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Heavy Metal Nephropathy

by Navin Jaipaul, MD, MHS

Exposure to heavy metals and other toxins can result in tubulointerstitial disorders.

Heavy metals (eg, lead, cadmium, copper) and other toxins can cause a form of chronic interstitial nephritis (see Chronic tubulointerstitial nephritis (CTIN)).


Chronic tubulointerstitial nephritis results as lead accumulates in proximal tubular cells. Short-term lead exposure causes proximal tubular dysfunction, including decreased urate secretion and hyperuricemia (urate is the substrate for saturnine gout), aminoaciduria, and renal glucosuria. Chronic lead exposure (ie, for 5 to 30 yr) causes progressive tubular atrophy and interstitial fibrosis, with renal insufficiency, hypertension, and gout. However, chronic low-level exposure may cause renal insufficiency and hypertension independent of tubulointerstitial disease. The following groups are at highest risk:

  • Children exposed to lead paint dust or chips

  • Welders

  • Battery workers

  • Drinkers of high-proof distilled (moonshine) alcohol

Exposed children may develop nephropathy during adulthood.

Hyperuricemia disproportionate to the degree of renal insufficiency (eg, urate > 9 mg/dL with serum creatinine < 1.5 mg/dL, or > 10 mg/dL with serum creatinine 1.5 to 2 mg/dL, and > 12 mg/dL with more advanced renal failure) and a bland urinary sediment are common. Diagnosis is usually made by measuring whole blood lead levels. Alternatively, x-ray fluorescence may be used to detect increased bone lead concentrations, which reflect high cumulative lead exposure. Treatment with chelation therapy (see Chronic Acetaminophen Poisoning : Treatment) can stabilize renal function, but recovery may be incomplete.


Cadmium exposure due to contaminated water, food, and tobacco and, mainly, due to workplace exposures can cause nephropathy. It can also cause a glomerulopathy that is usually asymptomatic. Early manifestations of cadmium nephropathy are those of tubular dysfunction, including low molecular weight tubular proteinuria (eg, β 2 -microglobulin), aminoaciduria, and renal glucosuria. Symptoms and signs, when they occur, are attributable to chronic kidney disease. Renal disease follows a dose-response curve. Diagnosis is likely with the following:

  • History of occupational exposure

  • Increased levels of urinary β 2 -microglobulin (missed by urinary dipstick protein testing but detected using radioimmunoassay)

  • Increased urinary cadmium levels (> 7 μg/g creatinine)

Treatment is elimination of cadmium exposure; chelation with Na calcium edetate (EDTA) may increase cadmium nephrotoxicity. Tubular proteinuria usually is irreversible.

Other heavy metals

Other heavy metals that are nephrotoxic include

  • Copper

  • Gold

  • Uranium

  • Arsenic

  • Iron

  • Mercury

  • Bismuth

  • Chromium

All cause tubular damage and dysfunction (eg, tubular proteinuria, aminoaciduria) as well as tubular necrosis, but glomerulopathies may predominate with some compounds (mercury, gold). Treatment involves removal of the patient from further exposure and either or both of the following:

  • Chelating agents (copper, arsenic, bismuth)

  • Dialysis (chromium, arsenic, bismuth), often used when chelation fails or simultaneously with chelation for severe arsenic poisoning

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