Every year, about 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a loved one or even a stranger. Immediate risks to kidney donors are low and well-understood. However, long- term donor safety has recently come into question, with large national studies reporting higher incidence of end stage renal disease (ESRD) in kidney donors. Given that these are healthy individuals undergoing an operation for the benefit of another person, at no benefit to themselves, it is vitally important to understand how kidney donors progress to ESRD and which donors might be at greatest risk of ESRD progression. The trajectory of renal function after donation using estimated glomerular filtration rate (eGFR) may show progression of renal failure. We may be able to demonstrate which donors are at greatest risk of ESRD by modeling the trajectory of eGFR after donation within different at-risk groups of donors. In the US, patients with hypertension (HTN) and/or diabetes mellitus (DM) are at higher risk for ESRD. A small minority of kidney donors has HTN or DM at time of donation; however, kidney donors have a higher risk of developing HTN after donation. Further, African American donors had a higher risk of developing HTN and DM compared to Caucasian donors. A more common comorbidity is obesity: over one-fifth of living kidney donors are obese at the time of donation. While short-term follow up has been shown to be safe, higher body-mass index is associated with lower eGFR and HTN post-donation. This proposal will study the trajectory of eGFR in donors who develop HTN, develop DM, or are obese at time of donation in order to evaluate whether these groups are at higher risk for ESRD. To accomplish this, we will leverage a major, ongoing, R01-funded, multicenter study to address the following: 1) to model the trajectory of renal function in living kidney donors after incident post-donation HTN, with further analysis of effect of race on eGFR trajectory; 2) to model the trajectory of renal function in donors after incident post-donation DM, with further analysis of effect of race; and 3) to model the trajectory of renal function in donors who are obese at time of donation, with further analysis of effect of race.
These aims are highly feasible given the rich primary data collection and secondary data linkage of the parent study. The unique contribution of this ancillary study will be data modeling for eGFR trajectory within each at-risk group of donors. We hypothesize that obesity at time of donation, post-donation incidence of HTN, and post-donation incidence of DM will be associated with subsequent decline in kidney function, and that African American donors will be at higher risk for this declin than Caucasian donors within each group. Better understanding the interplay between obesity, DM, HTN, and race in donors will help guide clinicians to better select candidates for donation, to facilitate informed consent of living kidney donors both in operative risks as well as post-donation outcomes, and to provide care to donors to ensure optimal outcomes.

Public Health Relevance

Every year, about 6000 healthy individuals undergo live donor nephrectomy in the United States to benefit a loved one or even a stranger, but recent data suggests donors have an increased risk of end stage renal disease (ESRD) and may have other risks which are not yet well-defined. In this study, we will investigate the trajectory of kidney function post-donation in donors with obesity, diabetes mellitus (DM), and hypertension (HTN), as well as analyze the effect of race, as African American donors have been shown to have a significantly higher risk of ESRD compared to Caucasian donors and to African American non-donors. Better understanding the interplay between obesity, DM, HTN, and race in live donors will help guide clinicians to better select candidates for donation, to facilitate informed consentof living kidney donors both in operative risks as well as post-donation outcomes, and to provide care to donors to ensure optimal outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK109662-03
Application #
9512987
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Rankin, Tracy L
Project Start
2016-07-01
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
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
Holscher, Courtenay M; Leanza, Joseph; Thomas, Alvin G et al. (2018) Anxiety, depression, and regret of donation in living kidney donors. BMC Nephrol 19:218
DiBrito, Sandra R; Olorundare, Israel O; Holscher, Courtenay M et al. (2018) Surgical approach, cost, and complications of appendectomy in kidney transplant recipients. Clin Transplant 32:e13245
Haugen, Christine E; Holscher, Courtenay M; Garonzik-Wang, Jacqueline et al. (2018) National Trends in Liver Transplantation in Older Adults. J Am Geriatr Soc 66:2321-2326
DiBrito, Sandra R; Alimi, Yewande; Olorundare, Israel O et al. (2018) Outcomes Following Colorectal Resection in Kidney Transplant Recipients. J Gastrointest Surg :
Henderson, Macey L; Adler, Joel T; Van Pilsum Rasmussen, Sarah E et al. (2018) How Should Social Media Be Used in Transplantation? A Survey of The American Society of Transplant Surgeons. Transplantation :
Henderson, Macey L; DiBrito, Sandra R; Thomas, Alvin G et al. (2018) Landscape of Living Multiorgan Donation in the United States: A Registry-Based Cohort Study. Transplantation 102:1148-1155
DiBrito, Sandra R; Haugen, Christine E; Holscher, Courtenay M et al. (2018) Complications, length of stay, and cost of cholecystectomy in kidney transplant recipients. Am J Surg 216:694-698
Ruck, Jessica M; Holscher, Courtenay M; Purnell, Tanjala S et al. (2018) Factors associated with perceived donation-related financial burden among living kidney donors. Am J Transplant 18:715-719
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
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

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