Introduction
Materials and methods
Patient population
Sampling
Data collection and outcome definition
All Patients | Excluding Patients With Preoperative CKD | |||||
---|---|---|---|---|---|---|
Variables | AKI N = 9 | No AKI N = 91 | P value | AKI N = 5 | No AKI N = 69 | P value |
Age, y | 74 (70-77) | 67 (56-73) | 0.015 | 75 (73-84) | 65 (55-72) | 0.003 |
Female, n | 2 (22.2%) | 31 (34.1%) | 0.47 | 1 (20.0%) | 19 (27.5%) | >0.99 |
Preoperative eGFR, mL/min/1.73 m2 | 61 (52-91) | 74 (62-88) | 0.58 | 86 (72-100) | 80 (70-92) | 0.52 |
Preoperative CKD, n | 4 (44.5%) | 22 (24.2%) | 0.23 | - | - | - |
LVEF <35%, n | 3 (33.3%) | 8 (8.8%) | 0.06 | 1 (20.0%) | 6 (8.7%) | 0.40 |
Atrial fibrillation | 6 (66.7%) | 25 (27.5%) | 0.015 | 4 (80.0%) | 18 (26.1%) | 0.025 |
Arterial hypertension | 8 (88.9%) | 65 (71.4%) | 0.26 | 5 (100.0%) | 48 (69.6%) | 0.31 |
COPD | 3 (33.3%) | 8 (8.8%) | 0.025 | 2 (40.0%) | 6 (8.7%) | 0.087 |
Diabetes mellitus, n | 3 (33.3%) | 17 (18.7%) | 0.38 | 0 (0.0%) | 12 (17.4%) | 0.58 |
PVD, n | 4 (44.5%) | 17 (18.7%) | 0.09 | 2 (40.0%) | 11 (15.9%) | 0.21 |
Biochemical analysis
Statistical analysis
Results
Sampling
Patient characteristics
All patients | Excluding patients with preoperative CKD | |||||
---|---|---|---|---|---|---|
Variables
|
AKI (
n
= 9)
|
No AKI (
n
= 91)
|
P
value
|
AKI (
n
= 5)
|
No AKI (
n
= 69)
|
P
value
|
CABG surgery, n (%) | 2 (22.2%) | 17 (18.7%) | 0.68 | 1 (20.0%) | 13 (18.8%) | >0.99 |
Valve surgery, n (%) | 4 (44.5%) | 46 (50.5%) | >0.99 | 2 (40.0%) | 37 (53.6%) | 0.66 |
CABG and valve surgery, n (%) | 3 (33.3%) | 21 (23.1%) | 0.68 | 2 (40.0%) | 14 (20.3%) | 0.29 |
Thoracic aortic surgery, n (%) | 0 (0.0%) | 7 (7.7%) | >0.99 | 0 (0.0%) | 5 (7.3%) | >0.99 |
Previous cardiothoracic operation, n (%) | 2 (22.2%) | 26 (28.6%) | >0.99 | 1 (20.0%) | 23 (33.3%) | >0.99 |
Duration of bypass, minutes | 125 (100 to 172) | 119 (91 to 158) | 0.62 | 109 (80 to 146) | 119 (90 to 156) | 0.57 |
Fluid balanceb, mL | 4,980 (3,000 to 16,200) | 3,100 (1,690 to 4,660) | 0.035 | 4,920 (450 to 16,200) | 3,100 (1,260 to 4,800) | 0.4 |
Furosemideb, n (%) | 9 (100%) | 84 (92.3%) | 0.39 | 5 (100.0%) | 63 (91.3%) | >0.99 |
Furosemideb, mg | 130 (60 to 460) | 50 (20 to 90) | 0.003 | 160 (35 to 672) | 45 (20 to 70) | 0.05 |
Vasopressor useb, n (%) | 7 (77.8%) | 65 (71.4%) | 0.69 | 5 (100.0%) | 49 (71.0%) | 0.32 |
Inotrope useb, n (%) | 8 (88.9%) | 51 (63.7%) | 0.13 | 4 (80.0%) | 45 (65.2%) | 0.66 |
Blood transfusionb, n (%) | 8 (88.9%) | 52 (57.1%) | 0.06 | 4 (80.0%) | 39 (56.5%) | 0.39 |
Blood transfusionb, mL | 1,000 (500 to 6,380) | 500 (0 to 500) | 0.005 | 1,250 (250 to 6,800) | 250 (0 to 500) | 0.048 |
LOS in hospital, days | 14 (8 to 19) | 9 (7 to 14) | 0.024 | 14 (8 to 19) | 9 (7 to 14) | 0.48 |
