Biomarkers specificity/selectivity testing

For best results in determining the presence and site of nephron damage, a battery of enzymes as opposed to a single biomarker should be examined, especially since the most sensitive assay is highly variable, depending on the toxicant and species. Additionally, since many of the enzymes are not completely specific to a selected nephron segment, use of a battery of tests allows more precise localization of the site of injury (Price 1982). 

Demonstration of selectivity and specificity of an assay for a biomarker must be considered in the context of whether the assay is a definitive quantitative assay or a relative quantitative assay (see Section 1.2). It can be difficult to show absolute specificity and selectivity for a relative assay due to the uncertainty of the exact species being measured and unknown components of the matrix. At a minimum, reproducible measurements of endogenous samples with and without spiking of the reference analyte should be demonstrated. On the other hand, likely truncated forms of a well-characterized biomarker measured by a definitive quantitative assay can be tested for specificity, as in the following example. 

Table 1 Sensitivity and specificity of the guinea pig papillary muscle action potential assay for QT and TdP liability using APD90 or APD3o 9o as predictive biomarkers. Predictive values were calculated for three tested pacing frequencies independently from the tested concentrations for all compounds. An in vitro result is considered positive for a compound if at least one concentration showed a statistically significant and/or > 10 % increase in the selected parameter (APD90 or APD3o 9o) vs. baseline values...

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