Traditional functional biomarkers

2 KIDNEY FUNCTIONAL BIOMARKERS (GLOMERULAR FILTRATION AND TUBULAR REABSORPTION) 

The most established and widely used kidney safety biomarkers are indices of renal function (GFR) including sCr 

O Qualified biomarkers O Tissue injury leakage markers O Tissue injury response markers O Functional markers 

FIGURE 28.2 Select qualified and unqualified biomarkers used when monitoring for drng-indnced kidney injury to specific nephron segments in rats. Adapted from Bonventre et al. (2010). (See insert for color representation of the figure.) 

ASSESSING AND PREDICTING DRUG-INDUCED KIDNEY INJURY, FUNCTIONAL CHANGE, AND SAFETY IN PRECLINICAL 

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FIGURE 28.1 Insensitive, delayed, and nonspecific traditional kidney injury/functional markers on a conceptnal framework of acute kidney injury (AKI), which is divided into several stages from the increased risk to damage, followed by a decrease in glomerular filtration rate (GFR), with progressing to kidney failure and death. Early, sensitive, and specific AKI biomarkers are not available or well qualified for AKI detection and safety assessment. indicates there are no biomarkers available for early AKI detection. Adapted from Lameire et al. (2008, pp. 392-402). (See insert for color representation of the figure.)... 

Many classical biomarkers detect Cd toxicity at a stage when functional damage is already advanced and perhaps irreversible. Moreover, results of recent studies have shown that even low ( normal ) levels of Cd exposure over a long period of time (CLCE) have subtle but insidious adverse effects on the kidney (see [3,4]), where traditional biomarkers may have their hmitations [94]. Therefore, there is an increasing need for sensitive biomarkers of early exposure to low Cd concentrations where no overt pathology is apparent. 

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