Case: routine examination and lab results
Mr. M’s height is 5’9″, weight is 195 lb, body mass index is 28.8 kg/m2, and BP is 128/78 mm Hg. The left great toe is swollen, warm, erythematous, and tender to touch, with chronic synovial changes. A complete blood count (CBC) and blood chemistry profile are unremarkable except for a serum uric acid level of 8.2 mg/dL and a serum creatinine of 1.5 mg/dL.
Mr. M expresses concern that his acute gout flares have become more frequent. The clinician discusses the patient’s medication and dietary history. Asked about his allopurinol regimen, Mr. M admits that he sometimes “forgets” to take the medication when he feels well between acute flares.
Discussion: treating CKD patients with gout
Clinicians face several challenges when treating gout in patients with impaired kidney function (Table).5,8,16 The first is a failure to understand that gout is a chronic condition, requiring ongoing rather than intermittent treatment.
The second is that chronic urate-lowering therapies with xanthine oxidase inhibitors such as allopurinol and febuxostat may be associated with gout exacerbation upon initiation of therapy, which should be recognized as a consequence of lowering uric acid levels and a sign of effective treatment.
These complicated issues must be discussed at length with patients, and compliance must be addressed and reinforced regularly. In the event of acute flares, the proper course is to add an anti-inflammatory agent.
Concerns about dosing of allopurinol, colchicine, and nonsteroidal agents in CKD also pose a challenge to clinicians. Consequently, many patients with hyperuricemia—with or without comorbidities—are not treated optimally and continue to experience attacks of gout.9 A study of 177,637 patients with gout found 58.1% had HTN, DM, dyslipidemia, and/or ischemic heart disease.9
During the 12-month study, 37% of patients reported an outpatient visit for a first gout claim. Of these, 42% of patients were prescribed NSAIDs, 31% received allopurinol, 21% were prescribed corticosteroids, and 17% were treated with colchicine. Overall, 39% of patients received no treatment for their gout complaint. Patients with cardiometabolic comorbidities, DM, or CKD were less likely to be treated than those without comorbidities, despite a higher risk for flares in patients with comorbidities that indicated a higher disease burden.9
Gout is often considered the chronic disease with the worst rate of adherence,17 which contributes to suboptimal management.
The laboratory “reference range,” which includes up to 20% of the U.S. population with asymptomatic hyperuricemia, should not be confused with a “normal range.” Indeed, for decades it has been advised that patients with gout should be treated toward a uric acid level no greater than 6.0 mg/dL.
Persistent elevation of serum uric acid and gout flares tend to occur in patients with self-reported prior noncompliance, longer disease duration, and kidney failure.17 Some patients even suspend treatment due to worsening of disease.16 The “intercritical” phase of gout—an asymptomatic phase following recovery from an acute flare—is an excellent time to address secondary causes of hyperuricemia other than adherence, including medications for comorbid conditions, dietary considerations, and alcohol consumption.18
Case: medication effectiveness
Mr. M asks what medication he can use to treat acute flares and if there are any new medications to lower his serum uric acid level, since the allopurinol seems to be losing effectiveness. The clinician reminds him that adherence to any long-term therapy for hyperuricemia is critical to prevent acute flares and worsening of the disease.
This is especially important because elevated serum uric acid may adversely affect his kidney function.4 The clinician explains that because of his CKD, NSAIDs are not a preferred therapy for an acute flare, and they discuss corticosteroid treatment to alleviate his current symptoms.5,8
Discussion: pharmacologic options
Pharmacologic options for management of acute gout flares include NSAIDs, colchicine, corticosteroids, and corticotropin; colchicine and NSAIDs must be used very carefully (or not at all) in older individuals and those with impaired kidney function (Table).
NSAIDs, for example, are associated with an increase in BP, decreased response to diuretics, and when used in combination with angiotensin-converting enzyme inhibitors and diuretics, can precipitate acute kidney injury.9 The importance of judicious use of NSAIDs or avoiding them entirely in CKD is well known to nephrologists.
Up to 20% of a dose of colchicine is excreted by the kidneys in individuals with normal kidney function.5,8 Colchicine clearance is reduced in patients with CKD and may accumulate in serum and cause gastrointestinal (GI) toxicity, even at low doses; dosing should be reduced in patients with kidney impairment. Neutropenia, neuropathy, and myopathy can occur with long-term use, and may only partially resolve with discontinuation of treatment.
Patients with CKD receiving colchicine at any dose should therefore be monitored regularly for leukopenia and myopathy. This is particularly true in kidney transplant recipients treated with cyclosporine. Colchicine is not a preferred agent for prophylaxis against gout and should not be used as prophylaxis for acute flares in patients with a GFR <50 mL/min.8 Colchicine should not be used in patients on hemodialysis.
Corticosteroids are used increasingly for acute gout attacks when comorbid conditions preclude NSAID or colchicine use.5,8 Intra-articular injections of a long-acting corticosteroid are useful for acute flares limited to a single joint or bursa, after septic arthritis has been ruled out by culture of aspirated synovial fluid. Oral, intramuscular, or intravenous corticosteroids can provide complete relief from acute attacks. Corticosteroids are typically given as prednisone or its steroid equivalent for 7-10 days.
Lack of corticosteroid effectiveness often results from inadequate dosing, or tapering too soon after initial resolution of acute symptoms. Because short courses of corticosteroids are used for acute gout flares, steroid-related adverse events are less of a concern than with long-term use, but blood glucose levels can rise significantly in patients with or without diabetes.
Corticotropins have similar indications for use as corticosteroids, although they are more costly than generic corticosteroids.5,8 Available in subcutaneous and intramuscular formulations, a single corticotropin dose is rapid, efficient, and well tolerated. Adverse effects include hyperglycemia, rebound arthritis, hypokalemia, and fluid retention, which pose a concern for patients with CKD or congestive heart failure.