0)	1348.0 (820.0, 2094.0)	1175.0 (630.0, 2020.0)	<0.001
AKI stage (%)					<0.001
1	1058 (16.4)	397 (18.5)	365 (17)	296 (13.8)
2	2895 (44.9)	1086 (50.5)	1037 (48.2)	772 (35.9)
3	2500 (38.7)	667 (31)	749 (34.8)	1084 (50.4)
Vital signs
Heart rate (bpm)	89.8 ± 17.6	86.1 ± 16.7	89.9 ± 17.5	93.6 ± 17.9	<0.001
MAP (mmHg)	78.8 ± 12.5	79.4 ± 11.8	78.2 ± 13.0	78.8 ± 12.5	0.007
Respiration rate (bpm)	20.5 ± 4.3	19.6 ± 3.8	20.3 ± 4.1	21.7 ± 4.6	<0.001
SPO2 (%)	96.9 ± 2.3	97.1 ± 2.0	97.0 ± 2.2	96.6 ± 2.7	<0.001
Scoring system, points
SOFA score	3.0 (2.0, 5.0)	3.0 (2.0, 5.0)	3.0 (2.0, 5.0)	4.0 (3.0, 6.0)	<0.001
APS III	69.2 ± 27.6	60.6 ± 24.1	68.3 ± 26.5	78.9 ± 28.9	<0.001
CCI	6.1 ± 3.0	6.1 ± 2.9	6.2 ± 2.9	6.0 ± 3.1	0.055
GCS	14.4 ± 1.9	14.4 ± 1.8	14.3 ± 2.0	14.4 ± 1.9	0.344
Laboratory results
Hemoglobin (g/dL)	9.7 ± 2.3	9.9 ± 2.2	9.7 ± 2.3	9.6 ± 2.3	<0.001
Platelets (k/uL)	152.0 (97.0, 220.0)	162.0 (109.0, 229.0)	158.0 (102.0, 227.0)	135.0 (78.0, 204.0)	<0.001
WBC (k/uL)	14.5 (10.1, 20.1)	13.0 (9.5, 17.8)	14.8 (10.4, 20.2)	16.1 (10.8, 22.3)	<0.001
Total bilirubin (mg/dL)	1.1 (0.6, 3.1)	0.8 (0.5, 2.1)	1.0 (0.6, 2.7)	1.7 (0.8, 4.5)	<0.001
LDH (IU/L)	309.0 (229.0, 478.0)	209.0 (176.0, 243.0)	311.0 (266.0, 366.0)	618.5 (468.0, 1060.0)	<0.001
Albumin (g/L)	29.2 ± 6.4	32.3 ± 5.9	28.6 ± 5.7	26.7 ± 6.1	<0.001
LAR (IU/g)	11.0 (7.6, 17.7)	6.8 (5.7, 7.6)	11.0 (9.7, 12.5)	23.2 (17.7, 38.9)	<0.001
SCr (mg/dL)	1.1 (0.8, 1.8)	1.0 (0.7, 1.6)	1.1 (0.8, 1.7)	1.3 (0.9, 2.1)	<0.001
Glucose (mg/dL)	134.0 (108.0, 176.0)	130.0 (106.0, 165.0)	135.0 (109.0, 177.0)	140.0 (109.0, 190.0)	<0.001
pH	7.3 ± 0.1	7.4 ± 0.1	7.4 ± 0.1	7.3 ± 0.1	<0.001
Chloride (mEq/L)	104.1 ± 7.4	103.7 ± 7.1	104.6 ± 7.4	104.0 ± 7.7	<0.001
Sodium (mEq/L)	138.3 ± 6.2	138.1 ± 6.0	138.4 ± 6.2	138.2 ± 6.4	0.184
Potassium (mEq/L)	4.3 ± 0.8	4.2 ± 0.7	4.2 ± 0.8	4.4 ± 0.9	<0.001
Bicarbonate (mEq/L)	21.6 ± 5.2	22.8 ± 5.2	21.8 ± 4.8	20.2 ± 5.1	<0.001
Interventions
Ventilator use (%)	5128 (79.5)	1710 (79.5)	1706 (79.3)	1712 (79.6)	0.976
Vasopressor use (%)	790 (12.2)	156 (7.3)	249 (11.6)	385 (17.9)	<0.001
RRT use (%)	238 (3.7)	35 (1.6)	57 (2.6)	146 (6.8)	<0.001
Loop diuretics use (%)	691 (10.7)	175 (8.1)	230 (10.7)	286 (13.3)	<0.001
Comorbidities
Septic shock (%)	832 (12.9)	223 (10.4)	280 (13)	329 (15.3)	<0.001
Hypertension (%)	1698 (26.3)	631 (29.3)	562 (26.1)	505 (23.5)	<0.001
Diabetes mellitus (%)	1931 (29.9)	676 (31.4)	671 (31.2)	584 (27.1)	0.002
Myocardial infarct (%)	1256 (19.5)	310 (14.4)	405 (18.8)	541 (25.1)	<0.001
Congestive heart failure (%)	2240 (34.7)	698 (32.5)	798 (37.1)	744 (34.6)	0.006
Chronic pulmonary disease (%)	1765 (27.4)	612 (28.5)	586 (27.2)	567 (26.3)	0.294
Malignant cancer (%)	997 (15.5)	294 (13.7)	325 (15.1)	378 (17.6)	0.002
Liver disease (%)	1598 (24.8)	439 (20.4)	497 (23.1)	662 (30.8)	<0.001
Site of infection
Lung (%)	2725 (42.2)	847 (39.4)	923 (42.9)	955 (44.4)	0.003
Urinary (%)	1385 (21.5)	477 (22.2)	477 (22.2)	431 (20)	0.139
Catheter (%)	202 (3.1)	65 (3.0)	64 (3.0)	73 (3.4)	0.691
Skin soft tissue (%)	45 (0.7)	14 (0.7)	13 (0.6)	18 (0.8)	0.626
Abdominal cavity (%)	407 (6.3)	162 (7.5)	125 (5.8)	120 (5.6)	0.016
28-day mortality (%)	1728 (26.8)	388 (18)	540 (25.1)	800 (37.2)	<0.001
90-day mortality (%)	2285 (35.4)	576 (26.8)	738 (34.3)	971 (45.1)	<0.001
In-hospital mortality (%)	1542 (23.9)	327 (15.2)	467 (21.7)	748 (34.8)	<0.001

