Value of Serum Thrombomodulin as a Marker and Predictor in Patients with Sepsis-Associated Acute Kidney Injury

Figures & data

Table 1 Characteristics of Study Population

Characteristics	General (n =71)	AKI (n = 38)	Non-AKI (n = 33)	p*
Age (years)	61.86 ± 17.82	64.05 ± 15.85	59.33 ± 19.80	0.269
Weight (kg)	62.35 ± 12.22	60.87 ± 11.19	64.06 ± 13.29	0.276
Height (cm)	162.23 ± 7.90	160.66 ± 7.41	164.03 ± 8.18	0.073
BMI (kg/m^2)	23.55 ± 3.57	23.44 ± 2.98	23.68 ± 4.19	0.770
Sex (Male/ Female)	71 (46/25)	38 (23/15)	33 (23/10)	0.420
Comorbidities n (%)
Diabetes type 2	19 (26.8%)	10 (26.3%)	9 (27.3%)	0.982
Hypertension	24 (33.8%)	12 (31.6%)	12 (36.4%)	0.671
Coronary artery disease	9 (12.7%)	4 (10.5%)	5 (15.2%)	0.724
COPD	6 (8.5%)	2 (5.3%)	4 (12.1%)	0.406
Cirrhosis	4 (5.6%)	4 (10.5%)	0 (0.0%)	0.118
Chronic heart failure	3 (4.2%)	2 (5.3%)	1 (3.0%)	0.641
Others	6 (8.5%)	4 (10.5%)	2 (6.1%)	0.679
Focus of infection
Respiratory system	27 (38.0%)	14 (36.8%)	13 (39.4%)	0.825
Gastrointestinal system	18 (25.4%)	11 (28.9%)	7 (21.2%)	0.455
Urinary tract	12 (16.9%)	6 (15.8%)	6 (18.2)	0.788
Skin and soft tissue	7 (9.9%)	3 (7.9%)	4 (12.1%)	0.697
Central nervous system	3 (4.2%)	2 (5.3%)	1 (3.0%)	0.641
Others	4 (5.6%)	2 (5.3%)	2 (6.1%)	0.884

Notes: n/a: non applicable; continuous data presented using the mean ± standard deviation and categorical data (n, %); p*: t-test.

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; AKI, acute kidney injury.

Table 2 Clinical Characteristics

Characteristics	General (n =71)	AKI (n = 38)	Non-AKI (n = 33)	p
Systolic Blood pressure (mmHg)	115 (75–180)	87 (75–153)	130 (95–180)	<0.001^a
Diastolic Blood pressure (mmHg)	67 (45–110)	54 (45–88)	76 (55–110)	<0.001^a
Mean blood pressure	85 (55–133.33)	63.5 (55–103.33)	93.3 (71.67–133.33)	<0.001^a
SpO2	99 (80–100)	93 (80–100)	100 (98–100)	<0.001^a
CVP	10 (1–25)	6 (1–25)	11 (6–20)	0.001^a
Glasgow	15 (10–15)	12 (10–15)	15 (13–15)	<0.001^a
APACHE II at hospital admission	16 (5–34)	20.5 (10–34)	13 (5–31)	0.004^a
SOFA at hospital admission	6 (2–14)	7.5 (2–14)	5 (2–13)	<0.001^a
Ventilator	35 (49.3%)	25 (65.8%)	10 (30.3%)	0.003^b
Septic shock	28 (39.4%)	24 (63.2%)	4 (12.1%)	<0.001^b
RRT	16 (22.5%)	12 (31.6%)	4 (12.1%)	0.003^b
Duration in ICU	8 (3–38)	9 (5–28)	5.5 (3–15)	0.067^a
Mortality within 28 days	21 (29.6%)	20 (52.6%)	1 (15.2%)	<0.001^c

Notes: p-value: ^amann–Whitney test; ^bChi-square test; ^cFisher exact test.

Abbreviations: RRT, Renal replacement therapy; SOFA, Sequential organ failure assessment score; APACHE II, Acute physiology and chronic health evaluation II; CVP, Central venous pressure.

