Background
Methods
Study design and participants
Procedures and measurements
Evaluation of kidney function
Follow-up and endpoints
Protein load and biomarker secretion in human kidney tubule cells
Statistical analysis
Results
Baseline characteristics
Control group† (n = 214) | Protein-loading group† (n = 110) | p-value | |
---|---|---|---|
Demographics | |||
Age, years | 63 (54 – 71) | 62 (54 – 71) | 0.693 |
Male sex, n (%) | 151 (71%) | 78 (71%) | 0.948 |
Race/ethnicity, n (%) | 0.856 | ||
White | 210 (98.1%) | 108 (98.2%) | |
Black | 4 (1.9%) | 3 (1.8%) | |
Weight, kg | 76 (65 – 85) | 77 (68 – 84) | 0.431 |
Body mass index, kg/m2 | 24.6 (22.2 – 28.3) | 25.5 (23.5 – 28.2) | 0.134 |
Comorbidities, n (%) | |||
Hypertension | 142 (66.4%) | 72 (65.5%) | 0.871 |
Atrial fibrillation | 29 (13.6%) | 24 (21.8%) | 0.057 |
Peripheral vasculopathy | 19 (8.5%) | 8 (7.3%) | 0.620 |
Type 2 diabetes mellitus | 15 (7.0%) | 7 (6.4%) | 0.827 |
Smoking status (former smoker or current smoker) | 76 (35.5%) | 40 (36.4%) | 0.745 |
Dyslipidemia | 65 (30.4%) | 25 (22.7%) | 0.146 |
Medication, n (%) | |||
Antiplatelet | 38 (17.8%) | 18 (16.4%) | 0.753 |
Beta-blocker | 108 (50.5%) | 41 (37.3%) | 0.024 |
ACEi or ARB | 99 (46.3%) | 50 (45.5%) | 0.890 |
Statin | 50 (23.4%) | 39 (35.5%) | 0.021 |
Diuretica | 57 (26.6%) | 27 (24.5%) | 0.684 |
Baseline clinical data | |||
Leucocytes, × 109/L | 6.40 (5.30 – 7.40) | 6.35 (5.43 – 7.62) | 0.727 |
Hemoglobin, g/dL | 14.2 (13.2 – 15.2) | 14.0 (13.1 – 14.8) | 0.198 |
Platelets, × 109/L | 204 (176 – 241) | 212 (184 – 246) | 0.186 |
Albumin, g/dL | 4.0 (3.8 – 4.1) | 3.9 (3.8 – 4.1) | 0.445 |
eGFR, mL/min/1.73 m2 b | 90 (80 − 98) | 91 (82 − 100) | 0.886 |
Urea, mg/dLc | 35.0 (30.0 – 41.3) | 36.0 (29.0 – 43.0) | 0.392 |
Troponin I, μg/L | 0.01 (0.01 – 0.01) | 0.01 (0.01 – 0.01) | 0.328 |
NYHA classification, n (%) | 0.697 | ||
1 | 75 (35.4%) | 43 (39.1%) | |
2 | 133 (62.1%) | 65 (59.1%) | |
3 | 6 (2.8%) | 2 (1.8%) | |
Left ventricular ejection fraction, % | 62.9 (58.0 – 68.0) | 61.0 (58.0 – 66.0) | 0.449 |
Systolic pulmonary arterial pressure, mm Hg | 30.0 (28.0 − 37.0) | 30.0 (22.3 − 38.0) | 0.334 |
EuroSCORE II for operative risk, %d | 1.17 (0.85 − 1.99) | 1.03 (0.69 − 1.83) | 0.294 |
STS risk score, %e | |||
Risk of mortality | 0.64 (0.34 – 1.13) | 0.60 (0.41 – 1.36) | 0.423 |
Risk of morbidity or mortality | 8.55 (6.50 − 10.87) | 8.47 (6.66 − 12.25) | 0.389 |
Risk of renal failure | 1.34 (0.90 − 2.22) | 1.29 (0.90 − 2.07) | 0.847 |
Thakar scoref | 0.326 | ||
0.4 | 165 (77.1%) | 90 (81.8%) | |
1.8 | 49 (22.9%) | 20 (18.2%) | |
Operative data | |||
Aortic cross-clamp, min | 79.5 (59.0 − 97.0) | 79.5 (60.0 − 104.5) | 0.445 |
Cardiopulmonary bypass time, min | 112.5 (90.0 − 138.0) | 115.0 (98.0 − 149.8) | 0.182 |
Procedure, n (%) | |||
Coronary artery bypass graft only | 8 (3.8%) | 4 (3.6%) | 0.507 |
Valve only | 107 (50.5%) | 58 (52.7%) | 0.457 |
Combined or other | 97 (45.8%) | 48 (43.6%) | 0.142 |
