Proteomics for Biomarker Discovery for Diagnosis and Prognosis of Kidney Transplantation Rejection

Renal transplantation is currently the treatment of choice for end-stage kidney disease, enabling a quality of life superior to dialysis. Despite this, all transplanted patients are at risk of allograft rejection processes. The gold-standard diagnosis of graft rejection, based on histological analysis of kidney biopsy, is prone to sampling errors and carries high costs and risks associated with such invasive procedures. Furthermore, the routine clinical monitoring, based on urine vol-ume, proteinuria, and serum creatinine, usually only detects alterations after graft histologic dam-age and does not differentiate between the diverse etiologies. Therefore, there is an urgent need for new biomarkers enabling to predict, with high sensitivity and specificity, the rejection processes and the underlying mechanisms obtained from minimally invasive procedures to be implemented in routine clinical surveillance. These new biomarkers should also detect the rejection processes as early as possible, ideally before the78 clinical outputs, while enabling balanced immunotherapy in order to minimize rejections and reducing the high toxicities associated with these drugs. Prote-omics of biofluids, collected through non-invasive or minimally invasive analysis, e.g., blood or urine, present inherent characteristics that may provide biomarker candidates. The current manu-script reviews biofluids proteomics toward biomarkers discovery that specifically identify subclin-ical, acute, and chronic immune rejection processes while allowing for the discrimination between cell-mediated or antibody-mediated processes. In time, these biomarkers will lead to patient risk stratification, monitoring, and personalized and more efficient immunotherapies toward higher graft survival and patient quality of life.