Quantitative Assessment of the Effect of Chronic Kidney Disease on Plasma P-Tau217 Concentrations

肾脏疾病 医学 定量评估 内科学 疾病 血浆浓度 重症监护医学 风险分析(工程)
作者
Joshua A. Bornhorst,Carly S. Lundgreen,Stephen D. Weigand,Daniel 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
出处
期刊:Neurology [Lippincott Williams & Wilkins]
卷期号:104 (3)
标识
DOI:10.1212/wnl.0000000000210287
摘要

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. This was a retrospective examination of data from 2 observational cohorts from either the Mayo Clinic Study of Aging or the Alzheimer's Disease Research Center cohorts. p-Tau217 was determined using the ALZpath Simoa p-tau217 immunoassay and an immunoprecipitation mass spectrometry assay that simultaneously measures p-tau217 and nonphosphorylated-tau217 (np-tau217) to determine %p-tau217 ([p-tau217/nonphosphorylated-tau217]) × 100%) (C2N 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. Participants (n = 202, mean age of 78 years, 38% female) with diagnoses of cognitive unimpairment (n = 109), mild cognitive impairment (n = 71), and dementia (n = 22) were included. In all, 114 (56%) of all participants were amyloid-PET positive (A+). In addition, 86 (43%) of all participants were classified as having CKD (CKD stages 3-4). p-Tau217 concentrations were significantly higher in A- participants with an eGFR of <60 (mL/min/1.73 m2), as compared with those with eGFR >60 A- participants. For an eGFR of 45 vs 60 in the A- cohort, the calculated percentage changes were +31%, +55%, and +19%, for ALZpath p-tau217, C2N p-tau217, and C2N %p-tau217, respectively. For the A+ cohort, the corresponding calculated percentage changes were +17%, +15%, and -5%, respectively. CKD was associated with increased p-tau217 concentrations when measuring p-tau217 by ALZpath and C2N 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. 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.
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