Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study.

OBJECTIVES: To examine associations of race/ethnicity and purported risk factors with hospitalised allopurinol-associated severe cutaneous adverse reactions (AASCARs). METHODS: We used US Medicaid data to identify incident allopurinol users between 1999 and 2012. We examined the risk of hospitalised AASCARs according to race/ethnicity and purported key risk factors and calculated relative risks (RR). RESULTS: Among 400 401 allopurinol initiators, we documented 203 hospitalised AASCAR cases (1 in 1972 initiators). The average AASCAR hospitalisation was 9.6 days and 43 individuals (21%) died. The multivariable-adjusted RRs for AASCARs among blacks, Asians and Native Hawaiians/Pacific Islanders compared with whites or Hispanics were 3.00 (95% CI 2.18 to 4.14), 3.03 (95% CI 1.72 to 5.34) and 6.68 (95% CI 4.37 to 10.22), respectively. Female sex, older age (≥60 years), chronic kidney disease and initial allopurinol dose (>100 mg/day) were independently associated with a 2.5-fold, 1.7-fold, 2.3-fold and 1.9-fold higher risk of AASCAR, respectively. In our combined demographic analysis, older women (≥60 years) of a high-risk race/ethnicity (blacks, Asians or Native Hawaiians/Pacific Islanders) had over a 12-fold higher risk of hospitalised AASCARs than younger men of a low-risk race/ethnicity (whites or Hispanics) (multivariable-adjusted RR, 12.25; 95% CI 6.46 to 23.25). CONCLUSIONS: This racially diverse (yet mostly white) cohort study indicates that the risk of hospitalised AASCAR is rare overall, although blacks, Asians and Native Hawaiians/Pacific-Islanders have a substantially higher risk of hospitalised AASCARs, particularly among older women. These data also support the practice of initiating allopurinol at a low dose (eg, ≤100 mg/day).

The independent association between parathyroid hormone levels and hyperuricemia: a national population study.

INTRODUCTION: Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults. METHODS: By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression. RESULTS: SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 µM (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 µM among those with GFR ≥ 60 versus < 60 ml/min per 1.73 m2, respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05). CONCLUSIONS: These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level.

Serum uric acid levels and the risk of type 2 diabetes: a prospective study.

PURPOSE: To evaluate the impact of serum uric acid levels on the future risk of developing type 2 diabetes independent of other factors. METHODS: We used prospective data from the Framingham Heart Study original (n=4883) and offspring (n=4292) cohorts to examine the association between serum uric acid levels and the incidence of diabetes. We used Cox proportional hazards models to estimate the relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides. RESULTS: We identified 641 incident cases of diabetes in the original cohort and 497 cases in the offspring cohort. The incidence rates of diabetes per 1000 person-years for serum uric acid levels <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 3.3, 6.1, 8.7, 11.5, and 15.9, respectively, in the original cohort; and 2.9, 5.0, 6.6, 8.7, and 10.9, respectively, in the offspring cohort (P-values for trends <.001). Multivariable relative risks per mg/dL increase in serum uric acid levels were 1.20 (95% confidence interval; 1.11-1.28) for the original cohort and 1.15 (95% confidence interval; 1.06-1.23) for the offspring cohort. CONCLUSIONS: These prospective data from 2 generations of the Framingham Heart Study provide evidence that individuals with higher serum uric acid; including younger adults, are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on cross-sectional associations between hyperuricemia and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.

Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey.

OBJECTIVE: Sugar-sweetened soft drinks contain large amounts of fructose, which may significantly increase serum uric acid levels and the risk of gout. Our objective was to evaluate the relationship between sugar-sweetened soft drink intake, diet soft drink intake, and serum uric acid levels in a nationally representative sample of men and women. METHODS: Using data from 14,761 participants age>or=20 years from the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between soft drink consumption and serum uric acid levels using linear regression. Additionally, we examined the relationship between soft drink consumption and hyperuricemia (serum uric acid level>7.0 mg/dl for men and >5.7 mg/dl for women) using logistic regression. Intake was assessed by a food-frequency questionnaire. RESULTS: Serum uric acid levels increased with increasing sugar-sweetened soft drink intake. After adjusting for covariates, serum uric acid levels associated with sugar-sweetened soft drink consumption categories (<0.5, 0.5-0.9, 1-3.9, and >or=4 servings/day) were greater than those associated with no intake by 0.08, 0.15, 0.33, and 0.42 mg/dl, respectively (95% confidence interval 0.11, 0.73; P<0.001 for trend). The multivariate odds ratios for hyperuricemia according to the corresponding sweetened soft drink consumption levels were 1.01, 1.34, 1.51, and 1.82, respectively (P=0.003 for trend). Diet soft drink consumption was not associated with serum uric acid levels or hyperuricemia (multivariate P>0.13 for trend). CONCLUSION: These findings from a nationally representative sample of US adults suggest that sugar-sweetened soft drink consumption is associated with serum uric acid levels and frequency of hyperuricemia, but diet soft drink consumption is not.