Effect of corrections for renal function on plasma phosphorylated tau performance for Alzheimer's disease

BackgroundBlood-based biomarkers (BBMs), including plasma phosphorylated tau (pTau), have been considered as a promising, less-invasive tool for detecting Alzheimer's disease (AD) pathology in real-world applications. Plasma pTau levels are known to be elevated in individuals with chronic kidney disease, which may require caution when corrected for renal function since it alters testing performance-decreased sensitivity and increased specificity.ObjectiveWe aimed to quantify how correcting for renal function affects BBM test performance.MethodsWe analyzed plasma pTau181 and pTau217 measured by multiple platforms, using data from our ongoing trial-ready cohort study in Japan and the ADNI study, in which approximately 30% of participants had mild or moderate renal impairment (eGFR < 60). We compared models with and without renal correction to predict amyloid PET positivity status.ResultsCompared to no correction, adjusting for renal function reduced sensitivity by 0.06-0.07 and increased specificity by 0.04-0.10. It also slightly increased positive predictive value, negative predictive value, balanced accuracy, and area under the curve-each by less than 0.02. These shifts by correction were more pronounced when the participant prevalence of those with renal function was higher, though mainly for sensitivity and specificity.ConclusionsOur findings demonstrated that applying renal function correction decreases sensitivity and increases specificity of BBM test depending on the prevalence of renal impairment, without undermining overall prediction accuracy. They emphasize the need of considering the background characteristics of the target population when interpreting BBM performances in the real-world settings.