Living Donor Kidney Transplantation

Thu Pham

John Leppert

Peter Schulam

Advances in immunosuppressive therapy, refinement in surgical techniques, in public awareness, altruism, and goodwill, have allowed living donor kidney transplantation to evolve from the first successful identical twin donor transplantation in 1954 to the current practice whereby virtually all biologically related and unrelated, medically and psychosocially suitable individuals can be considered as donors. During the decade from 1996 to 2006, the number of living donor kidney transplantations in the United States almost doubled to more than 6000 per year but has since fallen somewhat. The increased rates of living donation have been attributed to the superior patient and graft survival rates achieved with living compared with deceased donor transplantation, the advent of laparoscopic donor nephrectomy, improved patient and public awareness, and as a response to the long waiting lists for a deceased donor transplant.

Both within the United States and around the world, there are wide variations in the use of living and deceased kidney donors These differences reflect varying medical and societal cultural values and varying realities in the availability of sophisticated care for patients with advanced kidney disease (see Chapter 1). Differences can also be driven by the availability of deceased donor organs relative to the number of patients waiting for transplants, attitudes of local physicians regarding the risk of living donation, and the degree of government oversight. In Spain, for example, where a highly effective mechanism for identifying deceased donors has helped keep waiting lists short, living donation accounts for less than 5% of all transplants. In many European countries, living donation accounts for less than 10% of transplants, although in the United Kingdom, there has been a steady increase in living donation that accounted for close to 40% of all kidney transplants in 2008. In Japan, strong cultural and, until recently, legal barriers have limited deceased donor transplants, and living donation is the most common form of transplantation. Although illegal throughout the developed world (see Chapter 18) and proscribed by national and international professional transplantation organizations, commercial living donation, typically from vulnerable populations, remains a common practice in parts of the world. The World Health Organization has estimated that up to 10% of organ transplantations are performed in this manner. The Declaration of Istanbul on Organ Trafficking and Transplant Tourism (see Chapter 18 and Appendix) is designed to put an end to exploitation of living donors while promoting healthy and robust transplantation practice.

Part I of this chapter provides medical guidelines for evaluating a potential living donor candidate; part II reviews the relevant surgical issues and techniques; and part III discusses innovative and controversial aspects of living donation. Readers are referred to excellent resource material available on this topic, in particular the proceedings of the Amsterdam Conference on the Care of the Living Kidney Donor and the reviews authored by Davis and by Davis and Delmonico (see “Selected Readings”).

PART I. EVALUATION OF LIVING KIDNEY DONORS

INFORMED CONSENT

Informed consent is a core value in living kidney donation (Table 6.1). Living donor consent is also discussed in Chapter 17. Emphasis on the adequacy of the consent process is particularly important because, as opposed to standard medical procedures, living donation is not specifically designed to help the donor or advance the donor’s health. Moreover, living donation has the potential for contravening that basic tenet of medical ethics, primum non nocere. The person who gives consent to donate an organ must be a competent adult (possessing decision-making capacity); willing to donate; free from coercion; medically and psy-chosocially suitable; fully informed of the risks and benefits of donation; and fully informed of alternative treatments available to the recipient (i.e., to understand that in the absence of their donation, the patient can, in most circumstances, continue dialysis). Two other principles of living donor consent have been endorsed: that of equipoise—the benefits to both the donor and recipient must outweigh the risks associated with the donation and the transplantation of the live donor organ; and that it is clear to the potential donor that his or her participation is completely voluntary and may be withdrawn at any time. To ensure that these principles are applied, it has been recommended that programs performing living donor transplantations have an independent donor advocate who is not part of the team caring for the recipient. The availability of such an advocate (who may be the evaluating physician as long as he or she is not responsible for the care of the recipient) is now mandated in the United States.

A separate consent should be obtained for the donor evaluation. This helps ensure that, in addition to being informed of the risks of donation, the
donor is informed about all aspects of organ donation and the implications of the evaluation process (Table 6.2).

TABLE 6.1 Suggested Elements for Consent in the Living Donor Evaluation Process

The potential donor should understand the following:
	Undergoing evaluation is not a commitment to donate.
	I can stop at any time.
	The physicians may turn me down as a donor, and will inform me why.
	I will be evaluated by an independent donor evaluation doctor or team to protect my interests.
	The information obtained during the course of the evaluation is confidential.
	I will be tested for AIDS, hepatitis, and other infectious diseases.
	I may get unexpected information during the evaluation process that may have implications for my future health and insurability.
	There may be risks and discomfort associated with some of the testing (e.g., blood draws, intravenous contrast).
	There are potential financial costs to me related to time off work, travel expenses, and the like that might not be reimbursed.
	There are potential study uses to the information obtained during the evaluation. I may be asked to participate in a living donor registry.
	It may be suggested to me that I have routine long-term medical follow-up after kidney donation.
	There are alternative treatments available to the recipient other than my donating a kidney to him or her.
Modified from a personal communication from D. Cohen, M.D.

