Clinical Relevance of Computationally Derived Attributes of Arteries and Arterioles in focal segmental glomerulosclerosis and minimal change disease

BackgroundThe current semi-qualitative methods used to score sclerosis and hyalinosis in arteries and arterioles in clinical practice are limited in standardization and reproducibility. We developed a computational pipeline designed to accurately and consistently quantify prognostic arterial and arteriolar characteristics in digital kidney biopsies of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) through segmentation and pathomic feature extraction. MethodsWe utilized one trichrome-stained WSI from 225 participants in the NEPTUNE/CureGN studies, comprising 127 cases of focal segmental glomerulosclerosis (FSGS) and 98 cases of minimal change disease (MCD). We developed, validated, and quality-controlled deep learning models to segment muscular vessels and their internal compartments (lumen, intima, media, and hyalinosis), including (i) arcuate arteries, (ii) interlobular arteries, and (iii) arterioles with two muscle layers. Arterioles, interlobular, and arcuate arteries were visually scored for sclerosis and hyalinosis on a scale of 0 to 3. Area- and thickness-based pathomic feature extraction was performed on each compartment (lumen, intima, media, and hyalinosis) through radial sampling and ray casting. A correlation study was performed between pathomic and visual semiquantitative visual scores, and the association of both visual scores and pathomic features with disease progression (40% eGFR decline or renal failure) was assessed. Summary statistics (maximum, median, and 75th percentile) were computed for each WSI and analyzed using LASSO-regularized Cox proportional hazards models, adjusted for clinical and demographic factors. ResultsA total of 1,499 arterioles, 686 interlobular arteries, and 131 arcuate arteries were segmented. Statistically significant correlations were found between pathologists visual scores and the average intima-media thickness ratio (Spearman {rho} = 0.27, p < 0.001 for arterioles; {rho} = 0.69, p < 0.001 for interlobular arteries; and {rho} = 0.80, p < 0.001 for arcuate arteries) and arteriolar hyalinosis ({rho} = 0.46, p < 0.001). Incorporating pathomic features from trichrome-stained WSIs improved the prediction of disease progression, enhancing the concordance index from 0.70 to 0.75 in arterioles and from 0.69 to 0.74 in arcuate arteries, compared to using demographics and clinical characteristics alone. ConclusionOur computational approach offers a novel and reliable method for segmenting and analyzing the pathomic features of sclerosis and hylalinosis in arteries and arterioles. This technique has demonstrated potential as a valuable tool for enhancing the clinical assessment performed by pathologists. Key PointsO_LIA computational pipeline was developed and validated to segment arteries and arterioles and to quantify lumen, intima, media, and hyalinosis in kidney biopsies from patients with FSGS and MCD. C_LIO_LIPathomic features, such as intima-media thickness ratio and hyalinosis area, significantly correlated with pathologists semi-quantitative sclerosis and hyalinosis scores. C_LIO_LIIntegrating pathomic features into clinical models improved disease progression prediction accuracy C_LI