Discussion
The use of a panel of urinary kidney injury biomarkers emerged as an early, sensitive, and predictive tool to detect AKI showing enhanced sensitivity compared to current state-of-the-art markers.
Methods
In the rat, urinary biomarkers for kidney injury, i.e. albumin, beta-2-microglobulin (B2M), clusterin, cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and total protein (TP), were investigated in an AKI model using different hyperosmolar and high-dose solutions, i.e. mannitol, sucrose, and contrast medium (CM), as acute single insults leading to kidney injury. Additionally, dose-dependency of sucrose was investigated and effects were compared to the sucrose- and iron-containing marketed drug Venofer®.
Results
Levels of excreted urinary biomarkers correlated with severity of AKI, exhibited a dose-dependent response to sucrose treatment, and demonstrated evidence of recovery from kidney injury with transient and reversible changes. The exceptions were KIM-1 and NGAL, which showed later responses following CM and iron-induced renal injury. All biomarkers outperformed plasma creatinine (PCr), BUN, and histopathology, with regard to practicability and/or detection of proximal tubular injury.