The impact of hydroxychloroquine use on thrombosis and mortality in lupus-related end stage renal disease

羟氯喹的使用对狼疮相关终末期肾病血栓形成和死亡率的影响

• 批准号: 10192659
• 负责人: Anna Broder
• 金额: $ 12.14万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192659
• 关键词: Accounting; Address; Antiphospholipid Antibodies; Area; Autoimmune Diseases; Biometry; Caring; Cessation of life; Clinical; Clinical Research; Data; Data Analyses; Data Collection; Database Management Systems; Databases; Diagnosis; End stage renal failure; Enrollment; Event; Flare; Guidelines; Hemodialysis; Hydroxychloroquine; Individual; Intervention Studies; Kidney; Kidney Transplantation; Lead; Link; Lupus; Lupus Nephritis; Medicine; Mentors; Mentorship; Methods; Modality; Morbidity - disease rate; New York; Onset of illness; Outcome; Outcomes Research; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Pilot Projects; Prospective Studies; Publishing; Quality of life; Registries; Research; Research Personnel; Retrospective Studies; Risk; Role; Systemic Lupus Erythematosus; Testing; Thrombosis; Tissues; Transplantation; United States National Institutes of Health; Universities; Venous; Work; career development; clinical investigation; college; comparative effectiveness; cost effective; design; experience; graft failure; improved; individualized medicine; innovation; large datasets; large-scale database; medical schools; mortality; multidisciplinary; post-transplant; prospective; rheumatologist; skills; systemic inflammatory response; thrombotic; thrombotic complications; trial design

Abstract Systemic lupus erythematosus (SLE, lupus) is an autoimmune disease that causes systemic inflammation and tissue damage. Up to 60% of SLE patients develop kidney involvement (lupus nephritis), and 10-30% progress to end-stage renal disease (ESRD) within 10 years of diagnosis and despite treatment. Mortality in SLE ESRD is four-fold higher than in SLE with lupus nephritis alone, and twice as high as mortality in non-SLE ESRD, even though SLE patients are significantly younger at ESRD onset. Although numerous studies demonstrate poor outcomes, strategies to improve them have not been developed. Hydroxychloroquine use in SLE without ESRD has been associated with lower rates of SLE flares and thrombotic complications, as well as better overall survival. To date, there are no clinical studies exploring the benefits of hydroxychloroquine in SLE ESRD. Studying the effects of this drug directly in ESRD patients is important to develop individualized treatments and to decrease mortality. Our guiding hypothesis is that hydroxychloroquine use will decrease morbidity and mortality in SLE patients with ESRD undergoing the two most common renal replacement modalities, hemodialysis and kidney transplantation. To investigate this hypothesis we will analyze data from the NIH-sponsored US Renal Database Systems (USRDS), a US-wide registry of ESRD patients that includes 5,000 incident SLE patients enrolled over 5 years. Using USRDS data in Aims 1 and 2 provides a cost-effective and efficient way to study large numbers of SLE patients with ESRD that present well-defined outcomes. Additionally, we will prospectively collect SLE-specific longitudinal data not available in the USRDS The clinical investigation will be carried out at the Albert Einstein College of Medicine and the New York University School of Medicine under the mentorship of three senior investigators in SLE, outcomes research, and biostatistics. This project addresses an understudied and clinically important area. The specific aims are a significant extension of Dr. Broder’s previous retrospective work showing that hydroxychloroquine use is associated with lower mortality in SLE with ESRD. This project is essential groundwork for an interventional study. The multidisciplinary mentoring team and career development activities will enable Dr. Broder develop expertise in the following clinical and translational areas outlined in the NIH Lupus Research Action Plan: analysis of large scale databases; comparative effectiveness; individualized drug therapies; and innovative trial designs.

摘要 系统性红斑狼疮（SLE，lupus）是一种自身免疫性疾病，可引起全身性炎症， 组织损伤高达60%的SLE患者发生肾脏受累（狼疮性肾炎），10-30%的患者进展为 终末期肾病（ESRD）在诊断后10年内，尽管治疗。SLE ESRD的死亡率 是SLE合并狼疮肾炎患者的4倍，是非SLE终末期肾病患者死亡率的2倍， 尽管SLE患者在ESRD发病时明显更年轻。尽管许多研究表明， 成果不佳，尚未制定改善这些成果的战略。 在无ESRD的SLE患者中使用羟氯喹与较低的SLE发作率相关， 血栓并发症，以及更好的总体生存率。到目前为止，还没有临床研究探索 羟氯喹治疗SLE ESRD的益处直接在ESRD患者中研究这种药物的作用是 重要的是发展个性化治疗和降低死亡率。我们的指导假设是， 使用羟氯喹将降低接受两种治疗的SLE患者的发病率和死亡率。 最常见的肾脏替代方式，血液透析和肾移植。调查这一 假设我们将分析来自NIH赞助的美国肾脏数据库系统（USRDS）的数据， ESRD患者登记研究，包括5年内入组的5，000例新发SLE患者。使用USRDS数据 目的1和2中的研究提供了一种经济有效的方法来研究大量SLE患者的ESRD 呈现出明确的结果。此外，我们将前瞻性收集SLE特异性纵向数据， 在USRDS中可用 临床研究将在阿尔伯特·爱因斯坦医学院和纽约 在三名SLE高级研究人员的指导下， 和生物统计学。该项目涉及一个研究不足和临床重要的领域。具体目标是： Broder博士先前的回顾性工作的重要扩展，表明羟氯喹的使用是 与SLE合并ESRD患者的死亡率较低相关。该项目是一个干预性的重要基础， study.多学科的指导团队和职业发展活动将使布罗德博士发展 在NIH狼疮研究行动计划中概述的以下临床和翻译领域的专业知识： 大规模数据库分析;比较有效性;个体化药物治疗;和创新试验 的设计.

项目成果

Rapid Implementation of a Multidisciplinary COVID-19 Cytokine Storm Syndrome Task Force.

• DOI: 10.1002/acr2.11220
• 发表时间: 2021-03
• 期刊: ACR open rheumatology
• 影响因子: 3.4
• 作者: Ayesha B;Kumthekar A;Jain R;Patel S;Ramesh M;Ferastraoaru DE;Hudes G;Karagic M;Zafar S;Bartash R;Vasquez-Canizares N;Kitsis E;Tagoe C;Wahezi DM;Rubinstein T;Broder A
• 通讯作者: Broder A

Brief Report: Tubulointerstitial Damage in Lupus Nephritis: A Comparison of the Factors Associated With Tubulointerstitial Inflammation and Renal Scarring.

• DOI: 10.1002/art.40575
• 发表时间: 2018-11
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Londoño Jimenez A;Mowrey WB;Putterman C;Buyon J;Goilav B;Broder A
• 通讯作者: Broder A

Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study.

• DOI: 10.1016/j.semarthrit.2017.07.007
• 发表时间: 2018-03
• 期刊: Seminars in arthritis and rheumatism
• 影响因子: 5
• 作者: Broder A;Mowrey WB;Khan HN;Jovanovic B;Londono-Jimenez A;Izmirly P;Putterman C
• 通讯作者: Putterman C

Systemic lupus Erythematosus activity and Hydroxychloroquine use before and after end-stage renal disease.

• DOI: 10.1186/s12882-020-02083-2
• 发表时间: 2020-10-28
• 期刊: BMC nephrology
• 影响因子: 2.3
• 作者: Salgado Guerrero M;Londono Jimenez A;Dobrowolski C;Mowrey WB;Goilav B;Wang S;Broder A
• 通讯作者: Broder A