Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals

Abstract

Background: Previous studies have reported a negative relationship between thyroid-stimulating hormone (TSH) and renal function in euthyroid individuals, but others have found that higher free thyroxine (FT₄) was associated with an increased risk of chronic kidney disease. This study was designed to analyze the relationship between thyroid and renal function from a new perspective of sensitivity to thyroid hormone.

Methods: This retrospective study included 2831 euthyroid individuals who underwent a health examination at the First Hospital of China Medical University between January 2017 and December 2018. Parametric Thyroid Feedback Quantile-based Index (PTFQI_FT4), TSH index (TSHI), thyrotroph T₄ resistance index (TT₄RI), free triiodothyronine to FT₄ ratio (FT₃/FT₄), the secretory capacity of the thyroid gland (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD) were calculated. We also innovated the TT₃RI and PTFQI_FT3 indices based on FT₃ and TSH. Renal function was assessed by estimated glomerular filtration rate (eGFR) CKD-EPI and creatinine-cystatin C-KDIGO equations.

Results: After adjustment of basic characteristics and comorbidities, linear regression showed that eGFR _CKD-EPI was positively associated with FT₃/FT₄ (β = 23.31), and inversely correlated to PTFQI _FT4 (β= -2.69) (both p < .001). When comparing the fourth versus the first quartile of PTFQI _FT4, the odds ratio (OR) for a reduced renal function was 1.89 (95% CI 1.28-2.80), and the OR was 0.64 (95% CI 0.43-0.95) when comparing quartiles of FT₃/FT₄ (both p_{for trend}< .05). In addition, for every 1SD increase in PTFQI _FT4, the OR for a reduced renal function was 1.27 (95%CI 1.10-1.47). TSHI, TT₄RI and TT₃RI also showed a negative correlation to renal function. Similar results were obtained in SPINA-GD as in FT₃/FT₄.

Conclusions: In euthyroid individuals, decreased sensitivity to thyroid hormone is associated with reduced renal function. The composite PTFQI_FT4 index correlates more strongly to renal function than TSH or T₄ alone.KEY MESSAGESDecreased sensitivity to thyroid hormone is associated with reduced renal function in the euthyroid population.The recently developed composite index PTFQI_FT4 seems to correlate more strongly to renal function than individual TSH or FT₄ parameters.Innovative indices TT₃RI and PTFQI_FT3 based on the interaction between T₃ and TSH may also reflect sensitivity to thyroid hormone.

Keywords: Euthyroid individuals; renal function; sensitivity to thyroid hormone; thyroid feedback quantile-based index.