Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines
Abstract
:1. Introduction
2. Results
2.1. Lanthionine Concentration Is Increased in CKD and Hemodialysis Patients and in Higher VC Grades
2.2. Cytokine Concentrations and GFR Level
2.3. Cytokine Concentrations and Calcification Score
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Lanthionine Analysis by UHPLC/MS Method
4.3. Cytokinome Analysis
4.4. Other Analytes
4.5. Calcification Assessment
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable (pg/mL) | GFR < 45 mL/min/1.73 m2 (n = 28; 37.8%) | GFR ≥ 45 mL/min/1.73 m2 (n = 46; 62.2%) | p-Value (Mann–Whitney U Test) |
---|---|---|---|
Hu PDGF-bb | 7157 [4929; 8710] | 7492 [5802; 9657] | 0.382 |
Hu IL-1b | 2.3 [1.7; 4.3] | 1.8 [1.5; 3.5] | 0.206 |
Hu IL-1ra | 164.9 [119.8; 210.3] | 148.8 [127.8; 197.3] | 0.895 |
Hu IL-4 | 18.2 [15.7; 21] | 19.7 [18.2; 21.5] | 0.092 |
Hu IL-5 | 1.9 [1.1; 2.8] | 1.9 [1.4; 2.6] | 0.972 |
Hu IL-6 | 18.4 [12; 48.1] | 13.3 [10.1; 20.9] | 0.033 |
Hu IL-7 | 9.1 [5; 11.2] | 8.1 [6.9; 10.3] | 0.834 |
Hu IL-8 | 99.4 [48.8; 153.1] | 41.7 [25.9; 83] | 0.010 |
Hu IL-9 | 36.6 [26.4; 46.7] | 33.2 [27.2; 44.3] | 0.572 |
Hu IL-10 | 25.4 [12.4; 39.2] | 22.4 [15.1; 30.1] | 0.281 |
Hu IL-12 (P70) | 112.7 [89; 184.7] | 111.6 [72.4; 137.4] | 0.286 |
Hu IL-13 | 12.8 [8.9; 16.8] | 11.8 [9.3; 14.2] | 0.582 |
Hu IL-17 | 160.2 [125.4; 185.7] | 163.7 [128; 205.6] | 0.569 |
Hu Eotaxin | 264.7 [237.5; 327.4] | 198.7 [159.1; 286.7] | 0.009 |
Hu FGF basic | 36.2 [23.8; 42.1] | 30.4 [25.4; 36.7] | 0.173 |
Hu G-CSF | 74.1 [54.8; 95.7] | 73.6 [66.4; 84.3] | 0.599 |
Hu IFN-g | 94.3 [64.2; 127.3] | 99.1 [82; 122.7] | 0.158 |
Hu IP-10 | 1186 [863; 1623] | 1003 [764; 1302] | 0.057 |
Hu MCP-1 (MCAF) | 95.1 [64.7; 150.3] | 106.3 [67.7; 162.5] | 0.598 |
Hu MIP-1a | 7.2 [4.9; 11.4] | 5 [4.1; 7.4] | 0.067 |
Hu MIP-1b | 158.6 [104.2; 297.8] | 155.4 [101.7; 210.7] | 0.613 |
Hu RANTES | 31,075 [16,841; 37,995] | 31,100 [24,342; 36,450] | 0.828 |
Hu TNF- | 39.8 [29.2; 55.5] | 45.7 [33.6; 68.2] | 0.149 |
Hu VEGF | 293.4 [182.2; 453.2] | 232.4 [139; 371.3] | 0.179 |
Variable (pg/mL) | No Calcification (n = 34; 45.9%) | Calcification (n = 40; 54.1%) | p-Value (Mann–Whitney U Test) |
---|---|---|---|
Hu PDGF-bb | 7530 [5620; 8484] | 7282 [5540; 10,722] | 0.638 |
Hu IL-1b | 1.8 [1.5; 2.2] | 2.3 [1.7; 5] | 0.025 |
Hu IL-1ra | 148.8 [126.2; 194.1] | 174.6 [119.8; 211.1] | 0.508 |
Hu IL-4 | 18.7 [16.9; 21.2] | 19.6 [18.2; 21.8] | 0.344 |
Hu IL-5 | 1.9 [1.1; 2.7] | 1.9 [1.4; 2.6] | 0.876 |
Hu IL-6 | 13.3 [10.1; 24] | 16.5 [10.8; 44.1] | 0.114 |
Hu IL-7 | 7.4 [6; 9.2] | 9.2 [7.7; 11.1] | 0.009 |
Hu IL-8 | 43.2 [26.1; 90] | 80.1 [35.8; 159.8] | 0.046 |
Hu IL-9 | 33.9 [27.4; 48.5] | 34.5 [26.5; 44.4] | 0.719 |
Hu IL-10 | 19.8 [12.7; 30.1] | 24 [16.6; 34.7] | 0.269 |
