DOI: 10.5061/dryad.ksn02v788
title: Immunoassay and proteomics dataset: Identification and validation of urine CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis

description: Background: Acute tubulointerstitial nephritis (AIN) is one of
 the few causes of acute kidney injury with diagnosis-specific treatment
 options. However, due to the need to obtain a kidney biopsy for
 histological confirmation, AIN diagnosis can be delayed, missed, or
 incorrectly assumed. Here we identify and validate urine CXCL-9, an
 interferon-γ-induced chemokine involved in lymphocyte chemotaxis, as a
 diagnostic biomarker for AIN. Methods: In a
 prospectively-enrolled cohort with pathologist-adjudicated histological
 diagnoses (discovery cohort), we tested the association of 180 immune
 proteins measured by an aptamer-based assay with AIN and validated the top
 protein, CXCL-9, using sandwich immunoassay. We externally validated these
 findings in 2 cohorts with biopsy-confirmed diagnoses (validation cohorts)
 and examined mRNA expression differences in kidney tissue from patients
 with AIN and controls. Results: In aptamer-based assay, urine
 CXCL-9 was 7.6-fold higher in AIN than controls (P=1.23·10-5). Urine
 CXCL-9 measured by sandwich immunoassay was associated with AIN in the
 discovery cohort (n=204; 15% AIN) independently of currently available
 clinical tests for AIN (adjusted odds ratio for highest vs lowest
 quartile: 6.0; 95% CI: 1.8-20). Similar findings were noted in external
 validation cohorts, where CXCL-9 had an AUC of 0.94 (0.86-1.00) for AIN
 diagnosis. CXCL9 mRNA expression was 3.9-fold higher in kidney tissue from
 patients with AIN (n=19) as compared with controls (n=52; P=5.8·10-6).
 Conclusion: We identified CXCL-9 as a biomarker for AIN diagnosis using
 aptamer-based urine proteomics, confirmed this association using sandwich
 immunoassays in discovery and validation cohorts, and observed higher
 expression of this protein in kidney biopsies with AIN.
description: Immunoassay and proteomics dataset: Identification and validation of urine
 CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis
 10.5061/dryad.ksn02v788 \## Description of the Data and file structure
 Cross-sectional data from Yale AIN study including participants who
 underwent a kidney biopsy at two healthcare centers Observations: 249
 Variables: 26 13 Oct 2020 13:42
 \----------------------------------------------------------------------------------------------------------------------------------- Variable Storage Display Value name type format label Variable label \----------------------------------------------------------------------------------------------------------------------------------- sequenceno str17 %17s sequenceno diagnosis_histo byte %22.0g diagnosis1\_ Diagnosis1 ain_prebx byte %8.0g ain_prebx\_ Was AIN suspected before biopsy? ain_postbx_cl~n byte %8.0g ain Did the clinician think the cause was AIN after the biopsy? tnfa_urine double %10.0g Urine TNF- tnfatocreat_u~e float %9.0g TNF-a:Cr, ng/g il9_urine double %10.0g Urine IL-9 il9tocreat_ur~e float %9.0g IL9:Cr, ng/g ain_majority float %9.0g control1 All AIN (&gt;=2/3) vs. no AIN (&lt;=1/3) ain_consensus float %9.0g control1 Consensus AIN (Primary outcome) cxcl9_urine double %9.0g CXCL9/MIG (pg/ml), urine cxcl9tocreat_~e float %9.0g CXCL9:Cr, ng/g control_group float %9.0g graph1 AIN vs. all controls ain_model float %9.0g AIN statistical model \----------------------------------------------------------------------------------------------------------------------------------- \## Sharing/access Information Links to other publicly accessible locations of the data: None Was data derived from another source? No Missing data marked as: Missing