Glenn Dorey A, Zee Jarcy, Mansfield Sarah, O'Shaughnessy Michelle M, Bomback Andrew S, Gibson Keisha, Greenbaum Larry A, Mariani Laura, Falk Ronald, Hogan Susan, Mottl Amy, Denburg Michelle R
University of North Carolina, Chapel Hill, North Carolina.
The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Kidney Med. 2022 Oct 1;4(11):100553. doi: 10.1016/j.xkme.2022.100553. eCollection 2022 Nov.
RATIONALE & OBJECTIVE: Infections cause morbidity and mortality in patients with glomerular disease. The relative contributions from immunosuppression exposure and glomerular disease activity to infection risk are not well characterized. To address this unmet need, we characterized the relationship between time-varying combinations of immunosuppressant exposure and infection-related acute care events while controlling for disease activity, among individuals with glomerular disease.
Prospective, multicenter, observational cohort study.
SETTING & PARTICIPANTS: Adults and children with biopsy-proven minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or immunoglobulin A nephropathy/vasculitis were enrolled at 71 clinical sites in North America and Europe. A total of 2,388 Cure Glomerulonephropathy Network participants (36% aged <18 years) had at least 1 follow-up visit and were included in the analysis.
Immunosuppression exposure modeled on a weekly basis.
Infections leading to an emergency department visit or hospitalization.
Marginal structural models were used to estimate the effect of time-varying immunosuppression exposure on hazard of first infection-related acute care event while accounting for baseline sociodemographic and clinical factors, and time-varying disease activity.
A total of 2,388 participants were followed for a median of 3.2 years (interquartile range, 1.6-4.6), and 15% experienced at least 1 infection-related emergency department visit or hospitalization. Compared to no immunosuppression exposure, steroid exposure, steroid with any other immunosuppressant, and nonsteroid immunosuppressant exposure were associated with a 2.65-fold (95% CI, 1.83-3.86), 2.68-fold (95% CI, 1.95-3.68), and 1.7-fold (95% CI, 1.29-2.24) higher risk of first infection, respectively.
Absence of medication dosing data, lack of a control group, and potential bias in ascertainment of outcome events secondary to the coronavirus 2 pandemic.
Corticosteroids with or without concomitant additional immunosuppression significantly increased risk of infection leading to acute care utilization in adults and children with glomerular disease.
感染会导致肾小球疾病患者发病和死亡。免疫抑制暴露和肾小球疾病活动对感染风险的相对影响尚未得到充分描述。为满足这一未被满足的需求，我们在控制疾病活动的同时，对患有肾小球疾病的个体中免疫抑制剂暴露的时变组合与感染相关急性护理事件之间的关系进行了描述。
前瞻性、多中心、观察性队列研究。
北美和欧洲的71个临床地点招募了经活检证实患有微小病变病、局灶节段性肾小球硬化症、膜性肾病或免疫球蛋白A肾病/血管炎的成人和儿童。共有2388名治愈肾小球肾病网络参与者（36%年龄<18岁）至少进行了1次随访，并纳入分析。
以每周为基础模拟免疫抑制暴露情况。
导致急诊就诊或住院的感染。
使用边际结构模型来估计时变免疫抑制暴露对首次感染相关急性护理事件风险的影响，同时考虑基线社会人口统计学和临床因素以及时变疾病活动。
共对2388名参与者进行了中位3.2年的随访（四分位间距为1.6 - 4.6年），15%的参与者经历了至少1次与感染相关的急诊就诊或住院。与未暴露于免疫抑制剂相比，暴露于类固醇、类固醇与任何其他免疫抑制剂联合使用以及非类固醇免疫抑制剂分别使首次感染的风险增加2.65倍（95%置信区间，1.83 - 3.86）、2.68倍（95%置信区间，1.95 - 3.68）和1.7倍（95%置信区间，1.29 - 2.24）。
缺乏药物剂量数据、缺乏对照组以及由于2019冠状病毒病大流行导致结局事件确定存在潜在偏差。
使用或未使用额外免疫抑制剂的皮质类固醇显著增加了患有肾小球疾病的成人和儿童因感染导致急性护理利用的风险。
