Association of Thyrotropin Concentration with Chronic Kidney Disease in a Japanese General Population Cohort

Abstract

Background: Previous studies have indicated an association between hypothyroidism and kidney dysfunction; however, few studies have investigated whether thyroid dysfunction is a risk factor for chronic kidney disease (CKD) development. And their result is not consistent. Objectives: We evaluated the association of thyroid dysfunction with CKD prevalence and development by a multivariate logistic regression analysis. Method: In cross-sectional and longitudinal studies, 16,390 subjects and 7,609 subjects, respectively, who underwent annual health check-ups were analyzed. We categorized the subjects into the following 4 groups based on their serum thyrotropin (TSH) ­concentrations: below-normal (TSH < 0.54 mU/L), lower-normal ­(0.54–2.40 mU/L), higher-normal (2.41–4.26 mU/L) and above-normal (> 4.26 mU/L). Subjects with eGFR <60 mL/min/1.73 m² were determined to have CKD. Results: The cross-sectional study revealed a positive correlation between TSH concentration and CKD ­prevalence. Compared with the lower-normal TSH group, the ORs and 95% CIs of CKD prevalence were 0.61 (0.45–0.82, p = 0.001) for the below-normal group, 1.49 (1.33–1.67, p < 0.001) for the higher-normal group, and 1.90 (1.57–2.30, p < 0.001) for the above-normal group. The longitudinal study revealed that the risk of CKD development within 3 years was significantly higher in the above-normal TSH group than in the lower-normal TSH group (OR 1.58, 95% CI 1.02–2.45, p = 0.04). Conclusions: Our data indicate that higher TSH concentrations are positively correlated with CKD prevalence and that a high TSH concentration is a risk factor for CKD development.

Relationship between Thyroid and Kidney Function: Analysis from the Korea National Health and Nutrition Examination Survey Between 2013 and 2015

“…This may be because hypothyroidism is associated with increased age [41], bad habitual patterns [42,43], lipotoxicity [44], and systemic inflammation [45], which may also attenuate thyroid hormone metabolism [46]. When considered with other studies that have reported an association between renal hazard and increased TSH, within the TSH reference range [22,23,25], our study results may suggest that a lower TSH level is associated with better kidney function. Therefore, future prospective studies need to be conducted to confirm the potential renoprotective effects of earlier thyroid hormone replacement.…”

“…Chang et al [20] reported that the OR and 95% CI of SCH for CKD was 1.74 (1.18-2.56) after analyzing 74,356 subjects from Taiwan. Toda et al [23] also suggested that the ORs (95% CIs) of TSH 2.41-4.26 mIU/L and > 4.26 mIU/L for CKD were 1.49 (1.33-1.67, p < 0.001) and 1.90 (1.57-2.30, p < 0.001), respectively, in 7,609 Japanese subjects. However, no known studies have investigated the nonlinear relationship between TSH and eGFR.…”

“…eGFR, estimated glomerular filtration rate; ACME, average causal mediation effect; ADE, average direct effect; fT4, free thyroxine. not heavily considered when determining if treatment is necessary for SCH; however, numerous studies have revealed that SCH may cause a decline in kidney function [20][21][22][23][24]30]. If small changes in the thyroid hormone levels, which are within the reference range, have negative effects on the kidney health, earlier replacement of thyroid hormone may prevent the progression of CKD in SCH patients [30].…”

“…Experimental studies have suggested that a deficiency in thyroid hormones may reduce the glomerular filtration rate [18] by reducing cardiac output, renal plasma flow, and sodium resorption [19]. To date, many studies have suggested that SCH was associated with reduced kidney function [20][21][22][23][24]. Some have even reported that an elevated TSH level, but within the reference range, was associated with chronic kidney disease (CKD) [25][26][27].…”

Effect of Thyroid Hormones on Kidney Function in Patients after Kidney Transplantation

“…Large retrospective analyses have shown associations of estimated kidney function with thyroid function, including an inverse association between estimated GFR (eGFR) and prevalence of hypothyroidism 7 , as well as the risk of developing subclinical and overt hypothyroidism 8 . Conversely, hypothyroidism and subclinical hypothyroidism have been found to lead to higher prevalence of chronic kidney disease (CKD) over time 9 . Furthermore, even in the normal reference range low free triiodothyronine (FT3) and resulting high TSH values have been associated with higher risk for the development of CKD 10 .…”