Abstract

Background: Although albuminuria is an established risk factor for progression of kidney disease and cardiovascular outcomes, its association with subclinical arterial disease is unclear. [ 18 F]-sodium fluoride ([ 18 F]NaF) positron emission tomography (PET) imaging allows detailed early visualization of arterial microcalcification. This study aims to compare non-invasive imaging markers of subclinical arterial disease measured by microcalcification, macrocalcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without macroalbuminuria. Methods: Participants without cardiovascular history were age and sex matched in three groups: nonT2DM controls, patients with T2DM without albuminuria (MA-), patients with T2DM with macroalbuminuria (MA+). [ 18 F]NaF activity was scored visually (in the aorta and femoral arteries) and was quantified as background activity (blood pool) corrected mean standardized uptake value of the abdominal aorta, and iliac arteries, expressed as target-to-background ratio (TBR). Arterial macrocalcification was assessed with computed tomography (CT) and arterial stiffness with carotid-femoral pulse wave velocity (PWV). Results: Three groups with comparable estimated Glomerular Filtration Rate were included (n=10 per group); controls 91 [81-104] vs MA- 87 [84-93] vs MA+ 85 [60-103] (median [IQR] mL/min*1.73m 2 ). Femoral [ 18 F]NaF uptake was significantly increased in the MA+ group (228 [100-446] vs 33 [0-93] in MA- (p=0.002) and vs 75 [0-200] in controls (p=0.052)), while other imaging markers were not. PWV was significantly higher in the MA+ group compared with MA- group (11.15 vs 8.86 m/s (p=0.009)) while no differences in pulse pressure were found. The [ 18 F]NaF activity in femoral arteries correlated with PWV (r=0.516, p=0.020) and pulse pressure (r=0.508, p=0.012). Conclusions: This study suggests that the presence of macroalbuminuria in patients with T2DM is an indication of early phased arterial disease prior to the development of irreversible macrocalcification. Although larger [ 18 F]NaF PET studies are needed, these results underline the importance of macroalbuminura in T2DM for detecting subclinical arterial disease at an early potentially reversible stage.

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