Dynamic patterns of thyroid hormones and incident chronic kidney disease: evidence from 18 years of follow-up in the Tehran Thyroid Study.

BACKGROUND: This population-based cohort study aimed to determine if longitudinal patterns of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are associated with the risk of developing chronic kidney disease (CKD) over 18 years. METHODS: In this prospective cohort study, 3,851 adults aged ≥ 20 years from the Tehran Thyroid Study (TTS) who remained free of CKD during the thyroid trajectory assessment period (visits 1-3, approximately 9 years) were included. Serum TSH and FT4 were measured at three visits, and latent growth mixture modeling (LGMM) was used to identify distinct hormone trajectories. Incident CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², was prospectively ascertained during a subsequent outcome assessment period spanning visits 4-6 (approximately 9 years). Cox proportional hazards models were used to evaluate the association between thyroid hormone trajectories and CKD risk after adjustment for potential confounders. RESULTS: TSH trajectory patterns were characterized as high-increasing, mild-increasing, mild-decreasing, and moderate-decreasing, with 39% of participants experiencing a rising trend in TSH levels over time. Adults displaying a high-increasing TSH trajectory faced a significantly elevated risk of CKD (HR: 1.34; 95% CI: 1.06-1.70) compared to those with a mild-decreasing TSH trajectory, independent of baseline kidney function and other confounders. While a mild-increasing TSH trajectory was initially associated with a higher risk of CKD, the association did not persist after adjustment for initial eGFR. FT4 trajectories predominantly exhibited a decreasing trend, with four identified patterns ranging from stable to high decreasing levels, and showed no significant or consistent relationship with CKD incidence after full adjustment. CONCLUSION: A high-increasing TSH trajectory was associated with a higher subsequent hazard of incident CKD, whereas FT4 trajectories showed no consistent independent association. These findings should be interpreted cautiously and may reflect broader physiological dysregulation rather than a direct thyroid hormone-mediated renal mechanism.