Kidney Function and Blood and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease and Related Dementias

KEY POINTS: Lower kidney function is associated with higher concentrations of blood biomarkers for Alzheimer's disease and related dementia. Associations between kidney function and cerebrospinal fluid biomarkers for Alzheimer's disease and related dementia were heterogeneous and NS. Elevated blood biomarkers for Alzheimer's disease and related dementia in people with impaired kidney function may reflect reduced kidney clearance. BACKGROUND: Studies have shown that low kidney function may link to elevated Alzheimer's disease and related dementia fluid biomarkers, but the results are not consistent. This systematic review and meta-analysis aimed to investigate whether kidney function was associated with Alzheimer's disease and related dementia biomarkers (amyloid- β , tau, neurofilament light [NfL] protein, and glial fibrillary acidic protein [GFAP]) in blood and cerebrospinal fluid (CSF). METHODS: Human studies were identified through MEDLINE, EMBASE, Cochrane Library, and Web of Science (until May 2, 2025). Studies that reported the association between kidney function and Alzheimer's disease and related dementia biomarkers in blood or CSF among adults were included. Two authors independently screened and extracted data following preferred reporting items for systematic reviews and meta-analyses 2020 guidelines. Descriptive statistics and random-effects meta-analysis were used to analyze pooled effects. RESULTS: Of the 3024 studies screened, 93 met the inclusion criteria, encompassing 62,503 participants (mean age, 20-96 years; 54% female) from 21 countries. Ninety-one studies reported blood biomarkers, while ten reported CSF biomarkers. In meta-analysis of unadjusted correlation coefficients, kidney function (primarily eGFR) was inversely associated with concentrations of blood NfL, GFAP, Aβ40, β-amyloid 1-40 (A β 40), β-amyloid 1-42, and phosphorylated tau (p-tau181). In meta-analysis of adjusted regression coefficients, eGFR remained inversely associated with blood biomarker levels. Specifically, every 1 ml/min per 1.73 m 2 lower eGFR was associated with 0.19 pg/ml higher NfL (95% confidence interval [CI], 0.12 to 0.25), 0.11 pg/ml higher GFAP (95% CI, 0.04 to 0.18), and 0.29 pg/ml higher A β 40 (95% CI, 0.01 to 0.56). CSF biomarker findings were more heterogeneous and generally null. CONCLUSIONS: Low kidney function was associated with elevated blood biomarkers of Alzheimer's disease and related dementia (NfL, GFAP, and A β 40), whereas associations with CSF biomarkers were inconsistent and generally null.