The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease
Abstract
:1. Introduction
2. Results
2.1. Correlations between eGFR and Uremic Toxins, Inflammatory Biomarkers and BUCVR
2.2. Correlations between Plasma Levels Uremic Toxins, Inflammatory Biomarkers and BUCVR
2.3. Tissue Expression of Inflammatory Biomarkers and BUCVR in Human Renal Arteries
2.4. Comparisons between Plasma Levels Uremic Toxins, Inflammatory Biomarkers, Vascular Inflammation, BUCVR in Patients with and without Carotid Artery Plaques
2.5. Survival Analysis According to eGFR, Plasma Levels Uremic Toxins, Inflammatory Biomarkers and BUCVR
3. Discussion
4. Materials and Methods
4.1. Subjects
4.1.1. Pre-Dialysis CKD Patients
4.1.2. CKD Transplant Recipients
4.2. Material
4.2.1. Blood Sampling
4.2.2. Renal Arteries Samples
4.2.3. Clinical and Biochemical Characteristics of the Patients (Cohort 1)
4.3. Measurement of Plasma Levels of Uremic Toxins
4.4. Measurement of Plasma Levels of Inflammatory Biomarkers (IL-6, hsCRP, MCP-1, sICAM-1, sVCAM-1 and sFas)
4.5. Biomarkers of the Uremic Cardiovascular Response (BUCVR)-sCD36, Fractalkine and sRAGE Plasma Levels
4.6. Histology and Immunohistochemistry (IHC) of Arteries from CKD Patients and Healthy Controls
4.7. Non-Invasive Evaluation of Atherosclerotic CVD
4.8. Cardiovascular Events during the Follow Up
4.9. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
References
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Analyzed Parameters | |||||
---|---|---|---|---|---|
Patients, n | 67 | ||||
Traditional risk factors | CKD 1 (n = 7) | CKD 2 (n = 15) | CKD 3 (n = 20) | CKD 4 (n = 16) | CKD 5 (n = 9) |
Mean age ± SD, years | 45 ± 16.7 | 54 ± 11.2 | 61 ± 11.2 | 56 ± 14.9 | 61 ± 8.7 |
Gender, % females | 6 | 12 | 21 | 10 | 8 |
Race, % caucasians | 9 | 17 | 28 | 22 | 14 |
Mean BMI ± SD | 29.6 ± 5.3 | 28.2 ± 3.7 | 28.4 ± 4.0 | 28.4 ± 4.5 | 28 ± 6.1 |
Diabetes, % | 3 | 9 | 12 | 9 | 3 |
Hypertension, % | 3 | 12 | 19 | 15 | 8 |
CVD, % | 9 | 13 | 15 | 10 | 6 |
Dyslipidemia, % | 5 | 6 | 6 | 5 | 5 |
Smoking, % | 2 | 3 | 3 | 2 | 3 |
LVH, % | - | 6 | 6 | 9 | 3 |
Plaques, % | 3 | 5 | 8 | 9 | 6 |
Primary Kidney Disease | |||||
Diabetic nephropathy, % | 3 | 9 | 9 | 5 | 5 |
Glomeruloesclerosis hypertensive, % | - | 5 | 10 | 9 | 5 |
Chronic glomerulonephritis, % | 6 | 2 | 2 | 5 | - |
Others and unknown, % | 2 | 3 | 3 | 3 | 2 |
Laboratory Parameters | |||||
GFR (CKD-EPI), mL/min Median (range) | 101.0 90.6–125 | 74.6 60.1–89 | 41.4 30–59.3 | 19.4 15–27.5 | 12.3 8.1–14.4 |
