We submit this proposal titled ?Living donor Extended Time Outcomes (LETO)? as an ancillary study to the newly initiated ?APOL1 Long-term Kidney Transplantation Outcomes? (APOLLO) Network. The APOLLO Consortium represents the most ambitious national study addressing the implications of donor apolipoprotein L1 gene (APOL1) renal-risk variants on kidney transplant outcomes. However, the prospective design of the parent APOLLO is underpowered to assess postdonation kidney health in living donors and outcomes in recipients of their kidneys due to due to short follow-up duration and secular trends resulting in diminishing numbers of persons with 2 APOL1 renal-risk variants donating in recent calendar years. We propose a cost-effective ?hybrid? study design?jointly analyzing data collected at home-based research visits together with data collected as part of clinical care (as entered into a national registry)?that will greatly increase the number of person-years of follow-up and enhance study power. We will enroll 1,100 living donors who donated from 2001-2005 to generate data that will have a major impact on the clinical practice of living kidney donation in African Americans.
Our specific aims are:
Aim 1 : To determine in a nationally representative sample whether African American living kidney donors with 2 APOL1 renal-risk variants are at higher risk of developing clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) approximately two decades after donation.
Aim 2 : To determine whether other independent (or APOL1 interactive) gene variants associate with increased risk of clinically significant chronic kidney disease (estimated glomerular filtration rate <45 ml/min/1.73m2) in African American living kidney donors.
Aim 3 : To determine the impact of donor APOL1 renal-risk variants and other novel genetic risk factors on graft survival and recipient outcomes in a nationally representative sample of living donor kidney transplant recipients from African American living donors.

Public Health Relevance

?Living donor Extended Time Outcomes (LETO)? is an ancillary study to the newly initiated ?APOL1 Long-term Kidney Transplantation Outcomes? (APOLLO) Network. We will address key knowledge gaps regarding the implications of APOL1 genotype and other genetic risk factors for the renal outcomes of African American living donors and their transplant recipients. Our team includes experts in longitudinal studies of kidney disease, epidemiology, biostatistics, kidney donation and transplantation, APOL1 and genetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK120551-01
Application #
9708626
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Abbott, Kevin C
Project Start
2019-06-01
Project End
2024-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118