Sex-Specific Associations Between Changes in Triglyceride-Glucose (TyG) Index and Risk of Chronic Kidney Disease: A Cohort Study of Young and Middle-Aged Adults.

Background/Objectives: The triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance associated with chronic kidney disease (CKD). The effect of TyG index changes on the development of CKD in young adults remains unclear. Methods: We studied 353,140 Korean adults aged 18-49 years who underwent at least two health screenings. The TyG index changes between visits were categorized into quintiles. Incident CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or proteinuria. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for CKD risk. Results: Over 2.74 million person-years, 18,857 men and 13,394 women developed CKD. In the fully adjusted models, men in the highest quintile of TyG index increase had a higher CKD risk (HR 1.22, 95% CI 1.16-1.28), while those in the lowest quintile had a lower risk (HR 0.88, 95% CI 0.84-0.92). In women, the associations were in the same direction, but neither the highest (HR 1.01, 95% CI 0.95-1.07) nor the lowest quintile (HR 0.95, 95% CI 0.90-1.00) reached statistical significance. Risk gradients were stronger in those aged 40-49 years, with a baseline eGFR < 90 mL/min/1.73 m2, higher alcohol intake, or insulin resistance. Conclusions: Among relatively young adults, greater increases in the TyG index were associated with a higher CKD risk in men, whereas decreases were protective. In contrast, no significant associations were observed in women. Monitoring TyG index trajectories may help identify high-risk individuals for early intervention.