Urate lowering therapy (ULT) is a medical approach designed to decrease high concentrations of uric acid in the bloodstream. Uric acid is a natural byproduct created when the body breaks down substances called purines, which are present in the body’s cells and also found in many foods. While a certain amount of uric acid is normal and dissolves before being passed out by the kidneys, problems can arise. When the body produces too much uric acid or the kidneys excrete too little, levels become elevated in a condition known as hyperuricemia. The primary aim of ULT is to manage these levels to prevent related complications.
Conditions Requiring Urate Lowering Therapy
The most common reason for initiating urate lowering therapy is gout, a painful type of inflammatory arthritis. Gout occurs when high uric acid levels lead to the formation of sharp, needle-like monosodium urate crystals in and around the joints. These crystal deposits trigger an intense inflammatory response, causing sudden episodes of severe pain, swelling, and redness, often in the big toe. If unmanaged, these attacks, or “flares,” can become more frequent and lead to chronic pain and irreversible joint damage.
Beyond gout, ULT is used to prevent the formation of uric acid kidney stones, which can cause pain and block the urinary tract. It is also used to manage tumor lysis syndrome, a condition that can occur during cancer treatment. When chemotherapy rapidly kills cancer cells, they release large amounts of purines, causing a sudden spike in uric acid that can lead to acute kidney injury.
Medications Used in Urate Lowering Therapy
The most widely prescribed medications are xanthine oxidase inhibitors, such as allopurinol and febuxostat, which work by decreasing the body’s production of uric acid. These drugs block the action of xanthine oxidase, an enzyme responsible for converting purines into uric acid. Allopurinol is the first-line treatment, though some individuals of Southeast Asian or African American descent may require genetic screening for an allele (HLA-B5801) that increases the risk of a hypersensitivity reaction.
Another class of medications is uricosurics, such as probenecid. These drugs help the kidneys become more efficient at removing uric acid from the bloodstream through urine. They are often a second-line option or can be added to a xanthine oxidase inhibitor if target uric acid levels are not met. Side effects can include stomach upset or kidney stones, making it important to stay well-hydrated.
For severe and treatment-resistant gout, uricase agents like pegloticase may be used. This medication is an enzyme that breaks down existing uric acid into allantoin, a substance the body can easily eliminate. It is administered intravenously and is reserved for cases where other treatments have failed, particularly for patients with large urate crystal deposits called tophi.
Therapy Initiation and Management
ULT is recommended for individuals with certain clinical indicators. These include:
- Experiencing two or more gout flares per year
- Having visible joint damage on X-rays
- Developing tophi (large urate crystal deposits)
- Having a first gout flare combined with very high uric acid levels (above 9.0 mg/dL), chronic kidney disease, or a history of uric acid kidney stones
While it was once suggested to wait until a flare resolved, current guidelines support initiating ULT even during an acute gout attack. This is done as long as anti-inflammatory medications are also being used to manage the flare’s symptoms. This approach is often preferred because patients may be more motivated to start long-term treatment while experiencing an attack.
ULT is a long-term management strategy, often continued for life, not a short-term cure. Treatment starts with a low dose of medication that is gradually increased every two to five weeks based on blood tests. To prevent initial flares, doctors often prescribe a concurrent low-dose anti-inflammatory medication for the first three to six months of therapy.
Achieving Therapeutic Goals
The primary objective of ULT is to reduce and maintain the serum uric acid level below 6.0 mg/dL. Achieving this target brings the uric acid concentration below its saturation point. This prevents new urate crystals from forming and allows existing crystals in joints and soft tissues to slowly dissolve. For patients with tophi, an even lower target of less than 5.0 mg/dL may be set to promote faster resolution of these deposits.
Progress is monitored through regular blood tests, especially while the medication dosage is being adjusted. Once the target uric acid level is stable, monitoring can be reduced to about every six months.
Patients should know that gout flares can still occur during the first several months of treatment as uric acid levels fall. This does not mean the therapy is failing but is a sign that existing crystals are dissolving. Consistent, long-term adherence to the medication is necessary to prevent future attacks and joint damage.