Leveraging Urinary Proteomics to Advance Pathophysiologic and Biomarker Perspectives of Chronic Kidney Disease in Cats

Abstract Chronic kidney disease (CKD) is one of the most prevalent diseases in feline medicine. Mass spectrometry-based urinary proteomics offers powerful insight into biomarker candidates and disease subtyping in CKD by measuring protein profiles rather than individual proteins. This study aims to measure the urinary proteome to identify protein profiles in cats with and without CKD to gain pathophysiological insights into the disease and more precisely diagnose CKD. Here, we identify 2,219 urinary proteins in the feline urinary proteome. Using univariate biomarker analysis, we show that MMP-7 may be a promising biomarker of CKD in cats. We then demonstrate the power of using protein profiles rather than individual proteins by grouping proteins based on how they trend across disease states. The changes to the global urinary proteomes of individual cats showed three distinct groups of CKD cats with unique protein profiles, suggesting that different pathophysiological mechanisms mediate disease subtypes. We demonstrate that large-scale urinary proteomics may provide a powerful framework for discovering candidate biomarkers that advance the subtyping and mechanistic understanding of feline CKD.