Nephrotoxicity of Lithium and Drugs of Abuse

Lithium-induced nephrotoxicity is of little clinical significance 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. In the past several decades, the epidemiology of renal disease among drug abusers has radically changed. Heroin-associated focal and segmental glomerulosclerosis and secondary amyloidosis have been supplanted by an increase in the incidence and spectrum of nephrotoxicity associated with the use of opiates, cocaine, amphetamines and designer recreational drugs. These agents have been associated with nontraumatic rhabdomyolyis, acute tubular necrosis, acute interstitial nephritis, thrombotic microangiopathy, vasculopathy and podocytopathy.