Author Contributions
All authors made substantial contributions to conceptualization, F.M., A.O., M.C.R.F. and R.W.; methodology, N.R.C., E.P., M.M.J.Q., F.M., M.C.R.F. and R.W.; formal analysis, E.P., F.M., A.O., M.C.R.F. and R.W.; investigation, N.R.C., E.P., M.M.J.Q., F.M. and R.W.; resources, N.R.C., E.P., F.M., A.O., M.C.R.F. and R.W.; data curation, N.R.C., E.P., M.M.J.Q., F.M. and R.W.; writing—original draft preparation, N.R.C. and R.W.; writing—review and editing, N.R.C., E.P., F.M., M.M.J.Q., A.O., M.C.R.F. and R.W.; funding acquisition, A.O. and R.W. All authors have read and agreed to the published version of the manuscript.
Figure 1.
Serum creatinine (SCr) concentration (mg/dL) before surgery, at admission to the intensive care unit (ICU), and 12 h and 48 h after surgery in (a) patients that did not develop AKI (No AKI, n = 25) and patients that developed AKI (n = 19), as well as (b) patients that did not develop AKI (No AKI, n = 25), patients that developed stage 1 AKI (AKI-1, n = 11), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 8). Means ± SEM are displayed. * p < 0.05 vs. patients at their own basal level. + p < 0.05 vs. patients that did not develop AKI.
Figure 1.
Serum creatinine (SCr) concentration (mg/dL) before surgery, at admission to the intensive care unit (ICU), and 12 h and 48 h after surgery in (a) patients that did not develop AKI (No AKI, n = 25) and patients that developed AKI (n = 19), as well as (b) patients that did not develop AKI (No AKI, n = 25), patients that developed stage 1 AKI (AKI-1, n = 11), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 8). Means ± SEM are displayed. * p < 0.05 vs. patients at their own basal level. + p < 0.05 vs. patients that did not develop AKI.
Figure 2.
Glomerular filtration rate (GFR) before surgery, 6 months after surgery, and 12 months after surgery in (a) patients that did not develop AKI (n = 23) and patients that developed AKI (n = 12), as well as (b) patients that did not develop AKI (No AKI, n = 23), patients that developed stage 1 AKI (AKI-1, n = 7), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 5). + p < 0.05 vs. patients that did not develop AKI. Means ± SEM are displayed. + p < 0.05 vs. patients that did not develop AKI.
Figure 2.
Glomerular filtration rate (GFR) before surgery, 6 months after surgery, and 12 months after surgery in (a) patients that did not develop AKI (n = 23) and patients that developed AKI (n = 12), as well as (b) patients that did not develop AKI (No AKI, n = 23), patients that developed stage 1 AKI (AKI-1, n = 7), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 5). + p < 0.05 vs. patients that did not develop AKI. Means ± SEM are displayed. + p < 0.05 vs. patients that did not develop AKI.
Figure 3.
Concentration of SCr (mg/dL) in patients that showed high levels of GluAp (a), AlaAp (b), DPP4 (c), and NAG (d) at admission to the ICU (highest quartile, n = 11) and patients with low or medium levels of these markers (n = 33). Means ± SEM are displayed. * p < 0.05 vs. their own basal level. + p < 0.05 vs. the corresponding Low + Medium cluster.
Figure 3.
Concentration of SCr (mg/dL) in patients that showed high levels of GluAp (a), AlaAp (b), DPP4 (c), and NAG (d) at admission to the ICU (highest quartile, n = 11) and patients with low or medium levels of these markers (n = 33). Means ± SEM are displayed. * p < 0.05 vs. their own basal level. + p < 0.05 vs. the corresponding Low + Medium cluster.
Figure 4.
Concentration of SCr (mg/dL) in patients that showed high levels of proteinuria (a), albuminuria (b), and NGAL (c) at admission to the ICU (highest quartile, n = 11) and patients with low or medium levels of these markers (n = 33). Means ± SEM are displayed. * p < 0.05 vs. their own basal level.
Figure 4.
Concentration of SCr (mg/dL) in patients that showed high levels of proteinuria (a), albuminuria (b), and NGAL (c) at admission to the ICU (highest quartile, n = 11) and patients with low or medium levels of these markers (n = 33). Means ± SEM are displayed. * p < 0.05 vs. their own basal level.
Figure 5.
Glomerular filtration rate (mL/min/1.73 m2) in patients that showed high levels of GluAp (a), AlaAp (b), DPP4 (c), and NAG (d) at admission to the ICU (highest quartile, n = 10) and patients with low or medium levels of these markers (n = 25). Means ± SEM are displayed. * p < 0.05 vs. their own basal level. + p < 0.05 vs. the corresponding Low + Medium cluster.
Figure 5.
