A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Cohort Characteristics
2.3. Outcomes
2.4. Data Collection and Plasma Measurements
2.5. Design of Combined Biomarker
2.6. Sample Size Calculation
2.7. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. FEK Indicator and Prediction of AKI
3.3. FEK Indicator and Outcome Prediction
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | All Patients | Patients with AKI at Admission | Patients with AKI at Day 1–2 | Patients without AKI | |
---|---|---|---|---|---|
Demographic | |||||
Patients, n (%) | 164 (100%) | 50 (30.5%) | 55 (33.5%) | 59 (36.0%) | |
Mean age ± SD, yr | 63.4 ± 14.3 | 64.7 ± 16.6 | 63.7 ± 13.9 | 62.1 ± 12.6 | |
Men, n (%) | 103 (62.8%) | 33 (66.0%) | 38 (69.1%) | 32 (54.2%) | |
Hispanic race, n (%) | 164 (100%) | 50 (100%) | 55 (100%) | 59 (100%) | |
Hypertension, n (%) | 92 (56.1%) | 27 (54.0%) | 32 (58.2%) | 33 (55.9%) | |
Diabetes, n (%) | 35 (21.3%) | 13 (26.0%) | 11 (20.0%) | 11 (18.6%) | |
Coronary heart disease, n (%) | 20 (12.2%) | 7 (14.0%) | 8 (14.5%) | 5 (8.5%) | |
Baseline renal function | |||||
Serum creatinine ± SD, mg/dL | 0.85 ± 0.16 | 0.86 ± 0.16 | 0.85 ± 0.18 | 0.84 ± 0.15 | |
eGFR # ± SD, mL/min/1.73m2 | 85.2 ± 15.5 | 83.9 ± 13.9 | 86.5 ± 15.8 | 85.1 ± 16.7 | |
Infectious foci, n (%) | |||||
Pulmonary | 60 (36.6%) | 22 (44.0%) | 20 (36.4%) | 18 (30.5%) | |
Urinary | 26 (15.9%) | 8 (16.0%) | 10 (18.2%) | 8 (13.6%) | |
Abdominal | 78 (47.6%) | 20 (40.0%) | 25 (45.5%) | 33 (55.9%) | |
Emergency surgery required | 68 (41.5%) | 19 (38.0%) | 23 (41.8%) | 26 (44.1%) | |
Biochemical parameters at admission | |||||
Hematocrit ± SD, g/dL | 9.8 ± 2.1 | 9.3 ± 1.6 | 9.9 ± 1.8 | 10.9 ± 1.8 | |
Blood ureic nitrogen ± SD, mg/dL | 24.6 ± 9.8 | 33.1 ± 10.4 *** | 21.7 ± 7.1 | 20.1 ± 6.5 | |
Serum calcium ± SD, mg/dL | 8.8 ± 1.1 | 8.5 ± 1.1 * | 8.8 ± 0.9 | 9.0 ± 1.1 | |
Serum phosphate ± SD, mg/dL | 3.9 ± 0.9 | 4.0 ± 0.9 | 4.0 ± 0.9 | 3.8 ± 0.9 | |
Serum magnesium ± SD, mg/dL | 1.9 ± 0.2 | 1.8 ± 0.2 | 1.9 ± 0.2 | 2.0 ± 0.2 | |
Serum creatinine ± SD, mg/dL | 1.35 ± 0.90 | 2.35 ± 1.07 *** | 0.94 ± 0.21 | 0.89 ± 0.16 | |
Maximum serum creatinine ± SD, mg/dL | 1.91 ± 1.08 | 2.69 ± 1.09 *** | 2.22 ± 0.86 *** | 0.95 ± 0.14 | |
Clinical parameters at admission | |||||
Systolic arterial pressure ± SD, mmHg | 104.5 ± 21.1 | 100.2 ± 20.5 * | 103.9 ± 18.6 | 108.7 ± 23.2 | |
