Clinical and molecular epidemiology of acute kidney injury after lung transplant

肺移植术后急性肾损伤的临床和分子流行病学

• 批准号: 10231197
• 负责人: Michael G. S. Shashaty
• 金额: $ 65.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231197
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Age; Allografting; Back; Biological Markers; Blood; Calcineurin inhibitor; Cardiac Surgery procedures; Cessation of life; Characteristics; Chronic; Chronic Kidney Failure; Clinical; Clinical Data; Coagulation Process; Complication; Critical Illness; Cystic Fibrosis; Data; Diagnosis; Dialysis procedure; Enrollment; Epidemiology; Functional disorder; Funding; Future; Goals; Hour; Human; Incidence; Infrastructure; Injury; Injury to Kidney; Institution; Investments; Kidney; Kidney Transplantation; Knowledge; Lead; Life; Light; Link; Liquid substance; Literature; Low Prevalence; Lung; Lung Transplantation; Lung diseases; Mediator of activation protein; Medicare; Modeling; Molecular; Molecular Epidemiology; Multicenter Studies; Obesity; Outcome; Pathogenesis; Patients; Pennsylvania; Perioperative; Phase; Phenotype; Pilot Projects; Plasma; Plasma Proteins; Plasminogen Activator Inhibitor 1; Population; Populations at Risk; Positioning Attribute; Postoperative Period; Prevention strategy; Prospective cohort; Prospective cohort study; Protein C; Proteins; Proteomics; Pulmonary Emphysema; Pulmonary Fibrosis; Quality of life; Renal Replacement Therapy; Renal function; Reperfusion Injury; Reperfusion Therapy; Research; Resources; Risk; Risk Factors; Risk Reduction; Sampling; Savings; Severities; Site; Specimen; Structure; Syndrome; Testing; Therapeutic Trials; Thrombomodulin; Time; Transplant Recipients; Transplantation; United States National Institutes of Health; Universities; Urine; base; burden of illness; candidate marker; clinical epidemiology; clinical risk; cohort; comorbidity; cost; cystic fibrosis patients; design; disorder risk; effective therapy; endothelial dysfunction; flexibility; high risk; high risk population; improved; lung allograft; molecular marker; mortality; mortality risk; novel; operation; patient subsets; post-transplant; pre-clinical; predictive marker; predictive modeling; prevent; prospective; renal damage; renal ischemia; success; therapeutic target; translational study; transplant centers; treatment strategy

PROJECT SUMMARY/ABSTRACT Acute kidney injury (AKI), rapid loss of renal function over several days, occurs in up to 70% of lung transplant recipients postoperatively, far more common than after cardiac surgery despite a younger population with almost no pre-existing chronic kidney disease (CKD). While post-transplant AKI is associated with subsequent CKD and mortality, it is unclear if AKI impacts outcomes independently or is simply an epiphenomenon of lung allograft dysfunction and other early transplant complications. Knowledge of post-transplant AKI epidemiology is limited to relatively small, retrospective, single-center studies with limited assessment of AKI risk factors. Clarifying AKI’s independent impact on outcomes and identifying patients at high risk of AKI, particularly the severe forms more strongly linked to CKD and mortality, is critical since renal-protective strategies such as fluid administration carry risk to the allograft. Blood and urine biomarkers have shown predictive utility for AKI in critical illness and cardiac surgery populations but have not been studied in lung transplant patients. These predictive markers may also shed light on mechanisms underlying the high rate of AKI in this population. The Lung Transplant Outcomes Group (LTOG) is an NIH-funded multicenter prospective cohort started in 2002, coordinated by our institution and designed to study the clinical and molecular epidemiology of primary graft dysfunction (PGD), an acute lung allograft injury syndrome. With enrollment >2000, the LTOG is uniquely suited to support an ancillary, multicenter study of AKI epidemiology. We conducted pilot studies of clinical and plasma biomarker risk factors for AKI in a small group of LTOG subjects. Based on these studies and existing literature, we hypothesize that distinct clinical and molecular characteristics are associated with AKI after lung transplantation, with implications for AKI pathogenesis. We further hypothesize that these characteristics can be used to predict AKI risk to identify candidates for risk reduction strategies. Utilizing the robust multicenter structure of the LTOG to conduct a study 3 times the size of the largest to date, we propose the following aims in the lung transplant population: 1) Determine clinical risk factors for and outcomes of AKI, 2) Determine the association of established and novel plasma and urine biomarkers with AKI, and 3) Derive and validate predictive models for AKI. This proposal leverages the research investments already made in the LTOG in order to produce the first comprehensive study of AKI after lung transplant to establish the independent impact of AKI on outcomes, determine modifiable AKI risk factors, identify plasma and urine molecular markers associated with AKI, and enable AKI prediction. Completion of the aims will create a flexible infrastructure within the LTOG to support trials of current and novel renal-protective peri-transplant management strategies targeted to high-risk patients, with the ultimate goals of reducing CKD burden and maximizing the long-term success of lung transplant. In addition, our exploratory studies to identify novel AKI biomarkers may detect new predictors and point toward targetable AKI mechanisms for future study.

项目总结/文摘

项目成果

Development and validation of a population pharmacokinetic model to guide perioperative tacrolimus dosing after lung transplantation.

开发和验证群体药代动力学模型以指导肺移植后围术期他克莫司给药。

• DOI: 10.1101/2023.06.26.23291248
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Miano,ToddA;Feng,Rui;Griffiths,Stephen;Kalman,Laurel;Oyster,Michelle;Cantu,Edward;Yang,Wei;Diamond,JoshuaM;Christie,JasonD;Scheetz,MarcH;Shashaty,MichaelGS
• 通讯作者: Shashaty,MichaelGS