Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment
Abstract
:1. Introduction
2. Material and Methods
2.1. Experimental Design and Study Population
2.2. Clinical Variables
2.3. Histological Grading of Tubule-Interstitial Infiltrates
2.4. Sampling and Measurement of Urinary Cytokine Levels
3. Statistical Analysis
4. Results
4.1. Baseline Characteristics of the Population
4.2. Urinary Cytokine Levels Are Significantly Increased in ATIN Patients and Correlate with the Extend of Tubulointerstitial Infiltrate
4.3. Urinary Cytokine Levels Distinguish ATIN from ATN Patients
4.4. Urinary Cytokine Levels Decrease after Treatment and Recovery of Renal Function
5. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ATIN (n = 21) | ATN (n = 12) | p-Value | |
---|---|---|---|
Age (years) | 66.5 ± 13.52 | 63.5 ± 12.5 | 0.536 |
Sex (%male) | 57.10% | 81.80% | 0.248 |
Diabetes (% patients) | 33.3% | 41.66% | 0.365 |
Hypertension (% patients) | 57.14% | 50% | 0.432 |
Baseline creatinine (µmol/L) | 87.84 ± 19.17 | 89.58 ± 15.56 | 0.322 |
Creatinine (µmol/L) | 324.9 ± 141.8 | 321.7 ± 176.3 | 0.956 |
CRP (mg/L) | 74.9 ± 95.1 | 25.6 ± 59.7 | 0.129 |
Urinary leukocyte count (leukocytes/ μL) | 400 ± 1467 | 166.5 ± 452.7 | 0.613 |
Urinary erythrocyte count (leukocytes/ μL) | 248.6 ± 1075.5 | 46.8 ± 80.1 | 0.542 |
Proteinuria (g/mol) | 70.49 ± 114.9 | 94.8 ± 112.5 | 0.587 |
Eosinophil blood count (×106) | 257.2 ± 210.7 | 102.7 ± 105.4 | 0.03 * |
ATIN (n = 21) | ATN (n = 12) | Healthy Controls (n = 6) | p-Value | |
---|---|---|---|---|
I-TAC/CXCL11 | 129.5 ± 64.68 | 23.07 ± 19.01 | 2.35 ± 1.07 | 0.046 * |
MIG/CXCL9 | 1170 ± 739.5 | 1456 ± 896.2 | 43.37 ± 9.91 | 0.665 |
IL1B | 9.08 ± 5.84 | 14.56 ± 9.73 | 2.03 ± 0.53 | 0.241 |
CXCL10 | 909.9 ± 468.1 | 58.60 ± 16.74 | 35.31 ± 15.3 | 0.105 |
IL6 | 323.1 ± 235.1 | 24.09 ± 8.11 | 3.2 ± 0.2 | 0.029 * |
IL17 | 7.28 ± 5.15 | 4.67 ± 2.37 | 2.18 ± 0.65 | 0.83 |
TNFα | 5.46 ± 1.12 | 4.17 ± 0.89 | 2.84 ± 0.27 | 0.032 * |
IFNα | 23.04 ± 13.82 | 18.21 ± 6.99 | 27.48 ± 13.8 | 0.669 |
MCP1 | 12848 ± 4413 | 2221 ± 603.2 | 418 ± 217.6 | 0.002 * |
EGF | 3888 ± 851.3 | 3067 ± 1207 | 18748 ± 6454 | 0.003 * |
ATIN (n = 21) | Healthy Controls (n = 6) | p-Value | |
---|---|---|---|
I-TAC/CXCL11 | 129.5 ± 64.68 | 2.35 ± 1.07 | 0.002 * |
MIG/CXCL9 | 1170 ± 739.5 | 43.37 ± 9.91 | 0.629 |
IL1B | 9.08 ± 5.84 | 2.03 ± 0.53 | 0.693 |
CXCL10 | 909.9 ± 468.1 | 35.31 ± 15.3 | 0.034 * |
IL6 | 323.1 ± 235.1 | 3.2 ± 0.2 | <0.001 * |
IL17 | 7.28 ± 5.15 | 2.18 ± 0.65 | 0.781 |
TNFα | 5.46 ± 1.12 | 2.84 ± 0.27 | 0.027 * |
IFNα | 23.04 ± 13.82 | 27.48 ± 13.8 | 0.558 |
MCP1 | 12848 ± 4413 | 418 ± 217.6 | 0.001 * |
EGF | 3888 ± 851.3 | 18748 ± 6454 | 0.002 * |
ATIN (n = 21) | ATN (n = 12) | p-Value | |
---|---|---|---|
I-TAC/CXCL11 | 129.5 ± 64.68 | 23.07 ± 19.01 | 0.022 * |
