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The emergence of plasma biomarkers kidney function relationships has become a critical area of study as blood tests for Alzheimer's disease move into routine clinical practice. Since the kidneys filter many of these small proteins, any decline in the estimated glomerular filtration rate (eGFR) can lead to an accumulation of biomarkers in the blood. This elevation often occurs independently of any actual brain pathology. Consequently, clinicians must understand how to interpret these results in patients with chronic kidney disease (CKD), which is increasingly common in the aging population.
Research from the ALZAN cohort demonstrates that decreased kidney function significantly raises the plasma concentrations of several key neurodegenerative markers. For instance, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and various phosphorylated tau (p-tau) species show inverse correlations with eGFR. When renal filtration slows down, these proteins remain in the systemic circulation for longer periods. Therefore, a patient with impaired kidneys might present with elevated biomarker levels that mimic a neurodegenerative profile, leading to potential misdiagnosis.
Evaluating plasma biomarkers kidney function interactions reveals that individual markers like p-tau181 and NfL are particularly sensitive to renal changes. However, the study confirms that using biomarker ratios can effectively mitigate this confounding effect. Ratios such as Aβ42/Aβ40 and p-tau217/Aβ42 remain remarkably stable across different levels of kidney function. This stability occurs because the renal clearance rate affects both the numerator and the denominator of the ratio similarly. Thus, these ratios provide a much more accurate reflection of cerebral amyloidosis than individual protein concentrations alone.
For medical professionals, these findings suggest a shift in how neurodegenerative diagnostic panels should be ordered and interpreted. If a patient has a known history of CKD or a low eGFR, a standalone NfL or p-tau test may yield a false positive. Instead, clinicians should prioritize ratio-based assessments to ensure diagnostic precision. Furthermore, integrating eGFR levels into the clinical interpretation of blood-based biomarkers will help prevent unnecessary invasive procedures, such as CSF sampling or PET imaging, in patients whose elevated blood markers are purely a result of renal insufficiency.
The kidneys are responsible for the systemic clearance of many small proteins, including p-tau and NfL. When kidney function (eGFR) decreases, these proteins accumulate in the plasma, potentially leading to elevated levels that do not necessarily reflect brain pathology.
Biomarker ratios, such as Aβ42/Aβ40 and p-tau217/Aβ42, are the most reliable. These ratios normalize for the effects of decreased renal clearance and maintain their diagnostic accuracy for detecting cerebral amyloidosis even when kidney function is impaired.
While some research suggests adjusting cut-offs, the current evidence strongly favors the use of biomarker ratios as a more robust method to eliminate the confounding influence of renal impairment without needing complex mathematical corrections.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice and should not be used as a substitute for professional clinical judgment. Refer to the latest local and national guidelines for clinical practice.
References
Mondésert E et al. Influence of Decreased Kidney Function on Plasma Biomarkers of Neurodegenerative Disorders in Routine Care: Confirmation of the Interest of Ratios. Neurology. 2026 May 12. doi: 10.1212/WNL.0000000000214931. PMID: 41980230.
Sato C, et al. Integrating kidney function assessment into the clinical interpretation of plasma Alzheimer's disease biomarkers. Alzheimers Res Ther. 2025;17(1):48.
Janelidze S, et al. Mitigating the Associations of Kidney Dysfunction With Blood Biomarkers of Alzheimer Disease by Using Phosphorylated Tau to Total Tau Ratios. JAMA Neurol. 2023;80(5):493-501.
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Research highlights how decreased eGFR affects plasma biomarkers like p-tau and NfL, suggesting biomarker ratios as a more reliable diagnostic tool....
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