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Kidney transplantation in adults: Living unrelated donors

Kidney transplantation in adults: Living unrelated donors
Literature review current through: Jan 2024.
This topic last updated: Sep 12, 2022.

INTRODUCTION — The widening gap between the demand and supply of donor kidneys has led to a call for an expansion in the potential donor pool. Efforts have been made to increase the number of available grafts retrieved by expanding the donor criteria. Such efforts include using donors at the extremes of age, double kidney transplants from marginal donors, extended-criteria/Kidney Donor Profile Index (KDPI) >85 percent donors, and the use of living kidney donors [1-4]. Living kidney donation rates continue to fall, a trend that began in 2003 with a subsequent 15 percent decline to date. While the number of transplants as a result of kidney paired donation (KPD) networks has steadily increased from 19 in 2003 to 228 in 2008 to 525 in 2012, this has not kept pace with the overall decline in living kidney donation (figure 1) [5,6]. This trend is in the presence of a rapidly growing waiting list, longer times to transplant, and very modest increases in deceased donation rates over the past 10 years. Reasons for the decline in living donation (primarily driven by decreases in living related donation) may be due to a number of factors that include an aging transplant candidate population, concurrent medical unsuitability of prospective donors, economic uncertainty, and financial disincentives [7].

Kidney donation by biologically unrelated persons has been attempted in different areas of the world, including the Middle and Far East [8-10]. These donations have received adverse publicity because of a combination of factors, including [10-13]:

Unresolved ethical issues including donor payment and possible coercion

Unacceptably high donor and recipient morbidity and mortality

Poor allograft survival rates

However, such concerns have not materialized in patients accepting kidneys from unrelated donors in the United States [4,14]. In addition, donor payment is a federal offense (National Organ Transplant Act, 1984). Living unrelated donors comprise more than 30 percent of all living donors [15-18].

Issues pertaining to living unrelated kidney donation, including donor evaluation and outcome, are reviewed here. A review of general issues pertaining to the kidney donor, whether related or unrelated to the recipient, is presented separately. (See "Kidney transplantation in adults: Evaluation of the living kidney donor candidate".)

DONOR EVALUATION — The ethical considerations surrounding living unrelated organ donation in the United States are somewhat similar to those involved in living related organ donation. Thus far, living unrelated kidney donation has been based upon altruistic ideals and has not been driven by economic incentives; however, some clinicians argue that the debate concerning the sale of kidneys should be reopened [19]. Within the United States, Centers for Medicare and Medicaid Services (CMS) has mandated the participation of an "independent living donor advocate" (ILDA) into the evaluation of all living donors, whether related, unrelated, or altruistic. One of the primary roles of the ILDA is to ensure that the potential donor is free of coercion from the potential recipient or other involved individuals [20-22]. Importantly, the ILDA is independent of the transplant program and has veto power over the donor-selection process.

The basic medical evaluation is the same as that for living related donors. (See "Kidney transplantation in adults: Evaluation of the living kidney donor candidate" and "Kidney transplantation in adults: Prevention and treatment of antibody-mediated rejection".)

The purpose of the evaluation is not to find the "perfect" donor, but to ensure that a potential donor is not jeopardized to an extent beyond the operative risk and does not pose a risk of transmissible infection to the recipient.

RISK OF DONOR NEPHRECTOMY — A major concern about living donors is the long-term impact of having a solitary kidney with risk of developing hypertension, proteinuria, and chronic kidney disease. Studies suggested that the risk of such complications appears to be quite small [23]. To better understand these risks, there continue to be calls for the establishment of long-term living-donor registries [24]. (See "Kidney transplantation in adults: Risk of living kidney donation".)

ALLOGRAFT OUTCOME AFTER KIDNEY DONATION — The outcomes from a human leukocyte antigen (HLA)-mismatched pairing are similar to those of haploidentical relatives. The one-year values are comparable with graft survival rates for recipients of living-related-donor kidneys and better than that with deceased-donor kidneys (see "Kidney transplantation in adults: Risk factors for graft failure"). This survival benefit with living-unrelated-donor kidneys occurs despite a greater degree of HLA mismatching and a slightly increased rate of acute rejection [25].