Hu IL-12 (P70) | 104.8 [62.5; 120.2] | 124.2 [89.6; 184.7] | 0.018 |
Hu IL-13 | 11.6 [8.6; 14.6] | 12.4 [9.6; 15.8] | 0.364 |
Hu IL-17 | 163.7 [120.4; 182.8] | 161.4 [134.4; 220.5] | 0.285 |
Hu Eotaxin | 208 [160.9; 263.8] | 265.8 [184.3; 317.5] | 0.031 |
Hu FGF basic | 32.1 [23.3; 36] | 36.2 [27.7; 43.3] | 0.120 |
Hu G-CSF | 71.7 [60.1; 80.3] | 77.4 [65.9; 96.4] | 0.154 |
Hu IFN-g | 99.1 [75.7; 118.1] | 99.1 [73.2; 127.3] | 0.791 |
Hu IP-10 | 972 [789; 1317] | 1112 [819; 1585] | 0.235 |
Hu MCP-1 (MCAF) | 110.6 [72.9; 158.9] | 93.4 [62; 179.6] | 0.429 |
Hu MIP-1a | 5.4 [4.3; 10] | 5.8 [4.1; 10.2] | 0.870 |
Hu MIP-1b | 158 [110; 210.5] | 149.3 [101.4; 303.2] | 0.827 |
Hu RANTES | 30,480 [22,736; 35,399] | 31,453 [22,328; 37,531] | 0.576 |
Hu TNF- | 43.2 [31.1; 64] | 46.5 [33.6; 68.2] | 0.335 |
Hu VEGF | 174 [99.2; 353.9] | 298.3 [203.6; 467.8] | 0.012 |
Variable | Non-Calcified | Calcified |
---|---|---|
AGE (YEARS) | 53.6 ± 12.2 | 67.8 ± 8.7 |
SEX (M; %) | 66 | 85 |
DIABETES (%) | 8 | 25 |
HYPERTENSION (%) | 87 | 100 |
AGATSTON SCORE (AU) | 0 | 248 (2–734) |
BMI (KG/M2) | 27.8 ± 5.9 | 28.9 ± 5.4 |
E-GFR (ML/MIN) | 75 ± 41 | 71.7 ± 25 |
DURATION CKD (MONTHS) | 24.5 ± 43 | 17 ± 25 |
PROTEINURIA (MG/24H) | 303 ± 577 | 255 ± 476 |
CALCEMIA (MG/DL) | 9.5 ± 1.3 | 9.6 ± 0.5 |
PHOSPHOREMIA (MG/DL) | 3.7 ± 1.4 | 3.7 ± 0.4 |
PHOSPHATURIA (MG/24H) | 858 ± 370 | 807 ± 290 |
PTH (PG/ML) | 58 ± 20 | 53 ± 35 |
HOMOCYSTEINE (µMOLI/L) | 19 ± 9 | 19 ± 4 |
CRP (MG/L) | 0.4 ± 0.2 | 0.3 ± 0.1 |
URIC ACID (MG/DL) | 6.0 ± 1.3 | 6.2 ± 1.1 |
HEMOGLOBIN (G/DL) | 14.2 ± 1.1 | 14.9 ± 1.9 |
CHOLESTEROL (MG/DL) | 183 ± 48 | 195 ± 39 |
HDL-CHOLESTEROL (MG/DL) | 51 ± 14 | 40 ± 11 |
TRIGLYCERIDES (MG/DL) | 130 ± 52 | 182 ± 80 |
LDL-CHOLESTEROL (MG/DL) | 103 ± 41 | 110 ± 45 |
FIBRINOGEN (MG/DL) | 315 ± 79 | 366 ± 78 |
SAP (MMHG) | 127 ± 13 | 138 ± 8 |
DAP (MMHG) | 80 ± 13 | 82 ± 5 |
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Perna, A.F.; Russo, L.; D’Esposito, V.; Formisano, P.; Bruzzese, D.; Vigorito, C.; Coppola, A.; Lombari, P.; Russo, D.; Ingrosso, D. Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines. Int. J. Mol. Sci. 2021, 22, 6875. https://doi.org/10.3390/ijms22136875
Perna AF, Russo L, D’Esposito V, Formisano P, Bruzzese D, Vigorito C, Coppola A, Lombari P, Russo D, Ingrosso D. Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines. International Journal of Molecular Sciences. 2021; 22(13):6875. https://doi.org/10.3390/ijms22136875
Chicago/Turabian StylePerna, Alessandra Fortunata, Luigi Russo, Vittoria D’Esposito, Pietro Formisano, Dario Bruzzese, Carmela Vigorito, Annapaola Coppola, Patrizia Lombari, Domenico Russo, and Diego Ingrosso. 2021. "Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines" International Journal of Molecular Sciences 22, no. 13: 6875. https://doi.org/10.3390/ijms22136875