Lithium-induced kidney injury and fibrosis: A versatile model to explore cellular pathways of injury and repair.

Lithium-induced kidney injury is commonly associated with the development of nephrogenic diabetes insipidus. Longer term lithium exposure is associated with the development of chronic interstitial fibrosis. The mechanisms of lithium-induced kidney injury are multifaceted, affecting many intracellular cell signaling pathways associated with cell cycle regulation, cell proliferation, and subsequent increased extracellular matrix formation and interstitial fibrosis. Amiloride has been demonstrated to have multiple pleiotropic actions, independent of its competitive antagonism of ENaC, in reducing the progressive lithium-induced interstitial fibrosis. Further exploration of these interactions has the potential to expand our knowledge of pathways of tubular cell injury and repair, which in turn will lead to potential new therapeutic targets and drugs.