Lead and Other Heavy Metal Toxins
Shane M. Meehan, MBBCh
Key Facts
Terminology
Renal disease due to toxic effects of lead and other metals
Etiology/Pathogenesis
Principal toxic metals encountered include lead (Pb), mercury (Hg), gold (Au), and cadmium (Cd)
Direct tubular toxicity may be acute (high-dose toxicity) or chronic (low-dose prolonged toxicity)
Membranous glomerulopathy in Hg and Au toxicity due to immune complex deposition
Clinical Issues
History of recent or past exposure to toxic metals is critical for diagnosis
Blood and urinary levels of toxic metals are elevated in acute nephropathy
Microscopic Pathology
Acute nephropathy: Acute tubular injury
Eosinophilic nuclear inclusions (lead, bismuth) or pigment (iron, copper)
Hg and Au particles in proximal tubules by EM
Nonspecific chronic tubulointerstitial nephritis
Membranous glomerulonephritis in Hg and Au toxicity
Radiographic fluorescence or spectroscopy may be used to quantify metal content in tissues
Top Differential Diagnoses
Acute tubular injury/necrosis from drugs and infection
Chronic tubulointerstitial diseases (lithium, Balkan nephropathy, aristolochic acid)
TERMINOLOGY
Definitions
Group of disorders characterized by renal dysfunction due to toxic effects of lead and other metals
ETIOLOGY/PATHOGENESIS
Toxic Renal Injury
Principal toxic metals encountered include lead (Pb), mercury (Hg), gold (Au), cadmium (Cd), copper (Cu), chromium (Cr), bismuth (Bi), antimony (Sb), arsenic (As), uranium (U), platinum (Pt), iron (Fe), and lithium (Li)
Exposure to toxic metals may be environmental, occupational, iatrogenic, or secondary to metabolic and hematologic disease states
Routes of entry include ingestion, inhalation, and absorption through skin
Environmental exposure
Ingestion: Contamination of water supplies in lead pipes or lead soldered joints, moonshine stills, lead paint, contaminated foods
Inhalation: Lead, mercury, and cadmium vapors, fumes, or dust
Application of mercury-containing skin lightening products
Mercuric chloride and colloidal bismuth ingestion in suicide
Occupational exposure
Paint manufacture and spraying, plumbing, welding, smelting, mining, pesticides, thermometer manufacturing, and others
Iatrogenic exposure
Gold therapy in rheumatoid arthritis
Colloidal bismuth in treatment of peptic ulcer and syphilis
Copper intrauterine contraceptive devices
Lithium in bipolar disorders
Platinum in cancer chemotherapy
Iron for deficiency states
Metabolic and hematologic diseases
Hemochromatosis
Wilson disease
Hemolysis
Metals may be absorbed through gastrointestinal tract, lungs, or skin, entering bloodstream
Circulating metals are filtered by glomeruli, often secreted by tubules and excreted in urine
Renal injury is by 2 principal mechanisms
Direct tubular toxicity causes tubular injury
High-dose exposure leads to acute nephropathy
Low-dose prolonged exposure leads to chronic nephropathy
Glomerular immune complex deposition results in membranous glomerulopathy
Associated with gold and mercury toxicity
Neither metal is detected in immune deposits
CLINICAL ISSUES
Presentation
Acute nephropathy
Toxic metal exposures to Pb, Hg, Au, Cd, Cu, Cr, Bi, Sb, U, Pt, Fe can be associated with acute kidney injury
Proximal tubulopathy is often an early manifestation
Characterized by aminoaciduria, glycosuria, phosphaturia (Fanconi syndrome) and increased urinary β2-microglobulin excretion
Blood and urinary levels of toxic metals are elevated
Chronic nephropathy
Lead
Gouty arthropathy and hyperuricemia in 50%, chronic renal failure, hypertension, positive calcium-EDTA mobilization testStay updated, free articles. Join our Telegram channel
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