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Does Gender Influence Lithium-Induced Nephrotoxicity?

Published online by Cambridge University Press:  31 July 2026

A. Yildiz and
E. Sevim
A. Yildiz
Affiliation:
Department of Biochemistry, Başakşehir Çam & Sakura City Hospital, İstanbul, Türkiye
E. Sevim*
Affiliation:
Department of Biochemistry, Başakşehir Çam & Sakura City Hospital, İstanbul, Türkiye
*
*Corresponding author.

Abstract

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Introduction

Lithium remains the gold standard for bipolar disorder maintenance therapy, but its narrow therapeutic index and potential nephrotoxicity require close monitoring. Lithium-induced Chronic Kidney Disease (CKD) results from tubular and interstitial toxicity, leading to decreased estimated Glomerular Filtration Rate (eGFR) and elevated serum creatinine. Given lithium’s similarity to sodium and its renal tubular interactions, monitoring eGFR, creatinine, and sodium alongside serum lithium levels allows earlier detection of renal effects and better assessment of pharmacokinetic changes.

Objectives

To evaluate the potential nephrotoxic effects of lithium by comparing renal biochemical parameters (sodium, creatinine, and eGFR) between lithium-treated patients and healthy controls in a one-year retrospective study.

Methods

Lithium-treated patients and age- and sex-matched healthy controls were included. Sodium and creatinine were measured with the Roche Cobas 8000 analyzer, and eGFR was calculated using the CKD-EPI formula. Non-parametric data (p<0.05) were analyzed using the Mann–Whitney U test.

Results

In females receiving lithium therapy, serum creatinine levels were significantly higher (p<0.05) and eGFR values were significantly lower (p<0.05) compared to the control group, while no significant difference was observed in sodium levels (p=0.34). In males, eGFR was significantly lower in the lithium-treated group (p<0.05), whereas creatinine and sodium levels showed no significant differences between the groups (p>0.05)Table 1.

Renal Parameters in Lithium-Treated vs. Control Groups

Lithium-treated male patients n = 186Healthy male controls n = 149
Mean± SDMedianMean± SDMedianP value
Sodium (mEq/L)139.80 ± 2.67140140.34 ± 2.041400.63
Creatinine (mg/dL)0.83 ± 0.190.810.82 ± 0.060.830.64
eGFR (mL/min/1.73 m2)104.23 ± 17.50106117.64 ± 6.55119P<0.05
Lithium-treated female patients n = 139Healthy female controls n=183
Mean± SDMedianMean± SDMedianP value
Sodium(mEq/L)139.68± 2.81140139.51± 2.361390.34
Creatinine(mg/dL)0.84± 0.140.800.66± 0.080.65P<0.05
eGFR(mL/min/1.73 m2)100.94± 15.56102113.68± 9.67116P<0.05
Two tables comparing renal parameters in lithium-treated patients versus healthy controls, separated by sex. Significant differences are noted in e G F R for both sexes and creatinine for females. See long description.

* p<0.05: statistically significant, SD: Standard Deviation, eGFR: estimated Glomerular Filtration Rate

Conclusions

Lithium therapy reduces eGFR in both sexes, increasing the risk of renal dysfunction. The more pronounced increase in creatinine and decrease in eGFR observed in females suggest that the nephrotoxic effects of lithium may vary by sex. Therefore, in patients receiving lithium treatment, regular monitoring of renal parameters such as eGFR and creatinine, in addition to serum lithium levels, is clinically important to ensure patient safety and optimal therapeutic outcomes.

Disclosure of Interest

None Declared

Information

Type
Abstract
Information
European Psychiatry , Volume 69 , Special Issue S1: Abstracts of the 34th European Congress of Psychiatry , June 2026, pp. S501 - S502
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), 2026. Published by Cambridge University Press on behalf of European Psychiatric Association
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