Proteinuria, mg/24 h | 222.1 | 277.0 | 1091.0 | 879.0 | 3232.0 |
Albumin, mg/dL | 4.2 | 4.0 | 3.8 | 3.8 | 3.8 |
Glucose, mg/dL | 85.5 | 92.2 | 106.4 | 122.8 | 107.8 |
HDL cholesterol, mg/dL | 47.6 | 41.0 | 44.4 | 38.2 | 39.7 |
LDL cholesterol, mg/dL | 112.0 | 100 | 122 | 109.6 | 135.4 |
Triglycerides, mg/dL | 175.1 | 217.2 | 168.2 | 202.3 | 191.1 |
Calcium, mg/dL | 9.2 | 9.3 | 8.9 | 9.0 | 9.2 |
Phosphorus, mg/dL | 3.3 | 3.7 | 3.7 | 4.3 | 5.0 |
Hemoglobin, g/dL | 14.6 | 14.4 | 13.9 | 12.0 | 12.3 |
Analyzed Parameters | ||
---|---|---|
Traditional risk factors | Control group (n = 12) | CKD group (n = 14) |
Mean age ± SD, years | 41.6 ± 10.1 | 37.1 ± 13.1 |
Gender, % females | 50 | 43 |
Mean BMI ± SD | 24.7 ± 3.5 | 24.3 ± 3.2 |
Hypertension, % | 0 | 100 |
Primary Kidney Disease | ||
Hypertensive nephrosclerosis, % | - | 43 |
Chronic glomerulonephritis, % | - | 43 |
Others and unknown, % | - | 14 |
Laboratory Parameters | ||
Creatinine, mg/dL | 0.8 ± 0.2 | 8.6 ± 3.2 |
Glucose, mg/dL | 93 ± 17.2 | 112.0 ± 28.1 |
HDL cholesterol, mg/dL | 50.1 ± 10.7 | 45.4 ± 17.4 |
LDL cholesterol, mg/dL | 112 ± 28.2 | 114 ± 30.3 |
Calcium, mg/dL | 9.1 ± 0.5 | 9.5 ± 0.9 |
Phosphorus, mg/dL | 4.01 ± 1.0 | 5.8 ± 1.9 |
Hemoglobin, g/dL | 13.5 ± 1.9 | 10.6 ± 1.5 |
Analyzed Parameters | Mean ± SD | Median (Range) |
---|---|---|
Uremic Toxins | ||
IS, uM | 15.8 ±19.4 | 7.6 (1.1–100.5) |
pCS, uM | 91.5 ± 92.2 | 60.7 (0.9–501.0) |
IAA, uM | 0.80 ± 0.57 | 0.66 (0.06–3.28) |
Inflammatory Biomarkers | ||
IL-6, pg/mL | 4.91 ± 3.37 | 3.69 (0.67–11.0) |
hsCRP, mg/L | 5.18 ± 6.66 | 2.8 (0.30–39.9) |
MCP-1, pg/mL | 105.9 ± 31 | 102.9 (54.4 0–229.0) |
sVCAM, ng/mL | 806 ± 392 | 689 (378–1849) |
sICAM, ng/mL | 81 ± 14.5 | 80.8 (39.6–156.8) |
sFas pg/mL | 1339 ± 659 | 1253 (306–4181) |
BUCVR | ||
sCD36, ng/mL | 66.6 ± 34.4 | 60.9 (5.8–157.9) |
sRAGE, pg/mL | 2594 ± 1115 | 2552 (795–4827) |
Fractalkine, ng/mL | 1.30 ± 0.46 | 1.24 (0.27–2.42) |
IS | pCS | IAA | ||||
---|---|---|---|---|---|---|
r | p | r | p | r | p | |
IL-6, pg/mL | 0.13 | 0.29 | 0.236 | 0.055 | 0.078 | 0.53 |
hsCRP, mg/L | 0.10 | 0.42 | 0.024 | 0.84 | 0.020 | 0.87 |
MCP-1, pg/mL | 0.38 | 0.001 | 0.42 | <0.001 | 0.29 | 0.015 |
sVCAM, ng/mL | 0.29 | 0.019 | 0.29 | 0.017 | 0.27 | 0.025 |
sICAM, ng/mL | 0.047 | 0.71 | 0.12 | 0.34 | 0.087 | 0.48 |
sFas, pg/mL | 0.41 | 0.001 | 0.46 | <0.001 | 0.19 | 0.13 |
IS | pCS | IAA | ||||
---|---|---|---|---|---|---|
r | p | r | p | r | p | |
sCD36, ng/mL | 0.62 | <0.001 | 0.55 | <0.001 | 0.52 | <0.001 |
sRAGE, pg/mL | 0.48 | <0.001 | 0.48 | <0.001 | 0.20 | 0.108 |
