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Diuretics ineffective in gout management
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Diuretics, such as loop agents and thiazides, do not have a significant effect on managing gout, according to findings published in Arthritis Research and Therapy.
“There is a need to determine the impact of diuretics on gout management in clinical practice, especially after the incorporation of new [urate-lowering drugs (ULD)] and treat-to-target strategies,” Laura Ranieri, MD, of the Hospital General Universitario de Alicante, and colleagues wrote. “This knowledge could inform management plans for patients with gout who are taking diuretics, helping to achieve suitable [serum urate] reductions that ensure the cure of the disease.”
To determine the impact diuretics have on the response to ULD in patients with gout, the researchers conducted a retrospective analysis of an inception cohort from the Hospital General Universitario de Alicante Rheumatology Department. Patients included in the cohort were those who arrived at the unit for the first time with crystal-proven gout without having received any previous specialized care.
Among the 245 patients analyzed for the study, 208 received treatment with allopurinol, of which 66 were on diuretics; 35 received febuxostat (Uloric, Takeda), with 19 on diuretics; and 2 received benzbromarone. Ranieri and colleagues analyzed the patients’ ULD maximal dose as the primary outcome variable, as well as serum urate reduction, according to the type of treatment they received and their use of diuretics. Serum urate reduction targets were 6 mg/dL, 5 mg/dL, and 4 mg/dL.
According to the researchers, significantly fewer patients who received both allopurinol and diuretics achieved serum urate levels of less than 5 mg/dL. They did not find other significant differences in serum urate targets associated with diuretics. Linear regression analysis indicated an inverse relationship between diuretics and maximum ULD dose (beta = 0.125; P = .073), but this was not maintained in multivariable analysis (beta = 0.47; P = .833). Further, the researchers found no association with febuxostat (beta = 0.116; P = 0.514).
“Both loop agents and thiazides are diuretics that are commonly prescribed in patients with gout and have often been associated with impaired response to allopurinol and refractoriness, prompting recommendations for their discontinuation when possible,” Ranieri and colleagues wrote. “However, the results of the present study do not support prior observations related to the achievement of [serum urate] targets or the necessary ULD dosage, while they are in keeping with those recently reported by Kannangara et al. These findings require further confirmation through prospective, intervention studies.” – by Jason Laday
Disclosure: Ranieri reports no relevant financial disclosures. See the full study for additional authors’ disclosures.
Perspective
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N. Lawrence Edwards, MD, MACP, MACR
Ranieri and colleagues attempt to answer an important question about whether the use of diuretics interferes with medical management of gout when using xanthene oxidase inhibitors. The 2006 EULAR guidelines for the treatment of gout recommend the discontinuation of diuretics when medically feasible as part of controlling serum urate level (proposition 12), yet the 2012 ACR guidelines for gout management did not recommend diuretic discontinuation because of the lack of supporting data. Ranieri and colleagues shed some light on this topic with a retrospective, clinical practice-based analysis.
The researchers reviewed the records of 243 patients with crystal-proven gout who were naïve to urate-lowering therapy; allopurinol was initiated in 208 patients and febuxostat initiated in 35. Among the allopurinol patients, 32% were receiving diuretics whereas 58% of the febuxostat patients were receiving diuretics. The febuxostat patients also had worse baseline renal function.
There was no difference in the average maximum dose of either allopurinol or febuxostat that was required to achieve the target serum urate levels, whether patients were receiving a diuretic or not. The results of this study do not support a recommendation to discontinue diuretics as part of a urate-lowering strategy. Not addressed in this study was the potential effects of diuretics on uricosuric agents, such as lesinurad or probenecid.
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