Table 1.

Toxic effects of lithium on the kidney and proposed mechanisms

Effecta	Segment	Proposed Mechanism	References
NDI	Distal tubule and collecting duct	Reduced water uptake because of downregulation of AQP2 and loss of principal cells	38,40–42,80,117
Cellular remodeling (increase of intercalated versus principal cells)	Distal tubule and collecting duct	Not known; possibly a consequence of lithium–induced G2 arrest of collecting duct principal cells and/or lithium–induced metabolic acidosis	42,80,117
Interstitial fibrosis	Throughout all of the kidney	Not known; possibly a result from prolonged activation of the Wnt signaling pathway	69,71,75,118–120
Tubular atrophy	Proximal tubuleb	Not known but often linked with interstitial fibrosis in various renal diseases (interstitial fibrosis tubular atrophy)	69,71,74,75,118
Tubular dilation	Collecting ductb	Not known; likely a result from increased cell proliferation	75,83,86,120,121
Microcysts	Distal tubule and collecting duct	Not known; likely caused by increased cell proliferation	75,77,83,118,120
Glomerulosclerosis	Glomerulus	Not known; possibly a consequence of progressive renal damage	75,118

^aThe toxic lithium effects are arranged in chronological order of appearance.

^bDescribed for these segments, but studies did not exclude occurrence in other segments.