Genomic Medicine Pilot For Hypertension And Kidney Disease In Primary Care

描述(由申请人提供)：缺少并迫切需要用于同意、筛选、返回结果以及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的强大系统。我们认为，非洲血统社区中与高血压相关的CKD已经成为一个高度相关和非常合适的机会，可以用于解决初级保健环境中管理的常见慢性病的“原型”基因组医学示范项目。与白人相比，患有高血压(HTN)的非洲血统人群患慢性肾脏病(CKD)的风险高2至3倍，进展为终末期肾病(ESRD)的风险高5倍。最近的发现表明，22号染色体上APOL1基因座的可检测等位基因对非洲血统人群中高血压相关CKD及其进展为ESRD的几乎所有额外风险都有重要影响，并可解释这些额外风险。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整群随机试验。这项试验将测试在那些接受包含APOL1基因组风险信息的EMR使能肾脏护理CDS的机构中，与那些接受仅基于传统风险信息的肾脏护理CDS的机构相比，是否会显著改善正确的肾脏护理的极低概率，即适当地安排测试以评估CKD和CKD的进展，适当的处方肾保护肾素血管紧张素受体阻滞剂，适当控制患有非洲血统的蛋白尿的高血压患者的血压。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，并使非洲血统的人及其临床医生参与检测、咨询和适当的临床护理过程。2)开发系统和基于证据的建议消息，以便为初级保健提供者提供护理点临床决策支持(CDS)，使用我们的无基因组APOL1风险信息为肾脏护理实践指南提供建议。3)进行整群随机试验，分配8个不同的初级保健机构接受带有APOL1基因组风险信息的肾脏护理CDS(基因组肾脏护理机构)或具有传统风险信息的肾脏护理CDS(传统肾脏护理机构)，以指导患有高血压的非糖尿病非裔美国人的初级保健。从长远来看，拟议的基因组医学示范试点项目预计将产生重要的新见解，以便在不同的临床环境中可持续地采用和大规模传播基因组医学，一般为常见的成人发病疾病提供护理，特别是针对非糖尿病肾脏疾病负担较大的未得到充分服务的非洲后裔人口。

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.