# A Significant Decline of Glomerular Filtration Rate in the Majority of Long‐Term Lithium Users: Results of a Dutch Prospective 10‐Year Cohort Study

## TL;DR

Long-term lithium use is linked to significant kidney function decline, with higher doses and longer use causing faster decline.

## Contribution

This study provides evidence that most long-term lithium users experience significant eGFR decline, associated with lithium concentration and duration of use.

## Key findings

- 48% of lithium users had a yearly eGFR decline between 0.5 and 2.5 mL/min/1.73 m².
- Higher lithium serum concentration and longer duration of therapy are associated with faster eGFR decline.
- Discontinuation of lithium did not significantly alter eGFR decline in the studied cohort.

## Abstract

It remains unclear to what extent long‐term lithium use leads to significant eGFR decline. This study examines the course of eGFR in a 10‐year prospective cohort of lithium users and the association with duration of lithium use, lithium serum concentration, and comedication.

This 10‐year prospective cohort study included patients using lithium at inclusion. Medical records were reviewed for lithium concentration, eGFR, discontinuation of lithium, and other medication use. Primary outcome was a description of eGFR decline, quantified as delta eGFR per year of follow‐up.

In total 196 patients were analyzed (42% male, mean age 51.1 ± 12.2, median follow‐up time 8.8 years [IQR 1.3]). Median yearly decline was 0.79 mL/min/1.73 m2. Of the participants, 48% had a yearly decline between 0.5 and 2.5 mL/min/1.73 m2, while 11% showed a decline > 2.5 mL/min/1.73 m2. Duration of lithium use was associated with eGFR decline. A positive association between lithium serum concentration and kidney function decline was shown, when corrected for age, sex and duration of lithium use. Comedication was not associated with eGFR decline. In the participants who discontinued lithium (20%) during follow up, there was no significant difference in eGFR before and after cessation.

This study provides further evidence that eGFR decline occurs in most long‐term lithium users. Of this cohort, 59% of the participants had faster eGFR decline than the mean decline in the general population. Lithium exposure, quantified as mean serum lithium concentration, could be a contributing factor in this decline. eGFR trajectory was not altered by ceasing lithium.

In the majority of long‐term lithium users there is a significant decline in glomerular filtration rate.Higher mean serum lithium concentrations and longer duration of lithium therapy are associated with faster decline in glomerular filtration rate. Therefore, it seems reasonable to treat patients as short as possible with the lowest effective dose of lithium.In the small subset of patients who discontinued lithium during follow‐up in this cohort, no difference in eGFR decline before and after cessation was found, whether or not kidney function was the reason to stop using lithium.

In the majority of long‐term lithium users there is a significant decline in glomerular filtration rate.

Higher mean serum lithium concentrations and longer duration of lithium therapy are associated with faster decline in glomerular filtration rate. Therefore, it seems reasonable to treat patients as short as possible with the lowest effective dose of lithium.

In the small subset of patients who discontinued lithium during follow‐up in this cohort, no difference in eGFR decline before and after cessation was found, whether or not kidney function was the reason to stop using lithium.