Table 3 Laboratory Findings

Tests	General (n =71)	AKI (n = 38)	Non-AKI (n = 33)	p
White blood cells	15.56 ± 9.59	16.25 ± 10.59	14.76 ± 8.39	0.682^b
Hemoglobin	10.60 ± 2.25	10.65 ± 2.44	10.55 ± 2.06	0.858^b
Red blood cells	3.68 ± 0.78	3.64 ± 0.81	3.72 ± 0.76	0.675^b
Hematocrit	32.51 ± 6.59	32.64 ± 7.16	33.35 ± 5.98	0.85^b
Platelets	137 (7–439)	113.5 (7–405)	210 (9–439)	0.002^a
ALT	58 (5.29–3443)	77 (5.29–3443)	51.3 (5.63–500)	0.107^a
AST	70.24 (11.61–5970)	110.93 (12.67–5970)	56.20 (11.61–462)	0.019^a
Total Bilirubin	22.4 (4.3–526.7)	28.45 (6.2–417.7)	16.5 (4.3–526.7)	0.003^a
Albumin	27.14 ± 4.70	27.30 ± 4.40	26.95 ± 5.08	0.760^b
IL-6	296.3 (3.53–5000)	823.25 (3.53–5000)	176.2 (8.2–5000)	0.020^a
PCT	17.49 (0.129–100)	29.43 (0.23–100)	14.08 (0.129–100)	0.115^a
Lactate	2.80 (0.7–17.4)	3.45 (1.1–17.4)	2.1 (0.7–11.9)	0.005^a
Baseline creatinine (µmol/mL)	85.62±14.10	87.42 ± 14.3	83.55±13.8	0.251^b
Creatinine (µmol/l)	120 (41–325.5)	180.72 (101–325.5)	73 (41–120)	<0.001^a
sTM (ng/mL)	4.33 (1.51–6.46)	4.71 (3.87–6.46)	2.54 (1.51–5.94)	<0.001^a

Notes: p-value: ^aMann Whitney test; ^bt-test.

Abbreviations: sTMm, soluble thrombomodulin; PCT, procalcitonin; IL-6, interleukin-6; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase.

Table 4 Characteristics of Survival and Mortality Within 28 Days

Characteristics	General (n = 71)	Survival (n=50)	Mortality (n=21)	p
AKI	38 (53.5%)	18 (36%)	20 (95.2%)	< 0.001
Stage 1	16 (22.5%)	9 (18%)	7 (33.3%)
Stage 2	14 (19.7%)	7 (14%)	7 (33.3%)
Stage 3	8 (11.3%)	2 (4%)	6 (28.6%)
Age	61.86±17.82	61.22±19.0	63.38 ± 14.98	0.612^b
White blood cells	14.5 (0.3–200.6)	14.3 (0.3–200.6)	17.4 (0.4–48)	0.682^a
Platelets	137 (7–439)	157 (9–439)	111 (7–405)	0.002^a
Creatinine (µmol/l)	120 (41–325.5)	105.64 (41–320)	186 (90.42–325.5)	<0.001^a
Albumin	27.14 ±4.70	26.88 ±4.67	27.75±4.83	0.480^b
PCT	17.49 (0.129–100)	16.62 (0.13–100)	24.07 (1.5–100)	0.115^a
Lactate	2.80 (0.7–17.4)	2.4 (0.7–12.4)	3.6 (1.1–17.4)	0.005^a
IL-6	296.3 (3.53–5000)	199.85 (3.53–5000)	1520 (8.2–5000)	0.020^a
sTM	4.33 (1.51–6.46)	3.87 (1.51–5.90)	4.78 (2.88–6.46)	<0.001^a
SOFA	6 (2–14)	5 (2–9)	10 (3–14)	<0.001^a
APACHE II	16 (5–34)	14.5 (5–33)	30 (10–34)	0.004^a

Notes: p-value: ^aMann Whitney test; ^bt-test.

Abbreviations: sTM, soluble thrombomodulin; PCT, procalcitonin; SOFA, Sequential organ failure assessment score; APACHE II, Acute physiology and chronic health evaluation II.

Figure 1 Receiver operating characteristic (ROC) curve of sTM to predict AKI.

Figure 2 Receiver operating characteristic (ROC) curve of sTM, IL600, SOFA, and APACHE 2 in mortality prediction.

Table 5 Predictive Value of Serum Thrombomodulin for AKI and Mortality

	AKI (Logistic Regression Model)		Mortality (Cox Regression Model)
	OR (95% CI)	P value	HR (95% CI)	P value
sTM Per 1 ng/mL
Model 1^a	5.01 (2.41010.42)	<0.001	2.764 (1.68–4.56)	<0.001
Model 2^b	3.20 (1.33–7.70)	0.010	2.85 (1.22–6.62)	0.015

Notes: ^aUnadjusted model. ^bAKI: adjusted for Mean blood pressure, CVP, SOFA, Ventilator, IL-6, Lactate. Mortality: adjusted for PLT; Creatinine; Lactate; Septic shock; SOFA.