Levothyroxine treatment for subclinical hypothyroidism and risk of adverse renal outcomes: a population-based cohort study.

Abstract

Subclinical hypothyroidism has been linked to adverse renal outcomes, but it is unknown whether treatment of subclinical hypothyroidism reduces the risk of these adverse outcomes. We sought to assess whether treatment of subclinical hypothyroidism with levothyroxine is associated with a decreased risk of developing adverse renal outcomes. We conducted a population-based cohort study using a prevalent new-user design. Using the Clinical Practice Research Datalink in the United Kingdom, we assembled a study cohort of individuals aged 18 years and older with newly diagnosed subclinical hypothyroidism between 1998 and 2018. We matched individuals with subclinical hypothyroidism treated with levothyroxine to nontreated individuals with subclinical hypothyroidism based on age, sex, calendar time, duration of subclinical hypothyroidism, and time-conditional propensity score. We included several confounders, including data on demographics, clinical diagnoses, biochemical measures, lifestyle, and prescriptions, in the time-conditional propensity score estimate. The primary outcome was a composite end point of end-stage renal disease (requiring dialysis) and lowering of the estimated glomerular filtration rate of 50% or greater. We matched 76 697 individuals with subclinical hypothyroidism treated with levothyroxine to 76 697 nontreated individuals. The mean age of the study cohort was 63 years, and 77% of patients were female. During a median follow-up time of 1.6 years (levothyroxine treated: 1.0, interquartile range [IQR] 0.4-2.7, yr; nontreated: 2.5, IQR 0.9-5.7, yr), 2426 adverse renal events occurred among nontreated individuals (incidence rate 8.35, 95% confidence interval [CI] 8.02-8.69, per 1000 person-years), and 1255 adverse renal events occurred among levothyroxine-treated individuals (incidence rate 7.93, 95% CI 7.50-8.39, per 1000 person-years). Treatment with levothyroxine was not associated with the risk of adverse renal outcomes among people with subclinical hypothyroidism (adjusted hazard ratio 0.97, 95% CI 0.90-1.04). In this population-based cohort study, there was no evidence that levothyroxine treatment of subclinical hypothyroidism reduced the risk of adverse renal outcomes. Future studies in different populations and with longer duration of follow-up are needed to confirm these findings.