Long-term Deterioration of Kidney Allograft Function

同种异体移植肾功能的长期恶化

• 批准号: 8089858
• 负责人: ARTHUR J MATAS
• 金额: $ 112.86万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-28 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089858
• 关键词: Antibodies; Biopsy; Cardiovascular Diseases; Cessation of life; Chronic; Chronic rejection of renal transplant; Clinical; Clinical Trials; Data; Data Analyses; Data Collection; Data Quality; Databases; Deterioration; Development; Diagnosis; Failure; Functional disorder; Funding; Future; Gene Expression Microarray Analysis; General Population; Goals; Grant; HLA Antigens; Histologic; Histology; Human; Incidence; Individual; Inflammation; Injury; Institution; Intervention Trial; Kidney; Kidney Transplantation; Laboratories; Leukocytes; Literature; Natural History; Outcome; Pathogenesis; Pathologic; Patients; Probability; Process; Recording of previous events; Research; Research Infrastructure; Research Personnel; Risk Factors; Sample Size; Serological; Staining method; Stains; System; Terminology; Testing; Time; cohort; graft function; interest; kidney allograft; knowledge base; member; mortality; premature; programs; prospective; success

DESCRIPTION (provided by applicant): We plan a multi-center study to accurately describe the natural history of late kidney transplant failure, and to dissect out individual entities leading to late deterioration of function and to graft loss. Previous studies, and the current literature, attribute most chronic graft dysfunction (CGD) to a process called chronic rejection (CR) or chronic allograft nephropathy (CAN). Most recipients with this diagnosis have undergone biopsy late in their clinical course (if ever) at which time the histologic findings are non-specific. Our focus is to test the hypothesis that CGD is usually attributable to definable factors and not to a mysterious indefinable force known, as CR. Defining individual factors will permit future development of intervention trials. Our hypotheses are: 1) there are multiple, definable entities leading to CGD (and graft loss); 2) these entities can be differentiated by clinical, radiological, serologic, and pathologic studies. 3) progression of CGD is due to an identifiable, currently operating injurious process and not the consequence of a past injury. Specific Aims of this grant are to: 1) determine, in a previously tx cross-sectional cohort, whether clinical, laboratory, and pathologic studies (conventional histology, immunohistology, special stains) at the time of initial graft dysfunction will allow definition of different clinico-pathologic entities (possibly with differing clinical courses); 2) determine, in a prospective cohort, whether clinical, laboratory, and pathologic studies (conventional histology, immunohistology, special stains) at the time of initial graft dysfunction will confirm the definition of different entities (possibly with differing clinical courses); 3) determine whether markers of fibrogenic activity and/or inflammation, the presence of anti-human leukocyte antibody (HLA) antibodies, or other clinical correlates can define specific pathophysiologic features that correlate with progression and with the rate of progression of CGD. Defining clinico-pathologic entities (and their individual clinical courses) will provide a knowledge base for future studies of CGD.

描述（由申请人提供）：我们计划一项多中心研究，以准确描述晚期肾脏移植失败的自然历史，并剖析导致功能晚期恶化和移植物损失的个体实体。先前的研究以及当前的文献将大多数慢性移植功能障碍（CGD）归因于称为慢性排斥（CR）或慢性同种异体同种异体肾病（CAN）的过程。大多数接受此诊断的接受者在临床过程中（如果有的话）进行了活检，那时组织学发现是非特异性的。我们的重点是检验CGD通常归因于可定义的因素，而不是神秘的不确定的力量，称为CR。定义个人因素将允许将来开发干预试验。我们的假设是：1）有多个可定义的实体导致CGD（和移植损失）； 2）这些实体可以通过临床，放射学，血清学和病理学研究来区分。 3）CGD的进展是由于目前可识别的，目前正在运行的伤害过程，而不是过去受伤的后果。该赠款的具体目的是：1）在先前的TX横截面队列中确定临床，实验室和病理学研究（常规的组织学，免疫组织学，特殊染色，特殊染色）在初始移植功能障碍时是否允许定义不同的临床病理学实体（可能具有不同的临床课程）； 2）确定在前瞻性队列中，在初始移植功能障碍时，临床，实验室和病理学研究（常规组织学，免疫组织学，特殊污渍）是否都会证实不同实体的定义（可能有不同的临床课程）； 3）确定纤维化活性和/或炎症的标志物，是否存在抗人白细胞抗体（HLA）抗体或其他临床相关性的存在可以定义特定的病理生理特征，这些病理生理特征与进展和与CGD的进展率相关。定义临床病理学实体（及其个体临床课程）将为CGD的未来研究提供知识库。

项目成果

Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium.

• DOI: 10.1097/tp.0b013e318200e991
• 发表时间: 2011-02-15
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Jacobson PA;Oetting WS;Brearley AM;Leduc R;Guan W;Schladt D;Matas AJ;Lamba V;Julian BA;Mannon RB;Israni A;DeKAF Investigators
• 通讯作者: DeKAF Investigators

Multigene predictors of tacrolimus exposure in kidney transplant recipients.

• DOI: 10.2217/pgs.15.42
• 发表时间: 2015-07
• 期刊: Pharmacogenomics
• 影响因子: 2.1
• 作者: Pulk RA;Schladt DS;Oetting WS;Guan W;Israni AK;Matas AJ;Remmel RP;Jacobson PA;DeKAF Investigators
• 通讯作者: DeKAF Investigators

Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort.

使用大型多中心队列验证与肾移植受者急性排斥相关的单核苷酸多态性。

• DOI: 10.1111/j.1432-2277.2011.01359.x
• 发表时间: 2011
• 期刊: Transplant international : official journal of the European Society for Organ Transplantation
• 作者: Oetting,WilliamS;Schladt,DavidP;Leduc,RobertE;Jacobson,PamalaA;Guan,Weihua;Matas,ArthurJ;Israni,Ajay;DeKAFInvestigators
• 通讯作者: DeKAFInvestigators

Optimal cutoff point for immunoperoxidase detection of C4d in the renal allograft: results from a multicenter study.

• DOI: 10.1097/tp.0b013e3181f7fec9
• 发表时间: 2010-11-27
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Crary GS;Raissian Y;Gaston RC;Gourishankar SM;Leduc RE;Mannon RB;Matas AJ;Grande JP
• 通讯作者: Grande JP

Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients.

• DOI: 10.1111/ctr.13436
• 发表时间: 2018-12
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Wu JF;Muthusamy A;Al-Ghalith GA;Knights D;Guo B;Wu B;Remmel RP;Schladt DP;Alegre ML;Oetting WS;Jacobson PA;Israni AK
• 通讯作者: Israni AK