As kidney function decreases in patients with moderate-to-severe chronic kidney disease (CKD), the risk of hypothyroidism increases, according to a new study.

In a study looking at a nationally representative cohort of 461,607 veterans with Stage 3–5 CKD, researchers found that each 10 mL/min/1.73 m2 lower estimated glomerular filtration rate (eGFR) was associated with an 18% increased risk of hypothyroidism in adjusted analyses.

Hypothyroidism was determined by laboratory tests or receipt of thyroid hormone supplementation.

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The study, published in Nephrology Dialysis Transplantation (2015;30:282-287), also found that a 10 mL/min/1.73 m2 lower eGFR was associated with a 0.11 mIU/L higher serum level of thyrotropin (TSH).

“To our knowledge, this is the largest examination of the relationship between eGFR and thyroid functional status conducted to date,” wrote senior author Csaba P. Kovesdy, MD, of the University of Tennessee Health Science Center in Memphis and the Memphis Veterans Affairs Medical Center, and first author Connie M. Rhee, MD, MSc, of the University of California Irvine School of Medicine.

Study subjects underwent repeated measurements of serum creatinine and TSH at identical time points from October 2004 to September 2006. The investigators estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration formula.

Dr. Kovesdy and his collaborators cited case series showing that hypothyroid patients have decreased renal plasma flow and GFR measured by creatinine-based estimated equations and isotopic scans, which were reversed with thyroid hormone supplementation.

“Our findings add to a growing body of literature demonstrating a relationship between impaired kidney function and hypothyroidism,” the authors wrote.

Dr. Kovesdy’s group pointed out that the observational design of their study cannot establish a causal relationship between decreased eGFR and hypothyroidism. They noted that it has been hypothesized that hypothyroidism may directly worsen kidney function via decreases in cardiac output, increases in peripheral vascular resistance, intra-renal vasoconstriction, and alterations in glomerular structure.

One of the study’s strengths was its examination of a large sample size of nationally representative CKD patients, with comprehensive capture of sociodemographics, serum TSH, and creatinine and prescription data. Another strength was comprehensive adjustment for comorbidity factors as potential confounders of the kidney-thyroid function association.

The study also had some limitations. For example, the indications for which TSH were measured were unknown, “and it is possible that the requirement for TSH measurement may have resulted in a cohort with a higher-than-average perceived risk of thyroid functional disease.” Additionally, hypothyroidism may influence serum creatinine levels due to changes in muscle metabolism and volume status independent of its effects on GFR, “and we cannot exclude the possibility of residual confounding by these factors and other unmeasured covariates.”