Mediating role of inflammatory markers in the association between dietary isorhamnetin consumption and CKD risk.

The association between dietary isorhamnetin (ISO) intake and chronic kidney disease (CKD) risk remains unclear. Additionally, the role of inflammation as a potential mediator in this association warrants further investigation. This study aimed to explore the mediating role of inflammatory markers in the association between dietary ISO intake and CKD risk. This cross-sectional study used the data from the National Health and Nutrition Examination Survey 2007 to 2010 and 2017 to 2018 cycles. Dietary ISO intake was assessed through 24-hour dietary recalls. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio ≥30 mg/g. Weighted multivariable logistic regression models and restricted cubic splines were employed to assess the association between ISO intake and CKD risk. Mediation analysis was performed to examine the potential role of inflammatory markers, including white blood cell count, neutrophil count (NEUT), red cell distribution width, systemic immune-inflammation index, and neutrophil-to-lymphocyte ratio. Higher dietary ISO (ln-transformed) intake was significantly associated with a lower risk of albuminuria (Q4 vs Q1: odds ratio = 0.669, 95% confidence interval: 0.515-0.870, P for trend = .021) but not with CKD risk or estimated glomerular filtration rate decline. Restricted cubic splines analysis revealed a significant negative linear correlation between ISO (ln-transformed) intake and albuminuria (P = .037). The mediation analysis indicated that the protective effect of ISO on albuminuria was partially explained by the reductions in NEUT (8.9%), red cell distribution width (6.6%), systemic immune-inflammation index (6.7%), neutrophil-to-lymphocyte ratio (6.7%), and white blood cell count (4.3%), with NEUT exhibiting the strongest indirect effect. While our findings provide epidemiological evidence that higher dietary ISO intake is associated with reduced albuminuria risk, with inflammatory markers mediating a modest proportion of this association, the limited effect sizes warrant cautious interpretation regarding potential anti-inflammatory mechanisms. Further longitudinal and interventional studies are warranted to confirm these findings and explore the therapeutic potential of ISO in preventing CKD.