Long-term graft survival of living-unrelated-donor kidneys is also encouraging. In the 2008 annual report of the Scientific Registry of Transplant Recipients, for example, the unadjusted five-year survival of living-unrelated-donor kidneys was the same as that of living-related-donor kidneys (approximately 80 percent) [15]. (See "Kidney transplantation in adults: HLA matching and outcomes".)

Since the number of HLA mismatches is similar for spousal donors and the three-to-four HLA-mismatched cadaveric donors, the better results with living donors are best explained by less ischemic injury and the transplantation of "healthier" grafts. Other mechanisms that have been thought to contribute include improved patient compliance with immunosuppressive medications, less susceptibility to underlying kidney disorders (particularly focal segmental glomerulosclerosis and diabetes mellitus), and possible tolerance to spousal antigens by sexual contact [26]. However, the last hypothesis seems unlikely since recipients of living-unrelated-donor kidneys experience a similar number of acute rejection episodes and require as much immunosuppressive therapy as recipients of living related grafts [27].

EXPANSION OF LIVING UNRELATED DONOR POOL — There have been multiple efforts to expand the number of living donors [28,29]. One method is the establishment of kidney paired donation (KPD) programs [30,31]. In this system, living donors who are incompatible with their intended recipients either because of ABO incompatibility or because of sensitization (leading to a positive crossmatch) participate in a "donor pool," resulting in an expanded availability of organs [31].

The development of a national paired kidney exchange pilot program is underway [32]. The national Organ Procurement and Transplantation Network (OPTN), operated under federal contract by United Network for Organ Sharing (UNOS), is coordinating the project, although limited numbers of transplants have resulted thus far.

Another strategy is to consider a nondirected live kidney donor (sometimes referred to as altruistic donors). These individuals offer to donate a kidney, but do not identify the specific recipient [33-35]. A 2002 United States national conference report was published outlining some ethical and practical guidelines for centers considering the use of kidneys from a nondirected live kidney donor [36]. In the 2005 Scientific Registry of Transplant Recipients Report, there were 88 nondirected donations (among a total of 2343 living unrelated donors) [17]. Perhaps the most exciting development is the realization that an altruistic donor can trigger an open-ended chain of transplants.

Some regions of the UNOS region have also instituted a system where a person waiting for a deceased-donor kidney is given a higher priority if a living relative donates a kidney to another recipient, resulting in the patient coming off the waiting list [37,38]. This practice, however, may harm standard blood type O waiting-list candidates if ABO-incompatible donor-recipient pairs are allowed to participate.

An increase in living donation rates, whether living related or unrelated, may also occur if patient education is improved [39]. In one study, 122 patients were randomly assigned to clinic-based education alone or clinic-based plus home-based education [40]. The combined program resulted in significantly more living kidney donor transplantations (52 versus 30 percent).

Medically complex kidney donors — Ideally, living kidney donors have normal kidney physiology and anatomy in the absence of comorbidities such as hypertension or obesity. However, the gap between kidney supply and demand mentioned above has led to the utilization of more complex living donors who have one or more comorbidities. Medically complex living donors have been loosely characterized as those with advanced age, obesity, asymptomatic microhematuria, proteinuria, hypertension, and/or nephrolithiasis [41]. One study reported that almost 50 percent of potential living donors are excluded due to comorbidities such as these [42].

In a retrospective cohort study of live kidney donors using OPTN data, donors with hypertension, obesity or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were considered medically complex [43]. Among 9319 donors, 2254 (24 percent) were complex: 1194 (13 percent) were obese, 956 (10 percent) were hypertensive, and 392 (4 percent) had low eGFR. The mean proportion of medically complex donors at a center was 24 percent (range 0 to 65 percent). In a multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (odds ratio [OR] 1.29, 95% CI 1.06-1.56), low education (OR 1.19, 95% CI 1.04-1.37), older age (OR 1.01 per year, 95% CI 1.01-1.02) and non-United States citizenship (OR 0.70, 95% CI 0.51-0.97). Kidney transplant centers with the highest transplant volume and with a higher proportion of living donors were more likely to use medically complex donors.

