Pulse pressure mediation and hypertension modulation: the impact of TyG index on renal function deterioration in CKD patients under the CKM syndrome framework

Background: Under the Cardiovascular-Kidney-Metabolic (CKM) syndrome framework, insulin resistance (IR) is the core driver of renal damage. The triglyceride-glucose (TyG) index is a validated IR surrogate, but existing evidence is mostly limited to cross-sectional data or single-source databases, failing to clarify the longitudinal progression of renal injury and underlying mechanisms. Methods: This study integrated two independent prospective cohorts: the national community-based CHARLS cohort (4,476 middle-aged and elderly participants, 2011-2015 follow-up) and a hospital-based KDIGO 2012-defined CKD cohort (396 patients, median 1,019-day follow-up). We analyzed the association of TyG index with eGFR decline (CHARLS) and ESRD (CJFH), with pulse pressure as mediator, hypertension as moderator, via regression, mediation, survival and nonlinear analyses. Results: Elevated baseline TyG index was independently associated with renal function deterioration in both cohorts. Pulse pressure played a partial mediating role in this association, while baseline hypertension significantly amplified the adverse renal effect of TyG. The overall association was dominated by a negative linear trend with no significant risk threshold. Conclusion: TyG index is an independent risk factor for renal function deterioration, with its adverse effects partially mediated by elevated pulse pressure and amplified by hypertension. This study provides epidemiological evidence for the CKM "metabolism-vascular-renal" axis, supporting TyG-based early renal risk stratification in the general population and multi-dimensional interventions for CKD patients.