Current concepts and advances in biomarkers of acute kidney injury

Abstract

Despite advancements in standardizing the criteria for acute kidney injury (AKI), its definition remains based on changes in serum creatinine and urinary output that do not specifically represent tubular function or injury and that have significant limitations in the acute hospital setting. Much effort in nephrology has centered on identifying biomarkers of AKI to address these limitations. This review summarizes recent advances in our knowledge of biomarkers involved in pathophysiological processes during AKI and describes their potential clinical implications. Blood and urine biomarkers are released via various mechanisms during renal tubular injury. Urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), insulin-like growth factor-binding protein-7 (IGFBP-7), and tissue inhibitor of metalloprotease-2 (TIMP-2) are released from the proximal tubule while uromodulin (UMOD) is secreted from the loop of Henle and neutrophil gelatinase-associated lipocalin (NGAL) is released from the distal tubule. These biomarkers could therefore be used to localize specific segments of injured tubules. Biomarkers also have diverse roles in pathophysiological processes in AKI, including inflammation, repair, and fibrosis. Current evidence suggests that these biomarkers could be used to predict the transition to chronic kidney disease (CKD), decrease discard of AKI kidneys, differentiate between kidney dysfunction and injury, guide AKI management, and improve diagnosis of diseases such as acute interstitial nephritis (AIN). They could differentiate between disease phenotypes, facilitate the inclusion of a homogenous patient population in future trials of AKI, and shed light on therapeutic pathways to prevent the transition from AKI to CKD. However, a major limitation of current biomarker research in AKI is the lack of tissue correlation. The Kidney Precision Medicine Project, a large-scale national effort, is currently underway to construct a kidney tissue atlas and expand the use of biomarkers to assess nephron health. Numerous biomarkers are involved in distinct pathophysiological processes after kidney injury and have demonstrated potential to improve diagnosis and risk stratification as well as provide a prognosis for patients with AKI. Some biomarkers are ready for use in clinical trials of AKI and could guide management in various clinical settings. Further investigation of these biomarkers will provide insight that can be applied to develop novel therapeutic agents for AKI.

Keywords: Acute kidney injury; acute tubular injury; biomarker; chronic kidney disease.