TABLE 6.2 Consent for Medical Evaluation

The potential donor should be informed that he or she must undergo the following:
	A complete history and physical examination
	General laboratory testing
	Screening for HIV, hepatitis, and other infectious diseases
	Imaging studies requiring the use of intravenous contrast The potential donor should understand the following:
		I may get unexpected information during the evaluation process that may have implications for my future health and insurability.
		There may be risks and discomfort associated with some of the testing (e.g., blood drawn, intravenous contrast).
		There may be potential short- and long-term risks associated with the surgical procedure.
		I may need routine long-term follow-up after kidney donation.
		The benefits to both the donor and recipient must outweigh the risks associated with the donation and the transplantation of the live organ.

THE EVALUATION PROCESS

The major components of the evaluation of potential living kidney donors are shown in Figure 6.1.

Psychosocial Evaluation

The psychosocial evaluation is an important initial step in the evaluation of the potential donor (see also Chapters 17 and 20). It also presents a valuable forum for fulfilling the tenets of informed consent, exploring donor motivation, and excluding coercion. Significant psychiatric problems that would impair the person’s ability to give informed consent or that might be negatively affected by the stress of surgery are considered contraindications to living donation (see Chapter 17, Table 17.4). The social support of the potential donor should be deemed adequate. The psychosocial evaluation of so-called nondirected or altruistic donors (see below) and donors who do not have a significant personal relationship with the recipient is particularly important because these donors may not enjoy the psychological gain of seeing the recipient benefit from their altruism (see Chapter 17, Table 17.1). Most donors can look forward to stable or improved sense of psychological well-being and can be told of such.

The psychosocial evaluation must consider the possibility of economic or other forms of coercion. The principles by which donors can be reimbursed for legitimate expenses incurred as a result of the donation or preparation for donation are addressed in the Declaration of Istanbul (see Appendix) and in the National Organ Transplant Act (see Chapter 18). In the United States, all medical costs directly associated with donation are covered by the health insurance of the recipient. The federal government and other employers provide for salary benefits for a 1-month period after donation, some states offer limited tax deductions for donation-related expenses, and a National Living Donor Assistance Center provides reimbursement of legitimate out-of-pocket expenses for
donors who can document financial need. There is no mechanism however, for routine reimbursement of out-of-pocket expenses.

FIGURE 6.1 Major components of the evaluation of potential living kidney donors.

Medical Evaluation

Preliminary Laboratory Evaluation: Donor Typing to Determine the Risk for Acute Transplant Failure

Mandatory preliminary laboratory evaluation of a potential living donor includes determination of ABO blood group compatibility, crossmatching against the potential recipient, and HLA tissue typing. Because of the high costs of HLA laboratory testing and the availability of effective immunosuppressive therapy that minimizes the clinical significance of differences of HLA matching of living donors, some centers elect to perform HLA typing only in sensitized transplant candidates.

Which Donor to Choose?

In cases in which more than one donor is available, selection of the most appropriate donor depends on the degree of HLA matching and donor age. Biologically related donors are generally preferred over unrelated donors. When more than one family member is available, it is logical to commence evaluation of the
best matched relative (i.e., a two-haplotype match versus a one-haplotype match). If the donors have similar match grade (i.e., a one-haplotype-matched parent and a one-haplotype-matched sibling), it may be advisable to choose the older donor with the thought that the younger donor would still be available for donation if the first kidney eventually fails. When more than one one-haplotype-matched sibling is available, it may be worthwhile to check the tissue typing of one parent to determine which siblings shares the noninherited maternal antigens (see Chapter 3). Such sharing may improve long-term graft survival.

It is often a good prognostic sign when the donor attends the recipient’s pretransplantation evaluation appointments. The initial approach to the potential donor should ideally come from the patient and not the patient’s nephrolo-gist, transplant physician, or surgeon. In cases in which patients hesitate to approach family members, the nephrologist and transplant team should be prepared to facilitate the discussion of donation. Written material explaining the donation process can often help to alleviate the fears and anxiety of potential donors. Excellent educational material is available on the websites of major nephrology and transplant-related organizations. Educational material that is home-based and culturally sensitive may be particularly effective.

