Levothyroxine Provides Clinical and Economic Benefits Despite Limited Change in eGFR

Female kidney failure, computer artwork.
Currently, consensus is lacking on the benefits of thyroid replacement therapy on renal function in patients with CKD and subclinical hypothyroidism.

Levothyroxine treatment is associated with both economic and clinical benefits in patients with chronic kidney disease (CKD) and subclinical hypothyroidism, despite limited changes in estimated glomerular filtration rates (eGFR) in this patient population. This is according to research published in Advances in Therapy.

Researchers conducted a retrospective, observational cohort study using data from the US Veterans Health Administration in order to evaluate levothyroxine treatment outcomes in people with CKD and subclinical hypothyroidism. Currently, consensus is lacking on the benefits of thyroid replacement therapy on renal function in this patient population.

The primary study outcome was change in eGFR over time in treated vs nontreated patients over a 24-month follow-up period. Secondary outcomes included a comparison of treated vs nontreated participants in terms of CKD progression and healthcare resource utilization, all within a 24-month period.

After application of selection criteria and propensity score matching, 157 patients, mostly men, remained in each cohort (96.8% vs 95.5% in treatment vs nontreatment cohorts, respectively; mean age, 74.1 vs 75.2 years). The most common baseline comorbidities included hypertension, diabetes, and diabetic neuropathy.

Between-cohort comparisons did not identify any significant differences in mean eGFR values at 6, 12, 18, and 24 months; however, the treatment cohort had a numerically higher mean eGFR at 1 year that diminished during the second year of follow-up.

Findings from a mixed model with repeated measures (MMRM) analysis showed that eGFR change over time was not significant (coefficient of time, -0.01; P =.8851) and no significant difference in eGFR between the treatment and nontreatment cohorts (coefficient of treatment x time, -0.15; P =.1025).

In terms of secondary outcomes, no significant differences were observed between the cohorts in either propensity score match-adjusted analyses or MMRM model comparisons. In a generalized linear mixed model (GLMM) for pairwise comparisons, patients in the treatment cohort did have numerically lower odds of progression to a higher stage of chronic kidney disease at 12, 18, and 24 months, but this result was nonsignificant.

At 24 months, healthcare resource utilization measured by all-cause inpatient length of hospital stay was also nonsignificant, although GLMM results indicated that patients in the treatment cohort had shorter mean all-cause impatient length of stay compared with the nontreatment cohort (mean, 1.92 vs 3.30 days; P =.3483).

A significantly higher proportion of patients in the treatment group achieved thyroid stimulating hormone (TSH) levels within the target range at 6, 18, and 24 months. Of those patients, 85.4% achieved target TSH by month 24. These patients had favorable outcomes compared with those who did not achieve the TSH targets, including significant differences in mean eGFR at 6, 12, and 24 months.

No significant differences in chronic kidney disease progression were observed. Significantly shorter mean chronic kidney disease-related length of stay was noted within the treatment cohort (0.11 vs 1.38 days; P <.0001).

Study limitations include those inherent to claims analysis research; the use of ICD-9-CM codes for diagnosis, which are subject to potential miscoding; and a lack of uniformly available eGFR data at the prescribed intervals specific to the use of the Veterans Health Administration database. Results may not be generalizable to a wider population.

“We believe these results provide valuable insights into real-world clinical and economic outcomes of CKD patients with [subclinical hypothyroidism] treated with levothyroxine,” the researchers concluded. “Future research with larger patient sample sizes is needed to continue to build on the understanding of the clinical and economic impact [of treatment].”

Disclosure: This clinical trial was supported by AbbVie, and several authors also have financial relationships with AbbVie. Please see the original reference for a full list of authors’ disclosures.


Hennessey JV, Weir MR, Soni-Brahmbhatt S, Duan Y, Gossain VV. Effect of levothyroxine on kidney function in chronic kidney disease with subclinical hypothyroidism in US veterans: a retrospective observational cohort study. Published online December 23, 2020. Adv Ther. doi:10.1007/s12325-020-01589