Need for RRT, n (%) | 3 (33.3%) | 2 (2.2%) | 0.005 | 2 (40.0%) | 0 (0.0%) | 0.004 |
Hospital mortality, n (%) | 3 (33.3%) | 0 (0%) | 0.001 | 1 (20.0%) | 0. (0.0%) | 0.068 |
Urine hepcidin
Urine hepcidin adjusted to urine creatinine
All patients | Excluding patients with preoperative CKD | |||||
---|---|---|---|---|---|---|
Hepcidin index | No AKI ( n = 91) | AKI ( n = 9) | P value | No AKI ( n = 69) | AKI ( n = 5) | P value |
Urine hepcidin/urine creatinine, ng/mg | ||||||
Baseline | 308 (122 to 583) | 120 (34 to 295) | 0.07 | 309 (143 to 570) | 164 (100 to 633) | 0.6 |
6 hours after CPB start | 5,175 (2,086 to 9,539) | 1,229 (314 to 2,379) | <0.001 | 5,402 (2,100 to 9,300) | 1,400 (639 to 2,379) | 0.009 |
24 hours after CPB startb | 3,255 (1,576 to 6,652) | 1,345 (537 to 3,583) | 0.07 | 3,143 (1,798 to 6,585) | 1,345 (971 to 3,362) | 0.06 |
Friedman test | <0.001 | 0.005 | <0.001 | 0.11 | ||
Urine creatinine, mg/mL | ||||||
Baseline | 1.14 (0.57 to 1.74) | 0.92 (0.51 to 1.83) | 0.52 | 1.28 (0.60 to 1.96) | 1.66 (0.78 to 2.10) | 0.71 |
6 hours after CPB start | 0.19 (0.10 to 0.28) | 0.21 (0.10 to 0.30) | 0.84 | 0.19 (0.11 to 0.28) | 0.21 (0.12 to 0.30) | 0.97 |
24 hours after CPB startb | 0.46 (0.24 to 0.71) | 0.22 (0.12 to 0.29) | 0.008 | 0.52 (0.29 to 0.73) | 0.22 (0.18 to 0.37) | 0.022 |
Friedman test | <0.001 | 0.03 | <0.001 | 0.17 | ||
Urine/plasma hepcidin ratio | ||||||
Baseline | 2.6 (1.2 to 4.9) | 1.1 (0.2 to 5.6) | 0.18 | 2.8 (1.2 to 4.8) | 4.6 (1.6 to 8.4) | 0.41 |
6 hours after CPB start | 3.1 (1.5 to 5.3) | 1.0 (0.2 to 3.1) | 0.047 | 3.6 (1.9 to 5.9) | 3.0 (1.0 to 46.7) | 0.59 |
24 hours after CPB startb | 6.9 (2.0 to 13.3) | 1.2 (0.6 to 2.4) | 0.011 | 8.2 (3.8 to 15.1) | 2.3 (0.8 to 11.6) | 0.11 |
Friedman test | <0.001 | 0.69 | <0.001 | 0.74 | ||
Fractional hepcidin excretion, % | ||||||
Baseline | 2.4 (1.5 to 4.1) | 1.7 (0.7 to 2.5) | 0.17 | 2.3 (1.5 to 2.9) | 2.5 (1.8 to 4.7) | 0.58 |
6 hours after CPB start | 22.1 (12.2 to 30.0) | 8.3 (1.7 to 19.5) | 0.005 | 22.0 (15.1 to 30.5) | 16.3 (3.6 to 22.5) | 0.19 |
24 hours after CPB startb | 14.7 (9.5 to 25.2) | 8.1 (4.5 to 46.5) | 0.35 | 15.3 (9.9 to 25.2) | 8.1 (5.1 to 55.7) | 0.6 |
Friedman test | <0.001 | 0.021 | <0.001 | 0.47 |
Urine hepcidin/urine creatinine | AKI (n= 9) | No AKI (n= 91) | P value |
---|---|---|---|
Δ 6 to 0 hours, ng/mg | 1,079 (85 to 2,195) | 4,085 (1,998 to 8,736) | <0.001 |
Δ 6 to 0 hours, % | 626 (108 to 1,541) | 1,444 (867 to 3,269) | 0.016 |
Δ 24 to 0 hours, ng/mg | 1,142 (344 to 3,379) | 2,821 (1,266 to 6,482) | 0.119 |
Δ 24 to 0 hours, % | 925 (270 to 1,825) | 939 (338 to 2,458) | 0.717 |
Δ 24 to 6 hours, ng/mg | 325 (-397 to 1,959) | -1,051 (-4,350 to 1,531) | 0.079 |
Δ 24 to 6 hours, % | 139 (-29 to 235) | -33 (-71 to 71) | 0.02 |
Plasma hepcidin
