Abstract：
Allopurinol should be started at lower doses in patients with chronic kidney disease (CKD) to avoid adverse effects. We examined the risk of severe cutaneous reactions in older adults with CKD who were newly prescribed allopurinol at varied doses.
Population-based cohort study using linked health care databases.
Patients in Ontario, Canada (2008-2019) aged ≥66 years, with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, and who were new users of allopurinol.
A new prescription for allopurinol >100 mg/d versus a dose ≤100 mg/d.
The primary outcome was a hospital visit with a severe cutaneous reaction within 180 days of starting allopurinol. Secondary outcomes included all-cause hospitalization and all-cause mortality.
The exposure and referent groups were balanced on indicators of baseline health using inverse probability of treatment weighting on the propensity score. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression.
Of 47,315 patients (median age, 76 years; median eGFR, 45 mL/min/1.73 m2), 55% started allopurinol at >100 mg/d. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of a severe cutaneous reaction: number of events (weighted), 103 of 25,802 (0.40%) versus 46 of 25,816 (0.18%), respectively (weighted RR, 2.25 [95% CI, 1.50-3.37]; weighted RD, 0.22% [95% CI, 0.12%-0.32%]. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of all-cause hospitalization but not with all-cause mortality.
This study was underpowered to detect risk differences in the association of allopurinol dose with outcomes across eGFR categories (ie, 45-59, 30-44, and <30 mL/min/1.73 m2).
Older patients with CKD who started allopurinol at >100 mg/d versus ≤100 mg/d were twice as likely to visit a hospital with a severe cutaneous reaction in the next 180 days.
Population-based cohort study using linked health care databases.
Patients in Ontario, Canada (2008-2019) aged ≥66 years, with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, and who were new users of allopurinol.
A new prescription for allopurinol >100 mg/d versus a dose ≤100 mg/d.
The primary outcome was a hospital visit with a severe cutaneous reaction within 180 days of starting allopurinol. Secondary outcomes included all-cause hospitalization and all-cause mortality.
The exposure and referent groups were balanced on indicators of baseline health using inverse probability of treatment weighting on the propensity score. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression.
Of 47,315 patients (median age, 76 years; median eGFR, 45 mL/min/1.73 m2), 55% started allopurinol at >100 mg/d. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of a severe cutaneous reaction: number of events (weighted), 103 of 25,802 (0.40%) versus 46 of 25,816 (0.18%), respectively (weighted RR, 2.25 [95% CI, 1.50-3.37]; weighted RD, 0.22% [95% CI, 0.12%-0.32%]. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of all-cause hospitalization but not with all-cause mortality.
This study was underpowered to detect risk differences in the association of allopurinol dose with outcomes across eGFR categories (ie, 45-59, 30-44, and <30 mL/min/1.73 m2).
Older patients with CKD who started allopurinol at >100 mg/d versus ≤100 mg/d were twice as likely to visit a hospital with a severe cutaneous reaction in the next 180 days.
摘要：
在患有慢性肾脏疾病（CKD）的患者中，应开始使用较低剂量的别嘌呤醇，以避免不良反应。我们检查了CKD老年患者严重皮肤反应的风险，这些患者新服用不同剂量的别嘌呤醇。
使用关联医疗保健数据库的基于人群的队列研究。
安大略省的患者，加拿大（2008-2019）年龄≥66岁，估计肾小球滤过率（eGFR）<60mL/min/1.73m2，并且是别嘌呤醇的新使用者。
别嘌醇>100mg/d与剂量≤100mg/d的新处方。
主要结果是在开始使用别嘌呤醇后180天内出现严重皮肤反应的医院就诊。次要结局包括全因住院和全因死亡率。
使用倾向评分的治疗加权的逆概率，在基线健康指标上平衡暴露组和参考组。使用改进的Poisson回归获得加权风险比（RR），并使用二项回归获得加权风险差（RD）。
47,315名患者（中位年龄，76岁；eGFR中位数，45mL/min/1.73m2),55%以>100mg/d开始使用别嘌呤醇。在>100和≤100mg/d时开始使用别嘌呤醇与严重皮肤反应的风险增加相关：事件数（加权），25,802人中的103人（0.40%）与25,816人中的46人（0.18%），分别(加权RR，2.25[95%CI，1.50-3.37]；加权RD，0.22%[95%CI，0.12%-0.32%]。在>100和≤100mg/d时开始使用别嘌呤醇与全因住院风险增加相关，但与全因死亡率无关。
这项研究在检测不同eGFR类别的别嘌呤醇剂量与结局之间的风险差异方面的能力不足（即，45-59、30-44和<30mL/min/1.73m2)。
老年CKD患者开始服用别嘌呤醇>100mg/d和≤100mg/d时，在接下来的180天内就诊严重皮肤反应的可能性是老年CKD患者的两倍。
使用关联医疗保健数据库的基于人群的队列研究。
安大略省的患者，加拿大（2008-2019）年龄≥66岁，估计肾小球滤过率（eGFR）<60mL/min/1.73m2，并且是别嘌呤醇的新使用者。
别嘌醇>100mg/d与剂量≤100mg/d的新处方。
主要结果是在开始使用别嘌呤醇后180天内出现严重皮肤反应的医院就诊。次要结局包括全因住院和全因死亡率。
使用倾向评分的治疗加权的逆概率，在基线健康指标上平衡暴露组和参考组。使用改进的Poisson回归获得加权风险比（RR），并使用二项回归获得加权风险差（RD）。
47,315名患者（中位年龄，76岁；eGFR中位数，45mL/min/1.73m2),55%以>100mg/d开始使用别嘌呤醇。在>100和≤100mg/d时开始使用别嘌呤醇与严重皮肤反应的风险增加相关：事件数（加权），25,802人中的103人（0.40%）与25,816人中的46人（0.18%），分别(加权RR，2.25[95%CI，1.50-3.37]；加权RD，0.22%[95%CI，0.12%-0.32%]。在>100和≤100mg/d时开始使用别嘌呤醇与全因住院风险增加相关，但与全因死亡率无关。
这项研究在检测不同eGFR类别的别嘌呤醇剂量与结局之间的风险差异方面的能力不足（即，45-59、30-44和<30mL/min/1.73m2)。
老年CKD患者开始服用别嘌呤醇>100mg/d和≤100mg/d时，在接下来的180天内就诊严重皮肤反应的可能性是老年CKD患者的两倍。
