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Serum Lithium Concentration and the Risk of Chronic Kidney Disease

Published online by Cambridge University Press:  27 August 2024

G. Gislason*
Affiliation:
1Faculty of Medicine, University of Iceland
Ó. S. Indriðason
Affiliation:
2Division of Nephrology
R. Pálsson
Affiliation:
1Faculty of Medicine, University of Iceland 2Division of Nephrology
E. Sigurðsson
Affiliation:
1Faculty of Medicine, University of Iceland 3Mental Health Services, Landspitali–The National University Hospital of Iceland, Reykjavík, Iceland
*
*Corresponding author.

Abstract

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Introduction

Lithium is an important treatment option for individuals with mood disorders, but its use has been linked to the development of chronic kidney disease (CKD). Existing studies on this association have reported conflicting results.

Objectives

The aim of this study was to examine the risk of developing CKD with lithium use adjusting for common comorbidities.

Methods

This was a retrospective cohort study that included all individuals in Iceland receiving lithium therapy between 2008 and 2018. Lithium use was defined as at least one dispensed prescription for Lithium or at least one serum lithium concentration above the detection limit. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. CKD stages 3-5 were defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the serum creatinine (SCr) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid diseases were defined based on ICD-9 and ICD-10 codes. Individuals with fewer than 2 SCr measurements during the study period and those with CKD stages 3-5 prior to 2008 were excluded. Cox regression analysis with time dependent variables was performed to assess the risk of CKD.

Results

The study included 2046 individuals exposed to lithium, of whom 221 (10.9%) developed CKD in the study period. Among the 1220 control subjects, 39 (3.2%) developed CKD. Lithium use was associated with CKD (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.37–2.74) after adjusting for sex, age, and comorbid diseases. Other significant risk factors were age (per year, HR 1.03, 95% CI 1.02–1.04), initial eGFR (per mL/min/1.73 m2, HR 0.92-0.96, 95% CI 0.90–0.99), presence of diabetes (HR 1.73, 95% CI 1.15–2.48) and history of AKI (HR 1.89, 95% CI 1.32–2.70). When compared to the control group not exposed to lithium, the risk (HR) of CKD was 1.24 (95% CI 0.81–1.89), 2.88 (95% CI 1.97–4.20) and 5.23 (95% CI 3.31-8.26) for groups with a mean lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L, respectively.

Conclusions

Long-term lithium therapy seems to increase the risk of CKD in a concentration-dependent manner in individuals with bipolar and unipolar mood disorders. To mitigate this risk, it is essential to monitor blood levels carefully and use doses of lithium as low as possible for adequate mood stabilization and treatment.

Disclosure of Interest

None Declared

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of European Psychiatric Association
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