Glomerular filtration rate (mL/min/1.73 m2) in patients that showed high levels of GluAp (a), AlaAp (b), DPP4 (c), and NAG (d) at admission to the ICU (highest quartile, n = 10) and patients with low or medium levels of these markers (n = 25). Means ± SEM are displayed. * p < 0.05 vs. their own basal level. + p < 0.05 vs. the corresponding Low + Medium cluster.
Figure 6.
Glomerular filtration rate (mL/min/1.73 m2) in patients that showed high levels of proteinuria (a), albuminuria (b), and NGAL (c) at admission to the ICU (highest quartile, n = 10) and patients with low or medium levels of these markers (n = 25). Means ± SEM are displayed. + p < 0.05 vs. the corresponding Low + Medium cluster.
Figure 6.
Glomerular filtration rate (mL/min/1.73 m2) in patients that showed high levels of proteinuria (a), albuminuria (b), and NGAL (c) at admission to the ICU (highest quartile, n = 10) and patients with low or medium levels of these markers (n = 25). Means ± SEM are displayed. + p < 0.05 vs. the corresponding Low + Medium cluster.
Table 1.
Demographic characteristics of and long-term events in patients that developed AKI (n = 19) and patients that did not develop AKI (n = 25) after cardiac surgery.
Table 1.
Demographic characteristics of and long-term events in patients that developed AKI (n = 19) and patients that did not develop AKI (n = 25) after cardiac surgery.
| No AKI (n = 25) | AKI (n = 19) |
---|
Age (years) | 65.6 ± 2.31 | 71.7 ± 1.64 * |
Gender (male/female, %) | 36/64 | 47.4/52.6 |
Need for RRT (%) | 0 | 15.8 * |
Stay in ICU (days) | 9.25 ± 0.84 | 13.6 ± 2.87 |
Subsequent hospitalizations (%) | 25 | 35.3 |
Cardiovascular events (%) | 12.5 | 23.5 |
Exitus (%) | 0 | 21.1 * |
Table 2.
Demographic characteristics of and long-term events in patients that did not develop AKI (No AKI, n = 25), patients that developed stage 1 AKI (AKI-1, n = 11), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 8).
Table 2.
Demographic characteristics of and long-term events in patients that did not develop AKI (No AKI, n = 25), patients that developed stage 1 AKI (AKI-1, n = 11), and patients that developed stage 2 or 3 AKI (AKI-2 + 3, n = 8).
| No AKI (n = 25) | AKI-1 (n = 11) | AKI-2 + 3 (n = 8) |
---|
Age (years) | 65.6 ± 2.31 | 72.3 ± 2.08 | 71.0 ± 2.80 |
Gender (male/female, %) | 36/64 | 55/45 | 37.5/62.5 |
Need for RRT (%) | 0 | 9.09 | 25 * |
Stay in ICU (days) | 9.25 ± 0.84 | 10.7 ± 2.03 | 17.6 ± 6.20 |
Subsequent hospitalizations (%) | 25 | 40 | 28.6 |
Cardiovascular events (%) | 12.5 | 20 | 28.6 |
Exitus (%) | 0 | 18.2 | 25 |
Table 3.
Proteinuria (g/g Cr), albuminuria (mg/g Cr), NAG (U/g Cr), NGAL (mg/g Cr), GluAp (mg/g Cr), AlaAp (mg/g Cr), and DPP4 (mg/g Cr) in urine samples obtained at admission to the ICU in patients that did not develop AKI (n = 25) and in patients that developed AKI (n = 19).
Table 3.
Proteinuria (g/g Cr), albuminuria (mg/g Cr), NAG (U/g Cr), NGAL (mg/g Cr), GluAp (mg/g Cr), AlaAp (mg/g Cr), and DPP4 (mg/g Cr) in urine samples obtained at admission to the ICU in patients that did not develop AKI (n = 25) and in patients that developed AKI (n = 19).
| No AKI (n = 25) | AKI (n = 19) |
---|
Proteinuria (g/g Cr) | 11.6 ± 2.04 | 15.8 ± 3.42 |
Albuminuria (mg/g Cr) | 626 ± 95.8 | 966 ± 113 * |
NAG (U/g Cr) | 114 ± 23.7 | 211 ± 47.4 |
NGAL (mg/g Cr) | 15.1 ± 2.09 | 36.8 ± 12.5 |
GluAp (mg/g Cr) | 1.82 ± 0.80 | 17.8 ± 13.4 |
AlaAp (mg/g Cr) | 265 ± 82.3 | 432 ± 145 |
DPP4 (mg/g Cr) | 70.0 ± 11.5 | 150 ± 40.6 |
Table 4.