Minimally invasive | 141 (66%) | 72 (65%) | 0.468 |
Intraoperative diuresis, mL | 1000 (550 − 1377) | 800 (552 − 1200) | 0.252 |
Surgery fluid balance, mL | 3650 (2880 − 4327) | 3815 (2892 − 4537) | 0.378 |
Lowest mean arterial pressure, mmHg | 66.7 (63.3 − 66.7) | 66.7 (63.3 − 73.3) | 0.007 |
Lowest hemoglobin, g/dL | 10.5 (8.9 − 10.9) | 9.6 (8.7 − 10.8) | 0.329 |
Red blood cell transfusion, n (%) | 6 (2.8%) | 11 (10.0%)a | 0.012 |
ICU data | |||
Mechanical ventilation, days | 1.0 (1.0 − 1.0) | 1.0 (1.0 − 1.0) | 0.445 |
Intra-aortic balloon pump, n (%) | 5 (2.3%) | 3 (2.7%) | 0.830 |
Extra-corporeal membrane oxygenation, n (%) | 2 (0.9%) | 1 (0.9%) | 0.982 |
Myocardial infarction, n (%) | 0 (0%) | 1 (0.9%) | 0.501 |
Stroke, n (%) | 1 (0.5%) | 3 (2.7%) | 0.081 |
Re-intervention, n (%) | 6 (2.8%) | 2 (1.8%) | 0.588 |
Day 1 fluid balance, mL | − 718 (− 1274 to − 117) | − 150 (− 640 to 301) | 0.305 |
Day 2 fluid balance, mL | − 150 (− 640 to 301) | − 270 (− 1020 to 115) | 0.022 |
Weight difference, kgg | − 1.50 (− 3.00 to − 0.10) | - 2.05 (− 3.40 to − 0.02) | 0.170 |
ACEi or ARB use, n (%) | 53 (24.8%) | 22 (20.0%) | 0.335 |
Aminoglycoside use, n (%) | 2 (0.9%) | 0 (0%) | 0.309 |
Vancomycin use, n (%) | 3 (1.4%) | 0 (0%) | 0.212 |
NSAID drug use, n (%) | 4 (1.9%) | 0 (0%) | 0.149 |
Mean arterial pressure < 65 mmHg within the first 24 h, n (%) | 83 (38.8%) | 35 (31.8%) | 0.217 |
Inotropes, n (%) | 67 (31.3%) | 41 (37.3%) | 0.281 |
ICU stay, h | 57 (41 − 87) | 51 (41 − 71) | 0.569 |
Hospital stay, days | 6 (6 − 8) | 5 (4 − 6) | < 0.001 |
3-month follow-up data | |||
ACEi or ARB | 125 (58.4%) | 65 (59.6%) | 0.435 |
Readmission, n (%) | 4 (1.9%) | 5 (4.5%) | 0.165 |
3-month mortality, n (%) | 0 (0%) | 1 (0.9%) | 0.162 |
1-year follow-up data | |||
ACEi or ARB | 112 (52.8%) | 59 (54.1%) | 0.392 |
1-year mortality, n (%) | 2 (0.9%) | 1 (0.9%) | 0.982 |
AKI rates
Control group (n = 214) | Protein-loading group (n = 110) | p-value (unadjusted) | p-value (adjusted)a | |
---|---|---|---|---|
Serum creatinine, mg/dLb | ||||
Hospital admission | 0.85 (0.72 – 0.96) | 0.84 (0.73 – 0.96) | 0.998 | 0.930 |
Preoperative | 0.84 (0.72 − 0.95) | 0.83 (0.72 − 0.96) | 0.956 | 0.883 |
Postoperative day 1 | 0.77 (0.65 − 0.89) | 0.79 (0.70 − 0.88) | 0.181 | 0.148 |
Postoperative day 2 | 0.84 (0.70 − 0.96) | 0.82 (0.70 − 0.96) | 0.308 | 0.251 |
Hospital discharge | 0.8 (0.67 − 0.92) | 0.78 (0.69 − 0.93) | 0.990 | 0.924 |
3-month follow-up | 0.90 (0.76 − 1.00) | 0.83 (0.72 − 0.95) | 0.088 | 0.048 |
1-year follow-up | 0.95 (0.81 – 1.09) | 0.87 (0.76 – 0.93) | < 0.001 | < 0.001 |
eGFR, mL/min/1.73 m2 c | ||||
Hospital admission | 90 (80 − 98) | 91 (82 − 100) | 0.886 | 0.823 |
Preoperative | 91 (80 − 98) | 92 (82 − 100) | 0.886 | 0.823 |
Hospital discharge | 94 (85 − 102) | 93 (85 − 102) | 0.774 | 0.767 |
3-month follow-up | 87 (77 − 95) | 91 (82 − 100) | 0.033 | 0.028 |
1-year follow-up | 81 (70 − 88) | 88 (78 − 96) | < 0.001 | < 0.001 |
Albuminuria, mg/g creatinine | ||||
