Hypothyroidism Significantly Linked to Nephrotic Syndrome

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Thyroid dysfunction was greater among patients with more severe CKD coupled with a high urine protein level.

Regardless of antibodies and sex, a significant association between hypothyroidism and nephrotic syndrome (NS) was observed among patients with chronic kidney disease (CKD) with proteinuria, leading investigators to believe urinary loss of thyroid hormones is an influencing factor of hypothyroidism independent of autoimmunity. Results are according to a study published in Renal Failure.1

Previous research has evaluated the link between CKD and hyperthyroidism, although no definitive consensus has been drawn.2

“On the basis of our clinical experience, we concluded that many clinical manifestations of CKD are similar to those of hypothyroidism,” wrote Rena Yuasa, MD, PhD, professor, faculty of nursing, Toho University, Japan, and colleagues. “We often encounter symptoms such as general fatigue, edema, and shortness of breath, which are typical of both conditions. Thus, hypothyroidism may be masked in patients with CKD. We believe this to be one of the reasons why hypothyroidism in patients with CKD might go unnoticed, although it may require suitable treatment.”

In the cross-sectional study, investigators collected clinical data from 99 Japanese patients with CKD with proteinuria between November 2016 and August 2018 to evaluate the urine protein-associated underlying mechanisms of hypothyroidism. Previous data have demonstrated patients with CKD and hypothyroidism have a higher prevalence of urine protein compared with healthy individuals.

Thyroid function was measured using the thyroid-stimulating hormone (sTSH), serum free T3 (sFT3), and free T4 (sFT4), and kidney function was determined through the estimated glomerular filtration rate (eGFR). Participants were also tested for thyroid antibodies and albumin (Alb). A urine examination was conducted to assess total T3, total T4, TSH, Alb, preAlb, protein, and thyroid-binding globulin (TBG). NS was diagnosed using the Evidence-based Clinical Practice Guidelines for Nephrotic Syndrome 2020.

Among patients, the median age at enrollment was 60 years and 50.5% were male. The median sFT3, sFT4, and sTSH levels were within normal limits; however, approximately 70% of patients had thyroid dysfunction, including 41.6% with hypothyroidism categorized as either overt hypothyroidism (OH) or subclinical hypothyroidism (SH). Investigators mentioned there were fewer patients with a non-thyroidal illness than had be expected among this patient population.

Patients were categorized according to their CKD stages (1 – 5) as well as their thyroid function: normal (31.7%), OH (19.8%), SH (21.8%), low T3 syndrome (LT3S; 16.8%), and low T4 syndrome (LT4S; 9,9%).

The median eGFR was 20.3 ml/min/1.73 m2 and the Alb level was 3.8 g/dL.

Twenty-one patients (21.2%) had a diagnosis of NS. There were significant differences between age and Alb in patients with NS and those without, although sex and eGFR were not significant. However, the urinary T4 and TSH levels were higher in the NS cohort, indicating more severe hypothyroid. Although the OH and SH prevalence was higher in patients with NS, the condition was not as common in patients with LT3S or LT4S. Thyroid dysfunction was greater among patients with more severe CKD coupled with a high urine protein level.

Investigators noted they did not measure the concentration of serum TBG during the study period and could only determine UTBG levels were similar between the NS and non-NS cohorts. Thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies were only collected in 56 and 55 patients, respectively. Lastly, the study lacked a multivariate analysis.

“These results led us to confirm a proof-of-concept of nephrogenic hypothyroidism,” investigators concluded.


  1. Yuasa R, Muramatsu M, Saito A, et al. 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
  2. Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol. 2009;160(4):503–515. doi: 10.1530/EJE-08-0837.