Marking renal injury: can we move beyond serum creatinine?

Acute kidney injury (AKI) is a prevalent and devastating condition associated with significant morbidity and mortality. Despite marked improvements in clinical care, the outcomes for subjects with AKI have shown limited improvement in the past 50 years. A major factor inhibiting clinical progress in this field has been the inability to accurately predict and diagnose early kidney dysfunction. The current gold standard clinical and biochemical criteria for diagnosis of AKI, Risk Injury Failure Loss End-stage renal disease, and its modification, Acute Kidney Injury Network criteria, rely on urine output and serum creatinine, which are insensitive, nonspecific, and late markers of disease. The recent development of a variety of analytic mass spectrometry-based platforms have enabled separation, characterization, detection, and quantification of proteins (proteomics) and metabolites (metabolomics). These high-throughput platforms have raised hopes of identifying novel protein and metabolite markers, and recent efforts have led to several promising novel markers of AKI. However, substantial challenges remain, including the need to systematically evaluate incremental performance of these markers over and beyond current clinical and biochemical criteria for AKI. We discuss the basic issues surrounding AKI biomarker development, highlight the most promising markers currently under development, and discuss the barriers toward widespread clinical implementation of these markers.