The Partial Mediating Role of Arterial Stiffness in the Association Between Systemic Inflammation and Declining Renal...

Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation and increased arterial stiffness, both of which have been independently linked to declining renal function in diabetic nephropathy. This study aims to investigate whether arterial stiffness mediates the relationship between systemic inflammation and renal function in patients with T2DM, potentially revealing a novel pathophysiological pathway.

In this cross-sectional study of 307 T2DM patients, neutrophil-to-lymphocyte ratio (NLR) was calculated as an inflammatory marker, ambulatory arterial stiffness index (AASI) was derived from 24-hour ambulatory blood pressure monitoring, and estimated glomerular filtration rate (eGFR) was determined. Multiple linear regression models were used to examine the relationships between NLR, AASI, and eGFR. Mediation analysis with bootstrap resampling (5000 replications) was performed to assess whether AASI mediated the association between NLR and eGFR.

Patients with lower eGFR had significantly higher NLR and AASI than those with higher eGFR. After adjusting for confounders, both NLR (β = -8.27, 95% CI: -12.32 to -4.22, P < 0.001) and AASI (β = -22.55, 95% CI: -43.67 to -1.43, P = 0.037) were independently associated with reduced eGFR. Mediation analysis revealed that AASI accounted for 8.17% of the total effect in the fully adjusted model (mediation effect: -0.717, 95% CI: -1.570 to -0.067, P = 0.024), demonstrating a partial mediation of the relationship between NLR and eGFR.

AASI partially mediates the association between NLR and eGFR in T2DM patients, providing new insights into the pathophysiological links between inflammation, vascular dysfunction, and kidney damage. Therapeutic strategies targeting inflammation and arterial stiffness might offer synergistic benefits for preserving renal function.