High inflammatory burden may link non-albuminuric diabetic kidney disease to carotid atherosclerosis

Background: Individuals with diabetic kidney disease (DKD) exhibit markedly elevated cardiovascular (CV) risk, which may differ across DKD phenotypes. Non-albuminuric DKD (NA-DKD) has been proposed as a phenotype with high CV risk. Inflammation may contribute to the link between DKD and cardiovascular disease, but inflammatory patterns across distinct DKD phenotypes remains insufficiently characterized. This study evaluated an extensive panel of inflammatory markers in DKD and examined their relationship with the presence of carotid atherosclerotic plaque, particularly focusing on NA-DKD. Methods: A total of 180 adults with type 2 diabetes were stratified into patients with DKD (n = 132) and control group without DKD (n = 48) and subsequently in the different DKD phenotypes according to glomerular filtration rate (eGFR) and urinary to albumin creatinine ratio (UACR): albuminuric DKD (A-DKD, UACR ≥ 30 mg/g and eGFR ≥ 60 ml/min/1.73 m2; n = 46), NA-DKD (UACR < 30 mg/g and eGFR < 60 ml/min/1.73 m2; n = 44), albuminuric and low eGFR DKD (UACR ≥ 30 mg/g and eGFR < 60 ml/min/1.73 m2, n = 42). Participants underwent carotid and kidney ultrasonography, arterial stiffness assessment, and measurement of 37 inflammatory biomarkers. Logistic regression models adjusted for major confounders were used to assess associations between inflammatory markers and carotid atherosclerosis. Results: Individuals with DKD showed a higher prevalence of carotid plaques in comparison to controls (61.8 vs 39.6%, P = 0.008), a trend toward higher pulse wave velocity (11.45 ± 4.02 vs 10.11 ± 3.69 m/s, P = 0.082), and higher renal resistive index (0.75 ± 0.09 vs 0.71 ± 0.08, P = 0.016). Multiple inflammatory biomarkers—including soluble tumor necrosis factor receptors (sTNF-Rs)—were higher in DKD than in controls. When considering DKD phenotypes, sTNF-R1 was higher in NA-DKD in comparison to both controls and individuals with A-DKD. In the overall population, several inflammatory biomarkers correlated with estimated eGFR but not with UACR. Among participants with DKD, TNF-R1 levels in the top tertile group were independently associated with the presence of carotid plaques (OR 4.92, 95% CI 1.41–17.18, P = 0.010, q value = 0.0494). Conclusions: This study showed a higher inflammatory burden in DKD and particularly in NA-DKD. sTNF-R1 was associated with the presence of carotid atherosclerotic plaque, and this could partially explain the elevated cardiovascular risk associated with this phenotype. Graphical abstract: Supplementary Information: The online version contains supplementary material available at 10.1186/s12933-026-03157-5.