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Review
. 2021 Mar;41(2):133-143.
doi: 10.1016/j.semnephrol.2021.03.008.

The Interplay Between Thyroid Dysfunction and Kidney Disease

Yoko Narasaki  1 , Peter Sohn  1 , Connie M Rhee  2
Affiliations
Review

The Interplay Between Thyroid Dysfunction and Kidney Disease

Yoko Narasaki et al. Semin Nephrol. 2021 Mar.

Abstract

Hypothyroidism is a highly prevalent endocrine complication in chronic kidney disease (CKD) patients. A large body of evidence has shown that there is a bidirectional relationship between thyroid dysfunction and kidney disease, yet there are many remaining gaps in knowledge in regards to the clinical management of CKD patients with hypothyroidism, including those receiving hemodialysis and peritoneal dialysis. Given that hypothyroidism has been associated with many deleterious outcomes including a higher risk of (1) mortality, (2) cardiovascular disease, (3) impaired health-related quality of life, and (4) altered body composition in both non-CKD and CKD patients, future research is needed to establish the appropriate screening, diagnosis, and treatment approaches in these populations.

Keywords: Thyroid function; chronic kidney disease; dialysis; hyperthyroidism; hypothyroidism; thyrotropin.

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Conflict of interest statement

Conflict of Interest:

None of the authors have relevant disclosures to report.

Figures

Figure 1.
Figure 1.. Regulation of thyroid hormone synthesis by the hypothalamus-pituitary-thyroid axis.
Thyroid hormone synthesis is tightly regulated by the hypothalamus-pituitary-thyroid axis. Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the secretion of thyroid stimulating hormone (TSH) from the anterior pituitary gland. TSH in turn stimulates the production of thyroxine (T4) and triiodothyronine (T3). In peripheral organs including kidney, a large proportion T3 is produced through T4-to-T3 conversion by type 1 5’-deiodinase (D1) and type 2 5’-deiodinase (D2) as a metabolically inactive form of thyroid hormone; some parts of T4 are converted to reverse T3 (rT3) by the type 3 5’-deiodinase enzyme (D3) as a metabolically inactive form of thyroid hormone. More than 99% of T4 and T3 molecules are tightly bound to the carrier proteins (e.g., thyroid binding globulin [TBG], transthyretin, albumin) and only a very small percentage circulates as free hormone. These free hormones act on target tissues by binding onto thyroid receptors in the nuclei of target cells. In addition, they provide negative feedback to both the hypothalamus and the pituitary gland, closing the tightly regulated homeostatic thyroid hormone synthesis loop. Abbrev.: TRH, thyrotropin releasing hormone; TSH, thyrotropin; T4, thyroxine; T3, triiodothyronine; FT4, free T4; FT3, free T3; rT3, reverse T3; D1, type 1 5’-deiodinase; D2, type 2 5’-deiodinase; D3, type 3 5’-deiodinase.
Figure 2.
Figure 2.. Effects of hypothyroidism on kidney structure and function.
Abbrev.: GBM, glomerular basement membrane; RAAS, renin angiotensin aldosterone system.
Figure 3.
Figure 3.. Adverse sequelae of hypothyroidism on clinical outcomes in chronic kidney disease (CKD) patients.
Abbrev.: CV, cardiovascular; HRQOL, health related quality of life;↑, increased; ↓, decreased.
See this image and copyright information in PMC

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