Effect of Levothyroxine on Kidney Function in Chronic Kidney Disease with Subclinical Hypothyroidism in US Veterans: A Retrospective Observational Cohort Study

Abstract

Introduction Chronic kidney disease (CKD) may be associated with overt or subclinical hypothyroidism [SCH; defined as elevated serum thyroid-stimulating hormone (TSH) despite normal free thyroxine levels). Although some studies have demonstrated that thyroid replacement therapy may improve renal function in overt hypothyroidism, there is no consensus on its benefits in SCH. Clinical and limited economic outcomes were evaluated in levothyroxine-treated US veterans with CKD + SCH. Methods Veterans Health Administration claims data from April 2013 to March 2018 for levothyroxine-treated versus nontreated CKD + SCH patients were compared. Eligible patients with CKD + SCH (≥ 2 elevated TSH values recorded; ≥ 2 normal thyroxine values recorded) had ≥ 1 TSH values recorded during 24-month follow-up, and ≥ 1 estimated glomerular filtration rate (eGFR) measurement during baseline and follow-up. Continuous levothyroxine use (treatment cohort) was required during follow-up. The primary endpoint was eGFR at 6, 12, 18, and 24 months; secondary endpoints included eGFR change from baseline, CKD progression, and length of hospital stay (LOS). Propensity score matching (PSM) was performed. Results Of 453 eligible patients, 157 remained in each cohort after PSM. Most were male (96%) and white (88%); mean age was 75 years. No significant differences were observed between cohorts at any time point for eGFR, eGFR change from baseline, or CKD progression. Treated patients had numerically higher mean eGFR at 6 and 12 months, lower proportions of progression to higher CKD stages at 12, 18, and 24 months, and shorter mean all-cause LOS versus nontreated patients (1.92 vs. 3.30 days; P = 0.3483) within the 24-month follow-up period. A significantly shorter mean CKD-related LOS was observed versus nontreated patients (0.11 vs. 1.38 days; P < 0.0001) during the 24-month follow-up. Conclusion Levothyroxine use was associated with economic and clinical benefit in some patients with CKD + SCH, despite an absence of overall benefit on eGFR; confirmatory research is needed.

Protocol and methods: Role of levothyroxine on the progression of chronic kidney disease in subclinical hypothyroid populations (LP-CKD) – A multicenter randomized controlled trial

“…Recently, a retrospective database analysis on LVT treatment in CKD and SCH patients showed an absence of the overall benefit in eGFR; however, LVT use shortens the length of hospital stay. [ 42 ] There is possibly no association between low free thyroxine levels and CKD progression. [ 43 ] The progression of CKD was higher in the presence of proteinuria, with no effect on thyroxine levels.…”

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk

“…Some of the available data have been obtained in a retrospective observational cohort study of US Veterans, where levothyroxinetreated (n: 157) and nontreated CKD (n:157) + ScH patients followed for 24 months were analyzed for clinical outcomes. Despite an absence of overall benefit on eGFR or CKD progression, it was revealed that levothyroxine use was associated with a lower length of hospital stay for reasons related to CKD, which may translate into a possible economic benefit (33). Furthermore, in a previous retrospective Korean study, the decrease in renal function in 113 CKD patients with ScH was attenuated with levothyroxine after two years (34).…”