MIG/CXCL9 | 1170 ± 739.5 | 1456 ± 896.2 | 0.945 |
IL1B | 9.08 ± 5.84 | 14.56 ± 9.73 | 0.199 |
CXCL10 | 909.9 ± 468.1 | 58.60 ± 16.74 | 0.060 |
IL6 | 323.1 ± 235.1 | 24.09 ± 8.11 | 0.043 * |
IL17 | 7.28 ± 5.15 | 4.67 ± 2.37 | 0.664 |
TNFα | 5.46 ± 1.12 | 4.17 ± 0.89 | 0.300 |
IFNα | 23.04 ± 13.82 | 18.21 ± 6.99 | 0.473 |
MCP1 | 12848 ± 4413 | 2221 ± 603.2 | 0.026 * |
EGF | 3888 ± 851.3 | 3067 ± 1207 | 0.386 |
ATN (n = 12) | Healthy Controls (n = 6) | p-Value | |
---|---|---|---|
I-TAC/CXCL11 | 2 3.07 ± 19.01 | 2.35 ± 1.07 | 0.269 |
MIG/CXCL9 | 1456 ± 896.2 | 43.37 ± 9.91 | 0.732 |
IL1B | 14.56 ± 9.73 | 2.03 ± 0.53 | 0.110 |
CXCL10 | 58.60 ± 16.74 | 35.31 ± 15.3 | 0.298 |
IL6 | 24.09 ± 8.11 | 3.2 ± 0.2 | 0.105 |
IL17 | 4.67 ± 2.37 | 2.18 ± 0.65 | 0.944 |
TNFα | 4.17 ± 0.89 | 2.84 ± 0.27 | 0.301 |
IFNα | 18.21 ± 6.99 | 27.48 ± 13.8 | 0.387 |
MCP1 | 2221 ± 603.2 | 418 ± 217.6 | 0.022 * |
EGF | 3067 ± 1207 | 18748 ± 6454 | 0.655 |
AUC | Cut-Off | Sensitivity | Specificity | PPV | NPV | LR | |
---|---|---|---|---|---|---|---|
I-TAC/CXCL11 | 0.77 | 10.49 pg/mL | 66.70% | 90% | 92.30% | 60% | 6.66 |
CXCL10 | 0.71 | 131.50 pg/mL | 53% | 100% | 100% | 47.40% | 4.71 |
IL6 | 0.73 | 31.82 pg/mL | 63.20% | 80% | 85.70% | 53.30% | 3.15 |
MCP1 | 0.76 | 10,000 pg/mL | 53% | 100% | 100% | 55.60% | 5.3 |
Blood eosinophil count | 0.68 | 240 | 55% | 81.82% | 84.6% | 50% | 3.03 |
Urinary leukocyte count | 0.47 | 26/µL | 65% | 27% | 47.2% | 43.8% | 0.9 |
Model 1 | 84.2% | 83.3% | 88.9% | 76.9% | 5.04 | ||
Model 2 | 81% | 91.7% | 94.4% | 73.3% | 9.76 |
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Martinez Valenzuela, L.; Draibe, J.; Bestard, O.; Fulladosa, X.; Gómez-Preciado, F.; Antón, P.; Nadal, E.; Jové, M.; Cruzado, J.M.; Torras, J. Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment. J. Clin. Med. 2021, 10, 2986. https://doi.org/10.3390/jcm10132986
Martinez Valenzuela L, Draibe J, Bestard O, Fulladosa X, Gómez-Preciado F, Antón P, Nadal E, Jové M, Cruzado JM, Torras J. Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment. Journal of Clinical Medicine. 2021; 10(13):2986. https://doi.org/10.3390/jcm10132986
Chicago/Turabian StyleMartinez Valenzuela, Laura, Juliana Draibe, Oriol Bestard, Xavier Fulladosa, Francisco Gómez-Preciado, Paula Antón, Ernest Nadal, Maria Jové, Josep Maria Cruzado, and Juan Torras. 2021. "Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment" Journal of Clinical Medicine 10, no. 13: 2986. https://doi.org/10.3390/jcm10132986
APA StyleMartinez Valenzuela, L., Draibe, J., Bestard, O., Fulladosa, X., Gómez-Preciado, F., Antón, P., Nadal, E., Jové, M., Cruzado, J. M., & Torras, J. (2021). Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment. Journal of Clinical Medicine, 10(13), 2986. https://doi.org/10.3390/jcm10132986