Immunoassay and proteomics dataset: Identification and validation of urine CXCL-9 as a biomarker for diagnosis of acute interstitial nephritis
Data files
Jun 06, 2023 version files 169.28 KB
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CXCL9-dryad.csv
30.33 KB
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CXCL9-olink-dryad.csv
126.76 KB
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README.md
2.13 KB
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README1.md
10.06 KB
Dec 10, 2023 version files 169.23 KB
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CXCL9-dryad.csv
30.33 KB
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CXCL9-olink-dryad.csv
126.76 KB
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README.md
2.08 KB
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README1.md
10.06 KB
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.
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