Parents often are reluctant to turn to their children as potential donors, yet as those parents age, it becomes less and less likely that a donor from their own generation will be available. It is useful to point out to parents that their grown children are adults who are capable of making independent decisions; that the welfare of the donor will be protected in the evaluation and donation period; and that, if they exclude their children as donors, they may be preventing them from enjoying the psychological gain of helping a beloved parent. Older patients will often insist they would have been prepared to donate to their own parents while simultaneously expressing reluctance to permit their own children to donate to them.

Donor Age

Advanced age can increase the risk for perioperative complications, but there is no mandated upper age limit for living kidney donation. About 25% of programs in the United States exclude donors older than 65 years, and although many programs specify no upper age limit, donation after the age of 70 years is relatively uncommon. There is a trend toward using older donors, and the outcome of these donations, particularly to older recipients, is reported to be excellent.

With respect to younger donor age, most programs regard 18 years to be a firm lower age limit. Donors in their late teens and early 20s must be carefully evaluated for the maturity of their understanding of the donation process and to ensure they are not being subjected to overt or covert pressure. Their long life span and hence exposure to the risk for renal disease must be considered, particularly when there is a potential element of heredity in the etiology of the recipient’s renal disease.

Challenges in the Counseling of Older Transplant Recipients

Nearly 10% of all living donations are to recipients who are older than 65 years. Transplantation of living donor kidneys into recipients older than 70 years of age can be practically and ethically challenging. The elderly transplant candidates may be faced with a difficult dilemma: to wait for many years for a deceased donor kidney with the knowledge that their medical condition may continue to deteriorate, or to resort to a young family member for kidney donation while they are still medically suitable for the surgery and young and robust enough to enjoy the transplant.

When the potential donor is considerably younger than the recipient, the following questions should also be addressed: Is it reasonable to transplant a kidney from a very young donor into an elderly recipient who will only benefit from the kidney for a very limited number of years? Should the anticipated extra years of life gained by the recipient place any limitations to the living donor transplantation? There are no formal guidelines that address the acceptable age disparity between living donors and recipients. In most cases, it is best to leave the decision in the hands of an educated and informed potential donor.

Nonetheless, when an elderly transplant candidate does consider a living donor transplant, it is advisable that the transplant be performed as early as possible to maximize the benefit of the procedure. Furthermore, transplantation within a timely period has been shown to increase overall life expectancy, quality-adjusted life expectancy, and comorbidities for transplant recipients of all ages, whereas prolonged waiting time greatly decreased the clinical and economical benefit of transplantation.

General Assessment

The universal medical goals in the kidney donation evaluation process are to ensure that the potential donor has the following characteristics:

Is sufficiently healthy to undergo the surgical procedure
Has normal kidney function with minimal future risk for kidney disease
Represents no risk to the recipient in terms of communicable disease or malignancy transmission
Is not at increased risk for medical conditions that might require treatments that could endanger his or her residual renal function

History, Physical Examination, Laboratory Testing, and Imaging

Living donor evaluation requires a thorough history and physical examination supplemented by laboratory testing, age-appropriate medical screening, and renal imaging (Table 6.3). Donor history or characteristics known to confer significant risk to either the donor or recipient can automatically preclude donation. Obvious contraindications should be determined at the beginning of the donor assessment before subjecting unqualified donors to unnecessary tests (Table 6.4). Female patients should not be evaluated while pregnant or planning to become pregnant in the immediate future. The appropriate postpartum time when donor evaluation may be resumed has not been determined, but if the donor so desires, it is reasonable to evaluate for donation 6 months postpartum. Desire for future pregnancy does not contraindicate donation. Unilateral donor nephrectomy does not increase obstetrical risks or complications.

EVALUATION OF FUTURE DONOR RISK

The systematic evaluation of future donor risk focuses on renal function and covert renal disease; cardiovascular disease risk factors include hypertension, diabetes, and obesity; risk for communicable disease or malignancy transmission to the recipient; and assessment of surgical risks.

Assessment of Renal Function and Covert Renal Disease

Glomerular Filtration Rate

Measurement of creatinine clearance based on a 24-hour urine collection is generally adequate to assess the donor’s renal function, although some centers prefer iothalamate or diethylenetriamine pentaacetic acid (DTPA) clearance. Many centers start with a 24-hour urine collection for creatinine clearance and
only proceed to a renal nuclear scan study in cases with borderline renal function. It must be noted, however, that elderly donors, donors with low muscle mass, and vegetarians may have a low creatinine clearance without intrinsic renal disease. Creatinine-based prediction equations are not reliable in the donor population with relatively normal renal function and should not be used as the sole estimate of glomerular filtration rate (GFR). A 24-hour urine collection is the preferred method to assess renal function because it also offers accurate data for proteinuria.

