Transplantation Using Marginal Living Donors

THE DONOR ORGAN shortage continues to be the most pressing issue in kidney transplantation today. It is known that a transplant provides longer survival and better quality of life than dialysis.1, 2, 3 Thus, each year more patients with end-stage renal disease (ESRD) opt for a transplant, and each year more patients go on the deceased donor waiting list for a transplant than actually receive a deceased donor graft.4 The waiting list continues to grow and, consequently, the waiting time is longer. Currently, the median waiting time for a deceased donor transplant is about 5 years and is expected to increase.4 For the first time, significant numbers of ESRD patients are dying while on the waiting list.5 It is unlikely that increasing the number of deceased donor grafts will be sufficient to meet the growing demand of the ESRD population.6 Hence, living donor transplants are being increasingly emphasized and encouraged.

Living donor transplants, especially if performed preemptively, provide better outcome than do deceased donor transplants.7, 8 With living donor transplants, both short- and long-term graft survival rates are better and exposure to dialysis is minimized. However, living donor transplants have a significant disadvantage: the donor is required to have a major operative procedure that is associated with morbidity, mortality, and the potential for adverse long-term consequences secondary to living with a single kidney. Perioperative mortality after living kidney donation is 0.03%9, 10, 11; morbidity, including minor complications, is less than 10%.12 There are only a few studies of the long-term (>15 years) consequences of living with a single kidney.10, 13, 14 A major concern regarding the use of living donors is that unilateral nephrectomy might predispose to the development of kidney disease and/or premature death.

The use of living donors is a continuing ethical dilemma. Donation is the only operation with the potential for doing harm, without the potential for providing physical benefit for the patient (in this case the living donor). Yet living donor transplants provide extended life and better quality of life for the recipient. How do we decide how much risk is acceptable for the living donor?

In discussing transplant-related ethics, most bioethicists today refer to 4 principles outlined by Beauchamp and Childress: a) respect for autonomy; b) beneficence, including both the obligation to benefit others (positive beneficence) and to maximize good (utility); c) justice, the principle of fair and equitable distribution of benefits and burdens; and d) nonmaleficence, the obligation not to inflict harm.15 When applied to specific circumstances (eg, kidney donation), these principles often conflict; when they do, they must be balanced against each other.15

A key element of these principles is the respect for autonomy. If living donors wish to accept the risks of surgery, does the transplant center have the right to say no? Most ethicists would say that if the risk to the living donor is high (eg, almost certain death, likely disability), the center should say no. But many argue that if the risk to the living donor is only minimally increased, the potential donor should have the right to decide.16, 17, 18 Any decision rests on the living donor having sufficient information. Yet, one problem with providing potential living donors with sufficient information is that, as caregivers, we are not totally sure of all the facts. To date, long-term follow-up studies of carefully selected living donors have not identified any major problems; however, such studies have been incomplete, in that not all former living donors could be located.10, 13, 14 Furthermore, we know that some living donors (albeit not many) have developed ESRD.19

Because of the donor organ shortage, some centers are considering relaxing living donor acceptance criteria and using “marginal donors.” There are 2 important issues with the use of kidneys from such donors. First, is long-term donor outcome the same as that for other highly screened donors? Second, is recipient outcome the same when marginal donor kidneys are used? It will be important to demonstrate that recipients of such kidneys do better than waiting on dialysis for a better deceased donor kidney.

Textor et al published a follow-up of carefully selected white kidney living donors with essential hypertension.20 Selection criteria included absence of proteinuria and microalbuminuria, normal glomerular filtration rate, and modest hypertension. The living donors were studied 6 to12 months after donation; no adverse effects of donation on blood pressure were found. Textor et al concluded that selected living donors with essential hypertension might be acceptable.

Should we begin to accept selected living donors with hypertension? The follow-up time of the study by Textor et al was only 6 to 12 months (mean 282 days). Longer follow-up studies will be required before we can accept such living donors. Textor et al noted that the definition of hypertension has changed in the past 2 decades, such that many of their so-called “hypertensive” living donors would have been classified as normotensive in the past. However, other studies comparing normotensive and hypertensive living donors noted that the latter were at increased risk for worsening hypertension.21, 22, 23

In this issue of the American Journal of Kidney Diseases, Karpinski et al report on the impact on transplant rates of accepting living donors with mild hypertension or proteinuria.24 According to their multicenter review of potential living donors who were turned down, 31 (17%) were turned down for hypertension or proteinuria. Of these 31, 12 had only mild hypertension or proteinuria. Acceptance of these 12 would have resulted in transplants for 3% of the waitlisted candidates, and thus would have had only a small impact on transplant rates. Karpinski et al note only 35% of the waitlisted patients had a potential living donor evaluated; most of these potential living donors who were turned down (54%) were turned down for immunologic reasons (ABO incompatibility or positive crossmatch). Karpinski et al conclude that efforts to improve living donor rates and to overcome immunologic barriers may have a greater impact than accepting living donors with mild hypertension or proteinuria.

None of the aforementioned efforts need be mutually exclusive. There is no reason why transplant centers could not simultaneously work to increase living donor rates, overcome immunologic barriers, and accept living donors with mild hypertension. Each option has its own issues. Centers attempting to increase living donor rates also must be prepared to provide adequate information to prospective living donors and to have systems in place for thorough living donor evaluation. Centers working to overcome immunologic barriers must have systems in place to counsel prospective living donors and recipients as to the increased risks (including the potential for early, antibody-mediated graft loss). Centers performing living donor transplants, especially those using novel protocols (eg, accepting hypertensive donors, overcoming immunologic barriers) must have systems in place for long-term follow-up (both medical and psychosocial) to thoroughly assess safety and risks.

Is the glass half full or half empty? Karpinski et al argue that accepting living donors with mild hypertension or proteinuria will only lead to a slight (3%) increase in transplant rates. But every 3% counts—especially because transplants result in increased longevity and better quality of life. Such undeniable benefits for recipients must be weighed against the potential increased risks to living donors.