Lithium and the kidney; friend or foe?

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Theun de Groot from the Dept. of Physiology (Osmoregulation group Peter Deen), theme Renal disorders reveals novel insights on the renal effects of lithium via the publication of two articles in ‘The Journal of the American Society of Nephrology’ (JASN), the most prestigious renal journal (IF 9.3).

While administration of lithium is the mainline treatment for bipolar disorder patients, long-term lithium therapy comes in a substantial number of patients at the cost of severe renal side effects including nephrogenic diabetes insipidus (NDI) and end state renal disease. To treat NDI, patients are normally treated with the amiloride/thiazide therapy. Previously, we demonstrated that the mechanism by which this therapy works is different than previously thought and might involve the inhibition of carbonic anhydrases. To test this we treated mice with lithium-induced NDI with acetazolamide, a specific carbonic anhydrase inhibitor. Indeed, in this new study, performed in collaboration with Prof. Jack Wetzels from the department of Nephrology, acetazolamide not only attenuated the development of lithium-induced NDI in mice, but also caused less side effects compared to the amiloride/thiazide therapy. It remains to be established whether it can be used as a treatment in man. 

In contrast to the development of renal injury with intake of large amounts of lithium, different recent animal experiments demonstrate that subclinical lithium amounts can prevent renal damage. Lithium administration before, during or after the induction of acute kidney injury (AKI) strongly reduces renal pathology. Also long-term administration of lower lithium amounts prevents kidney damage in several chronic forms of kidney injury. In our second publication, we review these findings and enlighten the underlying mechanisms of these seemingly-paradoxical effects of lithium, in which fine-tuned regulation of GSK3, a prime target for lithium, seems to be key. The exciting new discoveries on the protective effect of lithium in AKI in rodents ask for follow-up studies in humans and question whether long-term therapies with low lithium concentrations may be beneficial in chronic kidney disease.

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