Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Cadmium Toxicity
Clinical Assessment - Laboratory Tests

Learning Objectives

At the end of this section, you will be able to

• describe the laboratory tests that can detect the effects of acute cadmium poisoning, and
• describe the laboratory evaluation for the possible health effects of chronic exposure to cadmium.

Introduction

The health effects of both acute and chronic cadmium exposure are well known. Therefore, there are medical tests that can measure exposure and cadmium body burden as well as standard and specialized clinical tests to measure the health effects of cadmium exposure.

Laboratory Tests for Acute Exposure

Tests that should be performed if cadmium inhalation is suspected.

• Chest X-ray – looking for chemical pneumonitis and pulmonary edema.
• Measurement of oxygen saturation.
• Renal and hepatic functions – to check for signs of liver or kidney damage.
• Cadmium blood levels. Blood cadmium indicates recent exposure and urine cadmium indicates body burden (ATSDR 1999).

Tests that should be performed in case of acute cadmium ingestion.

• Hepatic and renal functions.
• Electrolytes.

Approach to the Chronically Exposed Patient

Initial evaluation of patients with known or suspected chronic cadmium exposure should focus on the kidneys.

Initial renal tests should include

• BUN,
• cadmium in blood and urine,
• serum and urinary creatinine,
• serum creatinine (and/or calculated creatinine clearance),
• serum electrolytes, and
• urinary protein (low-molecular-weight proteins such as β₂-microglobulin and RBP).

Evaluation for chronic cadmium exposure may also include a complete blood count to check for anemia and liver function tests. In cases with renal complications, a set of skeletal X-rays should be ordered to check for bone-related complications of cadmium exposure such as osteomalacia, osteopenia, and skeletal fractures.

Direct Biological Measures

Urinary Cadmium

With low to moderate chronic exposure, urinary cadmium reflects integrated exposure over time and total body burden (Jarup 2002). Urinary cadmium levels do not rise significantly after acute exposure and are not useful for testing in the acute setting. In occupational settings, urine levels provide little or no useful information during the first year of exposure. According to the NHANES data, healthy young nonexposed nonsmokers in the United States have very low levels of urinary cadmium (average cadmium level of 0.08 µg/g creatinine; levels increase with age to .26 µg/gm of creatinine). “The Third National Report on Human Exposure to Environmental Chemicals" showed that during 2001-2002 the geometric means for adults age 20 and older was 0.210µg/gm creatinine, respectively (CDC 2005). The levels of cadmium increase with age. Clinicians should be aware that smokers in general will have higher urinary cadmium than non-smokers since tobacco smoke is a major source in non-occupationally exposed persons (Mannino et al. 2004).

If the kidney’s cadmium binding sites all become saturated after chronic high-level exposure, renal dysfunction results and urine cadmium levels increase dramatically. In that setting, urine levels reflect recent exposure rather than total body burden. Renal dysfunction is considered unlikely when urinary cadmium levels are less than 10 µg/g creatinine (Roels et al. 1999).

Blood Cadmium

Elevated blood cadmium levels confirm recent acute exposure, (Jarup 2002; ATSDR 1999) but do not correlate with body burden or clinical outcome, and should not be used to determine the need for treatment. The 95% confidence limit for blood cadmium levels in the United States for healthy nonexposed, nonsmokers is 0.4 micrograms per liter (µg/L) (CDC 2005). Occupationally exposed persons may have higher blood levels than the general population. OSHA (www.osha.gov) considers a whole blood level of 5 µg/l or higher hazardous.

Cadmium in Hair

Studies of exposed workers have not found a quantitative relationship between hair cadmium levels and body burden. Because of the potential for sample contamination, hair levels are not reliable either as predictors of toxicity or as indicators of occupational exposure.

Indirect Measures of Exposure

The following tests have been used to screen for renal damage in workers occupationally exposed to high cadmium levels and, under some circumstances, are required by OSHA. Their relevance to the evaluation of persons exposed only to lower environmental levels is uncertain. These are biomarkers that may indicate early toxic effects on the kidney from cadmium exposure. There is occupational data on their significance in exposed workers. (Bernard, 1997)

Urinary β₂-microglobulin

This low-molecular-weight (LMW) protein had been found in increased amounts in the urine of patients with long-term cadmium exposure and is considered a sensitive indicator of cadmium-induced tubular injury. However, other renal diseases, such as chronic pyelonephritis, can also increase β₂-microglobulin excretion. In healthy, unexposed persons, β₂-microglobulin levels average about 200 µg/g creatinine. Excretion increases with age and cadmium exposure. In cadmium workers, urine levels greater than 300 µg/g creatinine indicate possible early kidney disease, and such workers should be further evaluated.

Urinary Retinol Binding Protein (RBP)

RBP is a low molecular weight (LMW) protein found in the urine after chronic cadmium exposure. However, it is a nonspecific finding whenever tubular reabsorption is decreased by any cause. Therefore, it should only be used as a confirmatory test in cases of suspected cadmium exposure.

Urinary metallothionein, MTN

Urinary metallothionein, MTN is another LMW protein synthesized in response to exposure to cadmium and other metals. Urinary levels of MTN correlate well with urinary cadmium levels and can reflect total cadmium body burden; however, urinary concentration of the cadmium-MTN complex increases significantly once renal dysfunction has developed.

Key Points

• The best screening and diagnostic test for chronic cadmium exposure is a 24-hour urinary cadmium level, normalized to creatinine excretion.
• Urinary metallothionein and β₂-microglobulin excretion can be correlated with long-term cadmium exposure.

Progress Check