Coagulative biomarkers on admission to the ICU predict acute kidney injury and mortality in patients with septic shock caused by intra-abdominal infection

Figures & data

Figure 1 Flowchart of the enrolled patients.

Table 1 Baseline characteristics

Parameters	All (n=138)
Demographic data
Age (y), median (IQR)	69.0 (57.0–80.0)
Male sex, n (%)	85 (62)
Admission status data
Source of intra-abdominal infection
Gastroduodenal disease, n (%)	58 (42)
Biliary disease, n (%)	30 (22)
Colorectal disease, n (%)	21 (15)
Ileocecal and appendiceal disease, n (%)	15 (11)
Abdominal abscess, n (%)	9 (7)
Severe acute pancreatitis, n (%)	5 (4)
Comorbidities
Hypertension, n (%)	55 (40)
CCI, median (IQR)	1.0 (0.0–2.0)
Data for the first 24 hrs in the ICU
SOFA score, median (IQR)	10.0 (8.0–12.0)
APACHE II score, median (IQR)	19.5 (14.0–25.0)
Cumulative fluid balance (mL), median (IQR)	5827.5 (4795.0–7220.0)
Primary outcomes
No AKI, n (%)	73 (53)
Maximum AKI stage during ICU stay, n (%)
Stage 1	18 (13)
Stage 2	29 (21)
Stage 3	18 (13)
Death within 30 days, n (%)	44 (32)
RRT, n (%)	31 (22)
Ventilation duration (days), median (IQR)	4.4 (2.0–10.0)
Length of ICU stay (days), median (IQR)	6.1 (2.9–13.7)

Abbreviations: CCI, Charlson Comorbidity Index; SOFA score, Sequential Organ Failure Assessment score; APACHE II score, Acute Physiology and Chronic Health Evaluation II score; AKI, acute kidney injury; RRT, renal replacement therapy; ICU, intensive care unit.

Table 2 Univariable analysis of baseline characteristics

Variable	No AKI (n=73)	AKI (n=65)	Odds ratio (95% CI)	p-value	Survival within 30 days (n=94)	Nonsurvival (n=44)	Odds ratio (95% CI)	p-value
Age (years)	65.0 (55.0–78.5)	71.0 (60.5–82.0)	1.021 (1.000–1.044)	0.054	66.5 (56.0–79)	71.5 (61.3–82.8)	1.025 (1.000–1.050)	0.047
Male sex	43 (31)	42 (30)	1.274 (0.639–2.540)	0.491	56 (60)	29 (66)	1.312 (0.621–2.769)	0.476
Hypertension	21 (15)	34 (25)	0.368 (0.182–0.743)	0.005	37 (39)	18 (41)	1.067 (0.514–2.212)	0.863
CCI	1.0 (0.0–2.0)	1.0 (0.0–2.0)	1.225 (0.975–1.540)	0.082	1.0 (0.0–2.0)	2.0 (0.25–2.0)	1.310 (1.039–1.652)	0.022
PCT (ng/mL)	11.1 (2.8–48.8)	24.3 (7.3–100.0)	1.013 (1.003–1.022)	0.009	15.1 (5.0–55.8)	18.0 (2.8–88.0)	1.003 (0.994–1.013)	0.502
NT-proBNP (pg/mL)	1150.0 (391.0–2663.5)	3792.0 (1214.5–9115.0)	1.117 (1.040–1.199)	0.002	1716.0 (447.5–3640.0)	3746.0 (1258.0–13,848.0)	1.042 (1.042–1.170)	0.001
SCr (μmol/L)	68.0 (52.0–82.5)	174.0 (94.0–203.0)	1.043 (1.028–1.059)	<0.001	77.0 (56.0–129.8)	116.0 (75.8–197.8)	1.009 (1.004–1.015)	0.001
Lac (mmol/L)	2.7 (1.6–3.4)	3.6 (2.3–5.8)	1.181 (1.038–1.343)	0.011	2.8 (1.6–3.7)	4.0 (2.3–6.8)	1.240 (1.088–1.412)	0.001
SOFA score	9.0 (7.0–11.0)	12.0 (10.0–15.0)	1.478 (1.263–1.729)	<0.001	9.0 (8.0–11.0)	12 (10.3–15.8)	1.493 (1.273–1.752)	<0.001
APACHE II score	15.5 (13.0–21.0)	23.0 (19.0–27.8)	1.170 (1.097–1.249)	<0.001	16.0 (14.0–21.0)	24.5 (20.0–28.8)	1.170 (1.095–1.249)	<0.001
Cumulative fluid balance (mL)	2715.0 (1660.0–3579.0)	3500.0 (2042.5–5050.0)	1.290 (1.079–1.542)	0.005	2805.0 (1707.5–3592)	4050 (2658.8–5516.3)	1.490 (1.213–1.831)	<0.001
RRT	5 (4)	26 (19)	0.110 (0.039–0.310)	<0.001	8 (9)	23 (52)	0.085 (0.033–0.216)	<0.001
Ventilation duration	3.4 (1.2–9.3)	6.6 (2.7–12.6)	1.014 (0.979–1.050)	0.441	4.3 (1.5–9.8)	4.5 (2.6–11.8)	0.991 (0.954–1.030)	0.645
Length of ICU stay	5.0 (2.6–10.7)	7.6 (3.4–14.9)	1.014 (0.980–1.049)	0.415	6.5 (3.0–13.7)	5.4 (2.7–14.0)	0.975 (0.936–1.016)	0.234

