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

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.

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).

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.

CKD status, kidney function and urinary markers of kidney damage are significant confounders in the interpretation of plasma ATN biomarker levels.