Fractalkine, ng/mL | 0.77 | <0.001 | 0.77 | <0.001 | 0.41 | <0.001 |
MCP-1 | sICAM | sCD36 | sRAGE | Fractalkine | ||||||
---|---|---|---|---|---|---|---|---|---|---|
r | p | r | p | r | p | r | p | r | p | |
IL-6, pg/mL | 0.36 | 0.003 | NS | NS | NS | NS | ||||
hsCRP, mg/L | NS | 0.37 | 0.002 | NS | NS | NS | ||||
MCP-1, pg/mL | - | NS | 0.30 | 0.015 | 0.28 | 0.022 | 0.38 | 0.002 | ||
sVCAM, ng/mL | 0.41 | 0.001 | NS | 0.33 | 0.006 | NS | NS | |||
sICAM, ng/mL | NS | - | NS | NS | NS | |||||
sFas, pg/mL | NS | NS | 0.47 | <0.001 | 0.39 | 0.001 | 0.43 | <0.001 | ||
sCD36, ng/mL | 0.30 | 0.015 | NS | - | 0.42 | <0.001 | 0.73 | <0.001 | ||
sRAGE, pg/mL | 0.28 | 0.022 | NS | 0.42 | <0.001 | - | 0.50 | <0.001 | ||
Fractalkine, ng/mL | 0.38 | 0.002 | NS | 0.73 | <0.001 | 0.50 | <0.001 | - |
PLAQUES | ||||
---|---|---|---|---|
No (n = 44) | Yes (n = 20) | p | ||
UT | IS, uM | 16.6 ± 21.3 | 14.9 ± 16.0 | 0.957 |
pCS, uM | 74.9 ± 66.1 | 113 ± 96.5 | 0.160 | |
IAA, uM | 0.75 ± 0.47 | 0.92 ± 0.77 | 0.378 | |
Inflammatory Biomarkers | IL-6, pg/mL | 4.4 ± 3.1 | 5.9 ± 3.6 | 0.106 |
hsCRP, mg/L | 5.1 ± 7.5 | 5.3 ± 4.6 | 0.921 | |
MCP-1, pg/mL | 102.9 ± 27.9 | 113.4 ± 36.3 | 0.212 | |
sVCAM-1, ng/mL | 772.7 ± 341.1 | 884.1 ± 480.4 | 0.293 | |
sICAM-1, ng/mL | 81.0 ± 9.5 | 82.2 ± 22.3 | 0.762 | |
sFas, pg/mL | 1418.8 ± 694.8 | 1224.0 ± 584.7 | 0.289 | |
BUCVR | sCD 36, ng/mL | 61.0 ± 30.2 | 79.1 ± 40.1 | 0.049 |
sRAGE, pg/mL | 2661 ± 1108 | 2508 ± 1129 | 0.611 | |
Fractalkine, ng/mL | 1.25 ± 0.45 | 1.40 ± 0.45 | 0.223 |
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Share and Cite
Claro, L.M.; Moreno-Amaral, A.N.; Gadotti, A.C.; Dolenga, C.J.; Nakao, L.S.; Azevedo, M.L.V.; De Noronha, L.; Olandoski, M.; De Moraes, T.P.; Stinghen, A.E.M.; et al. The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. Toxins 2018, 10, 384. https://doi.org/10.3390/toxins10100384
Claro LM, Moreno-Amaral AN, Gadotti AC, Dolenga CJ, Nakao LS, Azevedo MLV, De Noronha L, Olandoski M, De Moraes TP, Stinghen AEM, et al. The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. Toxins. 2018; 10(10):384. https://doi.org/10.3390/toxins10100384
Chicago/Turabian StyleClaro, Ligia Maria, Andrea N. Moreno-Amaral, Ana Carolina Gadotti, Carla J. Dolenga, Lia S. Nakao, Marina L.V. Azevedo, Lucia De Noronha, Marcia Olandoski, Thyago P. De Moraes, Andréa E. M. Stinghen, and et al. 2018. "The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease" Toxins 10, no. 10: 384. https://doi.org/10.3390/toxins10100384