Internal Medicine Department, Rheumatology Unit, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts.
JAMA Intern Med. 2018 Nov 1;178(11):1526-1533. doi: 10.1001/jamainternmed.2018.4463.
Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines.
To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher.
DESIGN, SETTING, AND PARTICIPANTS: A time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis.
Allopurinol initiation at a dose of 300 mg or more per day.
Development of chronic kidney disease stage 3 or higher.
Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09).
In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.
当肾功能下降时,临床医生在痛风患者中使用别嘌呤醇时往往持谨慎态度。
评估痛风患者使用别嘌呤醇与发展为慢性肾脏病 3 期或更高阶段的风险之间的关系。
设计、设置和参与者:这是一项在英国一般实践电子健康记录数据库 Health Improvement Network(THIN)中进行的时间分层倾向评分匹配、基于人群的前瞻性队列研究,纳入了新诊断为痛风且开始使用别嘌呤醇(≥300mg/d)的患者(≥300mg/d)与未开始使用别嘌呤醇的患者进行比较。数据使用 Cox 比例风险回归进行分析。在年龄在 18 至 89 岁之间、新诊断为痛风的成年人中,我们将 4760 名起始剂量为 300mg 或更高剂量的别嘌呤醇(≥300mg/d)与相同数量的未起始别嘌呤醇的患者进行了倾向性评分匹配,排除了那些在痛风诊断前患有慢性肾脏病 3 期或更高阶段或尿酸降低治疗的患者。
起始剂量为 300mg 或更高剂量的别嘌呤醇。
发展为慢性肾脏病 3 期或更高阶段。
在 4760 名别嘌呤醇起始者(3975 名男性,785 名女性)和相同数量的非起始者(3971 名男性,789 名女性)中,分别有 579 名和 623 名发展为慢性肾脏病 3 期或更高阶段,平均随访时间分别为 5 年和 4 年,平均年龄分别为 57 岁,两组的平均体重指数(计算为体重公斤数除以身高米数的平方)均为 30。与非使用者相比,至少使用 300mg/d 的别嘌呤醇与较低的发展为慢性肾脏病 3 期或更高阶段的风险相关,风险比(HR)为 0.87(95%CI,0.77-0.97)。起始剂量小于 300mg/d 的别嘌呤醇与肾功能下降无关(HR,1.00;95%CI,0.91-1.09)。
在这项大型队列研究中,起始剂量至少 300mg/d 的别嘌呤醇与肾功能恶化的风险降低相关。由于别嘌呤醇似乎与肾功能下降无关,因此当痛风患者出现肾功能下降时,临床医生应考虑评估其他潜在原因。