Diastolic arterial pressure ± SD, mmHg | 55.9 ± 13.1 | 54.5 ± 13.3 | 54.8 ± 13.0 | 58.2 ± 12.8 | |
Mean arterial pressure ± SD, mmHg | 72.1 ± 13.0 | 69.8 ± 13.5 * | 71.1 ± 12.1 | 75.1 ± 13.0 | |
Total SOFA score | 5 [3–7] | 8 [6–10] *** | 5 [4–7] ** | 4 [3–5] | |
Non-renal SOFA score | 5 [3–6] | 6 [4–7] *** | 5 [3–6] ** | 4 [3–5] | |
Renal SOFA score | 0 [0–1] | 2 [1–3] *** | 0 [0–0] | 0 [0–0] | |
AKI severity (KDIGO criteria)—no. (%) | |||||
KDIGO 1 | 33 (20.1%) | 15 (30.0%) | 18 (32.7%) | 0 (0.0%) | |
KDIGO 2 | 38 (23.2%) | 19 (38.0%) | 19 (34.5%) | 0 (0.0%) | |
KDIGO 3 | 34 (20.7%) | 16 (32.0%) | 18 (32.7%) | 0 (0.0%) |
FGF23 (pg/mL) | EPO (mIU/mL) | Klotho (mIU/mL) | F.E.K. (A.U.) | ||
---|---|---|---|---|---|
All patients (n = 164) | 37.2 [24.0–56.8] | 16.6 [12.3–21.5] | 422.8 [284.4–504.6] | 1.52 [0.71–3.47] | |
AKI (+) at admission (n = 50) | 63.3 [48.5–83.0] | 20.1 [15.9–25.5] | 289.3 [194.4–368.7] | 4.33 [2.46–9.61] | |
KDIGO 1 (n = 15) | 45.2 [36.8–52.5] | 17.5 [14.1–20.4] | 369.9 [312.8–437.6] | 2.33 [1.29–3.16] | |
KDIGO 2 (n = 19) | 61.5 [49.9–73.3] | 17.9 [14.9–20.6] | 284.5 [236.7–353.6] | 3.50 [2.54–5.22] | |
KDIGO 3 (n = 16) | 88.7 [75.5–96.6] | 27.9 [24.1–32.0] | 186.7 [152.2–199.2] | 14.04 [9.61–17.26] | |
AKI (+) at day 1–2 (n = 55) | 43.2 [34.6–54.1] | 17.6 [14.6–23.8] | 392.2 [275.3–505.2] | 2.01 [1.21–3.03] | |
KDIGO 1 (n = 18) | 34.6 [32.0–37.1] | 15.4 [12.1–19.9] | 424.1 [375.4–563.7] | 1.29 [1.05–1.57] | |
KDIGO 2 (n = 19) | 42.6 [36.5–49.6] | 17.1 [14.8–22.4] | 416.4 [301.1–487.7] | 2.25 [1.51–2.90] | |
KDIGO 3 (n = 18) | 57.4 [44.7–79.3] | 19.7 [15.6–34.9] | 272.0 [197.4–490.2] | 4.86 [2.44–11.54] | |
AKI (−) (n = 59) | 21.3 [14.9–28.1] | 12.3 [8.9–17.0] | 493.1 [442.6–593.7] | 0.58 [0.25–0.78] |
Characteristic | All Patients | FEK < 0.87 A.U. | FEK ≥ 0.87 A.U. | |
---|---|---|---|---|
Demographic | ||||
Patients, n (%) | 164 (100%) | 59 (36.0%) | 105 (64.0%) | |
Mean age ± SD, yr | 63.4 ± 14.3 | 61.9 ± 11.4 | 64.3 ± 15.7 | |
Men, n (%) | 103 (62.8%) | 35 (59.3%) | 68 (64.8%) | |
Hypertension, n (%) | 92 (56.1%) | 34 (57.6%) | 58 (55.2%) | |
Diabetes, n (%) | 35 (21.3%) | 10 (16.9%) | 25 (23.8%) | |
Coronary heart disease, n (%) | 20 (12.2%) | 6 (10.2%) | 14 (13.3%) | |
Baseline renal function | ||||
Serum creatinine ± SD, mg/dL | 0.85 ± 0.16 | 0.84 ± 0.16 | 0.85 ± 0.17 | |
eGFR # ± SD, mL/min/1.73m2 | 85.2 ± 15.5 | 85.9 ± 16.4 | 84.9 ± 15.1 | |
Infectious foci, n (%) | ||||
