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狼疮患儿中肾素-血管紧张素-醛固酮系统抑制剂的应用与糖皮质激素停药时间。

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

机构信息

Center for Pediatric Clinical Effectiveness, Department of Pediatrics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA; Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Center for Pediatric Clinical Effectiveness, Department of Pediatrics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Division of Rheumatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

出版信息

Kidney Int. 2022 Aug;102(2):395-404. doi: 10.1016/j.kint.2022.04.023. Epub 2022 May 23.

Abstract

There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

摘要

关于血管紧张素肾素醛固酮系统(RAAS)抑制剂在儿童系统性红斑狼疮(SLE)患者中的应用,目前数据较少。在此,我们旨在描述儿童 SLE 中 RAAS 抑制剂的使用情况,并确定在狼疮肾炎患儿中早期使用 RAAS 抑制剂是否与减少慢性糖皮质激素暴露时间有关。我们对 2013 年至 2018 年 Truven MarketScan Medicaid 和商业数据库中患有 SLE 和/或狼疮肾炎的儿童(5-18 岁)进行了回顾性队列研究,并估计了 RAAS 抑制剂的使用情况。在新发生的肾炎病例中,我们使用竞争风险风险模型和治疗反概率加权来估计诊断后 180 天内开始使用 RAAS 抑制剂与以肾功能衰竭为竞争事件的糖皮质激素停药时间之间的关联。在 592 例肾炎患者和 1407 例非肾脏 SLE 患者中,分别有 67%和 15%的患者接受过 RAAS 抑制剂治疗。在 323 例新使用 RAAS 抑制剂的患者中,分别有 14 个月和 9 个月的 RAAS 抑制剂使用中位数。无论是否患有肾炎,Medicaid 参保均与 RAAS 抑制剂使用的可能性更大相关。在 158 例新发生的肾炎病例中,早期 RAAS 抑制剂的使用与糖皮质激素停药更快相关(调整后的亚分布风险比 1.81,95%置信区间[1.09-3.00])。因此,RAAS 抑制剂的早期使用可能在新诊断为狼疮肾炎的儿童中发挥作用;不仅适用于诱导治疗后存在难治性蛋白尿的患者。因此,综合健康系统数据可以用来证实这些发现,并优化儿科狼疮的辅助治疗。

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