Kidney function is associated with plasma ATN biomarkers among Hispanics/Latinos: SOL-INCA and HCHS/SOL results

Background: Plasma amyloid-tau-neurodegeneration (ATN) biomarker levels may be influenced by non-brain systems, such as kidney function, which could impact the interpretation of ATN biomarker results, particularly in groups like Hispanic/Latino individuals with higher rates of cardiometabolic health issues. Here, we examine the association between kidney function and plasma ATN markers among a diverse sample of Hispanic/Latino individuals living in the U.S. Methods: Data was collected from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL, Visit 1, 2008–2011), the largest prospective cohort study of noninstitutionalized Hispanic/Latino adults in the U.S., and its ancillary study, the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) which was conducted during the second visit of the parent HCHS/SOL study (Visit 2, 2015–2018). SOL-INCA aimed to examine the neurocognitive decline of middle-aged and older Hispanic/Latino adults, and the inclusion criteria were the age of 50-years and older by Visit 2 and completion of battery of neurocognitive tests at Visit 1. Survey linear regression models were used to examine associations between CKD status (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73m² or urine albumin-creatinine ratio [uACR]) > = 30 mg/g) and the plasma ATN biomarkers (β-amyloid 42/40 ratio [Aβ42/40 ratio], phosphorylated-tau181 [p-Tau181], neurofilament light [NfL], and glial fibrillary associated protein [GFAP]), independently. All models adjusted for sociodemographic and cardiometabolic factors (BMI, diabetes, and hypertension). Results: 5,968 participants were included in the study (mean age 63.4 ± 8.1, 54% women). CKD was associated with higher p-Tau181 (b = 0.82), NfL (b = 11.60) and GFAP levels (b = 31.41), and lower Aβ42/Aβ40 ratio (b=-0.004). Lower eGFR (i.e., reduced kidney function) was associated with higher p-Tau181, NfL, and GFAP levels (b ranges [-0.87 - -0.03]), and lower Aβ42/Aβ40 ratio (b = 0.000). Higher (natural log) uACR was associated with lower Aβ42/Aβ40 ratio and higher levels of all other biomarkers (b ranges [0.24–5.49]). Additionally, CKD, eGFR, and uACR were associated with ATN biomarkers in models adjusted for cardiometabolic risk factors, diabetes and hypertension. Conclusions: CKD status, kidney function and urinary markers of kidney damage are significant confounders in the interpretation of plasma ATN biomarker levels.