DOI: 10.1192/j.eurpsy.2026.11192 ISSN: 0924-9338

Does Gender Influence Lithium-Induced Nephrotoxicity?

A. Yildiz, E. Sevim
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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

Table 1. Long description.

Lithium-treated male patients n = 186
Healthy male controls n = 149
Mean± SD Median Mean± SD Median P value
Sodium (mEq/L)
139.80 ± 2.67
140 140.34 ± 2.04 140 0.63
Creatinine (mg/dL)
0.83 ± 0.19 0.81 0.82 ± 0.06 0.83 0.64
eGFR (mL/min/1.73 m 2 )
104.23 ± 17.50 106 117.64 ± 6.55 119 P<0.05
Lithium-treated female patients n = 139
Healthy female controls n=183
Mean± SD Median Mean± SD Median P value
Sodium(mEq/L)
139.68± 2.81
140 139.51± 2.36 139 0.34
Creatinine(mg/dL)
0.84± 0.14 0.80 0.66± 0.08 0.65 P<0.05
eGFR(mL/min/1.73 m 2 )
100.94± 15.56 102 113.68± 9.67 116 P<0.05

* 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

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