The outcomes of medically complex living donor transplants have not been well studied. One author in reviewing this topic stated that the lack of strong outcome data on donors with medical complexities "limits the clinician's ability to determine a convincing risk assessment" [44]. While one may speculate that donor complexity may associate with adverse outcomes, the magnitude of differences is poorly defined. On a positive note, one study reported that medically complex living donors demonstrate similar compensatory increases in function and volume of the remaining kidney, compared with standard donors, five years after donation [45]. Living kidney donors with three separate risk factors (older age, obesity, or hypertension) were reevaluated five years after donation. The function and volume of the remaining kidney were assessed and compared with those of standard donors. The body size correlated significantly with the kidney size and GFR at the time of donation. Five years after donation, the remaining kidney size increased by a mean of 29 percent and the GFR by 36 percent; the increase in GFR was uniform. In a univariate analysis, neither the changes in the kidney size nor the changes in the GFR were found to be associated with the risk factors.

KIDNEY PAIRED DONATION — Approximately 30 percent of live donors are incompatible with their intended recipients either because of ABO differences or the presence of preformed donor reactive antibody. Kidney paired donation (KPD) offers the best option for many such individuals and has grown to account for over 15 percent of live-donor transplants within the United States. KPD is currently administered through a variety of local, regional, and national initiatives. Some local KPD programs, such as the National Kidney Registry, have been remarkably successful. As an example, one study reported 134 KPD transplants performed over a three-year period [46]. Of the sensitized recipients transplanted by paired donation, 44 percent had calculated panel reactive antibody levels greater than 80 percent. A discussion of outcomes associated with KPD is presented separately. (See "Kidney transplantation in adults: Kidney paired donation".)

A single, national KPD system has been proposed that adheres to a set of clinical and ethical standards determined by a consensus of stakeholders including recipients, donors, providers, payers, and the United States federal government [47]. Proposed key features include the need for uniform tissue-typing algorithms, computerized matching programs, development of a single administrative structure, and a standardized organ acquisition charges. The United Network for Organ Sharing (UNOS) continues to develop its national KPD pilot program, although its success has been dwarfed by competing initiatives.

One of the barriers impeding widespread implementation of KPD is financial. Analogous to the recovery of deceased-donor kidneys, KPD requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching, administrative, and transportation charges represent additional financial challenges. A Medicare Demonstration Project has been proposed to develop a standard acquisition charge for KPD analogous to the proven strategy used for over 30 years to pay for deceased-donor solid organ transplantation in the United States [48]. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living-donor costs intended to lead to transplantation of a beneficiary of a different insurance provider [49,50].

VOUCHER DONORS — The National Kidney Registry provides living donors the opportunity to donate altruistically, or in advance of a potential recipient's transplant, and to receive a voucher that can be redeemed for a future transplant. Family vouchers allow a donor to identify multiple individuals within their immediate family, with the first person in that group in need of a transplant being prioritized to receive a kidney. (See "Kidney transplantation in adults: Kidney paired donation", section on 'Advanced donation and "voucher" for future kidney transplantation'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Kidney transplant (The Basics)" and "Patient education: Planning for a kidney transplant (The Basics)")

SUMMARY AND RECOMMENDATIONS

Efforts to increase the number of available kidney allografts include the use of living kidney donors. This includes kidney donation by biologically unrelated persons. (See 'Introduction' above.)

The ethical considerations surrounding living unrelated organ donation in the United States are somewhat similar to those involved in living related organ donation. Thus far, living unrelated kidney donation has been based upon altruistic ideals and has not been driven by economic incentives. The basic medical evaluation is the same as that for living related donors. (See 'Donor evaluation' above.)

A major concern about living donors is the long-term impact of having a solitary kidney. This is discussed separately. (See 'Risk of donor nephrectomy' above and "Kidney transplantation in adults: Evaluation of the living kidney donor candidate".)

The outcomes from a human leukocyte antigen (HLA)-mismatched pairing are similar to those of haploidentical relatives. The one-year values are comparable with graft survival rates for recipients of living-related-donor kidneys and better than that with deceased-donor kidneys. (See 'Allograft outcome after kidney donation' above.)

There have been multiple efforts to expand the living-unrelated-donor pool. One method is the establishment of paired kidney exchange programs, the most successful of which is the National Kidney Registry. Another strategy is to consider a nondirected live kidney donor (sometimes referred to as altruistic donors or "good samaritan" donors). These individuals offer to donate a kidney, but do not identify the specific recipient. An increase in living donation rates, whether living related or unrelated, may also occur if patient education is improved. (See 'Expansion of living unrelated donor pool' above.)

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References

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