The comparative effectiveness of kidney transplantation in advanced CKD

描述(由申请人提供)：摩根·E·格拉姆斯，医学博士，理工学院硕士，约翰霍普金斯大学肾病学系助理教授。她寻求获得以患者为导向的导师研究职业发展奖，以便获得必要的技能和指导研究经验，以便在慢性肾脏疾病领域成为一名内科科学家。该研究计划详细介绍了一项五年计划，其中包括临床流行病学的博士水平课程、约瑟夫·科雷什博士和多里·L·塞格夫博士的指导，以及与慢性肾脏疾病相关的心血管和死亡风险的流行病学研究。研究议程的具体目标是：1)确定晚期慢性肾脏疾病患者的心血管和死亡风险；2)确定优先列入名单的移植候选患者在肾脏替代治疗开始前后死亡和心血管终点的风险因素；3)估计存活的移植候选患者应该移植到的天然肾功能的最佳水平。直接的职业目标包括通过与研究计划相结合的学术课程掌握先进的荟萃分析技术、因果推理方法和马尔可夫决策过程模型。从长远来看，格拉姆斯博士的目标是领导独立的研究项目，研究晚期慢性肾脏疾病的最佳治疗和决策。拟议目标的完成将提供与100万美国透析前4-5期慢性肾脏疾病患者相关的重要信息。慢性肾脏疾病与极高的心血管发病率和死亡率有关，但对这一人群的最佳治疗仍不清楚。预防性肾移植，或在开始维持性透析前的移植，是一种越来越常见的治疗方法。类似于透析开始的趋势，它在慢性肾脏疾病进展过程中更早地进行。更好地了解肾移植的最佳时机可能会为管理已故供者肾脏名单和分配的国家政策提供依据，也可以改善有活体供者的透析前移植患者的临床决策。此外，识别与高心血管和死亡风险相关的特征可能被用于指导晚期慢性肾脏疾病人群的治疗和未来的试验。

DESCRIPTION (provided by applicant): Morgan E. Grams, MD, MHS, is an Assistant Professor in the Division of Nephrology at Johns Hopkins University. She seeks a Mentored Patient-Oriented Research Career Development Award in order to obtain essential skills and mentored research experience for an independent career as a physician scientist in the field of chronic kidney disease. The research proposal details a five-year plan consisting of doctoral-level coursework in Clinical Epidemiology, mentorship by Dr. Josef Coresh, MD, PhD, and Dr. Dorry L. Segev, MD, PhD, and epidemiologic research in the cardiovascular and mortality risks associated with chronic kidney disease. The specific aims of the research agenda are to: 1) Characterize cardiovascular and mortality risk among individuals with advanced chronic kidney disease; 2) Identify risk factors for death and cardiovascular endpoints in preemptively listed transplant candidates before and after the initiation of renal replacement therapy; and 3) Estimate the optimal level of native kidney function at which a viable transplant candidate should be transplanted. Immediate career goals include the mastery of advanced meta-analysis techniques, methods of causal inference, and Markov decision process models through an academic curriculum integrated with the research plan. Long-term, Dr. Grams aims to lead independent research programs investigating optimal treatment and decision-making in advanced chronic kidney disease. Completion of the proposed aims will provide vital information relevant to the one million U.S. patients with pre-dialysis stage 4-5 chronic kidney disease. Chronic kidney disease is associated with exceedingly high rates of cardiovascular morbidity and mortality, but the optimal treatment of this population remains unknown. Preemptive kidney transplantation, or transplantation prior to the initiation of maintenance dialysis, is an increasingly common therapy. Similar to trends in dialysis initiation, it is being performed earlie in the course of chronic kidney disease progression. A better understanding of the optimal timing of kidney transplantation may inform national policies governing deceased donor kidney listing and allocation, and also improve clinical decision-making for pre-dialysis transplant patients with living donors. Furthermore, identification of characteristics associated with high cardiovascular and mortality risk may be used to guide therapy and future trials in the advanced chronic kidney disease population.