Hospital admission | 7.0 (3.6 − 24.1) | 6.5 (3.3 − 21.0) | 0.273 | 0.265 |
3-month follow-up | 14.1 (4.3 − 62.1) | 7.9 (1.6 − 43.9) | 0.076 | 0.065 |
1-year follow-up | 20.9 (4.3 − 62.1) | 10.0 (1.8 − 26.0) | 0.024 | 0.020 |
Postoperative day 1 urine output/hour, mL | 2.7 (2 – 3.7) | 2.33 (1.86 − 3.11) | 0.021 | 0.031 |
Postoperative day 2 urine output/hour, mL | 1.42 (1.13 – 1.72) | 1.48 (1.2 − 1.87) | 0.324 | 0.277 |
AKI, n (%) | 0.945 | 0.945 | ||
Stage 1 | 18 (8.5%) | 10 (9.1%) | ||
Stage 2 | 6 (2.8%) | 4 (3.6%) | ||
Stage 3 | 2 (0.9%) | 1 (0.9%) | ||
Postoperative kidney replacement therapy, n (%) | 2 (0.9%) | 0 (0%) | 0.550 | 0.550 |
Type of AKI | 0.110 | 0.110 | ||
Serum creatinine criteria | 19 (9.0%) | 15 (13.6%) | ||
Urine output criteria | 4 (1.9%) | 0 (0%) | ||
Both criteria | 3 (1.4%) | 0 (0%) | ||
AKI reversal state at discharge, n (%) d | 0.139 | 0.139 | ||
Reversal | 21/26 (80.8%) | 15/15 (100%) | ||
Non-reversal | 5/26 (19.2%) | 0 (0%) |
Changes in eGFR
Control group | Protein-loading group | Difference (protein load vs. control) | p-value (unadjusted) | p-value (adjusted)b | |
---|---|---|---|---|---|
(a) eGFR values (in mL/min/1.73 m2)a | |||||
3 months | |||||
All patients (n = 323) | 86 (84–88) | 90 (87–93) | 3.9 (0.42–7.3] | 0.028 | 0.017 |
No AKI (n = 283) | 87 (85–89) | 91 [89–94) | 4.6 (1.1–8.1) | 0.011 | 0.005 |
AKI (n = 40) | 80 (73–87) | 79 (69–89) | 0.0 (− 13 to 12) | 0.936 | 0.619 |
Reversal (n = 35) | 83 (75–91) | 79 (70–89) | − 3.8 (− 16 to 8.7) | 0.538 | 0.323 |
Non-reversal | 66 (47–84) | – | – | – | |
12 months | |||||
All patients (n = 321) | 79 (77–81) | 87 (84–90) | 7.8 (4.5–11) | < 0.001 | < 0.001 |
No AKI (n = 283) | 81 (79–83) | 89 (86–91) | 7.9 (4.6–11) | < 0.001 | < 0.001 |
AKI (n = 38) | 65 (58–72) | 75 (66–84) | 9.6 (− 1.7 to 21) | 0.093 | 0.619 |
Reversalc (n = 34) | 69 (62–76) | 75 (67–83) | 5.8 (− 4.9 to 17) | 0.280 | 0.316 |
Non-reversal | 46 (19–73] | – | – | – | |
(b) Change in eGFR (in mL/min/1.73 m2)a relative to the preoperative values | |||||
3 months | |||||
All patients (n = 323) | − 3.3 (− 4.4 to − 2.2) | 0.15 (− 1.4 to 1.7) | 3.5 (1.6 to 5.4) | < 0.001 | < 0.001 |
No AKI (n = 283) | − 3.2 (− 4.3 to − 2.1) | 0.68 (− 0.87 to 2.2] | 3.9 (2.0 to 5.8) | < 0.001 | < 0.001 |
AKI (n = 40) | − 4.2 (− 8.7– 0.44) | − 3.5 (− 9.8 to 2.8) | 0.65 (− 7.1 to 8.4) | 0.865 | 0.817 |
Reversalc (n = 35) | − 1.5 (− 6.2 to 3.2) | − 3.5 (− 9.3 to 2.3) | − 2.0 (− 9.4 to 5.5) | 0.594 | 0.764 |
Non-reversal | − 15 (− 30 to − 0.2) | – | – | – | |
12 months | |||||
All patients (n = 321) | − 10 (− 11 to − 9.1) | − 2.7 (− 4.2 to − 1.2) | 7.5 (5.6 to 9.4) | < 0.001 | < 0.001 |
No AKI (n = 283) | − 9.1 (− 10 to − 8.1) | − 1.9 (− 3.4 to − 0.52) | 7.2 (5.4 to 8.9) | < 0.001 | < 0.001 |
AKI (n = 38) | − 19 (− 23 to − 14) | − 8 (− 14 to − 1.9] | 11 (3 to 18) | 0.008 | 0.011 |
Reversalc (n = 34) | − 15 (− 19 to − 11) | − 8 (− 13 to − 3.2) | 7.3 (1.1 to 14) | 0.022 | 0.028 |
Non-reversal | − 35 (− 61 to − 9.1) | – | – | – |