Question:

Lithium, an inhibitor of glycogensynthase kinase 3 (GSK3), is widely used in the treatment of bipolar disorders. Side effects of lithium include nephrogenic diabetes insipidus (NDI), leading to renal water loss. Dehydration in turn has been shown to downregulate Klotho, which is required for the downregulation of 1,25(OH)₂D₃ formation by fibroblast growth factor FGF23. FGF23 decreases and 1,25(OH)₂D₃ stimulates renal tubular phosphate reabsorption. The present study explored whether lithium influences renal Klotho expression, FGF23 plasma levels, 1,25(OH)₂D₃ formation and renal phosphate excretion.

Methods:

Mice were treated for 14 days with lithium (200 mg/kg/day s.c.) or with vehicle only. Serum FGF23 and 1,25(OH)₂D₃ were determined by ELISA, renal Klotho protein abundance and was analyzed by Western blotting, and serum phosphate and calcium concentrations by photometry.

Results:

Lithium treatment significantly decreased renal Klotho expression and increased the FGF23 serum level. Consequently, the serum 1,25(OH)₂D₃, phosphate and calcium concentration were significantly decreased upon a 14-day treatment with lithium.

Conclusions:

In mice, lithium upregulates FGF23 formation resulting in a decrease of serum 1,25(OH)₂D₃, calcium and phosphate concentrations. Those effects may counteract vascular calcification and ageing.