ICES, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada.
ICES, Ontario, Canada; Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada.
Am J Kidney Dis. 2022 Dec;80(6):730-739. doi: 10.1053/j.ajkd.2022.04.006. Epub 2022 May 27.
RATIONALE & OBJECTIVE: 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.
SETTING & PARTICIPANTS: Patients in Ontario, Canada (2008-2019) aged ≥66 years, with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m, 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 m), 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 m).
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.
在患有慢性肾脏病（CKD）的患者中，应使用较低剂量的别嘌醇以避免不良反应。我们研究了在新开始使用别嘌醇的 CKD 老年患者中，不同剂量别嘌醇的严重皮肤反应风险。
使用链接的医疗保健数据库进行基于人群的队列研究。
2008 年至 2019 年期间，加拿大安大略省年龄≥66 岁、估算肾小球滤过率（eGFR）<60 mL/min/1.73 m 且新开始使用别嘌醇的患者。
新处方的别嘌醇剂量>100 mg/d 与剂量≤100 mg/d。
主要结局为开始使用别嘌醇后 180 天内发生严重皮肤反应的住院就诊。次要结局包括全因住院和全因死亡率。
使用倾向评分的逆概率治疗加权法，在基线健康指标上平衡暴露组和参照组。使用校正泊松回归获得加权风险比（RR），使用二项式回归获得加权风险差（RD）。
在 47315 名患者中（中位年龄 76 岁，中位 eGFR 45 mL/min/1.73 m），55%的患者开始使用别嘌醇的剂量>100 mg/d。与剂量≤100 mg/d 相比，开始使用别嘌醇的剂量>100 mg/d 与严重皮肤反应的风险增加相关：事件数量（加权）分别为 25802 例（0.40%）和 25816 例（0.18%）（加权 RR，2.25 [95%CI，1.50-3.37]；加权 RD，0.22% [95%CI，0.12%-0.32%]）。与剂量≤100 mg/d 相比，开始使用别嘌醇的剂量>100 mg/d 与全因住院风险增加相关，但与全因死亡率无关。
本研究的效力不足以检测不同别嘌醇剂量与 eGFR 类别（即 45-59、30-44 和<30 mL/min/1.73 m）相关结局之间的风险差异。
与剂量≤100 mg/d 相比，开始使用别嘌醇的剂量>100 mg/d 的 CKD 老年患者在接下来的 180 天内因严重皮肤反应而住院的可能性增加了一倍。
