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Liquid Gold: the quirky chemistry of urinalysis

by Laurel Oldach
May 23, 2024 | A version of this story appeared in Volume 102, Issue 16


The pitfalls of clinical chemistry

A flat illustration shows a gloved hand holding a multicolored test strip above a sample vial of urine.
Credit: Yang H. Ku/C&EN/Shutterstock
Moonshine by mistake: Unrefrigerated urine samples high in glucose are apt to ferment.

Folks arrested in the US famously receive one free phone call from detention. Most people use it to reach a relative or a lawyer; not many would call their doctor. So it surprised Aaron Schwartz, a primary care physician at the University of Pennsylvania, when he received a call from a patient in danger of going to jail.

The man wasn’t under arrest, but he was on parole. Though he maintained that he hadn’t had a drink in months, his parole officer said that his last few urine tests—a condition of his parole—had tested positive for alcohol. In a post on X (formerly Twitter), Schwartz called the situation “puzzling. This guy had been on the right track; we had just made so much progress with his diabetes.”

Schwartz invited the patient for an appointment and tested his urine. The test came back not only devoid of ethanol but also free from an ethanol metabolite called ethyl glucuronide that lasts for days. However, it was very high in glucose.

It turned out that a medicine he took to help control his blood sugar was what landed the patient in trouble with the law. The drug, empagliflozin, encourages the kidneys to pass more glucose in urine. Even a person whose blood glucose stays in the normal, healthy range ends up with high urinary glucose. And as most chemists, brewers, and winemakers know, there’s one surefire way to turn sugary liquids into alcohol.

Schwartz learned that the parole office kept patient samples unrefrigerated, creating a paradise for microbes that ferment sugars. His lab technicians were able to reproduce the ethanol observation simply by leaving the sample out of the fridge overnight. Just as microbes turn grape juice to wine and mash to beer, they turned sugar to ethanol in this less palatable fluid. Having cleared the patient’s name, Schwartz published the observation in the New England Journal of Medicine to make other physicians aware of the toxicological false-positive risk (2024, DOI: 10.1056/NEJMc2313463).

It wasn’t the first time urine fermentation had graced the pages of the journal. Back when it was known as the Boston Medical and Surgical Journal, a chemist by the name of Joseph Pinkham reported a method for using fermentation to determine glucose concentration in diabetic urine (1868, DOI: 10.1056/NEJM186804230781201). But proper sample handling, it seems, is a lesson that never gets old.


A complimentary urinal

A 3D illustration shows a urinal with a Wi-Fi signal emerging from the top.
Credit: Yang H. Ku/C&EN/Shutterstock
Data stream: A Shanghai urinal sends test results to a user's smartphone.

If you’re concerned about chemistry happening in your urine sample between the restroom and the lab, perhaps the best solution is to cut out the travel time. At least, that’s the proposition of purveyors of smart toilets.

Documentary filmmaker Christian Petersen-Clausen, who lives in Shanghai, attracted more attention than he expected when he posted to X about his experience with the smart urinals he had seen popping up in public restrooms all over town. He paid RMB 20—about the cost of a bubble tea—and received results straight to his smartphone within minutes. The report called him, in translation, “a Porsche,” with 13 of 14 analytes in a healthy range. While his calcium ion concentration was a bit low, Petersen-Clausen reported in his thread, when he stopped off for another test several days later, it too tested within normal range.

Petersen-Clausen, who says he has fielded many queries from news outlets, declined to speak with Newscripts. But according to a patent held by Beijing Shaoduo Technology Company, which markets the urinal, it works by diverting urine to a regular paper test strip. Those strips work because they have a variety of reagents that change color in response to analytes. That calcium sensor, for example, probably relied on o-cresolphthalein,a chelator that turns purple when it binds to calcium ions.

For people who cannot pee standing up or would find it difficult to reach a men’s room in Shanghai, Newscripts is pleased to report that urinalysis test strips are also available direct to consumers. Unfortunately, they won’t say nice things about healthy results.

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