title: Lead nephrotoxicity and associated disorders: biochemical mechanisms.
abstract: Lead may exert toxic effects on several organ systems, but those in the kidney are the most insidious. Acute lead nephropathy is characterized by proximal tubular dysfunction with the development of a Fanconi-type syndrome, alterations in mitochondrial structure and the development of cytosolic and nuclear inclusion bodies. Intracellular lead is associated with specific high affinity proteins and can also bind to metallothionein. Chronic lead nephropathy is irreversible and is typically accompanied by interstitial fibrosis, both hyperplasia and atrophy of the tubules, glomerulonephritis and, ultimately, renal failure. In addition, lead produces renal neoplasms in experimental animals. Chronic lead exposure is also implicated in the development of saturnine gout and hypertension. The metal interacts with renal membranes and enzymes and disrupts energy production, calcium metabolism, glucose homeostasis, ion transport processes and the renin-angiotensin system. This review summarizes the biochemical effects of lead on the kidney to understand the mechanisms of lead-induced nephropathy and other associated disorders.
authors.affiliation: Department of Pharmacology and Toxicology, University of Rhode Island, Kingston 02881-0809.
authors.forename: C V
authors.initials: CV
authors.lastname: Nolan
authors.forename: Z A
authors.initials: ZA
authors.lastname: Shaikh
mesh_terms: D000818:Animals; D002118:Calcium / Q000633:toxicity; D002352:Carrier Proteins / Q000032:analysis; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D006073:Gout / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D002479:Inclusion Bodies / Q000648:ultrastructure; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced*; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000150:complications* / Q000652:urine; D008670:Metals / Q000633:toxicity; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D008670:Metals; C055217:lead-binding proteins; D007854:Lead; D005947:Glucose; D002118:Calcium