What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Adults with type 2 diabetes mellitus and moderate chronic kidney disease (CKD stage G3a/b; eGFR 30–59 mL/min/1.73 m²) without history of clinical cardiovascular disease (n=362). Primary outcome: Presence of subclinical atherosclerosis (SA) defined as carotid intima-media thickness (CIMT) ≥0.9 mm or ankle-brachial index (ABI) <0.9 (Adjusted OR per log-UACR 1.72, 95% CI 1.21–2.44, p=0.002).

What question did this study set out to answer?

This research aims to explore the relationship between albuminuria and inflammatory markers in type 2 diabetic kidney disease.

March 1, 2026Open Access

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

Q: What are the key findings of this study?

Albuminuria (log-UACR) was independently associated with subclinical atherosclerosis with adjusted OR 1.72 (95% CI 1.21–2.44; p=0.002) in adults with type 2 diabetes and moderate CKD.

Q: What question did this study set out to answer?

This research aims to explore the relationship between albuminuria and inflammatory markers in type 2 diabetic kidney disease.

Key Result

Albuminuria (log-UACR) was independently associated with subclinical atherosclerosis with adjusted OR 1.72 (95% CI 1.21–2.44; p=0.002) in adults with type 2 diabetes and moderate CKD.

Key Points

This research aims to explore the relationship between albuminuria and inflammatory markers in type 2 diabetic kidney disease.
Conducted a cross-sectional study with 362 subjects
Evaluated associations between albuminuria and inflammatory markers
Measured carotid intima-media thickness and ankle-brachial index for assessing subclinical atherosclerosis
Analyzed serum and gene expression levels of various inflammatory markers
46% of subjects presented with subclinical atherosclerosis
Albuminuria correlated positively with carotid intima-media thickness and negatively with ankle-brachial index
Higher levels of albuminuria were linked to increased IL6 and IL1β
IL6, IL1β, and TLR2 showed independent association with early atherosclerosis
Mediation analysis indicated IL6 and IL1β mediated a portion of the association between albuminuria and subclinical atherosclerosis

Study Design

Type

Cross-Sectional (n=362)

Multicenter

Structured PICO

Population

362 adults (>18 years) with type 2 diabetes mellitus for >1 year and moderate chronic kidney disease (CKD stage G3a/b, eGFR 30-59 mL/min/1.73 m²), persistent UACR ≥30 mg/g, on stable RAS blockers and statins, with no history of clinical atherosclerotic cardiovascular disease. Mean age 67.3, 49.2% male, Spain-based.

Outcome

Presence of subclinical atherosclerosis (SA), defined as carotid intima-media thickness (CIMT) ≥0.9 mm or ankle-brachial index (ABI) <0.9surrogate

In patients with type 2 diabetic kidney disease, albuminuria is associated with subclinical atherosclerosis, a relationship partially mediated by systemic and cellular inflammatory markers like IL6 and IL1β.

Main Result

Effect estimate: Adjusted OR per log-UACR 1.72 (95% CI 1.21–2.44)

Absolute Event Rate: 45.6% vs 54.4%

p-value: p=0.002

Limitations

Cross-sectional design precludes causal inference between albuminuria, inflammation, and atherosclerosis.
Single-center study with homogenous Spanish population limits generalizability.
Use of surrogate markers (CIMT and ABI) rather than direct imaging for atherosclerosis.
Potential unmeasured confounders (diet, gut microbiota, oxidative stress) were not assessed.
Study conducted before widespread use of SGLT2 inhibitors and finerenone; findings reflect pre-SGLT2/finerenone era.
Inflammatory markers measured only at one time point; potential variability not accounted for.
Mediation analyses assessed inflammatory markers independently despite possible pathway overlap.

Abstract

Background Albuminuria 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. Methods We 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. Results SA was present in 46% of patients. UACR correlated directly with CIMT (r=0.32, p0.001) and inversely with ABI (r=–0.29, p0.01). 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%. Conclusions Albuminuria 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.

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