Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract

Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p<0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p<0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p>0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.