Medical risks in living kidney donors: absence of proof is not proof of absence.

Living-kidney donation has become increasingly widespread, yet there has been little critical analysis of existing studies of long-term medical outcomes in living donors. This review analyzes issues in study design that affect the quality of the evidence and summarizes possible risk factors in living donors. Virtually all studies of long-term outcomes in donors are retrospective, many with large losses to follow-up, and therefore are subject to selection bias. Most studies have small sample sizes and are underpowered to detect clinically meaningful differences between donors and comparison groups. Many studies compare donors with the general population, but donors are screened to be healthier than the general population and this may not be a valid comparison group. Difficulties in measurement of BP and renal function may underestimate the impact of donation on these outcomes. Several studies have identified possible risk factors for development of hypertension, proteinuria, and ESRD, but potential vulnerability factors in donors have not been well explored and there is a paucity of data on cardiovascular risk factors in donors. Prospective registration of living kidney donors and prospective studies of diverse populations of donors are essential to protect living donors and preserve living-kidney donation.