Neutrophil gelatinase-associated lipocalin (NGAL): the clinician’s perspective

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL), originally discovered in the leukocyte neutrophil and than extensively studied in renal tissues, is now under focus as a “ prognostic ” biomarker, potentially useful in risk stratifi cation of a variety of cardiovascular as well as neoplastic and infl ammatory conditions. The same journey (i.e., from diagnostic to prognostic marker) has been covered by other biomarkers, including cardiac troponins (1) , natriuretic peptides (2) , copeptin (3) , C reactive protein (4) and procalcitonin (5) among others. Acute renal failure (ARF), also known as acute kidney injury (AKI) as now referred to in the scientifi c literature, is defi ned as an abrupt or rapid decline in renal fi ltration function. This condition is usually mirrored by an increase of serum creatinine concentration or azotemia [i.e., an elevation of blood urea nitrogen (BUN) concentration] (6) . Nevertheless, immediately after kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be a reduced urine output (7) . An increase of serum creatinine concentration may result from several medications (e.g., cimetidine, trimethoprim) that inhibit the kidney tubular secretion, whereas an elevation of serum BUN concentration may be due to increased production (i.e., gastrointestinal bleeding, steroid use, or protein loading), which may occur without concomitant renal injury, so that careful investigation must be performed before assessing as to whether kidney injury is really present (7) . AKI may be classifi ed into three general categories, as follows (7) : 1) prerenal – as an adaptive response to severe volume depletion and/or hypotension, with structurally intact nephrons. It represents the most common form of kidney injury and often leads to intrinsic AKI if it is not promptly corrected; 2) intrinsic – structural injury in the kidney is the hallmark of intrinsic AKI, and the most common form is acute tubular necrosis (ATN), either due to ischemic, infl ammatory or cytotoxic insults. Intrarenal vasoconstriction is the dominant mechanism for the reduced glomerular fi ltration rate (GFR) in patients with ATN; and 3) postrenal – from mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or urethra, resulting in obstructive uropathy or postrenal AKI. If the site of obstruction is unilateral, then a rise in the serum creatinine level may be counterbalanced by contralateral renal function, although a signifi cant loss of GFR still occurs and patients with partial obstruction may develop progressive loss of GFR when the obstruction is not relieved. Although this classifi cation is indeed useful for establishing a differential diagnosis, several pathophysiologic features are shared by the different categories. Patients who develop AKI may be oliguric or non-oliguric (oliguria being defi ned as a daily urine volume of < 400 mL; 50 % – 60 % of all cases), can have a rapid or slow rise in creatinine levels, and may display qualitative differences in urine solute concentrations and cellular content, depending on the variable nature of the injury. Classifying AKI as oliguric or non-oliguric retains prognostic value, oliguric patients displaying the worst prognosis. Anuria, defi ned as an urine output of < 100 mL/day, suggests bilateral obstruction or catastrophic injury to both kidneys when characterized by abrupt onset.