Evaluation of Novel Biomarkers of Acute Kidney Injury: The Possibilities and Limitations

Abstract

Despite the recent findings concerning pathogenesis and novel therapeutic strategies, the mortality rate in patients with acute kidney injury (AKI) remains very high. Early detection of patients with impaired renal function may help to ensure more aggresive treatment and to improve clinical outcome. Serum creatinine is still gold standard of kidney injury, although it is well known as an insensitive and unreliable biomarker (for example, its concentration does not increase significantly until about half of the kidney function is lost). Considering these data, researches and clinicians are making great efforts in the past decade in order to discover and validate novel AKI biomarkers. Kidney injury molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 (IL-18), Cystatin C (Cys-C) are some of new, promising markers of kidney damage which are currently in the focus of preclinical and clinical studies. Recent data suggest that some of these new biomarkers represent important parametars of acute tubular necrosis (ATN) and reliable predictors of development and prognosis of AKI. Beside that, monitoring of these markers could have significant importance for early diagnosis and clinical course, not only in patients with various forms of AKI and other renal diseases, but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracical surgical interventions, in the pediatric emergency setting etc. The aim of this review is to summarize the literature data concerning some new biomarkers, evaluate their role as well as their limitations in the early diagnosis and predict clinical outcome of some renal diseases.

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…It has a transmembrane domain and a short intracellular domain that contains a signaling protein for tyrosine phosphorylation (KIM-1b) [15]. The extracellular domain of KIM-1 is shed from the cell surface by a metalloproteinase-dependent process [81].…”

“…SCr is an integrator of various intrarenal and extrarenal functions, and its concentration indicates the balance between creatinine generation and excretion [12]. SCr not only is a delayed and insensitive biomarker of changes in kidney function [13], but its concentration does not differentiate structural kidney damage and functional hemodynamic triggers and could be affected by many factors [14,15]. In addition, patients with reduced muscle mass may not have a robust rise in SCr despite a substantial kidney injury.…”

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation

“…Recently, new AKI biomarkers of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were found to be more reliable and sensitive than BUN and creatinine in a number of experimental and clinical studies [25,26]. Compared with the vehicle group, APAP treatment enhanced the mRNA levels of NGAL and KIM-1 by 347-and 5-fold, respectively ( Fig.…”

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats

“…Therefore, there is an urgent demand for identification of more sensitive and reliable biomarkers, which may better predict minor kidney injury during drug development and chemical safety testing. Recently, it has been reported that tests for measuring levels of new biomarkers of acute kidney injury, such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, and interleukin-18, are more favorable than tests for BUN and creatinine levels in several experimental and clinical systems [67]. …”