Protecting Patients with Glomerular Disease from Vaccine-Preventable Infections

摘要 在肾小球疾病患者中发生的流感和肺炎球菌感染是可以预防的 造成过度医疗利用、发病率和死亡率的因素，并以大约30倍的速度发生 与美国普通人群相比，肾小球疾病患者的发病率更高。接种疫苗是一种 然而，疫苗的免疫原性和免疫原性 在这些高危患者群体中，有效性还没有得到充分的研究。接种疫苗可能不会产生效果 肾小球疾病患者的保护性或持续性免疫反应 免疫抑制药物，改变免疫细胞功能，尿免疫球蛋白丢失和 补充性因素。因此，关于这些抗体是否在- 预防流感和肺炎球菌感染的活体保护。需要解决的证据差距 针对这一人群感染预防措施的务实试验的准备工作包括 接种推荐疫苗的情况、感染并发症的传播情况以及流感和 肺炎球菌疫苗血清转换和血清保护。以前的研究一直受到样本量小的限制， 特征不充分的队列，以及使用非光学测量的分析，因此潜在的非光学 功能性抗体。 这项建议的目的是描述流感和肺炎球菌疫苗接种与 流感和肺炎球菌感染，并描述了功能性疫苗的免疫原性 肾小球疾病。为实现这一目标提出了三个项目：分析流感和 肺炎球菌疫苗的使用和有效性在全国医疗保健索赔数据库(MarketScan®)中，a 多中心NIDDK治疗肾小球疾病疫苗免疫原性检测研究 (CureGN)研究，并创建一个多中心队列来检查23价肺炎球菌疫苗 肾病综合征患儿的免疫原性。主要的假设是，独立于肾脏 功能、流感和肺炎球菌感染率以及次优疫苗反应将在#年更高 有活动性肾小球疾病、更多免疫抑制暴露、更多蛋白尿的个体 年纪还小。格伦博士的职业发展目标包括获得统计方法和 流行病学研究设计，重点分析纵向数据集、医疗保健索赔数据和 多中心疫苗免疫原性研究。格伦博士将接受艾米·莫特尔博士和罗纳德博士的指导 福尔克，都是肾小球疾病领域的专家。此外，格伦博士将有一项科学建议 委员会由疫苗免疫原性、传染病、医疗保健索赔数据分析、 和流行病学。这项工作将为开发R01应用程序提供信息，在该应用程序中，Glenn博士领导了一个 研究肾病综合征儿童肺炎球菌疫苗接种策略的务实试验。

ABSTRACT Influenza and pneumococcal infections occurring in individuals with glomerular disease are preventable contributors to excess healthcare utilization, morbidity, and mortality, and occur at a rate approximately 30 times higher among individuals with glomerular diseases compared to the general US population. Vaccination is a powerful and cost-effective method to reduce infectious burden, however, vaccine immunogenicity and effectiveness have not been adequately studied in this high-risk patient population. Vaccination may not yield protective or sustained immune responses in individuals with glomerular disease as a result of exposure to immunosuppressive medications, altered immune cell function, and urinary loss of immunoglobulin and complement factors. As a result, there remain pressing questions regarding whether these antibodies confer in- vivo protection from influenza and pneumococcal infection. Evidence gaps that need to be addressed in preparation for pragmatic trials focused on infection-prevention measures in this population include frequency of administration of recommended vaccines, pervasiveness of infectious complications, and rates of influenza and pneumococcal vaccine seroconversion and seroprotection. Prior studies have been limited by small sample size, insufficiently characterized cohorts, and the use of assays that measure non-opsonic, and thus potentially non- functional, antibodies. The objective of this proposal is to describe the association of influenza and pneumococcal vaccination with influenza and pneumococcal infections and describe functional vaccine immunogenicity in patients with glomerular disease. Three projects have been proposed to achieve this objective: an analysis of influenza and pneumococcal vaccine use and effectiveness in a nationwide healthcare claims database (MarketScan®), a study examining vaccine immunogenicity in the multicenter NIDDK-sponsored Cure Glomerulonephropathy (CureGN) study, and creation of a multicenter cohort to examine 23-valent pneumococcal vaccine immunogenicity in children with nephrotic syndrome. The primary hypothesis is that, independent of kidney function, rates of influenza and pneumococcal infection and suboptimal vaccine response will be higher in individuals with active glomerular disease, greater immunosuppression exposure, greater proteinuria, and younger age. Dr. Glenn’s career development goals include gaining advanced training in statistical methods and epidemiologic study design, with a focus on the analysis of longitudinal datasets, healthcare claims data, and multicenter vaccine immunogenicity studies. Dr. Glenn will receive mentorship from Dr. Amy Mottl and Dr. Ronald Falk, both experts in the field of glomerular kidney disease. Additionally, Dr. Glenn will have a scientific advisory committee comprised of experts in vaccine immunogenicity, infectious disease, healthcare claims data analysis, and epidemiology. This work will inform the development of an R01 application in which Dr. Glenn leads a pragmatic trial investigating pneumococcal vaccination strategies among children with nephrotic syndrome.