A patient’s urine sample holds a trove of health information, but sometimes what it reveals has less to do with the patient and more to do with what happens to the specimen after collection and before it reaches the lab.
New research has identified a surprising source of arsenic contamination in urine samples, and it’s caused by a routine test frequently performed in the clinician’s office.
Until recently, laboratory scientists had no way to know the arsenic was a contaminant and therefore interpreted it as originating from the patient. When this happens, the inaccurate results can lead to unnecessary interventions and patient stress.
Why arsenic speciation matters
A clinician orders urinary arsenic testing to look for acute or chronic poisoning, evaluate unexplained symptoms, or investigate workplace and environmental hazards. However, not all arsenic is created equal, so high levels alone are not enough to guide clinical decisions. Physicians must first know what form of arsenic is present because treatment pathways vary widely depending on the type of arsenic the patient has in their system.
Most organic arsenic species are not toxic in humans, and exposure usually occurs through consumption of fish, shellfish, and other seafood. Inorganic arsenic, however, is toxic and causes serious health problems. The most common source of inorganic arsenic exposure is drinking water. Symptoms of acute arsenic toxicity include vomiting, abdominal pain, diarrhea, numbness and tingling of the extremities, muscle cramping, and in extreme cases, death. Long-term effects can cause skin lesions and certain types of cancer.
Because identifying the type of arsenic present in a patient is essential for treatment, laboratories first screen urine for the heavy metal and, if detected at high enough levels, reflex to more complex testing that distinguishes between organic and inorganic forms. In some specimens, laboratory scientists may detect an unidentified arsenic species that they cannot classify as organic or inorganic, which can complicate clinical management. Thanks to new research, scientists have now identified one of those unknown species, and it’s not arsenic from the patient; it’s from mishandling the sample.
A common source of arsenic contamination in lab samples
Two recent publications in the Journal of Trace Elements in Medicine and Biology and Therapeutic Drug Monitoring report a source of arsenic in urine that is suspected to originate from a routine urinalysis performed on the sample before it is sent to the lab. During this common point-of-care test, a plastic strip with chemical pads is dipped into the urine, providing important clinical information about a patient’s health. Many brands of these plastic strips contain p-arsanilic acid (ASA), an arsenic compound used to measure urine nitrite levels.
If a urine specimen comes into contact with this strip, it may contaminate the sample, and the laboratory may detect exogenous arsenic during analysis. This finding is particularly concerning because labs cannot differentiate between post-collection contamination and arsenic originating from the patient, which means the patient receives an incorrect result. Because staff should perform urinalysis and arsenic testing on separate urine containers, this contamination indicates improper specimen management.
In the lab, this preanalytical contamination appears as either an unknown species or, in some cases, laboratory scientists can mistake it for arsenic 5 (AsV), an inorganic form of arsenic that looks similar to the contaminant on certain laboratory instruments. Before this research, when ASA was present, laboratory scientists could not distinguish between sample contamination and patient exposure. The patient would therefore receive a false positive arsenic result, which could lead to additional laboratory testing, unwarranted investigations, and unnecessary treatments.
Protecting patients from unnecessary interventions
If the lab is unable to identify arsenic, the physician cannot assume it is the toxic inorganic form, but they also can't confidently dismiss it as organic either. A patient’s care team may wait and retest later or rely on other laboratory tests to better understand the patient’s condition; however, if this ASA contaminant is misidentified as the highly toxic AsV, the situation becomes more urgent.
When a medical toxicologist suspects inorganic arsenic exposure, the patient’s care team may involve public health officials to investigate a potential exposure source and determine whether treatment is warranted based on the laboratory results and clinical presentation. Chelation therapy is a treatment for patients with severe heavy metal poisoning. These drugs bind to harmful heavy metals, allowing the body to excrete them through urine or stool.
Heavy metals not bound to chelating agents are less likely to be flushed out, leaving them free to settle in organs, bones, and other tissues and cause long-term damage. Because this therapy can have serious adverse effects, if the patient is otherwise healthy and asymptomatic, and laboratory levels are not extremely high, the physician may choose to monitor the patient while removing the exposure source.
A major win for clinical laboratories
Identifying ASA as a dipstick contaminant is a major win for clinical laboratories and patient care. Before researchers officially identified this species, laboratory scientists could easily misinterpret the previously unknown species as a dangerous environmental exposure. Knowing it comes from a dipstick improves result accuracy so the patient can receive proper treatment.
Ultimately, these studies emphasize the importance of maintaining sample integrity during collection and processing. A laboratory test is only as good as the sample received, and a compromised sample produces a compromised result.
