Beyond Serum Creatinine: Emerging Biomarkers for Early Detection and Prognosis of Acute Kidney Injury

Abstract

The diagnosis of acute kidney injury (AKI) is a major cause of morbidity and mortality as traditional markers such as serum creatinine and urine output only reflect kidney functional decline at a time when these kidneys have already sustained some degree of renal stress and injury. Emerging biomarkers provide a more biologically meaningful option by measuring damage to the tubules, cellular stress, changes in filtration, inflammation, metabolic disturbance and failure to recover at various stages of AKI. This review aims to present the latest evidence of the use of conventional and emerging biomarkers for early detection, risk stratification, clinical decision making and prognostic assessment. Special focus will be on neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, liver-type fatty acid-binding protein, TIMP-2, IGFBP7, CCL14, soluble urokinase plasminogen activator receptor, proenkephalin, microRNAs, and metabolomic signatures, along with urinary oxygen partial pressure. Existing data suggest that these markers have the potential to supplement serum creatinine to identify subclinical injury, distinguish between reversible and irreversible injury, assess the risk of kidney replacement therapy, and predict renal recovery and kidney disease progression. The performance is however dependent on clinical setting, assay method, when the measurement is taken and patient heterogeneity. Multimarker strategies and serial biomarker profiling might therefore offer a greater diagnostic and prognostic ability than single markers. Standardization of assays, clinically validated thresholds, multicenter evaluation and demonstration of benefit of using biomarker-driven management for meaningful outcomes will be required for future progress. Combining functional, structural, stress, and molecular markers with clinical monitoring could potentially allow for earlier recognition, more accurate prognosis, personalized monitoring, and improved short and long-term outcomes in AKI in a variety of acute care and critical care settings around the world.