Proteomic biomarkers for the early detection of acute kidney injury

Acute kidney injury (AKI) comprises several syndromes that are associated with a sudden decrease in renal function. AKI is a common condition especially among critically ill patients. It is typically multifactorial and of great prognostic significance. The incidence of AKI has increased while the associated mortality rate has remained unchanged over the last years. Recent definitions of AKI, namely the Risk, Injury, Failure, Loss of renal function and End-stage kidney disease (RIFLE) classifycation or the Acute Kidney Injury Network (AKIN) criteria, incorporate serum creatinine and urine output as the principal markers to define and detect AKI. However, elevated serum creatinine or oliguria were demonstrated to detect AKI at late stages of renal injury when preventive strategies may be less effective. Therefore, there has recently been a great scientific interest in obtainng valuable markers for early AKI detection. In the last 5 years numerous new markers such as neutrophil-gelatinase associated lipo-calin, interleukin-18, cystatin C and kidney injury molecule 1 in the urine and/or serum have been studied and proposed as early detection markers of AKI. Persistently, these markers performed well in initial pilot trials. However, these promising results could often not be confirmed in later, larger multicentre trials and limitation of these biomarkers in the early diagnosis of renal injury were discovered. Furthermore, as AKI is multi-factorial and heterogeneous in origin, it seems likely that not one single marker but a panel of biomarkers will be required to detect all subtypes of AKI early during their evolution. This has initiated proteomic studies to develop panels of biomarkers which may facilitate early detection of AKI. The present review will focus on the most important clinical studies evaluating the ability of single AKI biomarkers and on those in clinical proteomics that attempted to establish panels of biomarkers in urine for early and accurate AKI diagnosis and prognosis.