Nephrotic Syndrome Rare Disease Clinical Research Network III

肾病综合征罕见病临床研究网络III

• 批准号: 10700978
• 负责人: Matthias Kretzler
• 金额: $ 152.77万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10700978
• 关键词: APOL1 gene; Address; Adopted; Adult; Affect; Africa South of the Sahara; African American; African American population; Ancillary Study; Award; Biocompatible Materials; Biological Markers; Biopsy; Budgets; Child; Childhood; China; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Data; Data Coordinating Center; Data Set; Diagnosis; Disease; Disease remission; Drug Industry; Economic Burden; Education and Outreach; End stage renal failure; Enrollment; Environmental Risk Factor; Europe; Faculty; Focal and Segmental Glomerulosclerosis; Funding; Genetic; Genotype; Goals; Health; Histologic; Histology; Histopathology; India; Individual; Infrastructure; Interest Group; International; Kidney; Kidney Diseases; Knowledge; Membranous Glomerulonephritis; Mentors; Molecular; Natural History; Nephrology; Nephrotic Syndrome; Online Systems; Outcome; Participant; Pathway interactions; Patients; Pediatric cohort; Phase; Phase II Clinical Trials; Phenotype; Physicians; Pilot Projects; Postdoctoral Fellow; Privatization; Proteinuria; Proteomics; Protocols documentation; Rare Diseases; Research; Research Infrastructure; Research Personnel; Resources; Scientist; Sister; Taxonomy; Time; Training; Training Programs; Translational Research; Variant; base; causal variant; clinical phenotype; clinical trial readiness; cohort; cost effective; disease classification; empowerment; follow-up; forging; genetic architecture; health disparity; improved; individual patient; innovation; interest; kidney biopsy; knowledge of results; method development; molecular phenotype; molecular targeted therapies; new therapeutic target; outreach; participant enrollment; patient engagement; patient stratification; phenotypic data; precision medicine; programs; public-private partnership; recruit; social factors; therapeutic target; therapy development; transcriptomics; treatment response

ABSTRACT Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN), presenting as Nephrotic Syndrome (NS), are rare diseases causing catastrophic complications and end stage kidney disease, generating enormous individual, societal and economic burdens. The clinical, histopathology-based taxonomy of NS is inadequate and fails to capture the molecular bases of these diseases and does not adequately predict their natural history or response to therapy. A Precision Medicine (PM) approach is necessary to define NS in molecular terms, to identify therapeutic targets and match patients to treatments. NEPTUNE was applied an innovative, investigational strategy to improve the diagnosis, management and treatment of NS. In the first two project periods, a translational and clinical research infrastructure has been established, participants enrolled, biosamples collected, key collaborations forged and an outreach strategy deployed. NEPTUNE has established a robust investigative infrastructure encompassing 26 academic centers and two patient interest groups, has recruited more than 750 rigorously phenotyped NS participants with detailed clinical, histological, genetic, transcriptomic and proteomic data sets. This comprehensive information has been integrated in the NEPTUNE Knowledge Network for easy access by the NS research community. With substantial support from the patient interest group NephCure Kidney International, NEPTUNE has established robust training and ancillary study programs with 112 ancillary studies ranging from methods development to successful Phase II clinical trials. These critical advances have resulted in a significant interest in NS clinical trials, with more than 15 trials now in the advanced planning or enrollment phase. In this renewal application, we propose to leverage the NEPTUNE resources to catalyze discovery, training and outreach as we strive to improve health outcomes for individuals affected by NS. The overarching goal is to apply a PM approach to NS, leveraging the extensive NEPTUNE Knowledge Network established over the past 9 years. NEPTUNE will implement this PM strategy to permit discovery of novel therapeutic targets and deploy the patient stratification approach developed in the current funding cycle to help identify the right trial for the right patient at the right time: Patient stratification approaches will be utilized for targeted enrollment into clinical trials. Patients will undergo intense profiling at the time of disease presentation or at follow-up renal biopsy in order to match the disease mechanism active with ongoing clinical trials in a precompetitive, public private partnership with leading companies in the field. Training, pilot and ancillary study programs will continue with significant funding support from NKI. NEPTUNE will maintain its engagement with lay communities, clinicians, scientists, regulatory agencies and the pharmaceutical industry to identify and move therapeutic targets to our patients through an effective translational research pipeline for NS.

摘要

项目成果

A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.

• DOI: 10.1016/j.kint.2021.10.041
• 发表时间: 2022-07
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: McNulty, Michelle T.;Fermin, Damian;Eichinger, Felix;Jang, Dongkeun;Kretzler, Matthias;Burtt, Noel P.;Pollak, Martin R.;Flannick, Jason;Weins, Astrid;Friedman, David J.;Sampson, Matthew G.
• 通讯作者: Sampson, Matthew G.

Clinical Relevance of Computationally Derived Attributes of Peritubular Capillaries from Kidney Biopsies.

• DOI: 10.34067/kid.0000000000000116
• 发表时间: 2023-05-01
• 期刊: Kidney360
• 作者: Chen Y;Zee J;Janowczyk AR;Rubin J;Toro P;Lafata KJ;Mariani LH;Holzman LB;Hodgin JB;Madabhushi A;Barisoni L
• 通讯作者: Barisoni L

Discoidin domain receptor 1 activation links extracellular matrix to podocyte lipotoxicity in Alport syndrome.

• DOI: 10.1016/j.ebiom.2020.103162
• 发表时间: 2021-01
• 期刊: EBioMedicine
• 影响因子: 11.1
• 作者: Kim JJ;David JM;Wilbon SS;Santos JV;Patel DM;Ahmad A;Mitrofanova A;Liu X;Mallela SK;Ducasa GM;Ge M;Sloan AJ;Al-Ali H;Boulina M;Mendez AJ;Contreras GN;Prunotto M;Sohail A;Fridman R;Miner JH;Merscher S;Fornoni A
• 通讯作者: Fornoni A

Nephrotic syndrome disease activity is proportional to its associated hypercoagulopathy.

• DOI: 10.1016/j.thromres.2021.02.007
• 发表时间: 2021-05
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Waller AP;Troost JP;Parikh SV;Wolfgang KJ;Rovin BH;Nieman MT;Smoyer WE;Kretzler M;Kerlin BA;NEPTUNE Investigators
• 通讯作者: NEPTUNE Investigators

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

• DOI: 10.1016/j.stem.2018.04.022
• 发表时间: 2018-06-01
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Czerniecki SM;Cruz NM;Harder JL;Menon R;Annis J;Otto EA;Gulieva RE;Islas LV;Kim YK;Tran LM;Martins TJ;Pippin JW;Fu H;Kretzler M;Shankland SJ;Himmelfarb J;Moon RT;Paragas N;Freedman BS
• 通讯作者: Freedman BS