A Urinary Proteomics Approach to Predict Treatment Response in Acute Antibody-Mediated Rejection

Abstract

Acute antibody-mediated rejection (AMR) is a severe complication affecting kidney allografts' long-term survival. Timely detection and appropriate treatment of AMR are crucial for improving graft outcomes. This study aimed to discover non-invasive urinary biomarkers that can predict the response to therapy in patients with AMR. Materials and Methods: In this case-control study, urine samples from 21 biopsy-proven AMR patients underwent proteomics using label-free quantification. The patients were divided into two groups: responders and non-responders to treatment based on their graft function. Urinary proteins were identified, and their expressions were compared between the two groups to identify potential candidate biomarkers. Out of the 1020 identified proteins, 257 proteins were found to be differentially expressed between the two groups. Among these, 153 proteins showed increased expression in non-responder patients, while 104 proteins showed decreased expression. Non-responder patients exhibited higher activation of complement pathway and extracellular matrix degradation than responders. Insulin-like growth factor binding protein 6 (IGFBP-6) emerged as the most sensitive and specific biomarker for predicting non-response to treatment in patients with AMR. Our study has successfully identified urinary proteome biomarkers that can distinguish and predict non-responder patients with AMR. These biomarkers are associated with various biological processes that reflect the pathogenesis and severity of AMR. Further research is necessary to validate these findings.