Notes: Continuous variables with normal distribution are presented as the mean ± standard deviation (SD), continuous variables with non-normally distribution are presented as the median (interquartile range (IQR) and categorical variables are presented as n (%).

Abbreviations: CCI, Charlson Comorbidity Index; PCT, serum procalcitonin; NT-proBNP, serum N-Terminal pro-brain natriuretic peptide; SCr, serum creatinine; Lac, serum lactate; SOFA score, Sequential Organ Failure Assessment score; APACHE II score, Acute Physiology and Chronic Health Evaluation II score; RRT, renal replacement therapy; ICU, intensive care unit.

Table 3 The relationship between coagulative biomarkers and AKI according to multivariable logistic regression analysis

Coagulative biomarkers	AKI Median (IQR)	Non-AKI Median (IQR)	Unadjusted OR (95% CI)	p-value	Adjusted: model 1 OR (95% CI)	p-value	Adjusted: model 2 OR (95% CI)	p-value
APTT	49.5 (42.3–60.9)	44.3 (37.2–49.6)	1.050 (1.018–1.083)	0.002	1.074 (1.030–1.120)	0.001	1.074 (1.032–1.118)	<0.001
PT	18.5 (16.1–23.2)	17.2 (15.5–19.3)	1.115 (1.031–1.206)	0.007	1.162 (1.037–1.302)	0.010	1.168 (1.052–1.298)	0.004
INR	1.53 (1.30–2.0)	1.41 (1.28–1.66)	2.571 (1.209–5.470)	0.014	3.923 (1.322–11.640)	0.014	-	-
D-dimer	3770.0 (2445.0–9130.0)	2810.0 (723.5–5095.0)	1.108 (1.024–1.198)	0.011	1.098 (1.002–1.202)	0.045	1.096 (1.003–1.197)	0.042
Fg	3.2 (2.5–4.5)	3.4 (1.7–4.8)	0.924 (0.788–1.085)	0.336	-	-	-	-
PLT	106.0 (67.5–141.5)	124.0 (80.5–172.0)	0.995 (0.989–1.000)	0.046	1.001 (0.994–1.009)	0.752	0.996 (0.989–1.003)	0.262

Notes: Model 1 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and SOFA score; Model 2 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and APACHE II score.

