Hepatic and renal function impact concentrations of plasma biomarkers of neuropathology

Abstract

Introduction The impact of hepatorenal function on plasma biomarkers of neuropathology is unknown. Herein, we measured several plasma biomarkers in patients with cirrhosis. Methods Plasma phosphorylated tau (p‐tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t‐tau), and ubiquitin carboxyl‐terminal hydrolase L1 (UCHL1) were measured in 135 adults with cirrhosis and 22 healthy controls using Simoa. Within cirrhosis, associations between biomarkers and hepatorenal function were explored using linear regression. Results p‐tau181, NfL, t‐tau, and UCHL1 were increased 2‐ to 4‐fold in cirrhosis, whereas GFAP was not increased. Within cirrhosis, creatinine moderately correlated with p‐tau181 (β = 0.75, P < .01), NfL (β = 0.32, P < .01), and t‐tau (β = 0.31, P < .01), but not GFAP (β = –0.01, P = .88) or UCHL1 (β = –0.05, P = .60), whereas albumin showed weak, inverse correlations: p‐tau181 (β = –0.18, P < .01), NfL (β = –0.22, P < .01), GFAP (β = –0.17, P < .05), t‐tau (β = –0.20, P = .02), and UCHL1 (β = –0.15, P = .09). Conclusions Elevated p‐tau181, NfL, and t‐tau in cirrhosis were associated with renal impairment and hypoalbuminemia, suggesting that hepatorenal function may be important when interpreting plasma biomarkers of neuropathology.

Elevation of plasma phosphorylated tau181 during neurological illnesses affecting consciousness and kidney dysfunction

“…Recent studies also found that cirrhosis, history of stroke, and myocardial infarction is associated with increased plasma p‐tau181. 9 , 10 Such associations cannot be evaluated in our small study. Finally, due to the design, we cannot obtain the baseline cognitive performance in this population.…”

“…We also found an unequivocal negative correlation between plasma p‐tau181 and kidney function, which is consistent with previous reports. 9 , 10 Indeed, plasma p‐tau can reach several fold of the cut‐off values in non‐AD patients with severe kidney dysfunction. Nonetheless, impaired renal clearance cannot explain all false positive cases.…”

“…5,6 Few studies had explored the influence of non-neurologic factors on plasma levels of neurofilament light chain (NfL) and recently for other biomarkers. [7][8][9][10] They consistently identified the association of chronic kidney disease and elevation of most biomarkers. However, studies so far largely excluded individuals with other significant neurological disorders.…”

Head-to-head comparison between plasma p-tau217 and Flortaucipir-PET in amyloid-positive patients with cognitive impairment

“…This hypothesis is consistent with recent observations that plasma p-tau217 concentrations are influenced by non-neurodegenerative comorbidities, including renal and hepatic diseases. [33][34][35] These factors could result in plasma-specific measurement error that would weaken associations with other variables.…”

The iterative process of fluid biomarker development and validation in Alzheimer's disease

“…Berry et al. examined the influence of liver cirrhosis and biomarker evidence of kidney dysfunction on blood concentrations of AD‐related biomarkers 6 . Windon et al.…”