Genomic Medicine Pilot For Hypertension And Kidney Disease In Primary Care

描述（由申请人提供）：目前缺乏健全的系统来同意、筛选、返回结果，并评估将基因组风险信息纳入常见慢性病临床护理的过程和结果。我们提出，非洲祖先社区中与高血压相关的CKD已经成为一个“原型”基因组医学示范项目的高度相关和非常合适的机会，该项目解决了在初级保健机构中管理的常见慢性疾病。与白人相比，非洲裔高血压（HTN）人群发生慢性肾病（CKD）的风险高出2- 3倍，进展为终末期肾病（ESRD）的风险高出5倍。最近的发现表明，22号染色体上APOL1位点的可测试等位基因对非洲血统人群中高血压相关CKD及其进展为ESRD的几乎所有过度风险都有主要影响和解释。在这个基因组医学示范试点项目中，我们计划在哈莱姆区和布朗克斯区社区卫生中心网络的初级保健设施以及西奈山医疗中心实施一项集群随机试验。该试验将检验正确的肾脏护理(即适当安排评估CKD和CKD进展的检查顺序、适当开具肾保护性肾素血管紧张素阻滞剂处方、适当控制非洲血统蛋白尿高血压患者的血压、与仅接受基于常规风险信息的肾保健CDS的机构相比，接受纳入APOL1基因组风险信息的emr肾保健CDS的机构将显著改善。该项目将有三个具体目标：1)了解有关APOL1检测的知识、态度和信念，返回结果，并使非洲人及其临床医生参与到检测、咨询和适当临床护理的过程中来。2)开发系统和基于证据的建议信息，使初级保健提供者能够在没有基因组APOL1风险信息的情况下，为肾脏护理实践指南提供护理点临床决策支持（CDS）。3)进行一项随机分组试验，指定8个不同的初级保健机构接受含有APOL1基因组风险信息（genomic renal care FACILITY）或常规风险信息（conventional renal care FACILITY）的肾脏保健CDS，以指导非糖尿病非裔美国高血压患者的初级保健。从长远来看，拟议的基因组医学示范试点项目预计将为基因组医学在各种临床环境中的可持续采用和大规模传播提供重要的新见解，这些临床环境一般为成人常见疾病提供护理，特别是为服务不足的非洲血统人群提供非糖尿病肾病的大量额外负担。

DESCRIPTION (provided by applicant): Robust systems to consent, screen, return results, and to evaluate processes and outcomes of incorporating genomic risk information in clinical care for common chronic diseases are missing and urgently needed. We propose that hypertension-associated CKD in African ancestry communities has emerged as a highly relevant and well-suited opportunity for a 'prototype' genomic medicine demonstration project that addresses common chronic illnesses managed in primary care settings. African ancestry populations with hypertension (HTN) have 2- to 3-fold higher risk of developing CKD, and a 5-fold increased risk to progress to end stage renal disease (ESRD) when compared with whites. Recent discoveries demonstrate that testable alleles of the APOL1 locus on chromosome 22 have a major effect on and explain almost all of the excess risk for hypertension-associated CKD and its progression to ESRD in African ancestry populations. In this genomic medicine demonstration pilot project, we plan to implement a cluster randomized trial at primary care facilities of a network of community health centers in Harlem and the Bronx and at Mount Sinai Medical Center. The trial will test whether the desperately low probabilities of correct renal care i.e. appropriate ordering of tests to evaluate CKD and CKD progression, appropriate prescription of renoprotective renin angiotensin blockade, appropriate control of blood pressure in hypertensive patients with albuminuria of African ancestry, will be improved significantly in those facilities that receive EMR-enabled renal care CDS incorporating APOL1 genomic risk information compared with those facilities that receive renal care CDS based on conventional risk information only. The project will have three Specific Aims: 1) Understand knowledge, attitudes, beliefs about testing for APOL1, returning results, and engaging people of African ancestry and their clinicians into a process of testing, counseling and appropriate clinical care. 2) Develop systems and evidence-based advice messages to enable point of care Clinical Decision Support (CDS) for primary care providers advising renal care practice guidelines with our without genomic APOL1 risk information. 3) Conduct a cluster randomized trial assigning eight distinct primary care facilities to receive either renal care CDS with APOL1 genomic risk information (GENOMIC RENAL CARE FACILITY) or with conventional risk information (CONVENTIONAL RENAL CARE FACILITY) to guide primary care for non-diabetic African Americans with hypertension. In the long-term, the proposed genomic medicine demonstration pilot project is expected to generate essential new insights for sustainable adoption and large-scale dissemination of genomic medicine in diverse clinical settings providing care for common adult-onset diseases in general, and for underserved African Ancestry populations with large excess burden of non-diabetic kidney diseases specifically.