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Impact of Long-Term Lithium Treatment on Renal Function in Patients With Bipolar Disorder Based on Novel Biomarkers

Dastych, Milan, MD, CSc*; Synek, Oldřich, MD; Gottwaldová, Jana, Mgr*

Journal of Clinical Psychopharmacology: May/June 2019 - Volume 39 - Issue 3 - p 238–242
doi: 10.1097/JCP.0000000000001030
Original Contributions

Background Lithium in the form of lithium carbonate (Li2CO3) has become one of the most effective and widely prescribed drugs for mood stabilization. However, lithium has adverse effects on renal tubular functions, such as decreased concentrating function of the kidneys, and even occasional symptoms of nephrogenous diabetes insipidus occur with additional evidence of glomerular disruption in lithium-treated patients.

Methods We assessed the kidney function of patients with bipolar disorder who are under long-term lithium treatment using novel markers of kidney damage such as plasma neutrophil gelatinase–associated lipocalin, cystatin C, albuminuria, estimated glomerular filtration rate, Chronic Kidney Disease–Epidemiology Investigation using creatinine and cystatin C, and serum and urinary osmolality, and compared the results with those of age-matched patients with bipolar disorder not treated with lithium. The study enrolled 120 patients with bipolar disorder, consisting of 80 (30 male and 50 female patients) who have been receiving lithium for 0.5 to 20 (mean, 7) years and 40 (10 male and 30 female patients) who had never been exposed to lithium treatment.

Results Patients treated with lithium had significantly decreased urine osmolality (mean ± SD, 405 ± 164 vs 667 ± 174 mmol/kg) and urine-to-serum osmolality ratio (1.35 ± 0.61 vs 2.25 ± 0.96). No significant difference was found in creatinine, estimated glomerular filtration rate values calculated using the Chronic Kidney Disease–Epidemiology Investigation using creatinine and cystatin C, neutrophil gelatinase–associated lipocalin, cystatin C, and albuminuria between both groups. We found no significant difference in renal biomarkers between patients treated with lithium for 6 to 24 months and those treated for 25 to 240 months.

Conclusions We found significantly decreased kidney concentrating ability in the long-term lithium-treated patients compared with the control group. Other renal function markers did not indicate any significant signs of renal dysfunction.

From the *Department of Clinical Biochemistry, University Hospital Brno, and Department of Laboratory Methods, Faculty of Medicine Masaryk University; and

Department of Psychiatry, University Hospital Brno, Faculty of Medicine Masaryk University, Brno, Czech Republic.

Received September 18, 2018; accepted after revision January 25, 2019.

Reprints: Milan Dastych, MD, CSc, Department of Clinical Biochemistry, University Hospital Brno, Jihlavská 20, 62500 Brno, Czech Republic (e-mail:

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