Pulmonary | 60 (36.6%) | 20 (33.9%) | 40 (38.1%) | |
Urinary | 26 (15.9%) | 8 (13.6%) | 18 (17.1%) | |
Abdominal | 78 (47.6%) | 31 (52.5%) | 47 (44.8%) | |
Emergency surgery required | 68 (41.5%) | 27 (45.8%) | 41 (39.0%) | |
Biochemical parameters at admission | ||||
Blood ureic nitrogen ± SD, mg/dL | 24.6 ± 9.8 | 20.6 ± 6.2 | 26.9 ± 10.7 *** | |
Serum calcium ± SD, mg/dL | 8.8 ± 1.1 | 8.9 ± 1.1 | 8.7 ± 1.0 | |
Serum phosphate ± SD, mg/dL | 3.9 ± 0.9 | 3.8 ± 0.9 | 4.0 ± 0.9 | |
Serum creatinine ± SD, mg/dL | 1.35 ± 0.90 | 0.90 ± 0.17 | 1.60 ± 1.04 *** | |
Maximum serum creatinine ± SD, mg/dL | 1.91 ± 1.08 | 1.07 ± 0.49 | 2.38 ± 1.03 *** | |
Clinical parameters at admission | ||||
Systolic arterial pressure ± SD, mmHg | 104.5 ± 21.1 | 109.1 ± 23.0 | 101.9 ± 19.6 * | |
Diastolic arterial pressure ± SD, mmHg | 55.9 ± 13.1 | 58.7 ± 12.8 | 54.4 ± 13.0 * | |
Mean arterial pressure ± SD, mmHg | 72.1 ± 13.0 | 75.5 ± 13.0 | 70.2 ± 12.7 * | |
Total SOFA score | 5 [3–7] | 4 [3–5] | 6 [4–9] *** | |
Non-renal SOFA score | 5 [3–6] | 4 [3–5] | 5 [4–6] *** | |
Renal SOFA score | 0 [0–1] | 0 [0–0] | 1 [0–2] *** | |
AKI development—no. (%) | ||||
No AKI (−) | 59 (36.0%) | 53 (89.8%) | 6 (5.7%) *** | |
AKI at admission | 50 (30.5%) | 0 (0%) | 50 (47.6%) *** | |
AKI at day 1–2 | 55 (33.5%) | 6 (10.2%) | 49 (46.7%) *** |
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Toro, L.; Rojas, V.; Conejeros, C.; Ayala, P.; Parra-Lucares, A.; Ahumada, F.; Almeida, P.; Silva, M.F.; Bravo, K.; Pumarino, C.; et al. A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort. Biomolecules 2023, 13, 1481. https://doi.org/10.3390/biom13101481
Toro L, Rojas V, Conejeros C, Ayala P, Parra-Lucares A, Ahumada F, Almeida P, Silva MF, Bravo K, Pumarino C, et al. A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort. Biomolecules. 2023; 13(10):1481. https://doi.org/10.3390/biom13101481
Chicago/Turabian StyleToro, Luis, Verónica Rojas, Carolina Conejeros, Patricia Ayala, Alfredo Parra-Lucares, Francisca Ahumada, Paula Almeida, María Fernanda Silva, Karin Bravo, Catalina Pumarino, and et al. 2023. "A Combined Biomarker That Includes Plasma Fibroblast Growth Factor 23, Erythropoietin, and Klotho Predicts Short- and Long-Term Morbimortality and Development of Chronic Kidney Disease in Critical Care Patients with Sepsis: A Prospective Cohort" Biomolecules 13, no. 10: 1481. https://doi.org/10.3390/biom13101481