REDUCED kidney function may influence levels of key Alzheimer’s disease and related dementia biomarkers in blood, according to a new systematic review and meta-analysis. The findings highlight the potential importance of considering renal health when interpreting biomarker-based tests increasingly used in dementia research and clinical practice.
Researchers analysed data from 93 human studies involving more than 62,000 participants across 21 countries, examining whether kidney function was associated with established neurodegenerative biomarkers, including amyloid-β (Aβ), tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Studies were identified through major databases up to May 2025 and assessed using PRISMA 2020 guidelines.
Lower eGFR Associated with Higher Alzheimer’s Biomarkers Including NfL and GFAP
The analysis showed that lower estimated glomerular filtration rate (eGFR), a key marker of kidney function, was consistently linked to higher concentrations of several blood biomarkers associated with neurodegeneration. Specifically, declines in eGFR were associated with increases in NfL, GFAP, Aβ40, Aβ42, and phosphorylated tau (p-tau181) levels. Even after statistical adjustments, reduced kidney function remained significantly associated with elevated biomarker levels. For example, each 1 ml/min/1.73 m² reduction in eGFR corresponded to measurable increases in circulating NfL, GFAP, and Aβ40.
In contrast, associations between kidney function and biomarkers measured in cerebrospinal fluid (CSF) were inconsistent and largely non-significant. The authors suggested that peripheral clearance mechanisms or systemic factors related to renal impairment may influence blood biomarker concentrations more strongly than central nervous system measures.
Future Research Needed to Clarify Kidney-Brain Connections
The findings may have important implications as blood-based biomarkers become increasingly central to Alzheimer’s disease diagnosis and monitoring. Elevated biomarker levels are often interpreted as reflecting neurodegenerative pathology; however, this study indicates that reduced kidney function could partially influence these readings, potentially affecting diagnostic accuracy or risk assessment.
The researchers concluded that clinicians and investigators should consider renal function when interpreting blood biomarker results in dementia research and clinical settings. Further studies are needed to clarify underlying biological mechanisms and to determine whether adjusting for kidney function could improve the reliability of biomarker-based screening and prognostic tools.
Reference
Yuwei L et al. Kidney function and blood and cerebrospinal fluid biomarkers in Alzheimer’s disease and related dementias. J Am Soc Nephrol. 2026;doi: 10.1681/ASN.0000001007.
