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.