Gout is a painful form of inflammatory arthritis that occurs in the setting of hyperuricemic monosodium urate crystals deposited in joints and tissues. Almost 40% of patients with gout have chronic kidney disease (CKD). Incidence of gout increases as kidney function decreases.
The kidneys excrete uric acid, predisposing CKD patients to hyperuricemia. Unfortunately, these patients have contraindications to a number of agents used in the management of gout. In addition, thiazide and loop diuretics, medications that elevate serum uric acid levels, are often the first-line treatments for CKD.5 According to guidelines recently published by the American College of Rheumataology (ACR), CKD is an indication for urate-lowering therapy (ULT) in patients with a history of gout attacks or hyperuricemia.
Each year there are 3.9 million patient visits for gout, and the majority of cases are managed by a primary-care provider (PCP). This article is designed to help guide PCPs in the management of gout in CKD patients while reflecting the 2012 ACR recommendations. Table 1 describes the stages of CKD.
Despite greater efficacy of febuxostat as a ULT agent compared with allopurinol, does cost limit how you prescribe it?
The ACR acknowledges that diet and lifestyle modifications alone are not likely to lower serum uric acid to therapeutic levels or serve as gout prophylaxis. The primary goals of diet and lifestyle changes are to promote overall health and better management of comorbidities. For all patients, the ACR task force recommends weight loss if obese, overall healthy diet, exercise, smoking cessation, and good hydration.
While recognizing an improved diet is insufficient monotherapy for most, the panel did recommend specific dietary guidelines. All gout patients are advised limit alcohol intake, particularly beer.5 Regardless of gout activity, alcohol overuse should be avoided in all patients (the ACR defines alcohol overuse as more than one serving per day for women and more than two servings per day for men). Avoidance of food and sodas sweetened with high fructose corn syrup is also recommended.
Table 1. GFR categories in CKD
|G1||>90||Normal or high|
|G3a||45-59||Mildly to moderately decreased|
|G3b||30-44||Moderately to severely decreased|
|Source: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013; 3:1-150.|
Both thiazide and loop diuretics promote hyperuricemia. The ACR suggests eliminating offending agents if deemed nonessential. However, both types of diuretics are often first-line choices for BP management in the CKD patient. Given the health-related quality-of-life concerns of many gout patients, substitution of a non-urate-elevating antihypertensive should be considered whenever possible. Sufficient BP control is rarely achieved with monotherapy in the CKD patient. A diuretic may be required in the future to control BP and reduce extracellular fluid.
CKD stage 2 through stage 5 with hyperuricemia and a history of acute gout activity is, by itself, an indication to initiate ULT. The target serum uric acid should <6 mg/dL. To achieve symptomatic relief, target serum levels may need to be 5 mg/dL. When initiating ULT, acute gout prophylaxis should be started simultaneously.
The ACR addressed the misconception that ULT may not be initiated during active flares. As long as appropriate anti-inflammatory management is administered (e.g., oral corticosteroid taper), ULT can be started during acute flares. The xanthine oxidase inhibitors (XOIs) allopurinol and febuxostat (Uloric) are recommended as first-line ULT agents for patients with CKD.
While cost was not taken into consideration in the ACR recommendations, reserving febuxostat to those patients with intolerance or a contraindication to allopurinol due to cost issues has been suggested. Probenecid (Benemid, Probalan) is a uricosuric agent recommended as an alternative ULT agent if XOIs are not tolerated or ineffective. Probenecid is not recommended in patients with a creatinine clearance <50 ml/min.
For any patient, the initial dose of allopurinol should be <100 mg/day and <50 mg/day in patients with CKD stage 4 or stage 5. Starting at a low dose is a strategy designed to decrease gout flares associated with initiation of ULT and to lessen the risk of allopurinol hypersensitivity and other adverse reactions.
Allopurinol should be increased every two to five weeks based on serum uric acid levels and clinical response. The maintenance dose can be >300 mg/day, even in patients with CKD, as long as patients receive education and providers monitor for adverse events and hypersensitivity. Providers should monitor for pruritis, rash, elevated hepatic transaminases, and eosinophilia. There is an algorithm for dosing allopurinol based on creatinine clearance, but it was not recommended by the ACR because it is not evidence-based.
Patient education is essential for successful treatment of gout in individuals with CKD. Once palpable tophi and symptoms of acute and chronic gout have dissipated, pharmacologic and nonpharmacologic ULT should be maintained indefinitely. PCPs should inform each patient that ULT has to be taken daily, especially when symptom-free, to prevent gout from recurring. Allopurinol should be thought of as “the cure.”
Because lower serum uric acid levels are associated with less frequent acute flares, ULT is considered the mainstay in gout management. However, the initiation of ULT is also associated with increased acute gout attacks.6 Thus, prophylactic therapy should be started at the same as or just prior to ULT.
For patients with gout, the ACR recommends low-dose colchicine or low-dose nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line prophylactic agents. Low-dose oral prednisone or prednisolone are considered second-line agents. In patients with CKD, however, NSAIDs can cause acute worsening of eGFR and are contraindicated in all stages of CKD.
Colchicine is excreted renally and can accumulate to toxic levels in renal impairment. Colchicine is not contraindicated, but dose adjustment and close monitoring is suggested. Signs of toxicity include leukopenia, elevation of aspartate aminotransferase, and neuropathy.
The pain of an acute gout flare can be excruciating. Pharmacologic therapy should be started promptly; preferably within 24 hours for the most effective relief. Oral corticosteroids provide relief of pain and inflammation and are a good choice for the patient with CKD. The ACR recommends prednisone 0.5 mg/kg for two to five days at full dose, then tapered over seven to 10 days and stopped. Corticosteroids are not contraindicated in patients with diabetes, but blood glucose should be monitored. Adjustments to glycemic agents may be needed.
Intra-articular corticosteroids are also appropriate for acute management. The size and number of joints involved, as well as practice setting, can limit this option. Since injections require an office visit, intra-articular injections are less convenient than oral medications, which can be initiated by patients at home when symptoms arise. If using intra-articular corticosteroids, the provider must confirm that the joint is not infected.
In late 2012, the ACR published new guidelines for gout management. Part one of the guidelines is dedicated to the nonpharmacologic and pharmacologic management of hyperuricemia, and part two addresses management of acute attacks and prophylaxis.
In addition, the ACR guidelines emphasize recognizing comorbidities and discuss diet and lifestyle modifications, the elimination of offending agents, and therapy education. These guidelines also offer pharmacologic recommendations for the CKD patient with gout.
Mary Rogers Sorey, ACNP-BC, works in the nephrology division at Duke University Medical Center in Durham, N.C.
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- Wallace SL, Singer JZ, Duncan GJ, et al. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol. 1991;18:264-269.
- Juraschek SP, Kovell LC, Miller ER 3rd, Gelber AC. Association of kidney disease with prevalent gout in the United States in 1988-1994 and 2007-2010. Semin Arthritis Rheum. 2013;42:551-561.