The mediating role of systolic blood pressure in the association between estimated glucose disposal rate and renal prognosis: a nationwide prospective cohort study

Aim: Despite the well-documented pathogenic role of insulin resistance (IR) and hypertension in nephropathy progression, the prognostic value of the estimated glucose disposal rate (eGDR) for incident renal dysfunction remains unclear. This population-based longitudinal analysis specifically examined the eGDR-renal dysfunction relationship in middle-aged and elderly populations, with a particular focus on the potential mediating role of systolic blood pressure (SBP) based on a nationwide longitudinal study. Methods: Utilizing data from 8,136 participants in the China Health and Retirement Longitudinal Study (CHARLS, 2011- 2015), we conducted multivariable-adjusted logistic regression analyses combined with a restricted cubic spline model to assess the association between eGDR and incident renal dysfunction. Mediation analysis was employed to assess the proportion of the association mediated by SBP in this relationship. Results: Over a median follow-up period of 4 years, 2,223 participants developed renal dysfunction. Both eGDR and SBP were significantly and independently associated with incident renal dysfunction. The odds ratio (OR) for eGDR was 0.73 (95%CI: 0.58- 0.92), while the OR for SBP was 1.20 (95%CI: 1.05- 1.38). Restricted cubic spline analysis identified critical thresholds, with eGDR levels below 11.6 mg/kg/min and SBP levels above 125 mmHg being associated with a higher risk of renal dysfunction. Mediation analysis further demonstrated that SBP acted as a significant mediator in the relationship between eGDR and renal dysfunction, accounting for 42.6% of the total effect (95%CI: 19.9%- 86.7%). Conclusion: This prospective cohort study identifies eGDR as an independent predictor of renal dysfunction, with nearly half of its effect mediated by SBP. These findings highlight the potential benefit of integrated management strategies targeting both insulin sensitivity and blood pressure control to reduce the risk of renal dysfunction in aging populations.