Mechanisms of lead and cadmium nephrotoxicity.
Exposure to lead results in accumulation in proximal renal tubular lining cells in the form of morphologically discernible inclusion bodies which are lead-protein complexes. Acute nephrotoxicity consists of proximal tubular dysfunction and can be reversed by treatment with chelating agents. Chronic lead nephrotoxicity consists of interstitial fibrosis and progressive nephron loss, azotaemia and renal failure. Potential complications of lead nephropathy include gout and hypertension. Cadmium accumulates in renal tubular lining cells bound to metallothionein, a small protein containing 30% cystine. Metallothionein protects against nephrotoxicity by binding cadmium in a nontoxic form. Renal tubular dysfunction and chronic interstitial fibrosis occur when cadmium levels in the renal cortex exceed the critical concentration of about 200 micrograms/g. Recommendations are made for specific research needs.
Goyer
R A
RA
Department of Pathology, University of Western Ontario, London, Canada.
D058186:Acute Kidney Injury / Q000139:chemically induced*; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007854:Lead / Q000378:metabolism / Q000633:toxicity*
D002104:Cadmium; D007854:Lead