Data Sheet 1_Inflammatory markers associated with albuminuria and early atherosclerosis in type 2 diabetic kidney disease: a cross-sectional study.docx

BackgroundAlbuminuria is a recognized marker of renal injury in diabetic kidney disease (DKD), and growing evidence suggests it may also drive systemic inflammation and atherosclerosis. However, mechanisms linking albuminuria to vascular disease remain unclear.
MethodsWe conducted a cross-sectional study including 362 subjects with type 2 diabetes and moderate chronic kidney disease (CKD) to evaluate the associations between albuminuria, circulating and leukocyte inflammatory markers, and measures of subclinical atherosclerosis (SA). SA was defined by carotid intima-media thickness (CIMT) ≥0.9 mm or ankle-brachial index (ABI) <0.9. Serum levels of hs-CRP, IL6, IL1β, IL10, and TNFα and gene expression in peripheral blood leukocyte cells for IL6, IL1β, TNF, IL10, TLR2, TLR4, CCL2, NFκB, and CD36 were measured.
ResultsSA was present in 46% of patients. UACR correlated directly with CIMT (r=0.32, p<0.001) and inversely with ABI (r=–0.29, p<0.01). Higher UACR was associated with increased circulating IL6 and IL1β, and elevated expression of TNF, CD36, and TLR2 in leukocytes. In multivariable analysis, serum IL6and IL1β, and leukocyte IL6 and TLR2 were independently associated with SA. Mediation analysis showed that IL6 (serum and leukocyte expression) accounted for approximately 20% of the UACR–SA association, serum IL1β mediated 17%, and leukocyte TLR2 mediated 7%.
ConclusionsAlbuminuria was positively associated with heightened systemic and cellular inflammation, and several inflammatory markers were also associated with greater CIMT and the presence of early atherosclerosis. Exploratory mediation analyses suggested that inflammatory pathways may partly account for the association between albuminuria and SA, with IL6, IL1β, and TLR2 as key mediators; however, these findings should be interpreted cautiously due to the cross-sectional design.