Trajectory of post-donation renal function in living kidney donors

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 DESCRIPTION (provided by applicant): 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.