Conventional oral urate-lowering therapies frequently to fail to achieve target serum uric acid (sUA) levels in patients with chronic kidney disease and uncontrolled refractory gout. This can lead to increased urate burden and complications, including worsening kidney disease, cardiovascular events, and metabolic syndrome. Tune in to find out how to incorporate targeted therapies when managing uncontrolled refractory gout and improve your patients’ quality of life.
Is Gout Hiding in the Nephrology Clinic?
Is Gout Hiding in the Nephrology Clinic?
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This is CME on ReachMD. I’m Dr. Abdul Abdellatif. Here with me today is Dr. Richard Johnson.
Richard, what is the association between serum uric acid level and CKD [chronic kidney disease]?
So as chronic kidney disease worsens, as the kidney function worsens, we accumulate more and more uric acid. Sometimes we refer to this as the uric acid burden. People who have a very high serum uric acid, like 9 or 10, almost inevitably have kidney disease. But not only is it associated with kidney disease, but a rising uric acid is associated with increasing frequencies of obesity, of diabetes, of heart disease, of high blood pressure and of many other metabolic complications. One connecting factor is inflammation. Uric acid crystals are extraordinarily inflammatory, and when they get in the joints, they cause systemic inflammation and fever.
In one study, over 80% of people with gout have uric acid crystals localizable to their blood vessels, like their aorta and coronary arteries. And this has been due to the discovery of a method to look for crystals called the dual energy CT scan, or DECT scan. There’s also been evidence that uric acid, even soluble uric acid, can be associated with increased risk for hypertension and heart disease, and this has been confirmed recently with studies that are called Mendelian randomization studies.
Abdul, what do you think our target serum uric acid should be?
Guidelines recommend that to lower the uric acid below 6 because we know at below 6 the uric acid then is more soluble and is able to be eliminated by the kidney. We also know if the patient is not treated to target of less than 6, that the longer they have a higher uric acid than 6, the faster they can build those crystals and tophi in their different joints and, as you mentioned, in different organs. But also, it’s been shown that the lower the uric acid, the faster you can get rid of those tophi in those patients with tophaceous gout.
In a study of more than 300 patients comparing the current available urate-lowering agents, which is allopurinol, febuxostat, we were only able to control patients to less than 6 using febuxostat in about 53% of the patients. It may rise up to 60% if the dose was higher, as they use in Europe. However, in the United States, our maximum dose is 80, and that’s why they showed about 53% reduction. As for allopurinol, only 21% of those patients actually reached target, which shows that a lot of our patients with chronic gout who need to be at target, they’re actually hard to control if we don’t pursue other alternative therapies for these patients, or more advanced treatment. It’s also been shown that out of those patients diagnosed with gout, which is now close to 10 million adults in the United States, unfortunately, it’s only about 3.3 million adults receiving treatment. And out of those receiving treatment, if they were on maximum dose of therapy, maybe about 60% of them may be less than 6, but unfortunately, if they have chronic kidney disease with GFR [glomerular filtration rate] less than 30, only about 25% of these patients are reaching target of uric acid less than 6 mg/dL.
So it’s very important for us when we treat the patient, we treat the target. We teach the patient that if we’re treating you for gout, it’s a chronic disease, lifelong disease just like diabetes, hypertension. We have a target for our treatment option, which is lowering the uric acid to less than 6. And if you’re still symptomatic, having gout flare, we have to go further lower level. If you still have tophi, we have to go even further down. Therefore, alternative therapies may be indicated, such as IV therapies that are available now called pegloticase, that we can actually treat those patients with to get them to target much faster and to get them to base much faster.
Well, this has been a brief but great discussion. Thanks again, Abdul, for your insights, and that’s the end of this session.
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In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Richard Johnson, MD
Professor of Medicine
University of Colorado
Anschutz Medical Campus
Research: National Institute of Health
Ownership Interest: Colorado Research Partners, XORTX Therapeutics
Receives Royalties: Elsevier, BenBella Books
Consulting Fees: Dinora, Horizon Pharma
Abdul A. Abdellatif, MD, FASN
Division of Nephrology
Baylor College of Medicine and CLS Health
No relevant relationships reported
John K. Botson, MD, RPh
Director of Rheumatology
Orthopedic Physicians Alaska
Research: Horizon Therapeutics
Patent Holder: Horizon Therapeutics
Consulting Fee: AbbVie, Amgen, Eli Lilly, Horizon Therapeutics, Novartis
Brittany Weber, MD, PhD
Director, Cardio-Rheumatology Clinic
Associate Physician, Prevention Cardiology & Cardiovascular Imaging
Brigham and Women’s Hospital
Research: AHA, NIH
Consulting Fees:, Agepha, Horizon Therapeutics, Kiniksa, Novo Nordisk
- Cindy Davidson has nothing to disclose.
- Hany Ibrahim, MD, has nothing to disclose.
- Samantha Keehn has nothing to disclose.
- John Maeglin has nothing to disclose.
- Brian McDonough has nothing to disclose.
- Tim Person has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Discuss the pathophysiology and prevalence of high uric acid levels and uncontrolled gout in patients with renal disease and the contribution of chronic gout to chronic kidney disease (CKD) progression, associated comorbidities, and increased mortality
- Apply knowledge of available diagnostic tools to identify patients with elevated serum uric acid (sUA) levels early in the progression of CKD to initiate proper urate-lowering therapy (ULT) and reduce urate burden
- Summarize the limitations of standard ULT options in patients with CKD
- Incorporate emerging urate-lowering therapies, including pegloticase-methotrexate combined therapy and clinical trial evidence, into clinical practice in the treatment of appropriate patients with uncontrolled gout
- Discuss gout as an independent risk factor for CVD and its association with CVD morbidity and mortality, necessitating early screening and treatment to attain target sUA levels
This activity is designed to meet the educational needs of nephrologists, rheumatologists, cardiologists, primary care physicians, and others who encounter, diagnose, and treat gout.
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Global Learning Collaborative (GLC) designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for 1.0 nursing contact hour. Nurses should claim only the credit commensurate with the extent of their participation in the activity.
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This activity is supported by an independent educational grant from Horizon Therapeutics, USA, Inc.
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