Discovery of Novel Digital Biomarkers for Type 2 Diabetic Nephropathy Classification via Integration of Urinary Proteomics and Pathology.
medRxiv
; 2023 May 03.
Article
in En
| MEDLINE
| ID: mdl-37205413
ABSTRACT
Background:
The heterogeneous phenotype of diabetic nephropathy (DN) from type 2 diabetes complicates appropriate treatment approaches and outcome prediction. Kidney histology helps diagnose DN and predict its outcomes, and an artificial intelligence (AI)-based approach will maximize clinical utility of histopathological evaluation. Herein, we addressed whether AI-based integration of urine proteomics and image features improves DN classification and its outcome prediction, altogether augmenting and advancing pathology practice.Methods:
We studied whole slide images (WSIs) of periodic acid-Schiff-stained kidney biopsies from 56 DN patients with associated urinary proteomics data. We identified urinary proteins differentially expressed in patients who developed end-stage kidney disease (ESKD) within two years of biopsy. Extending our previously published human-AI-loop pipeline, six renal sub-compartments were computationally segmented from each WSI. Hand-engineered image features for glomeruli and tubules, and urinary protein measurements, were used as inputs to deep-learning frameworks to predict ESKD outcome. Differential expression was correlated with digital image features using the Spearman rank sum coefficient.Results:
A total of 45 urinary proteins were differentially detected in progressors, which was most predictive of ESKD (AUC=0.95), while tubular and glomerular features were less predictive (AUC=0.71 and AUC=0.63, respectively). Accordingly, a correlation map between canonical cell-type proteins, such as epidermal growth factor and secreted phosphoprotein 1, and AI-based image features was obtained, which supports previous pathobiological results.Conclusions:
Computational method-based integration of urinary and image biomarkers may improve the pathophysiological understanding of DN progression as well as carry clinical implications in histopathological evaluation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
MedRxiv
Year:
2023
Document type:
Article
Affiliation country: