The Role of Thyroid in Renovascular Function: Independent Association of Serum TSH With Renal Plasma Flow

Abstract

Abstract Context There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state. Objective This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals. Methods This cross-sectional, multicenter study of the HyperPATH Consortium took place in 5 US and European academic institutions. A total of 789 individuals, aged 18 to 65 years, with serum thyrotropin (TSH) 0.4 to 5.5 mIU/L, participated; individuals with uncontrolled or secondary hypertension or on medication affecting the hypothalamus-pituitary-thyroid axis were excluded. Hemodynamic parameters including RPF, thyroid function testing, and the Thr92Ala deiodinase 2 (D2) polymorphism were assessed in the setting of a liberal and restricted salt diet. We searched for associations between thyroid function and renovascular parameters and accounted for confounding factors, such as older age, hypertension, and diabetes. Results Serum TSH was inversely associated with RPF assessed in the setting both of liberal and restricted salt diets. This association remained significant and independent when accounting for confounding factors, whereas free thyroxine index (fTI) and the Thr92Ala polymorphism, associated with lower D2 catalytic activity and disrupted thyroid hormone tissue availability, were not independently associated with RPF. Serum TSH remained an independent predictor of RPF on a liberal salt diet when the analysis was restricted to healthy young individuals. Conclusion Serum TSH levels, but not fTI nor the Thr92Ala D2 polymorphism, were independently inversely associated with RPF in individuals of the HyperPATH Consortium. These findings suggest a direct interconnection between TSH and renovascular dynamics even with TSH within reference range, warranting further investigation.