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Heavy Metal Nephropathy

By

Frank O'Brien

, MD, Washington University in St. Louis

Last full review/revision Jun 2020| Content last modified Jun 2020
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Exposure to heavy metals and other toxins can result in tubulointerstitial disorders.

Lead nephropathy

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 years) 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.

Common findings include a bland urinary sediment and hyperuricemia disproportionate to the degree of renal insufficiency:

  • Serum urate > 9 mg/dL (535.4 micromol/L) with serum creatinine < 1.5 mg/dL (132.6 micromol/L)

  • Serum urate > 10 mg/dL (594.9 micromol/L) with serum creatinine 1.5 to 2 mg/dL (132.6 micromol/L to 176.8 micromol/L)

  • Serum urate > 12 mg/dL (713.8 micromol/L) with serum creatinine > 2 mg/dL (176.8 micromol/L)

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.

Cadmium nephropathy

Cadmium exposure due to contaminated water, food, or 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, beta2-microglobulin), aminoaciduria, and renal glucosuria. Symptoms and signs, when they occur, are attributable to chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease . Renal disease follows a dose-response curve.

Diagnosis of cadmium nephropathy is likely with the following:

  • History of occupational exposure to cadmium

  • Increased levels of urinary beta2-microglobulin (missed by urinary dipstick protein testing but detected using radioimmunoassay)

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

Treatment is elimination of cadmium exposure; note that chelation with ethylenediaminetetraacetic acid (EDTA) may aggravate renal toxicity in acute cadmium poisoning but has been used successfully in cases of chronic cadmium exposure. Tubular proteinuria usually is irreversible.

Other heavy metal nephropathies

Other heavy metals that are nephrotoxic include

  • Copper

  • Gold

  • Uranium

  • Arsenic

  • Iron

  • Mercury

  • Bismuth

  • Chromium

All of these metals 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:

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