Abstract
Capillary electrophoresis coupled with mass spectrometry (CE-MS) has been used as a platform for discovery and validation of urinary peptides associated with chronic kidney disease (CKD). CKD affects ∼ 10% of the population, with high associated costs for treatments. A urinary proteome-based classifier (CKD273) has been discovered and validated in cross-sectional and longitudinal studies to assess and predict the progression of CKD. It has been implemented in studies employing cohorts of > 1000 patients. CKD273 is commercially available as an in vitro diagnostic test for early detection of CKD and is currently being used for patient stratification in a multicentre randomized clinical trial (PRIORITY). The validity of the CKD273 classifier has recently been evaluated applying the Oxford Evidence-Based Medicine and Southampton Oxford Retrieval Team guidelines and a letter of support for CKD273 was issued by the US Food and Drug Administration. In this article we review the current evidence published on CKD273 and the challenges associated with implementation. Definition of a possible surrogate early endpoint combined with CKD273 as a biomarker for patient stratification currently appears as the most promising strategy to enable the development of effective drugs to be used at an early time point when intervention can still be effective.