The demand for kidney transplantation continues to exceed the supply. Increasing the number of living kidney donors is a major priority. Historically, living donors were healthy and free of isolated medical abnormalities (IMA) at the time of donation. Recently, general US population demographics have changed, and in response, transplant centers now include donors with IMAs such as pre-hypertension (pre-HTN), obesity, and metabolic syndrome. At a general population level, individuals with IMAs, particularly African Americans (AA), are more likely to develop comorbidities, such as diabetes, HTN, and chronic kidney disease. Recent data suggest that AA living kidney donors are more likely to have a pre-donation IMA. It remains unclear what impact, if any, living donation will have on development of these comorbidities, and whether racial disparities in risk attributable to donation exist. Current methods for assessing living donor long-term health risks are imprecise, relying heavily on traditional factors such as family and social histories. Morphometric measures (e.g. vascular calcifications; fat distribution), using radiologic imaging, have emerged as strong predictors of cardiovascular risk. Pre-donation imaging, routinely acquired during donor evaluations to assess renal anatomy, can be leveraged to identify novel morphometric risk predictors for post-donation comorbidities. I hypothesize that morphometric measures will greatly improve prediction of post-donation comorbidities, including risk directly attributable to donation. Given significant knowledge gaps in risk prediction and stratification of donors with IMAs, I propose an ancillary study that will leverage data from an ongoing R01-funded cohort study of live donors to create the largest cohort of IMA donors studied and will address unique aims: (1) explore the association of novel morphometric measures and traditional risk factors with post-donation comorbidity stratified by race; (2) develop a risk tool for predicting post-donation comorbidities; and (3) estimate risk attributable to living kidney donation. Utilization o novel morphometric measures obtained from routine pre- donation imaging is innovative, highly practical, and will create a level of risk prediction of living donor outcomes that currently does not exist. Precise risk prediction will improve informed consent, donor autonomy in medical decision making, and will change the practice of live kidney donor selection in the US. Resources and infrastructure at the University of Alabama at Birmingham, including the most AA living kidney donors in the US, are keenly in-line with the proposed aims, and will provide the necessary foundation to see the proposed project to its successful completion. The mentored award will foster my growth as an independent investigator by affording me opportunities to focus on building an expertise in novel risk prediction research and enhancing my exposure to health disparities and chronic disease epidemiology in minority populations. This additional training will inform my path toward long-term career goals of research independence as a surgeon-scientist and R01 funding.

Public Health Relevance

As the demand for kidneys continues to exceed the supply, transplant centers have begun to relax selection criteria to include living donors with obesity and/or high blood pressure. Expansion of selection criteria has occurred despite a paucity of supporting safety data. It is critical to balance increasing live donation for transplant candidate against the responsibility of understanding long-term risks specific to donors at the extremes of current selection criteria for the purposes of donor selection, informed consent, and post-donation care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DK103918-01A1
Application #
8966934
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-07-15
Project End
2020-04-30
Budget Start
2015-07-15
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
$180,977
Indirect Cost
$13,195
Name
University of Alabama Birmingham
Department
Surgery
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Reed, Rhiannon D; Sawinski, Deirdre; Shelton, Brittany A et al. (2018) Population Health, Ethnicity, and Rate of Living Donor Kidney Transplantation. Transplantation 102:2080-2087
Reed, Rhiannon D; Shelton, Brittany A; MacLennan, Paul A et al. (2018) Living Kidney Donor Phenotype and Likelihood of Postdonation Follow-up. Transplantation 102:135-139
Mustian, Margaux N; Cannon, Robert M; MacLennan, Paul A et al. (2018) Landscape of ABO-Incompatible Live Donor Kidney Transplantation in the US. J Am Coll Surg 226:615-621
Cohen, Jordana B; Eddinger, Kevin C; Locke, Jayme E et al. (2017) Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist. Clin J Am Soc Nephrol 12:974-982
Locke, Jayme E; Reed, Rhiannon D; Massie, Allan et al. (2017) Obesity increases the risk of end-stage renal disease among living kidney donors. Kidney Int 91:699-703
Locke, Jayme E; Mehta, Shikha; Sawinski, Deirdre et al. (2017) Access to Kidney Transplantation among HIV-Infected Waitlist Candidates. Clin J Am Soc Nephrol 12:467-475
Locke, Jayme E; Gustafson, Sally; Mehta, Shikha et al. (2017) Survival Benefit of Kidney Transplantation in HIV-infected Patients. Ann Surg 265:604-608
Locke, Jayme E; Sawinski, Deirdre; Reed, Rhiannon D et al. (2017) Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors. Ann Surg :
Freedman, Barry I; Locke, Jayme E; Reeves-Daniel, Amber M et al. (2017) Apolipoprotein L1 Gene Effects on Kidney Transplantation. Semin Nephrol 37:530-537
Locke, Jayme E; Carr, J Jeffrey; Nair, Sangeeta et al. (2017) Abdominal lean muscle is associated with lower mortality among kidney waitlist candidates. Clin Transplant 31:

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