Abbreviations: APTT, activated partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; Fg, plasma fibrinogen; PLT, platelet; CCI, Charlson Comorbidity Index; PCT, serum procalcitonin; NT-proBNP, serum N-Terminal pro-brain natriuretic peptide; Lac, serum lactate; SOFA score, Sequential Organ Failure Assessment score; APACHE II score, Acute Physiology and Chronic Health Evaluation II score.

Table 4 The AUC of coagulative biomarkers for predicting AKI after adjustment for baseline characteristics in model 1 or model 2

Coagulative biomarkers	AUC	95% CI	Sensitivity (%)	Specificity (%)	Youden Index
Adjusted: model 1
APTT	0.857	0.797–0.918	76.9	80.8	0.577
PT	0.832	0.765–0.898	78.5	72.6	0.511
D-dimer	0.844	0.780–0.909	83.1	75.3	0.584
INR	0.828	0.761–0.895	83.1	69.9	0.530
Adjusted: model 2
APTT	0.848	0.784–0.912	69.2	89.0	0.582
PT	0.826	0.757–0.894	75.4	79.5	0.549
D-dimer	0.820	0.749–0.892	81.5	75.3	0.568

Notes: Model 1 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and SOFA score; Model 2 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and APACHE II score.

Abbreviations: APTT, activated partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; CCI, Charlson Comorbidity Index; PCT, serum procalcitonin; NT-proBNP, serum N-Terminal pro-brain natriuretic peptide; Lac, serum lactate; SOFA score, Sequential Organ Failure Assessment score; APACHE II score, Acute Physiology and Chronic Health Evaluation II score.

Figure 2 Comparison of the area under the curve (AUC) of coagulative biomarkers for predicting AKI. (A) Comparison of the AUC for APTT, PT, INR and D-dimer level after adjustment for model 1. (B) Comparison of the AUC for APTT, PT and D-dimer level after adjustment for model 2.

Table 5 Multivariate Cox regression analysis for 30-day mortality

Coagulative biomarkers	Survivors Median (IQR)	Nonsurvivors Median (IQR)	Unadjusted OR (95% CI)	p-value	Adjusted: model 1 OR (95% CI)	p-value	Adjusted: model 2 OR (95% CI)	p-value
APTT	44.9 (39.0–50.9)	51.0 (43.7–64.0)	1.044 (1.015–1.074)	0.003	1.065 (1.025–1.107)	0.001	1.061 (1.023–1.102)	0.002
PT	17.2 (15.5–19.6)	18.7 (16.1–23.1)	1.058 (0.993–1.127)	0.083	-	-	-	-
INR	1.5 (1.3–1.7)	1.6 (1.3–2.0)	1.852 (0.982–3.493)	0.057	-	-	-	-
D-dimer	3345.0 (947.5–6097.5)	3245.0 (2252.5–7780.0)	1.017 (0.944–1.095)	0.663	-	-	-	-
Fg	3.5 (2.6–5.0)	3.1 (1.6–3.8)	0.809 (0.649–1.008)	0.059	-	-	-	-
PLT	131.0 (88.8–165.3)	91.5 (49.3–132.8)	0.990 (0.983–0.997)	0.003	0.995 (0.987–1.004)	0.293	0.990 (0.981–0.998)	0.016

Notes: Model 1 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and SOFA score; Model 2 included age, sex, hypertension, CCI, PCT, NT-proBNP, Lac and APACHE II score.

Abbreviations: APTT, activated partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; PLT, platelet; CCI, Charlson Comorbidity Index; PCT, serum procalcitonin; NT-proBNP, serum N-Terminal pro-brain natriuretic peptide; Lac, serum lactate; SOFA score, Sequential Organ Failure Assessment score; APACHE II score, Acute Physiology and Chronic Health Evaluation II score.

Figure 3 (A) Kaplan-Meier survival curves of 30-day mortality according to plasma APTT levels. (B) The 30-day mortality rates according to the interquartile range of plasma APTT levels. (Q1, APTT ≤39.8 s; Q2, 39.8 s < APTT ≤46.8 s; Q3, 46.8 s < APTT ≤53.3 s; Q4, APTT >53.3 s).