Plasma Phosphorylated Tau 217 Varies With Kidney Function Even Without Chronic Kidney Disease
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Importance
Plasma phosphorylated tau 217 (p-tau217) is entering clinical use with fixed diagnostic threshold that do not account for kidney function. Chronic kidney disease (defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m 2 ), raises plasma p-tau217 concentrations and can produce false positive results. It remains unclear whether milder reductions in kidney function, above the CKD threshold, have the same effect.
Objective
To determine whether plasma p-tau217 is elevated with mildly reduced kidney function, above the chronic kidney disease threshold, in adults without neurological disease.
Design
Cross-sectional analysis of a cohort enrolled between 2023 and 2025 and biomarker analysis blinded to clinical data.
Setting
Two private psychiatric inpatient facilities in Australia.
Participants
Adults admitted with psychiatric disorders and free of neurological disease.
Exposures
eGFR calculated from serum creatinine using the CKD-EPI 2021 equation.
Main Outcomes and Measures
Plasma p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), measured on the Simoa platform. Multivariable linear regression compared eGFR groups (< 60, 60 to 90, and ≥ 90 mL/min/1.73 m 2 ), adjusted for age, BMI, and sex.
Results
Among 180 participants (median age, 50.5 years [IQR, 38.0-61.5]; 94 [52%] female), eGFR was ≥ 90 mL/min/1.73 m 2 in 106 (59%), 60 to 90 in 61 (34%), and < 60 in 13 (7.2%). Compared with an eGFR ≥ 90, plasma p-tau217 was 36% higher in both the 60 to < 90 group (β = 0.42 [95% CI: 0.11, 0.74]; P = .008) and 116% higher in the < 60 group (β = 1.05 [95% CI: 0.43, 1.72]; P = .002). Plasma NfL and GFAP were elevated in the < 60 group but differences in the 60 to < 90 group did not reach significance. Modelled continuously, plasma p-tau217 was 9.5% lower per 10 mL/min/1.73 m 2 higher eGFR (95% CI: 3.3%, 15.4%).
Conclusions and Relevance
Plasma p-tau217 was elevated in adults with mildly reduced kidney function, above the CKD threshold, in a cohort free of neurological disease. Kidney function across its full range should be incorporated into plasma p-tau217 reference ranges and clinical interpretation to reduce false positive and false negative results.
KEY POINTS
Question
Is plasma p-tau217 elevated at mildly reduced kidney function, above the chronic kidney disease (CKD) threshold?
Findings
In this cross-sectional study of 180 inpatients free of neurological disease, plasma p-tau217 was 36% higher in participants with an estimated glomerular filtration rate (eGFR) between 60 and 90 mL/min/1.73 m 2 , and 116% higher in those below 60, compared with those at 90 or above.
Meaning
Given that plasma p-tau217 varies with kidney function across its range, not only in CKD, eGFR should be incorporated into reference ranges and the interpretation of results to reduce false positive and false negative findings.