Proteinuria (g/g Cr), albuminuria (mg/g Cr), NAG (U/g Cr), NGAL (mg/g Cr), GluAp (mg/g Cr), AlaAp (mg/g Cr), and DPP4 (mg/g Cr) in urine samples obtained at admission to the ICU in patients that did not develop AKI (n = 25) and in patients that developed AKI stage 1 (n = 11) and stage 2 or 3 (n = 8).
Table 4.
Proteinuria (g/g Cr), albuminuria (mg/g Cr), NAG (U/g Cr), NGAL (mg/g Cr), GluAp (mg/g Cr), AlaAp (mg/g Cr), and DPP4 (mg/g Cr) in urine samples obtained at admission to the ICU in patients that did not develop AKI (n = 25) and in patients that developed AKI stage 1 (n = 11) and stage 2 or 3 (n = 8).
| No AKI or AKI-1 (n = 36) | AKI-2 + 3 (n = 8) |
---|
Proteinuria (g/g Cr) | 13.3 ± 2.25 | 13.8 ± 2.36 |
Albuminuria (mg/g Cr) | 723 ± 81.1 | 979 ± 198 |
NAG (U/g Cr) | 129 ± 21.1 | 277 ± 94.4 * |
NGAL (mg/g Cr) | 27.8 ± 6.81 | 9.50 ± 2.45 |
GluAp (mg/g Cr) | 2.32 ± 1.06 | 37.5 ± 31.5 * |
AlaAp (mg/g Cr) | 261 ± 62.5 | 679 ± 313 |
DPP4 (mg/g Cr) | 71.9 ± 8.43 | 251.4 ± 85.8 |
Table 5.
Cut-off value (COV), predictive positive value (PPV, %), predictive negative value (PNV, %), sensitivity (Sens, %), specificity (Spec, %), and percentage of correctly diagnosed patients (CDP) for diagnosis of AKI at admission to the ICU for the highest quartile of each biomarker and AKIN criteria. Patients that developed AKI were taken as true positives (n = 19), and No AKI patients were taken as true negatives (n = 25).
Table 5.
Cut-off value (COV), predictive positive value (PPV, %), predictive negative value (PNV, %), sensitivity (Sens, %), specificity (Spec, %), and percentage of correctly diagnosed patients (CDP) for diagnosis of AKI at admission to the ICU for the highest quartile of each biomarker and AKIN criteria. Patients that developed AKI were taken as true positives (n = 19), and No AKI patients were taken as true negatives (n = 25).
Marker | COV | PPV (%) | NPV (%) | Sens (%) | Spec (%) | CDP (%) |
---|
Proteinuria (g/g Cr) | 16.2 | 54.5 | 60.6 | 31.6 | 80 | 59.1 |
Albuminuria (mg/g Cr) | 1246 | 63.6 | 63.6 | 36.8 | 84 | 63.6 |
NAG (U/g Cr) | 174 | 63.6 | 63.6 | 36.8 | 84 | 63.6 |
NGAL (mg/g Cr) | 23.1 | 54.6 | 60.6 | 31.6 | 80 | 59.1 |
GluAp (mg/g Cr) | 1.840 | 63.6 | 63.6 | 36.8 | 84 | 63.6 |
AlaAp (mg/g Cr) | 323 | 54.6 | 60.6 | 31.6 | 80 | 59.1 |
DPP4 (mg/g Cr) | 105 | 63.6 | 63.6 | 36.8 | 84 | 63.6 |
AKIN Criteria | | 100 | 59.5 | 10.5 | 100 | 61.4 |
Table 6.
Cut-off value (COV), predictive positive value (PPV, %), predictive negative value (PNV, %), sensitivity (Sens, %), specificity (Spec, %), and percentage of correctly diagnosed patients (CDP) for diagnosis of stage 2 or 3 AKI at admission to the ICU for the highest quartile of each biomarker and AKIN criteria. Patients that developed stage 2 or 3 AKI were taken as true positives (n = 8). No AKI patients and patients in stage 1 AKI were taken as true negatives (n = 36).
Table 6.
Cut-off value (COV), predictive positive value (PPV, %), predictive negative value (PNV, %), sensitivity (Sens, %), specificity (Spec, %), and percentage of correctly diagnosed patients (CDP) for diagnosis of stage 2 or 3 AKI at admission to the ICU for the highest quartile of each biomarker and AKIN criteria. Patients that developed stage 2 or 3 AKI were taken as true positives (n = 8). No AKI patients and patients in stage 1 AKI were taken as true negatives (n = 36).