Independent predictors of AKI
Model 0 (R2 = 0.42) | Model 1 (R2 = 0.63) | Model 2 (R2 = 0.43) | Model 3(R2 = 0.50) | |||||
---|---|---|---|---|---|---|---|---|
Risk factors and biomarkers | Regression coefficient (B) (SE) | P value | Regression coefficient (B) (SE) | P value | Regression coefficient (B) (SE) | P value | Regression coefficient (B) (SE) | P value |
Age, years | -0.2 (0.1) | 0.015 | -0.2 (0.1) | 0.06 | -0.1 (0.1) | 0.06 | -0.2 (0.1) | 0.036 |
LVEF <35% | -2.9 (1.1) | 0.009 | -4.1 (1.6) | 0.008 | -2.7 (1.1) | 0.011 | -3.0 (1.2) | 0.01 |
COPD | -2.2 (1.0) | 0.036 | -2.4 (1.3) | 0.06 | -2.0 (1.0) | 0.044 | -2.5 (1.1) | 0.026 |
Log urine hepcidin/urine creatinine, ng/mg | 2.9 (1.1) | 0.011 | ||||||
Log urine hepcidin, ng/mL | 1.2 (0.7) | 0.09 | ||||||
Log plasma hepcidin, ng/mL | 2.7 (2.5) | 0.56 |
Correlation of urine and plasma hepcidin levels
Urine/plasma hepcidin ratio and fractional excretion of hepcidin
Influence of exclusion of patients with preoperative chronic kidney disease
Biomarkers | AUC-ROC (95% CI) | Sensitivity | Specificity | Cutoff |
---|---|---|---|---|
Urine hepcidin, ng/mL | ||||
6 hours after CPB start | 0.81 (0.67 to 0.96) | 62.30% | 100.00% | >545 |
24 hours after CPB start | 0.83 (0.74 to 0.92) | 79.70% | 100.00% | >475 |
Urine hepcidin/urine creatinine, ng/mg | ||||
6 hours after CPB start | 0.87 (0.75 to 0.99) | 70.00% | 100.00% | >2820 |
24 hours after CPB start | 0.75 (0.57 to 0.94) | 76.50% | 80.00% | >1,762 |
Plasma hepcidin, ng/mL | ||||
6 hours after CPB start | 0.70 (0.46 to 0.98) | 69.00% | 80.00% | >175 |
24 hours after CPB start | 0.54 (0.23 to 0.86) | N/A | N/A | N/A |
Baseline variables | Spearman's ρ | Preoperative eGFR |
---|---|---|
Urine hepcidin | Correlation coefficient | 0.15 |
Significance (two-sided) | 0.15 | |
Number of patients | 100 | |
Urine hepcidin adjusted to urine creatinine | Correlation coefficient | 0.07 |
Significance (two-sided) | 0.51 | |
Number of patients | 100 | |
Plasma hepcidin | Correlation coefficient | 0.043 |
Significance (two-sided) | 0.67 | |
Number of patients | 100 | |
Urine/plasma hepcidin ratio | Correlation coefficient | 0.16 |
Significance (two-sided) | 0.11 | |
Number of patients | 100 |
Discussion
Key findings
Relation to previous studies
Significance of study findings
Strengths and limitations
Future studies
Conclusions
Key messages
-
Cardiopulmonary bypass increases plasma and urine hepcidin levels.
-
The increase in urinary hepcidin levels is greater in patients who do not develop AKI.
-
Urine hepcidin has additive value in ruling out acute kidney injury in patients after cardiac surgery.
-
Urine hepcidin is predictive of not needing postoperative RRT.
-
Plasma hepcidin does not rule out the development of acute kidney injury.