Urinary excretion of thyroid hormone in CKD patients: a proof-of-concept of nephrogenic hypothyroidism

Abstract

Purpose Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. Methods Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. Results The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m 2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. Conclusion We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.

Interrelationship between thyroid hormones and reduced renal function, a review article

“…It has been indicated that CKD patients had higher levels of TSH, which was due to thyroid hormone loss in urine [ 30 ]. It was suggested that thyroid hormones and thyroid-binding proteins are wasted in the urine in CKD patients, leading to hypothyroidism [ 7 ].…”

“…Thyroid dysfunction in CKD patients may be due to metabolic acidosis, malnutrition, chronic inflammation, and uremic toxins [ 5 ]. Moreover, the loss of thyroid hormones and thyroid-binding proteins in the urine may cause hypothyroidism [ 7 ]. In this narrative review, we searched the literature to find the complex interplay between thyroid hormones, thyroid dysfunctions, and chronic kidney diseases.…”