Marker | COV | PPV (%) | NPV (%) | Sens (%) | Spec (%) | CDP (%) |
---|
Proteinuria (g/g Cr) | 16.2 | 27.3 | 84.8 | 37.5 | 77.8 | 70.5 |
Albuminuria (mg/g Cr) | 1246 | 36.4 | 87.8 | 50 | 80.6 | 75 |
NAG (U/g Cr) | 174 | 27.3 | 84.8 | 37.5 | 77.8 | 70.5 |
NGAL (mg/g Cr) | 23.1 | 0 | 75.8 | 0 | 69.4 | 56.8 |
GluAp (mg/g Cr) | 1.840 | 54.5 | 93.9 | 75.0 | 86.1 | 84.1 |
AlaAp (mg/g Cr) | 323 | 36.4 | 87.8 | 50 | 80.6 | 75 |
DPP4 (mg/g Cr) | 105 | 45.5 | 90.9 | 62.5 | 83.3 | 79.5 |
NGAL (mg/g Cr) | 23.1 | 0 | 75.8 | 0 | 69.4 | 56.8 |
AKIN Criteria | | 0 | 81.8 | 0 | 100 | 81.8 |
Table 7.
Length of stay in ICU (days) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 33).
Table 7.
Length of stay in ICU (days) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 33).
| Low + Medium (n = 33) | High (n = 11) |
---|
Proteinuria (g/g Cr) | 9.47 ± 0.82 | 16.2 ± 4.65 |
Albuminuria (mg/g Cr) | 9.56 ± 0.86 | 15.9 ± 4.63 |
NAG (U/g Cr) | 11.1 ± 1.78 | 11.5 ± 1.58 |
NGAL (mg/g Cr) | 11.6 ± 1.79 | 9.91 ± 1.47 |
GluAp (mg/g Cr) | 9.50 ± 0.88 | 16.1 ± 4.57 |
AlaAp (mg/g Cr) | 10.3 ± 1.75 | 13.8 ± 1.57 |
DPP4 (mg/g Cr) | 9.38 ± 0.83 | 16.5 ± 4.60 |
Table 8.
Subsequent hospitalizations (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 10) in comparison with patients that showed lower or medium levels of biomarkers (n = 31).
Table 8.
Subsequent hospitalizations (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 10) in comparison with patients that showed lower or medium levels of biomarkers (n = 31).
| Low + Medium (n = 31) | High (n = 10) |
---|
Proteinuria (g/g Cr) | 35.5 | 10.0 |
Albuminuria (mg/g Cr) | 35.5 | 10.0 |
NAG (U/g Cr) | 29.0 | 30.0 |
NGAL (mg/g Cr) | 32.3 | 20.0 |
GluAp (mg/g Cr) | 32.3 | 20.0 |
AlaAp (mg/g Cr) | 25.8 | 40.0 |
DPP4 (mg/g Cr) | 29.0 | 30.0 |
Table 9.
Need for RRT (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 33).
Table 9.
Need for RRT (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 33).
| Low + Medium (n = 33) | High (n = 11) |
---|
Proteinuria (g/g Cr) | 6.06 | 9.09 |
Albuminuria (mg/g Cr) | 9.09 | 0 |
NAG (U/g Cr) | 9.09 | 0 |
NGAL (mg/g Cr) | 9.09 | 0 |
GluAp (mg/g Cr) | 3.03 | 18.2 |
AlaAp (mg/g Cr) | 6.06 | 9.09 |
DPP4 (mg/g Cr) | 6.06 | 9.09 |
Table 10.
Cardiovascular events (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 10) in comparison with patients that showed lower or medium levels of biomarkers (n = 31).
Table 10.
Cardiovascular events (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 10) in comparison with patients that showed lower or medium levels of biomarkers (n = 31).
| Low + Medium (n = 31) | High (n = 10) |
---|
Proteinuria (g/g Cr) | 22.6 | 0 |
Albuminuria (mg/g Cr) | 22.6 | 0 |
NAG (U/g Cr) | 19.4 | 10.0 |
NGAL (mg/g Cr) | 19.4 | 10.0 |
GluAp (mg/g Cr) | 22.6 | 0 |
AlaAp (mg/g Cr) | 16.1 | 20.0 |
DPP4 (mg/g Cr) | 19.4 | 10.0 |
Table 11.
Exitus (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 32).
Table 11.
Exitus (%) in patients that showed higher levels of urinary biomarkers at admission to the ICU (n = 11) in comparison with patients that showed lower or medium levels of biomarkers (n = 32).
| Low + Medium (n = 32) | High (n = 11) |
---|
Proteinuria (g/g Cr) | 9.38 | 9.09 |
Albuminuria (mg/g Cr) | 12.5 | 0 |
NAG (U/g Cr) | 12.5 | 0 |
NGAL (mg/g Cr) | 12.5 | 0 |
GluAp (mg/g Cr) | 6.25 | 18.2 |
AlaAp (mg/g Cr) | 9.38 | 9.09 |
DPP4 (mg/g Cr) | 9.38 | 9.09 |