Lowering and Raising Serum Urate Levels: Off-Label Effects of Commonly Used Medications

Leung, Nicole; Yip, Kevin; Pillinger, Michael H.; Toprover, Michael

doi:10.1016/j.mayocp.2022.02.027

Cited by 20 publications

(14 citation statements)

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“…Data on participant demographics (eg, age, sex, body mass index [BMI], serum urate blood test results, and estimated glomerular filtration rate [eGFR]), prespecified medical conditions, and treatment status were retrieved from the SLHCD. We used data on medication use for angina, myocardial infarction, transient ischemic attack, cerebral infarction, hypertension, diabetes, dyslipidemia, chronic kidney disease, tuberculosis, and nontuberculosis mycobacteria infections because these conditions can be treated with medications that can potentially change serum urate levels . Examples of these medications include aspirin, diuretics, calcium blockers, angiotensin receptor blockers, sodium-glucose cotransporter 2 inhibitors, statins, pyrazinamide, and ethambutol.…”

Section: Methodsmentioning

confidence: 99%

“…We used data on medication use for angina, myocardial infarction, transient ischemic attack, cerebral infarction, hypertension, diabetes, dyslipidemia, chronic kidney disease, tuberculosis, and nontuberculosis mycobacteria infections because these conditions can be treated with medications that can potentially change serum urate levels. 25 Examples of these medications include aspirin, diuretics, calcium blockers, angiotensin receptor blockers, sodium-glucose cotransporter 2 inhibitors, statins, pyrazinamide, and ethambutol. The lifestyle questionnaires included smoking status (never, previous, or current), daily physical activity (very low, low, moderate, or high), exercise level (<1, 1-2, 3-5, or >5 days per week with at least 20 minutes of light, sweaty exercise), and frequency of dietary intake of carbohydrate (eg, rice, bread, and noodles), meat and eggs, seafood, vegetables, fruits, milk and milk products, soy, fat (eg, fried foods, animal fat, and other fatty meals), and sweets.…”

Section: Study Participants and Data Collectionmentioning

confidence: 99%

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Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content

et al. 2023

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ImportanceDifferences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated.ObjectiveTo examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content.Design, Setting, and ParticipantsThis retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke’s International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021.ExposuresConsumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey.Main Outcomes and MeasuresSerum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed.ResultsThis study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with β coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P &lt; .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P &lt; .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with β coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, −0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, −0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages.Conclusions and RelevanceThe results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

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Section: Methodsmentioning

confidence: 99%

Section: Study Participants and Data Collectionmentioning

confidence: 99%

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content

et al. 2023

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“…We conducted a drug-drug interaction analysis between mAbs and other drugs that may induce hyperkalemia, 27 hypocalcemia, 28 and hyperuricemia. 29,30 We used the Ω shrinkage 31 to measure the drug-drug interactions because a previous study 32 showed it is the most conservative among multiple algorithms. The detection criterion is the lower limit of the 95% CI of the Ω (Ω 025 ) > 0.…”

Section: Drug-drug Interaction Analysismentioning

confidence: 99%

Tumor Lysis Syndrome Associated with Monoclonal Antibodies in Patients with Multiple Myeloma: A Pharmacovigilance Study Based on the FAERS Database

Xia

Gong

Zhao

et al. 2023

Clin Pharma and Therapeutics

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Although some tumor lysis syndrome (TLS) cases have been reported with patients with multiple myeloma (MM) taking monoclonal antibodies (mAbs), the association between TLS and mAbs remains mostly unknown. We aim to investigate the association between TLS and mAbs and describe clinical features. We conducted a disproportionality analysis to investigate the link between mAbs and TLS by excluding known confounders and compared with other anticancer drugs. The association between mAbs and TLS was evaluated using information component (IC). Drugdrug interaction signals were calculated based on the Ω shrinkage measure. Parametric distribution with the goodness-of-fit test was used for the reported time-to-onset analysis. From 2016 Q1, to 2022 Q4, a total of 274 TLS with mAbs were reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. There were 27% of patients with TLS with mAbs who died and 20.1% occurred a life-threatening situation. Daratumumab, elotuzumab, and belantamab mafodotin presented a robust disproportionate signal of TLS after excluding known confounders (IC 025 > 0). Daratumumab had the highest disproportionate signal of TLS among all anticancer drugs for MM. Reported time-to-onset analysis showed the median days for TLS with daratumumab, isatuximab, elotuzumab, and belantamab mafodotin were 1.5, 14.5, 5.5, and 5.5 days, respectively. The drugdrug interaction analysis showed the co-administration of drugs known to increase urate, induce hyperkalemia, or hypocalcemia elevated the reporting frequency for TLS with mAbs (Ω 025 > 0). Our postmarketing pharmacovigilance analysis detected the reporting association of TLS and mAbs in patients with MM. Additional studies with robust epidemiological study designs that can validate these findings are warranted.

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“…Low-dose aspirin, which is frequently used for primary or secondary prevention of cardiovascular and cerebrovascular events, may increase urate levels . Indeed, aspirin had been shown to have a biphasic effect on serum urate levels .…”

mentioning

confidence: 99%

“…At low doses, salicylate acts as an exchange substrate to facilitate urate reabsorption, but at high doses it can inhibit urea tubular reabsorption . Moreover, other frequently used drugs, such as diuretics, β-blockers and insulin, may also increase serum uric acid levels and potentiate the effect of aspirin.…”

mentioning

confidence: 99%

Gout Flare and Cardiovascular Events

Fonseca

2023

JAMA

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To the Editor A recent study 1 reported that experiencing a recent gout flare was associated with subsequent cardiovascular events among individuals with gout. While these results are interesting, I am concerned that the authors did not control for use of low-dose aspirin, which is commonly prescribed for people who are at higher risk of myocardial infarction or stroke. In this study, more individuals with gout and cardiovascular events had a history of cardiovascular disease and high to very high cardiovascular risk than matched controls with gout who did not have cardiovascular events.Low-dose aspirin, which is frequently used for primary or secondary prevention of cardiovascular and cerebrovascular events, may increase urate levels. 2 Indeed, aspirin had been shown to have a biphasic effect on serum urate levels. 3 Low doses of aspirin (≤2 g/d), which are commonly used for prevention of cardiovascular events, elevate serum urate levels, while high doses (>3 g/d) decrease serum urate. 3 These effects are explained by 2 modes of salicylate interaction with urate monocarboxylate exchanger 1. At low doses, salicylate acts as an exchange substrate to facilitate urate reabsorption, but at high doses it can inhibit urea tubular reabsorption. 4 Moreover, other frequently used drugs, such as diuretics, β-blockers and insulin, 2 may also increase serum uric acid levels and potentiate the effect of aspirin.A study 4 that evaluated use of low-dose aspirin and risk of recurrent gout attacks among patients with gout reported an adjusted odds ratio (OR) for gout attack of 1.81 (95% CI, 1.30-2.51) in patients using 325 mg per day or less of aspirin on 2 consecutive days, compared with no aspirin use. This study 4 found an even higher OR of 1.91 (95% CI, 1.32-2.85) with use of lower doses of aspirin (≤100 mg). Therefore, it would be informative if the authors of this study 1 could report their results controlling for the use of low-dose aspirin.

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Lowering and Raising Serum Urate Levels: Off-Label Effects of Commonly Used Medications

Cited by 20 publications

References 123 publications

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content

Tumor Lysis Syndrome Associated with Monoclonal Antibodies in Patients with Multiple Myeloma: A Pharmacovigilance Study Based on the FAERS Database

Gout Flare and Cardiovascular Events

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