Inflammatory markers associated with albuminuria and early atherosclerosis in type 2 diabetic kidney disease: a cross-sectional study.

Subclinical atherosclerosis was present in 46% of the study population of type 2 diabetic patients with moderate CKD.

• Cross-sectional study including 362 subjects with type 2 diabetes and moderate chronic kidney disease.
• Subclinical atherosclerosis (SA) was defined by carotid intima-media thickness (CIMT) ≥0.9 mm or ankle-brachial index (ABI) <0.9.
• 46% of patients met criteria for SA.

Urinary albumin-to-creatinine ratio (UACR) was directly correlated with CIMT and inversely correlated with ABI.

• UACR correlated directly with CIMT (r=0.32, p<0.001).
• UACR correlated inversely with ABI (r=-0.29, p<0.01).
• These correlations indicate that higher albuminuria was associated with greater carotid intima-media thickness and lower ankle-brachial index, both markers of subclinical atherosclerosis.

Higher UACR was associated with increased circulating IL6 and IL1β, and elevated leukocyte expression of TNF, CD36, and TLR2.

• Serum levels of hs-CRP, IL6, IL1β, IL10, and TNFα were measured.
• Gene expression in peripheral blood leukocyte cells was assessed for IL6, IL1β, TNF, IL10, TLR2, TLR4, CCL2, NFκB, and CD36.
• Higher UACR was specifically associated with increased circulating IL6 and IL1β at the serum level.
• At the cellular level, higher UACR was associated with elevated leukocyte expression of TNF, CD36, and TLR2.

In multivariable analysis, serum IL6 and IL1β, and leukocyte IL6 and TLR2 were independently associated with subclinical atherosclerosis.

• Multivariable analysis was conducted to assess independent associations with SA.
• Both circulating (serum) and leukocyte expression levels of IL6 were independently associated with SA.
• Serum IL1β was independently associated with SA.
• Leukocyte TLR2 expression was independently associated with SA.

Mediation analyses indicated that IL6, IL1β, and TLR2 partially mediated the association between UACR and subclinical atherosclerosis.

• IL6 (serum and leukocyte expression combined) accounted for approximately 20% of the UACR-SA association.
• Serum IL1β mediated approximately 17% of the UACR-SA association.
• Leukocyte TLR2 mediated approximately 7% of the UACR-SA association.
• These findings are described as exploratory and should be interpreted cautiously due to the cross-sectional design.