Point-of-Care Uric Acid Testing

In June 2022, I listened to several presentations on gout at EULAR’s European Congress of Rheumatology. Most began with data confirming a sad truth that we, as rheumatology providers, are all aware of: too many patients are taking subtherapeutic doses of urate-lowering therapy (ULT).^1,2 Recommendations from the American College of Physicians in 2017 advocated for a treat-to-symptom approach, as opposed to the ACR, which advocates a treat-to-target approach (i.e. bringing the serum urate level below 6 mg/dL). The ACP deemed the evidence for monitoring serum urate (SU) levels insufficient, leading to mixed messaging to rheumatologists and other practitioners who treat patients with gout.³

Physician understanding isn’t the only barrier to good gout care. Patients—no matter how good their intentions—may struggle to obtain the frequent labs required for ULT dose titration.

My best friend has been suffering from recurrent gout attacks for two years. He’s an educated, 37-year-old man. I referred him to an excellent rheumatologist with whom I trained. He went to the appointment and understood the game plan. He started allopurinol with flare prophylaxis months ago, but hasn’t been back to the clinic for repeat labs since. He knows he needs to go. But this father of a rambunctious 1-year-old works full time and travels frequently, and he just hasn’t found the time to return to the clinic. Hyperuricemia persists, and he continues to have gout flares.

All of this got me thinking. Why isn’t uric acid point-of-care (POC) testing a thing? Home monitoring exists for other burdensome situations, such as international normalized ratio (INR) monitoring. Wouldn’t this make sense for gout? Am I really the first person to ever think of this? In short, the answer is no. No, I’m not the first person to think about this. It exists.

History

POC testing is generally defined as a diagnostic test and analysis performed where care is provided, close to or near the patient.

POC testing isn’t new. Urinalysis is more than 6,000 years old. Although Hippocrates is credited as the first uroscopist, the Sumerians and Babylonians documented urine assessments on clay tablets as early as 4,000 B.C.⁴ Synovial fluid crystal analysis is distinctly younger; microscopes of sufficient magnifying power were not invented until the late 17th century.⁵

Antoni van Leeuwenhoek described the appearance of monosodium urate crystals from a tophus in 1679, although their chemical composition was not elucidated until many years later.⁶ Interestingly, he also discovered bacteria by accident. He was a cloth merchant who simply wanted to take a better look at the cloth he sold—and lo and behold, the cloth was covered in microorganisms. What’s more, he discovered human sperm. He was analyzing the ejaculate of a patient with gonorrhea and compared it to his own.⁵ But I digress.

Uric Acid POC Testing

When we order uric acid tests in the clinic, SU is measured by a uricase-based laboratory assay on plasma samples obtained after venous puncture. For ease of administration, POC testing would have to involve a capillary blood sample, similar to home glucose monitoring. Can it be done?

Believe it or not, uric acid POC testing was invented as early as 2001.⁷ A routine internet search finds a couple different meters available for commercial purchase in the U.S. and abroad. You could buy one on Amazon for about $100. However, a literature search for the evidence to support use yields few studies.

Small studies have demonstrated the reliability and validity of POC testing with the HumaSens^plus meter, with close correlation between capillary uric acid values and venous SU values.⁸ Discrepancies between POC testing and laboratory values that would influence treatment escalation decisions were observed in 9% of patients (for the second generation HumaSens2.0^plus device).⁹ Of note, hematocrit can influence POC uric acid measurements by modifying the blood viscosity of whole blood. Thus, the manufacturer of these meters recommends restricting use to hemoglobin ranges of 10.0 g/dL to 18.3 g/dL. Factors that affect glucose monitoring—like finger temperature, tissue perfusion and acid-base status, apply too.

Glucose meters require a maximum 15% (percent deviation) accuracy compared with the reference method, with 95% of the measurements in the acceptance range, to achieve regulatory approval.¹⁰ So these uric acid POC testing meters would meet the mark.

Potential Benefits

As a rheumatologist, I think the benefits of uric acid POC testing are self-evident. But for the sake of completeness, I discussed the concept with Alan Baer, MD, professor of medicine, Division of Rheumatology, Johns Hopkins University, Baltimore. Dr. Baer is a gout expert and an ACR Master to whom I have looked up since my intern year. He has taken care of people with gout for a long time. And he had never heard of uric acid POC testing.

