Blood‐based Biomarkers, Kidney Disease, and Albuminuria in the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract

AbstractBackgroundThere is significant current interest in the use of non‐invasive blood biomarkers to characterize risk for, and progression to, Alzheimer’s’ disease (AD) and related dementias. Population‐based cohorts have examined the relationship between protein markers of AD and neurodegeneration, showing consistent associations with the presence of comorbidity, and in particular, chronic kidney disease (CKD). However, these studies have had limited racial diversity, and have not examined relationships with urinary albumin excretion.MethodWe assayed amyloid beta 40 (Aβ40), Aβ42, total tau, and neurofilament light chain (NfL) in stored blood samples from 508 participants (≥60 years) in SPRINT. We computed the ratio of Aβ42/Aβ40, and converted all measures to standardized Z‐scores in order to compare estimates. Using linear models, we examined the association of chronic kidney disease (CKD) with the blood measures, defined as a baseline estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. We also considered several additional analyses, including utilizing eGFR based on Cystatin‐C versus serum creatinine, as well as examining the relationship of albuminuria and race/ethnicity with the blood measures in participants without CKD at trial baseline.ResultParticipants (42.7% female, 31.9% non‐white) with a mean age of 69.9 years. There was a significant association between CKD and total tau, Nfl (p<0.001), but not with Aβ42/Aβ40 (p = 0.09). Participants with CKD exhibited higher levels of both total tau (least squares (LS) mean = 0.27, 95% CI: 0.12, 0.43) and NfL (LS mean = 0.67, 95% CI: 0.52, 0.83). Relationships were similar for eGFR based on cystatin C versus serum creatinine. After excluding participants with CKD (N = 352, 39.8% female, 34.1% non‐white, mean age of 68.8), there were not significant relationships between albuminuria with any of the biomarkers (p>0.05), nor was there a significant association between race/ethnicity and total tau, NfL, or Aβ42/Aβ40 (p>0.05).ConclusionIn a racially diverse subgroup of SPRINT participants, there were significant relationships between kidney function, defined via eGFR, with total tau and NfL, but not for the ratio of Aβ42/Aβ40. We did not observe any association between albuminuria and these blood measures of Alzheimer’s disease and non‐disease‐specific neurodegeneration.