title: Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients.
abstract: Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation.
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Rhee
authors.affiliation: Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Departments of Medicine and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Brent
authors.affiliation: Division of Nephrology, Memphis Veterans Affairs Medical Center, Memphis, TN, USA Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Offie P
authors.initials: OP
authors.lastname: Soldin
authors.affiliation: Department of Medicine, University of California Irvine, Orange, CA, USA.
authors.forename: Danh
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Division of Cardiology, LA Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: Division of Nephrology, Brigham and Women's Hospital, Boston, MA, USA DaVita Clinical Research, Minneapolis, MN, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Brunelli
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA Department of Medicine, University of California Irvine, Orange, CA, USA Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications / Q000175:diagnosis*; D015897:Comorbidity; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000175:diagnosis*; D007668:Kidney / Q000503:physiopathology; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology*; D012307:Risk Factors; D013959:Thyroid Diseases / Q000150:complications / Q000175:diagnosis*; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin
keywords: cardiovascular risk; hyperthyrotropinemia; hypothyroidism; renal failure; thyroid functional disease