Circulating antithyroid antibodies contribute to the decrease of glomerular filtration rate in lithium-treated patients: a longitudinal study

Alberto Bocchetta,Fernanda Velluzzi,Caterina Chillotti,Andrea Loviselli,Gioia Baggiani,Claudia Pisanu,Antonello Pani,Luca Ambrosiani,Raffaella Ardau,Doloretta Piras

doi:10.1186/s40345-017-0114-4

Abstract

BackgroundConcerns about the adverse effects of long-term treatment with lithium include reduced renal function. In the present study, we examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years.MethodsWe studied 394 patients who were treated with lithium for ≥ 5 years. The potential role of comorbidities (diabetes, concurrent antihypertensive medication, treatment with l-thyroxine, and presence of antithyroid peroxidase/microsomes, anti-thyroglobulin, and/or anti-thyrotropin-receptor antibodies) was analysed. We focused on the categories of patients with an estimated glomerular filtration rate (eGFR) lower than 60 or 45 mL/min/1.73 m2 as calculated from serum creatinine according to the Modification of Diet in Renal Disease Study Group. We applied multivariate regression analysis and Cox survival analysis to study the effects exerted by sex, age, duration of lithium treatment, and comorbidities using eGFR categories as the dependent variable. Kaplan–Meier curves were generated to measure the time to decline to an eGFR lower than 45 mL/min/1.73 m2 in patients with positive or negative thyroid antibodies.ResultsAge was associated with a decline to an eGFR lower than 60 mL/min/1.73 m2 after controlling for sex, duration of lithium treatment, and comorbidities. Circulating thyroid antibodies were associated with a decline to an eGFR lower than 45 mL/min/1.73 m2.ConclusionsThe present study is the first to suggest a potential role of circulating thyroid antibodies in the severe decline of eGFR in lithium-treated patients.

Highlights

Concerns about the adverse effects of long-term treatment with lithium include reduced renal function
In an initial study of 139 patients from our lithium clinic, we found a positive correlation between the duration of lithium treatment and reduced estimated glomerular filtration rate (Bocchetta et al 2013)
It must be noted that we found only 14 cases of type-I diabetes, whereas cases of type-II diabetes were typically found in older patients and their effect was perhaps included in the age-related decline of estimated glomerular filtration rate (eGFR) that we already found in the entire cohort of patients treated with lithium (Bocchetta et al 2015)

Summary

Introduction

Concerns about the adverse effects of long-term treatment with lithium include reduced renal function. We examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years. Adverse renal effects of lithium have long been known, varying from very frequent reversible polyuria (Schou 1958) to irreversible kidney damage (Hestbech et al.1977; Aurell et al 1981). Thereafter, several studies based on various kinds of data sources have addressed the potential risk factors for chronic kidney disease (CKD) in lithium-treated patients. Principal factors under study include sex, age, duration of lithium treatment, Bocchetta et al Int J Bipolar Disord (2018) 6:3 concurrent medications, and comorbidities that are already known to predispose to CKD. We extended the study to 953 patients treated for at least one year and found that eGFR was lower in women, in older patients, and in patients with longer duration of lithium treatment (Bocchetta et al 2015)

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