Nephrotoxicity of Lithium and Drugs of Abuse

Lithium-induced nephrotoxicity is of little clinical consequence in most patients, especially if maintenance serum levels are kept at the lower end of the therapeutic range. However, it appears that advanced renal failure may develop in a susceptible subgroup of patients on maintenance lithium therapy after decades of treatment. Identification and characterization of this susceptible subgroup remain elusive. Moreover, data are contradictory as to whether it is chronic tubulointerstitial injury or glomerular injury that is primarily responsible for the development of advanced renal failure in a minority of lithium-treated patients. Because nephrotoxicity may be associated with clinical episodes of lithium intoxication or elevated serum lithium levels, an effort should be made to maintain the lowest therapeutic serum lithium level. Isolated polyuria due to impaired concentrating ability may respond to amiloride. A modest reduction in glomerular filtration rate or mildly impaired urinary concentrating ability may not necessarily be a forerunner of progressive renal failure. However, renal function should be monitored regularly, and the risks of nephrotoxicity for individual patients must be weighed against the therapeutic benefit from continued lithium therapy.