Immunoassay and proteomics dataset: Identification and validation of urine CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis
Cite this dataset
Moledina, Dennis (2023). Immunoassay and proteomics dataset: Identification and validation of urine CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis [Dataset]. Dryad. https://doi.org/10.5061/dryad.ksn02v788
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.
README
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
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Variable Storage Display Value
name type format label Variable label
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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 (>=2/3) vs. no AIN (<=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
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## 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
Funding
National Institute of Diabetes and Digestive and Kidney Diseases, Award: R01DK128087
National Institute of Diabetes and Digestive and Kidney Diseases, Award: K23DK117065