Transplant centers struggle with the development of criteria to define a potential living kidney donor as acceptably “normal.” These centers must evaluate the health of a potential donor and define the level of risk associated with the long-term effects of removing kidney mass in living donation.
Surveys of US transplant programs indicate that criteria for living donation vary widely. Most programs set arbitrary limits on age, blood pressure, body weight, and associated medical conditions that take potential donors out of the running.
While long-term health outcomes for most kidney donors seem to be at least comparable to those of the general population, the ever-growing list of patients needing a kidney transplant forces programs to consider ever-widening pools of donor candidates. Some of these potential donors will face long-term health risks from kidney disease themselves.
For this reason, the Mayo Clinic Kidney–Pancreas Transplant Program has developed a strategy to “stratify” criteria for acceptable kidney donors based mainly on age. In this case, “age before beauty” makes practical sense.
Defining Donor Risk
Because kidney donation entails submitting otherwise healthy individuals to the hazards of anesthesia, surgery, and nephrectomy for no direct medical benefit to the donor, this entire enterprise raises unique ethical and practical questions: Exactly what are the levels of donor risk? Exactly what risks are we discussing? Over what period of time will such risks develop?
As the relationships between donors and recipients are evolving to include more peripherally acquainted individuals—such as those who met through Internet connections or paired kidney exchanges, or those who are nondirected donor-recipient pairs—it has become more important than ever to precisely define these risks.
Many in the field are concerned that donor nephrectomy may raise blood pressure or that higher blood pressures for any reason may accelerate damage to the remaining kidney. Hence, “hypertension” has often been considered a relative exclusion for kidney donation. Because the thresholds associated with cardiovascular risk have lowered the upper boundaries of “normal” blood pressure over the last two decades, more and more individuals are now defined as “hypertensive” at ever younger ages.
Fortunately, outcome studies conducted 25 to 30 years after donor nephrectomy in primarily Caucasian donors reassure us that risks associated with these blood pressures have been very low, almost negligible, even though the donor nephrectomies were performed when higher blood pressures were considered “normal.”
In most cases, potential long-term risks of living kidney donation are related to accelerated injury in the remaining kidney should one develop kidney disease or potential exacerbation of cardiovascular risks related to hypertension or the effects of reduced kidney function. Previous studies suggest that these theoretical risks take many years to unfold—more than 15 to 30 years—if they occur at all.
In addition to these medical questions about the actual hazards, there are cultural and philosophical questions related to the acceptance of risk. Some cultures resist living kidney donation out of a pervasive belief that it crosses allowable barriers of human interaction. In the United States, living-donor transplantation is generally accepted, but controversies remain regarding optimal selection of candidates for the procedure.
Older and Wiser
The demographics of potential kidney transplant recipients in the United States are changing, with the majority of transplant recipients now older than 50. As a result, potential living donors, such as siblings, spouses, and friends, are aging, too.
In the past, the ideal kidney donor appeared to be the young and healthy individual with no definable medical abnormalities whatsoever. Kidneys from these donors, who have a median age under 30, understandably seemed to provide the best probable outcome for the recipient and to best tolerate the stresses of surgery, rejection, antirejection medications, and infections.
In recent years, however, improvements in clinical transplantation have produced excellent results from older donors, even those with minor associated comorbidities, including obesity, hypertension, subclinical kidney stones, and trace hematuria, as long as these issues were acceptably evaluated and controlled.
In terms of potential harms to the older versus the younger donor, hypertension and diabetes—and, more recently, obesity—are long-term conditions that likely pose cumulative risk over many years.
Hence, it may be argued that older individuals face less lifelong “exposure” to such risk. Their natural lifespan may come to an end before adverse effects from donor nephrectomy play a role.
Conversely, young individuals inherently face a longer exposure during their expected life and may experience some shortening of lifespan from these effects.
Two other factors come to bear when comparing older versus younger potential donors:
* The diagnostic power to identify risk for age-associated conditions such as hypertension and type 2 diabetes is limited in the healthy young adult. These conditions only begin to appear in later decades.
* Factors that determine much of this risk depend upon behavior, including “modifiable risk factors,” such as smoking, exercise, weight control, and dietary habits, that remain incompletely defined for the young adult. Many individuals solidify their habits, degree of adherence to medical follow-up (including gaps in insurance coverage), and lifestyle only later in life.
Taken together, these issues make the 25 year old an “undefined” risk, whereas overall health risk in the 55 year old is far clearer.
Stratifying by Risk
Given the excellent recipient outcomes with kidneys from older donors and the ability to better identify risks in these older donors, some active kidney transplant programs, including the Mayo Clinic Kidney–-Pancreas Transplant Program, have come to view the preferred living donor as being older—above age 50—versus the ostensibly “perfectly healthy” younger donor below age 30. Rates of living-donor kidney transplantation have risen to 40% to 70% of all kidney transplants, depending upon the center, and about 26% of living donors are now older than 50.
Our program defines upper boundaries for blood glucose, blood pressure, body weight, and kidney function (glomerular filtration rate measured by iothalamate) that differ by age groups: 18-30, 31-50, and older than 50. All of these tolerate less “stringent” criteria with advancing age.
We believe this more fairly distributes long-term risk and recognizes the inherent changes in health with aging. Taking blood pressure, for example, data indicate that population blood-pressure levels rise with age in all Western societies. Hence, “normal” blood pressure for a 25 year old is lower than that observed in a 55-year-old or older individual.
Fortunately, outcomes of donors from previous decades have been remarkably good. It must be recognized that population demographics are changing, along with expectations about lifespan.
As transplant programs struggle to meet the clinical needs of end-stage kidney disease patients with successful transplantation, they must also carefully define and limit the risks faced by living donors. In this case, at least, favoring “age before beauty” builds in important safeguards for the long-term benefit of the donor. •