“Gout is something for which we’ve had effective treatment since the 1960s,” says Dr. Baer. “It’s a shame that gout continues to be treated inadequately. We are so good at preventing erosive joint disease in rheumatoid arthritis, but [we] fail miserably in gout.”

How might uric acid POC testing make a difference? Let us count the ways.

1. Titration of ULT to achieve target SU: With convenient home POC testing, uric acid levels could be checked as often as every two weeks, allowing for rapid titration of ULT to achieve target SU as per ACR guidelines.¹¹
2. Positive feedback to improve adherence to ULT: “Many patients that I see with ‘refractory’ or tophaceous gout tell me they took allopurinol in the past, but continued to have gout flares and thus stopped it due to apparent inefficacy,” says Dr. Baer. “Some tell me that it made their gout worse. I tell them that allopurinol takes time to work, and that lowering the uric acid to levels of less than 6 mg/dL is essential for dissolving the gout crystals in their joints. I also detail the importance of taking colchicine as a prophylactic agent in this setting. POC testing could give such patients positive feedback, allowing them to watch their uric acid levels fall over time.”

   Studies confirm that medication adherence is poor in gout.¹² The immediate feedback offered by POC hemoglobin A1c testing improves glycemic control.¹³ One can imagine that what POC testing did for diabetes, it could also do for gout.

3. Fewer skipped doses of ULT: “I had a gout patient the other day whose SU was 11.0, but at our prior visit it was 5.0,” says Dr. Baer. “He admitted that sometimes he skipped his daily dose of allopurinol due to stomach upset. I asked him to take half the dose in the morning and the other half in the afternoon to alleviate this side effect and to repeat the uric acid test after taking the allopurinol faithfully for three consecutive days. His repeat SU level was 5.0. Patients don’t realize that if they skip a dose, uric acid levels rise quickly. So POC testing could give them a sense of how important it is to take ULT daily.”
4. POC testing prior to pegloticase infusion: Reinfusions of pegloticase shouldn’t be administered to patients with high uric acid levels, and POC testing could provide quick results.¹⁴ This would only be useful to a small fraction of patients, but useful nonetheless.
5. Cost saving: Self-management of oral anticoagulation therapy via home INR monitoring has proven to be cost effective, so one might infer that uric acid POC testing could yield similar savings for gout.¹⁵ However, the true value to both patients and the healthcare system would be in better gout care. The economic burden of uncontrolled gout cannot be overstated.¹⁶ According to a 2016 systematic literature review, cost estimates for gout treatment in the U.S. range from $7.7 billion for gout-specific costs to greater than or equal to $20 billion for total costs.¹⁷

Conclusion

POC testing uric acid testing exists. A five-minute phone call between two rheumatologists yielded a list of five compelling arguments to support its use, and there are likely more. What will it take to make uric acid POC testing as common for gout patients as glucose monitors are for people with diabetes?

Samantha C. Shapiro, MD, is the executive editor of Harrison’s Principles of Internal Medicine. As a clinician educator, she practices telerheumatology and writes for both medical and lay audiences.

References

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2. Shapiro SC. Refractory gout is a myth: Tips from an expert. The Rheumatologist. 2022 Jul 2. https://www.the-rheumatologist.org/article/refractory-gout-is-a-myth-tips-from-an-expert/.
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15. Sawicki PT, for the Working Group for the Study of Patient Self-Management of Oral Anticoagulation. A structured teaching and self-management program for patients receiving oral anticoagulation: A randomized controlled trial. JAMA. 1999 Jan 13;281(2):145–150.
16. Flores NM, Nuevo J, Klein AB, et al. The economic burden of uncontrolled gout: How controlling gout reduces cost. J Med Econ. 2019;22(1):1–6.
17. Kabadi S, Myers J, Bly C, et al. Health economics of uncontrolled gout in the United States: A systematic literature review [abstract]. Arthritis Rheumatol. 2016;68(suppl 10). https://acrabstracts.org/abstract/health-economics-of-uncontrolled-gout-in-the-united-states-a-systematic-literature-review.