Allan B. Massie, PhD, is an Assistant Professor of Surgery and Epidemiology at Johns Hopkins. He seeks a Mentored Research Scientist Development Award in order to gain training and experience in nephrology, genetic epidemiology, and the conduct of cohort studies and to transition to independent research. Every year, 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a relative, friend, or stranger with end-stage renal disease (ESRD). The largest cohort study of kidney donors to date - the foundation of the conventional wisdom that live kidney donation is safe - involved a > 99% Caucasian population. However, African-American (AA) donors are at elevated risk of post-donation ESRD and death compared to Caucasians. Unfortunately, risk prediction in this critically important population is poor, hampering donor screening and informed consent, depriving AA kidney donors of accurate information about their personal risk after kidney donation, and limiting opportunities to mitigate long-term risk in this population. The proposed research is nested within an ongoing, NIH-funded multicenter cohort study of AA donors.
The aims of the project are: 1) to identify the association between high-risk variants of the APOL1 gene and CKD following donation in AA live kidney donors; 2) to identify risk factors for long-term eGFR decline in AA kidney donors; and 3) to compare post-donation eGFR trajectories in AA donors to those in AA nondonors.
Aim 1 will implement a nested case-cohort study within the parent study;
Aim 2 will draw on donor medical records obtained via the parent study;
and Aim 3 will compare eGFR calculated from medical records of the parent study to data from the ARIC and CARDIA cohorts. The proposed research leverages a large cohort of AA donors, but is distinct from the parent study in its study design, novel collection of biologica specimens to understand genetic determinants, and novel collection of longitudinal data to study eGFR trajectories. The research proposal outlines a detailed proposal to give Dr. Massie the training required to complete the research, under the leadership of mentor Dr. Dorry Segev MD PhD and Dr. Josef Coresh MD PhD, drawing from the advice of an advisory team that includes experts in nephrology, genetic epidemiology, study design, and biostatistics. Dr. Segev is a transplant surgeon, Director of Clinical Research in the Division of Transplantation at Johns Hopkins, and PI of the parent study for the proposed research. Dr. Coresh is an epidemiologist, Director of the Cardiovascular Epidemiology Program at Johns Hopkins and leader of the Chronic Kidney Disease Consortium. Dr. Massie hopes eventually to lead independent research programs investigating long-term outcomes of transplant recipients and live organ donors. Completion of the proposed aims will improve risk prediction for AA live kidney donors and prospective donors, aid in medical decision-making, enhance informed consent, and provide vital information relevant to the long-term health outcomes of the 14,000 AA live kidney donors living in the United States.

Public Health Relevance

While the risks of chronic kidney disease (CKD), end stage renal disease (ESRD) and death are higher for African-American live kidney donors than for Caucasian donors, the risks to an individual donor are currently poorly understood; consequently, physicians are unable to properly counsel prospective donors considering live donation. The goal of this project is to more accurately describe post-donation eGFR trajectory and model the risks of post-donation CKD for potential AA donors, taking into account sociodemographic factors and genetics. Our investigation of eGFR trajectory and risk factors for CKD following live kidney donation will improve risk prediction for AA live kidney donors and prospective donors, aid in medical decision-making, enhance informed consent, and provide vital information relevant to the long-term health outcomes of the 14,000 AA live kidney donors living in the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK101677-03
Application #
9352837
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-09-15
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Surgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Durand, Christine M; Halpern, Samantha E; Bowring, Mary G et al. (2018) Organs from deceased donors with false-positive HIV screening tests: An unexpected benefit of the HOPE act. Am J Transplant 18:2579-2586
Ishaque, Tanveen; Massie, Allan B; Bowring, Mary G et al. (2018) Liver transplantation and waitlist mortality for HCC and non-HCC candidates following the 2015 HCC exception policy change. Am J Transplant :
Holscher, Courtenay M; Ishaque, Tanveen; Garonzik Wang, Jacqueline M et al. (2018) Living donor postnephrectomy kidney function and recipient graft loss: A dose-response relationship. Am J Transplant 18:2804-2810
Eno, Ann K; Thomas, Alvin G; Ruck, Jessica M et al. (2018) Assessing the Attitudes and Perceptions Regarding the Use of Mobile Health Technologies for Living Kidney Donor Follow-Up: Survey Study. JMIR Mhealth Uhealth 6:e11192
Holscher, Courtenay M; Jackson, Kyle; Thomas, Alvin G et al. (2018) Temporal changes in the composition of a large multicenter kidney exchange clearinghouse: Do the hard-to-match accumulate? Am J Transplant 18:2791-2797
Durand, Christine M; Bowring, Mary G; Thomas, Alvin G et al. (2018) The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States: A National Registry Study. Ann Intern Med 168:702-711
Bowring, Mary G; Massie, Allan B; Craig-Schapiro, Rebecca et al. (2018) Kidney offer acceptance at programs undergoing a Systems Improvement Agreement. Am J Transplant 18:2182-2188
Jackson, Kyle R; Covarrubias, Karina; Holscher, Courtenay M et al. (2018) The national landscape of deceased donor kidney transplantation for the highly sensitized: Transplant rates, waitlist mortality, and posttransplant survival under KAS. Am J Transplant :
Ruck, Jessica M; Zhou, Sheng; Thomas, Alvin G et al. (2018) Electronic messaging and communication with living kidney donors. Clin Transplant 32:
Bowring, Mary G; Holscher, Courtenay M; Zhou, Sheng et al. (2018) Turn down for what? Patient outcomes associated with declining increased infectious risk kidneys. Am J Transplant 18:617-624

Showing the most recent 10 out of 28 publications