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

Moledina, Dennis1

Research facility: Yale University
Published Jun 06, 2023; Updated Dec 10, 2023 on Dryad. https://doi.org/10.5061/dryad.ksn02v788

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Jun 06, 2023 version files 169.28 KB
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Abstract

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.