Quantitative Assessment of the Effect of Chronic Kidney Disease on Plasma P-Tau217 Concentrations
Joshua A. Bornhorst, Carly S. Lundgreen, Stephen D. Weigand, Daniel J. Figdore, Heather J. Wiste, Michael Griswold, Prashanthi Vemuri, Jonathan Graff‐Radford, David S. Knopman, Petrice Cogswell, Clifford R. Jack, Ronald C. Petersen, Alicia Algeciras‐Schimnich
Abstract
BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is known to be associated with increased plasma phosphorylated tau217 (p-tau217) concentrations, potentially confounding the utility of plasma p-tau217 measurements as a marker of amyloid pathology in individuals with suspected Alzheimer disease (AD). In this study, we quantitatively investigate the relationship of plasma p-tau217 concentrations vs estimated glomerular filtration rate (eGFR) in individuals with CKD with and without amyloid pathology. METHODS: N Diagnostics). Amyloid positivity was defined by amyloid-PET and a centiloid of ≥25. Log-log linear regression fits were used to quantitatively predict increases in plasma p-tau217 associated with decreasing eGFR. RESULTS: N %p-tau217, respectively. For the A+ cohort, the corresponding calculated percentage changes were +17%, +15%, and -5%, respectively. DISCUSSION: N methodologies, but the effect was mitigated by the use of %p-tau217. These results indicate limitations for the utility of plasma p-tau217 measurements in individuals with significant renal impairment (eGFR <45 or CKD stage 3b or greater). Determination of eGFR should be considered to avoid inaccurate classification of the presence of AD-related pathology by plasma p-tau217 in individuals with CKD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals with CKD stage 3 (especially stage 3b) or higher, p-tau217 concentrations are increased, with a greater increase in amyloid-PET-negative individuals.