Urinary biomarkers of renal transplant outcome.

Abstract

Renal allograft loss remains an important cause of morbidity and mortality. The objective of this review was to provide a rationale for noninvasive monitoring to identify patients at high risk for graft loss; discuss key steps in prognostic biomarker development from bench-to-bedside; and review promising biomarkers for late renal allograft outcomes. In a multicentre prospective cohort, early 6-month urinary CCL2 was demonstrated to be associated with the development of 24-month interstitial fibrosis/tubular atrophy and inflammation (IFTA+i). These findings were extended to a single centre cohort, which showed that 6-month urinary CCL2 was a predictor of death-censored graft loss independent of donor-specific antibody and delayed graft function. In a large, multicentre prospective observational study (CTOT-01), 6-month urinary CXCL9 was significantly associated with more than 30% decline of graft function at 24 months. Urinary chemokines may identify recipients who are at high risk of graft loss. The early detection of high-risk recipients may allow for more intensive posttransplant surveillance; avoidance of drug minimization/withdrawal protocols; and the identification of patients who may benefit from enrolment in novel interventional trials. Prospective trials are needed to demonstrate that urinary chemokine-guided posttransplant surveillance strategies improve long-term graft outcomes.