Abstract
Abstract Background and Aims Acute tubulointerstitial nephritis (ATIN) diagnostic lays on the kidney biopsy given the absence of non-invasive biomarkers for disease demonstration and follow-up. The aim of this study was to evaluate the accuracy of ten urinary inflammatory-related cytokines in the diagnostic of ATIN and its clinical distinction from acute tubular necrosis (ATN). Method Observational prospective study including 21 ATIN and 12 ATN patients, and 6 healthy controls. We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay. We registered clinical, analytical and histological data from the medical records. Results Urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were higher in ATIN compared to healthy controls. In contrast, healthy controls exhibited higher EGF urinary levels compared to ATIN patients. Follow-up samples available from 11/21 ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Urinary levels of I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN compared to ATN patients, with I-TAC/CXCL11 as the best discriminatory biomarker based on its higher AUC in the ROC curve and likelihood ratio. The combinatory model of the three cytokines increased the sensitivity of the individual biomarkers in the distinction of ATIN/ATN but the best results were obtained when blood eosinophil count and leukocyturia were added to the model. We found a positive correlation of the extent of the tubulointerstitial infiltrate in kidney biopsies with the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF, indicating the potential renal source of the cytokines Conclusion the higher cytokine levels in ATIN compared to ATN patients and healthy controls, the significant decline after treatment and the positive correlation of the cytokines with the grade of the inflammatory infiltrate allows us to propose I-TAC/CXCL11, CXCL10, IL6 and MCP-1 as candidate biomarkers in this disease.
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