Discovery and validation of circulating protein markers of chronic kidney disease in domestic cats

Chronic kidney disease (CKD), a prevalent condition in older cats, is characterized by progressive and irreversible renal damage. Early detection is crucial for timely intervention, potentially slowing disease progression and extending the lifespan of affected cats. Given some of the limitations of current diagnostic tools, this study aimed to identify novel, non-invasive protein biomarkers for feline CKD. Mass spectrometry (MS)-based proteome profiling was employed to analyse serum samples from CKD-affected and healthy control cats across two independent cohorts. In the discovery cohort, proteins with altered levels in CKD and distinct proteomic signatures corresponding to various disease stages were identified. Notably, an elevated serum level of retinol-binding protein 4 (RBP4) was detected and corroborated with vitamin A concentration. In the validation cohort, kinesin-like protein, RBP4, and cathelicidin were confirmed as candidate biomarkers for CKD. Their performance on the classification of CKD and healthy cats was assessed using receiver operating characteristic (ROC) curve, providing an area under the ROC curve of 0.880, 0.960, and 0.875 in the validation cohort, respectively. This pioneering study leverages MS-based proteomics to elucidate serum proteome alterations in feline CKD, underscoring its adaptability and utility in domestic animal research.