Immunoassay and proteomics dataset: Identification and validation of urine CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis

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.