Abstract

Extensive pre-clinical studies have established the biological role, plausibility, and proof of concept of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute kidney injury (AKI). In AKI, there is a rapid and massive upregulation of NGAL in the kidney. The biological role of NGAL induction is attenuation of apoptosis and an enhanced proliferative response, as well as defense of the urinary system from bacteria. These actions are mediated by chelation of siderophores, removal of iron from extracellular environments and redirection to intracellular sites. In AKI, both urine and plasma NGAL are derived largely from the damaged nephron. NGAL expression in the kidney, urine, and plasma is directly proportional to the duration and severity of kidney injury, temporally correlated with the inciting stimulus, and specific to intrinsic AKI. These findings have now been successfully translated to multiple human studies, and NGAL has emerged as an excellent biomarker in the urine and plasma for early diagnosis, risk stratification, severity prediction, differential diagnosis, and outcomes prediction in several common clinical AKI scenarios. The deployment of standardized clinical platforms has further facilitated the validation of urine and plasma NGAL as an AKI biomarker. Some relevant patents are also summarized in this review.

Keywords: Acute kidney injury, biomarker, lipocalin, NGAL, siderocalin, Differential Diagnosis, Prognosis of AKI, serum creatinine, kidney transplant rejection, pre-renal azotemia.