The interaction between thyroid and kidney disease: an overview of the evidence

Abstract

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD.

Spontaneous primary hypothyroidism in 7 adult cats

“…The pathophysiology of hypothyroid‐induced azotemia is complex but is related in large part to decreases in cardiac output, renal blood flow, and glomerular filtration rate . Unless patients have concurrent, primary kidney disease, azotemia is reversible with adequate thyroid hormone replacement treatment, leading to a consistent fall in serum creatinine concentrations . Cats in our study demonstrated similar decreases in serum creatinine concentrations after treatment, with serum creatinine normalizing (falling back into within the reference interval) in the 4 azotemic cats.…”

“…Azotemia is a well‐recognized complication of hypothyroidism in humans, developing in over half of patients in some reports . The pathophysiology of hypothyroid‐induced azotemia is complex but is related in large part to decreases in cardiac output, renal blood flow, and glomerular filtration rate . Unless patients have concurrent, primary kidney disease, azotemia is reversible with adequate thyroid hormone replacement treatment, leading to a consistent fall in serum creatinine concentrations .…”

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

“…An association between thyroid function and kidney function has been reported [6][7][8][9]. Previous cross-sectional studies showed that the prevalence of hypothyroidism DOI: 10.1159/000497326 increased with impaired kidney function [10][11][12].…”

Thyroid Status and Mortality in a Prospective Hemodialysis Cohort

“…For example, some TSH aberrations have been reported in kidney disease, such as impaired glycosylation and function, blunted response to thyrotropin-releasing hormone, altered clearance, decreased pulsatility, and increased half-life (19,35), and we cannot exclude confounding of the TSH-mortality association on this basis. TSH levels may also be altered in illness states.…”

“…Although T3 and T4 levels may be used to distinguish severity of thyroid disease (i.e., subclinical vs overt thyroid functional disease) and other etiologies of thyroid functional test abnormalities (i.e., nonthyroidal illness), in patients with end-stage renal disease (1) T3 levels may be confounded by underlying illness (i.e., the peripheral conversion of T4 to T3 is highly sensitive to mild illness, malnutrition, and inflammation) (19,34,35), and (2) routinely used free-T4 assays measuring the minute fraction of bioactive T4 (e.g., free-T4 analog assay or free-T4 index) are hormoneprotein binding dependent and may not be accurate in dialysis patients (i.e., conditions in which circulating substances such as uremic toxins impair hormone-protein binding, routinely used-free T4 assays may result in spurious levels) (19,35,36).…”