Effect of kidney function on fluid biomarkers of Alzheimer’s disease: a systematic review and meta-analysis

Fluid biomarkers in plasma and cerebrospinal fluid (CSF) are crucial for Alzheimer's disease (AD) diagnosis. Emerging evidence suggests a link between kidney function and these biomarkers, but the relationship remains unclear. This study provides a systematic review and meta-analysis of the effect of renal function indicators (eGFR and serum creatinine) on AD fluid biomarkers in older adults. We searched PubMed, Cochrane, Web of Science, and EMBASE databases on July 4, 2025. Eligible studies were selected, and data were extracted for meta-analysis. Correlation coefficients were aggregated using a random-effects model. Our search yielded 11,057 articles, with 25 studies included in the meta-analysis of 9 plasma biomarkers. Lower eGFR (indicating worse renal function) was significantly associated with elevated plasma levels of neurofilament light chain (NfL) ( r = −0.40), amyloid-β (Aβ)42 ( r = −0.37), Aβ40 ( r = −0.46), phosphorylated tau (p-tau)181 ( r = −0.22), p-tau217 ( r = −0.32), total tau (t-tau) ( r = −0.38), and glial fibrillary acidic protein (GFAP) ( r = −0.26). It was also associated with a lower plasma Aβ42/Aβ40 ratio ( r = 0.06). No significant association was found for plasma p-tau231. An additional 18 articles were included in the qualitative review. Our findings demonstrate significant associations between renal function indicators and AD fluid biomarkers, particularly in plasma. However, given that approximately 80% of plasma tau and a substantial portion of plasma Aβ40 are of peripheral origin, these associations should be interpreted with caution as they may partly reflect systemic clearance and physiological effects rather than AD-specific pathology. These results underscore the critical importance of considering renal function for the accurate interpretation of blood-based AD biomarker profiles in both clinical and research settings, highlighting it as a crucial co-factor and potential confounder. Calculation formulas have been proposed to quantify the impact of renal function on plasma biomarkers.