Data are presented as the mean ± SD or median (IQR) for skewed variables or numbers (proportions) for categorical variables; T1, LAR < 8.59; T2, 8.59 ≤ LAR <14.66; T3, LAR ≥14.66. bpm: beats per minute; MAP: mean arterial pressure; SOFA score: sequential organ failure assessment score; APS III: acute physiology score III; CCI: Charlson comorbidity index; GCS: Glasgow Coma Scale; WBC: white blood cell count; LDH: lactate dehydrogenase; LAR: lactate dehydrogenase to albumin ratio; SCr: serum creatinine; RRT: renal replacement treatment; AKI: acute kidney injury.

Table 2. Hazard ratio (HR) [95% confidence intervals (CIs)] for mortality across groups divided according to the ratio of lactate dehydrogenase to albumin (LAR) level.

Variable	Unadjusted		Model 1		Model 2		Model 3
	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
Primary outcomes
28-day mortality
LAR (log2)	1.46 (1.39−1.53)	<0.001	1.55 (1.48–1.63)	<0.001	1.37 (1.3–1.44)	<0.001	1.14 (1.09–1.18)	<0.001
T1 (LAR < 8.59)	1 (Ref)		1 (Ref)		1 (Ref)		1 (Ref)
T2 (8.59 ≤ LAR <14.66)	1.44 (1.26−1.64)	<0.001	1.45 (1.28–1.66)	<0.001	1.40 (1.22–1.60)	<0.001	1.20 (1.05–1.38)	<0.001
T3 (LAR ≥ 14.66)	2.37 (2.1−2.68)	<0.001	2.59 (2.29–2.93)	<0.001	2.17 (1.9–2.47)	<0.001	1.61 (1.41–1.84)	<0.001
P for trend		<0.001		<0.001		<0.001		<0.001
Secondary outcomes
90-day mortality
LAR (log2)	1.37 (1.31−1.43)	<0.001	1.47 (1.41–1.54)	<0.001	1.32 (1.25–1.38)	<0.001	1.11 (1.07–1.15)	<0.001
T1 (LAR < 8.59)	1 (Ref)		1 (Ref)		1 (Ref)		1 (Ref)
T2 (8.59 ≤ LAR <14.66)	1.35 (1.21−1.5)	<0.001	1.36 (1.22–1.52)	<0.001	1.29 (1.16–1.45)	<0.001	1.12 (1–1.26)	0.046
T3 (LAR ≥ 14.66)	2.01 (1.81−2.23)	<0.001	2.23 (2.01–2.47)	<0.001	1.91 (1.71–2.14)	<0.001	1.46 (1.3–1.63)	<0.001
P for trend		<0.001		<0.001		<0.001		<0.001
In-hospital mortality^a
LAR (log2)	1.69 (1.58−1.81)	<0.001	1.79 (1.67–1.92)	<0.001	1.56 (1.44–1.69)	<0.001	1.21 (1.14–1.28)	<0.001
T1 (LAR < 8.59)	1 (Ref)		1 (Ref)		1 (Ref)		1 (Ref)
T2 (8.59 ≤ LAR <14.66)	1.55 (1.32−1.81)	<0.001	1.56 (1.33–1.82)	<0.001	1.46 (1.24–1.73)	<0.001	1.25 (1.05–1.49)	0.013
T3 (LAR ≥ 14.66)	2.97 (2.56−3.44)	<0.001	3.21 (2.77−3.73)	<0.001	2.56 (2.17–3.00)	<0.001	1.87 (1.57–2.23)	<0.001
P for trend		<0.001		<0.001		<0.001		<0.001

Model 1 is adjusted for sex and age.

