Long-Term Lithium Exposure May Damage Kidney Function

A steep annual decline in estimated glomerular filtration rate (eGFR) among patients with bipolar disorder (BD) or schizoaffective disorder is attributed to long-term lithium use, according to study results published in The Lancet Psychiatry.

Researchers conducted a cross-sectional study that used data from the Lithium-Study into Effects and Side-effects (LiSIE) and Northern Sweden WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) cohorts. The relationship between lithium use and age-associated decline in creatinine-based eGFR was evaluated and compared between patients (LiSIE) and the general population (MONICA).

For the LiSIE cohort, medical records from patients in Norrbotten and Västerbotten in Sweden with BD or schizoaffective disorder diagnoses were evaluated for serum lithium concentrations between 1997 and 2017. For the MONICA cohort, the general population in the same regions of Sweden were surveyed and blood samples were collected in 2014.

The LiSIE (n=785) and MONICA (n=1549) cohorts comprised 63% and 52% women with a mean age of 49.8 and 51.9 years, respectively. Participants had a mean eGFR of 81.1 and 79.9 mL/min/1.73 m², respectively.

Among the LiSIE cohort, 361 participants had been exposed to lithium for less than 1 year, 138 were exposed for 1 to 5 years, 108 were exposed for more than 5 to 10 years, and 178 were exposed for over 10 years.

Compared with the general population, the patients with BD or schizoaffective disorder had a significantly greater annual rate of eGFR decline compared with the general population (mean, 0.69 mL/min/1.73 m²; P =.0013), which was attenuated by adjusting for lithium exposure (mean, 0.57 mL/min/1.73 m²; P =.97).

Stratified by lithium use duration, the patients with more than 10 years of exposure had a significantly greater annual rate of decline than the general population (mean, 0.99 mL/min/1.73 m²; P <.0001) or compared with other lithium-exposed groups (all P ≤.0009).

Among the patients with BD or schizoaffective disorder with an eGFR of less than 45 mL/min/1.73 m² (n=24), 83% had been exposed to lithium.

The study was limited in that because the 2 datasets were not linked and data were collected in the same regions, it is possible that individuals were represented in both datasets.

Study authors concluded, “All patients treated with lithium should be considered at high risk [for] kidney complications…. Patients on a fast trajectory should be referred to a nephrologist early to rule out other treatable causes of kidney disease. Shared decision making between nephrologists and psychiatrists is paramount to achieve the best outcome for the individual patient affected.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.