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

Ren Fail. 2023;45(2):2293224. doi: 10.1080/0886022X.2023.2293224. Epub 2023 Dec 12.

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 m2 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.

Keywords: CKD; hypothyroidism; independent of autoimmunity; nephrogenic hypothyroidism; proteinuria; thyroid hormone-binding proteins; urinary excretion of thyroid hormones.

MeSH terms

  • Female
  • Humans
  • Hypothyroidism* / complications
  • Male
  • Middle Aged
  • Nephrotic Syndrome* / complications
  • Renal Insufficiency, Chronic*
  • Thyroid Hormones / metabolism
  • Thyrotropin

Substances

  • Thyroid Hormones
  • Thyrotropin