Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Association between PBUTs and Peak Cardiac Performance
2.2.1. Peak Cardiac Power Output (CPOmax)
2.2.2. Peak Cardiac Output (Peak Qt)
2.2.3. Peak Mean Arterial Pressure (Peak MAP)
2.2.4. Peak Heart Rate (Peak HR)
2.3. Association between PBUTs and Aerobic Exercise Capacity
2.3.1. Aerobic Exercise Capacity (VO2max)
2.3.2. Arteriovenous O2 Difference [C(a-v)O2]
2.4. Independent Association of PBUTs with CPOmax and VO2max
2.5. Association between Non-Protein-Bound Uremic Toxin and Peak Cardiac Performance and Aerobic Exercise Capacity
2.6. Association between PBUTs and Cardiac Dimensions
2.7. Effect of Beta Blockers
3. Discussion
4. Limitations
5. Conclusions
6. Materials and Methods
6.1. Study Subjects
6.2. Assessment of Peak Cardiac Performance
Cardiopulmonary Exercise Test
6.3. Echocardiogram
6.4. Protein-Bound Uremic Toxin Assays
6.5. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Patient Characteristics | CKD 2 (n = 14) | CKD 3 (n = 15) | CKD 4 (n = 16) | CKD 5 (n = 11) | ANOVA (p) |
---|---|---|---|---|---|
Age (years) | 38.1 ± 8.8 | 52.2 ± 9.1 | 48.6 ± 12.7 | 47.9 ± 15.4 | 0.01 * |
BMI (kg/m2) | 26.6 ± 3.6 | 28.6 ± 4.1 | 26.6 ± 4.2 | 29.5 ± 4.1 | 0.16 |
Biochemistry | |||||
eGFR (mL/min) | 73.5 ± 7.9 | 43.2 ± 7.9 | 21.5 ± 4.3 | 11.9 ± 2.4 | <10−3 * |
Creatinine (μmoL/L) | 104.6 ± 10.9 | 158.1 ± 2.6 | 294.8 ± 56.7 | 550.1 ± 227.4 | <10−3 * |
Urea (mmoL/L) | 7.3 ± 1.8 | 11.5 ± 2.4 | 20.1 ± 3.6 | 27.0 ± 8.7 | <10−3 * |
Calcium (mmoL/L) | 2.4 ± 0.1 | 2.4 ± 0.1 | 2.3 ± 0.1 | 2.3 ± 0.2 | 0.54 |
Phosphate (mmoL/L) | 1.1 ± 0.2 | 1.1 ± 0.1 | 1.2 ± 0.1 | 1.6 ± 0.7 | 0.001 * |
Bicarbonate (mmoL/L) | 28 ± 2.5 | 25.9 ± 2.5 | 22.9 ± 3.3 | 21.0 ± 3.5 | <10−3 * |
Uric acid (mg/dL) | 8.6 ± 2.0 | 10.9 ± 2.3 | 9.7 ± 2.2 | 10.4 ± 2.2 | 0.05 |
PTH (pmoL/L) | 6.1 ± 4.8 | 16.9 ± 25.7 | 25.4 ± 17.4 | 47.6 ± 38.9 | 0.005 * |
Haemoglobin (g/dL) | 15.1 ± 1.2 | 14 ± 1.4 | 13.2 ± 1.6 | 12.1 ± 1.3 | <10−3 * |
CPX parameters | |||||
Peak Qt (L/min) | 22.1 ± 2.1 | 20.1 ± 2.1 | 19.1 ± 2.2 | 19.1 ± 1.9 | 0.001 * |
Peak MAP (mmHg) | 106.4 ± 8.9 | 107.6 ± 7.9 | 104.2 ± 10.0 | 101.0 ± 8.9 | 0.32 |
Peak HR (beats/min) | 169.7 ± 18.1 | 151.8 ± 12.8 | 149.3 ± 23.7 | 145.1 ± 18.5 | 0.007 * |
CPOmax (W) | 5.23 ± 0.76 | 4.79 ± 0.61 | 4.44 ± 0.55 | 4.29 ± 0.63 | 0.002 * |
VO2max (L/min) | 3.13 ± 0.57 | 2.70 ± 0.47 | 2.61 ± 0.63 | 2.43 ± 0.30 | 0.009 * |
Peak C(a-v)O2 (dL/min) | 14.2 ± 2.1 | 13.4 ± 2.0 | 13.5 ± 2.04 | 12.8 ± 1.7 | 0.40 |
Uremic Toxins | Serum Concentration Median (25th pct, 75th pct) (n = 56) | |
---|---|---|
IXS (mg/dL) | Total | 0.222 (0.101, 0.598) |
Free | 0.006 (0.002, 0.015) | |
PCS (mg/dL) | Total | 0.782 (0.303, 1.418) |
Free | 0.017 (0.007, 0.031) | |
PCG (mg/dL) | Total | 0.013 (0.004, 0.035) |
Free | 0.011 (0.002, 0.029) | |
IAA (mg/dL) | Total | 0.057 (0.040, 0.101) |
Free | 0.005 (0.003, 0.011) | |
HA (mg/dL) | Total | 0.255 (0.119, 0.379) |
Free | 0.084 (0.038, 0.137) | |
CMPF (mg/dL) | Total | 0.071 (0.035, 0.156) |
Study Parameters | IXS | PCS | PCG | IAA | CMPF | HA |
---|---|---|---|---|---|---|
CPOmax | −0.44 ** | −0.58 ** | −0.52 ** | −0.33 * | −0.35 ** | |
Peak Qt | −0.41 ** | −0.48 ** | −0.45 ** | −0.27 * | −0.42 ** | |
Peak MAP | −0.35 ** | −0.30 * | ||||
Peak HR | −0.41 ** | −0.27 * | −0.30 * | |||
VO2max | −0.36 ** | −0.53 ** | −0.43 ** | −0.37 ** | −0.30 * | |
Peak C(a-v)O2 | −0.36 ** | −0.26 * | −0.31 * | |||
LVMI | ||||||
IVSd | 0.30 * |
Study Parameters | IXS | PCS | PCG | IAA | HA |
---|---|---|---|---|---|
CPOmax | −0.48 ** | −0.51 ** | −0.52 ** | −0.40 ** | −0.29 * |
Peak Qt | −0.41 ** | −0.44 ** | −0.45 ** | −0.33 * | −0.40 ** |
Peak MAP | −0.29 * | −0.29 * | |||
Peak HR | −0.41 ** | −0.31 * | |||
VO2max | −0.41 ** | −0.48 ** | −0.42 ** | −0.41 ** | −0.38 ** |
Peak C(a-v)O2 | −0.332 * | −0.31 * | |||
LVMI | |||||
IVSd | 0.33 * | 0.32 * |
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Chinnappa, S.; Tu, Y.-K.; Yeh, Y.C.; Glorieux, G.; Vanholder, R.; Mooney, A. Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease. Toxins 2018, 10, 520. https://doi.org/10.3390/toxins10120520
Chinnappa S, Tu Y-K, Yeh YC, Glorieux G, Vanholder R, Mooney A. Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease. Toxins. 2018; 10(12):520. https://doi.org/10.3390/toxins10120520
Chicago/Turabian StyleChinnappa, Shanmugakumar, Yu-Kang Tu, Yi Chun Yeh, Griet Glorieux, Raymond Vanholder, and Andrew Mooney. 2018. "Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease" Toxins 10, no. 12: 520. https://doi.org/10.3390/toxins10120520