A blood-based multi-omic landscape for the molecular characterization of kidney stone disease†

Abstract

Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which continues to be highly prevalent and with increasing incidence. For the identification of novel therapeutic targets in KSD, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteomic data and DNA methylation data from blood samples of normal and KSD individuals. Our research delineated the profiling of exosomal proteins and DNA methylation in both healthy individuals and those afflicted with KSD, finding that the overexpressed proteins and the demethylated genes in KSD samples are associated with immune responses. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our insights into the molecular landscape of KSD pave the way for a deeper understanding of its pathogenic mechanism, providing an opportunity for more precise diagnosis and targeted treatment strategies for KSD.