Model 2 is adjusted as is Model 1 and is also adjusted for ethnicity, heart rate, MAP, SpO₂, UO, hemoglobin, platelets, WBC, SCr, glucose, pH, chloride, sodium, potassium, and bicarbonate.

Model 3 is adjusted as is Model 2 and is also adjusted for AKI stage, SOFA score, APSIII, CCI, septic shock, hypertension, diabetes mellitus, myocardial infarct, congestive heart failure, malignant cancer, liver disease, loop diuretic use, RRT use, vasopressor use and site of infection.

^aLogistic regression was used to evaluate the association between the LAR and in-hospital mortality. The results are expressed as odds ratios (95% CIs).

LAR; lactate dehydrogenase to albumin ratio; HR: hazard ratio; CI: confidence interval.

Figure 2. (A): Kaplan–Meier curve of 28-day mortality for patients with SA-AKI. (B) Kaplan–Meier curve of 90-day mortality for patients with SA-AKI.

Table 3. Subgroup analysis of the association between 28-day mortality and LAR.

	No. of patients	Lactate dehydrogenase to albumin ratio			p for interaction
		T1	T2	T3
		LAR < 8.59	8.59 ≤ LAR <14.66	LAR ≥ 14.66
Sex					0.381
Male	3745	1 (Ref)	1.45 (1.21–1.74)	2.21 (1.85–2.64)
Female	2708	1 (Ref)	1.23 (1–1.52)	1.76 (1.44–2.15)
Age					0.078
<60	3118	1 (Ref)	1.30 (1–1.68)	1.55 (1.21–1.98)
≥60	3335	1 (Ref)	1.37 (1.17–1.61)	2.24 (1.91–2.62)
APS III					0.232
<42	1001	1 (Ref)	1.64 (0.93–2.88)	2.63 (1.47–4.69)
≥42	5452	1 (Ref)	1.3 (1.13–1.49)	1.87 (1.64–2.15)
RRT					0.299
Yes	238	1 (Ref)	1.12 (0.46–2.7)	1.23 (0.58–2.59)
No	6215	1 (Ref)	1.36 (1.19–1.56)	2.02 (1.76–2.31)
Vasopressor use					0.465
Yes	790	1 (Ref)	1.19 (0.79–1.78)	2.00 (1.37–2.92)
No	5663	1 (Ref)	1.38 (1.2–1.6)	1.98 (1.72–2.28)
Loop diuretics use					0.099
Yes	691	1 (Ref)	2 (1.33–3)	2.11 (1.41–3.16)
No	5762	1 (Ref)	1.3 (1.12–1.5)	2 (1.74–2.3)
Myocardial infarct					0.017
Yes	1256	1 (Ref)	1.66 (1.18–2.35)	3.13 (2.26–4.33)
No	5197	1 (Ref)	1.31 (1.13–1.52)	1.82 (1.57–2.11)
Congestive heart failure					0.686
Yes	2240	1 (Ref)	1.36 (1.09–1.69)	2.18 (1.75–2.7)
No	4213	1 (Ref)	1.42 (1.19–1.68)	2.01 (1.7–2.38)
Malignant cancer					0.436
Yes	997	1 (Ref)	1.49 (1.08–2.04)	2.67 (1.96–3.63)
No	5456	1 (Ref)	1.32 (1.13–1.53)	1.87 (1.61–2.16)
Septic shock					0.439
Yes	832	1 (Ref)	1.31 (0.95–1.81)	1.83 (1.35–2.49)
No	5621	1 (Ref)	1.37 (1.18–1.59)	2.03 (1.75–2.34)
AKI stage					0.090
1	1058	1 (Ref)	1.78 (1.19–2.66)	2.08 (1.36–3.18)
2	2895	1 (Ref)	1.31 (1.04–1.65)	2.25 (1.79–2.83)
3	2500	1 (Ref)	1.32 (1.09–1.59)	1.71 (1.44–2.04)
Liver disease
Yes	1598	1 (Ref)	1.33 (1.04–1.69)	1.47 (1.16–1.86)	<0.001
No	4855	1 (Ref)	1.37 (1.16–1.61)	2.37 (2.02–2.78)

HRs (95% CIs) were derived from Cox proportional hazards regression models. Each stratification was adjusted for all factors included in Model 3 in Table 2 except the stratification factor itself. APS III, acute physiology score; RRT, renal replacement treatment; AKI, acute kidney injury.

Figure 3. Curve fitting of the LAR (log₂) and 28-day mortality in patients with SA-AKI.

Table 4. Threshold effect analysis of the relationship between the LAR (log₂) and 28-day mortality in patients with SA-AKI.

Threshold of LAR (log2)	HR (95% CI)	p Value
<5.57	1.29 (1.20, 1.38)	<0.001
≥5.57	1.00 (0.84, 1.20)	0.95
Likelihood ratio test		<0.001

The data have been adjusted for all of the factors included in Model 3 in Table 2.

Data availability statement

In this work, we investigated publicly accessible datasets. These datasets are available at https://physionet.org/content/mimiciv.