Parkin Lianne, Sharples Katrina J, Barson David J, Blank Mei-Ling
Department of Preventive and Social Medicine, Dunedin School of Medicine, Division of Health Sciences, University of Otago, Dunedin, New Zealand.
Department of Mathematics and Statistics, Division of Sciences, University of Otago, Dunedin, New Zealand.
PLoS One. 2017 Jul 28;12(7):e0182066. doi: 10.1371/journal.pone.0182066. eCollection 2017.
Inconsistent findings from four observational studies suggest that the risk of acute kidney injury (AKI) may increase with increasing statin dose or potency, but none of the studies took statin-related severe muscle injury, including rhabdomyolysis, into account. We undertook a nationwide nested case-control study in New Zealand to examine the risk of AKI without concurrent serious muscle injury according to simvastatin dose in two cohorts: people without a history of renal disease and people with non-dialysis dependent chronic kidney disease.
A total of 334,710 people aged ≥ 18 years without a history of renal disease (cohort 1) and 5,437 with non-dialysis dependent chronic kidney disease (cohort 2) who initiated simvastatin therapy between 1 January 2006 and 31 December 2013 were identified using national pharmaceutical dispensing and hospital discharge data. Patients who developed AKI without concurrent serious muscle injury during follow-up (cases) were ascertained using hospital discharge and mortality data (n = 931 from cohort 1, n = 160 from cohort 2). Up to 10 controls per case, matched by date of birth, sex, and cohort entry date were randomly selected from the relevant cohort using risk set sampling.
Relative to current use of 20mg simvastatin daily, the adjusted odds ratios and 95% confidence intervals (95% CI) in cohort 1 for current use of 40mg and 80mg were 0.9 (95% CI 0.7-1.2) and 1.3 (95% CI 0.7-2.3), respectively. The adjusted odds ratio for 40mg in cohort 2 was 1.1 (95% CI 0.7-1.9); the numbers taking 80mg were very small and the confidence interval was correspondingly wide.
The findings of this study suggest that a relationship between statin dose and AKI may not exist independent of serious muscle injury.
四项观察性研究结果不一致,提示急性肾损伤(AKI)风险可能随他汀类药物剂量增加或效力增强而升高,但这些研究均未考虑他汀类药物相关的严重肌肉损伤,包括横纹肌溶解症。我们在新西兰开展了一项全国性巢式病例对照研究,以根据辛伐他汀剂量,在两个队列中研究无并发严重肌肉损伤的AKI风险:无肾脏疾病病史者和非透析依赖性慢性肾脏病患者。
利用全国药物配给和医院出院数据,确定了2006年1月1日至2013年12月31日期间开始使用辛伐他汀治疗的334710名年龄≥18岁且无肾脏疾病病史者(队列1)和5437名非透析依赖性慢性肾脏病患者(队列2)。利用医院出院和死亡率数据确定随访期间发生无并发严重肌肉损伤的AKI患者(病例)(队列1中n = 931,队列2中n = 160)。采用风险集抽样方法,从相关队列中为每个病例随机选取多达10名对照,对照按出生日期、性别和队列入组日期进行匹配。
相对于当前每日使用20mg辛伐他汀,队列1中当前使用40mg和80mg辛伐他汀的校正比值比及95%置信区间(95%CI)分别为0.9(95%CI 0.7 - 1.2)和1.3(95%CI 0.7 - 2.3)。队列2中40mg辛伐他汀的校正比值比为1.1(95%CI 0.7 - 1.9);服用80mg的人数非常少,因此置信区间相应较宽。
本研究结果提示,他汀类药物剂量与AKI之间的关系可能并非独立于严重肌肉损伤而存在。