Figures
- FIGURE 1
Biomarker measurements of a) cDPP3 and b) bio-ADM on day 1, 3 and 7 of ICU admission. Results of 28-day survivors and non-survivors are displayed, respectively. The median, interquartile ranges and Tukey's hinges are displayed. cDPP3: circulating dipeptidyl peptidase 3; bio-ADM: biologically active adrenomedullin. *: p<0.05; **: p<0.01; ***: p<0.001.
- FIGURE 2
Areas under the receiver operating characteristic curve (AUC) of cDPP3 and bio-ADM on days 1, 3 and 7 of ICU admission. Separate graphs display different study outcomes. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Bio-ADM: bioactive adrenomedullin; cDPP3: circulating dipeptidyl peptidase 3.
- FIGURE 3
Kaplan–Meier analysis of 28-day mortality in critically ill COVID-19 patients on day 7 after ICU admission. Groups are based on high cDPP3 (>40 ng·mL−1) versus low cDPP3 (<40 ng·mL−1), as well as high bio-ADM (>70 pg·mL−1) versus low bio-ADM (>70 pg·mL−1). The reported hazard ratio compares the group with high cDPP3 and high bio-ADM levels to the other three groups (curves displayed separately in figure for illustrative purposes). Bio-ADM: bioactive adrenomedullin; cDPP3: circulating dipeptidyl peptidase 3.
- FIGURE 4
Graphical overview of sensitivity, specificity and accuracy for associations of cDPP3 and bio-ADM with 28-day mortality and all-stage AKI. Cut-offs for cDPP3 and bio-ADM were >40 ng·mL−1 and >70 pg·mL−1, respectively. Bio-ADM: bioactive adrenomedullin; cDPP3: circulating dipeptidyl peptidase 3. *: p<0.05; **: p<0.01.
- FIGURE 5
Biomarker kinetics of cDPP3 and bio-ADM based on subgroups combining study outcomes of 28-day mortality and AKI. a) Subgroups based on survival status and occurrence of KDIGO stage 1 AKI. b) Subgroups based on survival status and occurrence of KDIGO stage 3 AKI. Median and interquartile ranges are displayed. AKI: acute kidney injury; bio-ADM: bioactive adrenomedullin; cDPP3: circulating dipeptidyl peptidase 3; ICU: intensive care unit. *: p<0.05; **: p<0.01; ***: p<0.001.
Tables
- TABLE 1
Admission baseline characteristics of the total cohort, as well as admission characteristics of 28-day survivors versus non-survivors
Total Non-survivors Survivors p-value Subjects n 80 18 62 Demographics Sex, male 60 (75.0) 14 (77.8) 46 (74.2) 1.000 Age years 65 (57–70) 64 (58–71) 65 (57–69) 0.809 BMI kg·m−2 27.5 (25.4–31.0) 29.6 (27.0–32.1) 27.0 (24.6–30.6) 0.037 Medical history COPD 4 (5.0) 0 (0.0) 4 (6.5) 0.570 Diabetes 31 (38.8) 7 (38.9) 24 (38.7) 1.000 Hypertension 41 (51.2) 9 (50.0) 32 (51.6) 1.000 Immune-deficiency 7 (8.8) 3 (16.7) 4 (6.5) 0.185 Characteristics during hospitalisation Leukocytes 8.5 (6.2–12.4) 9.5 (7.3–11.5) 8.4 (6.0–12.5) 0.541 Creatinineday1 µmol·L−1 80 (61–119) 125 (72–269) 77 (58–100) 0.004 Lactateday1 mmol·L−1 1.2 (1.0–1.6) 1.5 (1.0–1.9) 1.2 (1.0–1.6) 0.102 Troponin-Tday1 ng·L−1 23 (14–56) 68 (19–130) 22 (11–42) 0.013 P/F ratio 146 (96–200) 88 (66–183) 165 (118–203) 0.036 Vasopressors 38 (47.5) 7 (38.9) 31 (50.0) 0.289 Inotropics 3 (3.8) 1 (5.6) 2 (3.2) 0.540 Mechanical ventilation 66 (82.5) 15 (83.3) 51 (82.3) 1.000 AKI (any KDIGO stage) 34 (42.5) 9 (50.0) 25 (40.3) 0.590 AKI (KDIGO stage 3) 15 (18.8) 7 (38.9) 8 (12.9) 0.034 Severity scores Admission SOFA 6 (4–7) 6 (3–9) 6 (4–7) 0.731 Data presented as n (%) or median (IQR) unless stated otherwise. BMI: body mass index; COPD: chronic obstructive pulmonary disease; P/F ratio: PaO2/FIO2 ratio; AKI: acute kidney injury; KDIGO: Kidney Disease: Improving Global Outcomes; SOFA: sequential organ failure assessment.
- TABLE 2
Correlation coefficients between different predictor variables compared to cDPP3 and bio-ADM measurements
Variable r-coefficient p-value cDPP3 correlation Bio-ADM 0.144 0.089 Creatinine 0.162 0.058 Troponin-T 0.176 0.103 ALAT 0.530 <0.001 ASAT 0.714 <0.001 Bilirubin 0.181 0.065 Lactate 0.374 <0.001 P/F ratio −0.138 0.138 Urine output −0.310 0.027 IL-6 0.277 0.075 Bio-ADM correlation cDPP3 0.144 0.089 Creatinine 0.617 <0.001 Troponin-T 0.215 0.046 ALAT 0.005 0.910 ASAT 0.008 0.363 Bilirubin 0.196 <0.001 Lactate 0.334 <0.001 P/F ratio 0.104 0.268 Urine output −0.009 0.937 IL-6 0.353 0.023 cDPP3: circulating dipeptidyl peptidase 3; Bio-ADM: biologically active adrenomedullin; ALAT: alanine-aminotransferase; ASAT: aspartyl-aminotransferase; P/F ratio: PaO2/FIO2 ratio; IL-6: interleukin-6.