TABLE 6.3 Living Donor Medical Evaluation

Laboratory Tests
		Blood group, HLA typing, crossmatch
		Urinalysis and urine culture
		Twenty-four-hour urine collection for protein and creatinine clearance or glomerular filtration rate determination by nuclear medicine test
		Complete blood count, prothrombin time, partial thromboplastin time
		Comprehensive metabolic panel (electrolytes, transaminase levels, albumin, bilirubin, calcium, phosphorus, alkaline phosphatase)
		Viral serologies: HIV, hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus, herpes simplex virus, RPR
		Prostate-specific antigen in men 50 years and older (in African American men older than 40 years and in those with two or more first-degree relatives with prostate cancer)
		Human chorionic gonadotropin quantitative pregnancy test in women younger than 55 years
		Serum protein electrophoresis in prospective donors older than 60 years
Other Tests
		Electrocardiogram
		Chest radiograph
		Papanicolaou test (for women)
		Mammogram for women 40 years and older
		Renal imaging: spiral computed tomography (CT), CT angiogram, or magnetic resonance angiogram
Further Testing Depending on Age, History, Abnormal Laboratory Findings, and Family History Screening
		Colonoscopy if 50 years or older
		Cardiac screening: echocardiograph, nuclear medicine stress test Twenty-four-hour ambulatory blood pressure monitoring
		Renal biopsy
		Cystoscopy
		PPD skin test
		Screening for hypercoagulability
		Glucose tolerance test with family history of diabetes mellitus or risk factors for development of diabetes (see text)

Although there is no absolute consensus on the level of renal function below which a person would not be deemed an acceptable donor, most centers use a cutoff GFR of 80 mL/min/1.73 m². Considerations for the lower limit of
renal function allowable for kidney donation include a predicted fall in GFR to 75% of predonation level and the normal decline in GFR with aging at a rate 4 to 5 mL/min/1.73 m² per decade of life starting at age 20 years. Other criteria used to preclude kidney donation include a projected GFR with removal of one kidney at 80 years of less than 40 mL/min/1.73 m². Healthy vegetarians tend to have a lower GFR than meat-eaters.

TABLE 6.4 Contraindications to Living Kidney Donation^*

Absolute Contraindications
		Evidence of renal disease (glomerular filtration rate < 80 mL/min, microalbuminuria or overt proteinuria)
		Significant renal or urologic abnormalities
		Transmissible infectious disease (HIV infection, hepatitis B, hepatitis C)
		Active malignancy
		Chronic illness that places patient at significant risk to undergo surgery
		Poorly controlled psychiatric illness or active substance use
		Cognitive deficit
		Current pregnancy
		Hypertension, uncontrolled or requiring multiple medications
		Diabetes mellitus
		Recurrent nephrolithiasis or bilateral stones
		History of thrombotic disorders with risk factors for future events or inherited hyper-coagulable states^†
Relative Contraindications
		Age < 18 or > 65 years
		Borderline or mild hypertension (see text)
		Borderline urinary abnormalities in the absence of renal function impairment
		Single prior episode of nephrolithiasis without evidence of secondary risk
		Obesity
		Young donor with risk factors for future development of diabetes mellitus (see text)
		Jehovah’s Witness patient
^*Criteria may differ among transplantation centers. ^†For example, the presence of lupus anticoagulant or anticardiolipin antibody, Factor V Leiden, or prothrombin gene mutation (FII-20210).

Abnormal Urinalysis Results

Proteinuria. Proteinuria greater than 250 mg per day, in general, is a sign of renal disease and precludes donation. The collection should be repeated and its accuracy checked when the result is abnormal. An overestimate of proteinuria should be suspected if total urine creatinine-to-body weight ratios are greater than 25 mg/kg (>20 μmol/kg), especially in those with low muscle mass. An underestimate of proteinuria may have occurred if the total urine creatinine-to-body weight ratios are less than 15 mg/kg (<132 μmol/kg). In those with borderline high proteinuria, it is especially important to rule out undercollections. Spot protein-to-creatinine ratios are not recommended because minimal yet clinically significant proteinuria may be missed.

Transient causes of proteinuria, including fever, urinary tract infection, or intense exercise, should be excluded. Orthostatic proteinuria, defined as elevated
urine protein with assumption of the upright posture and normal protein excretion during recumbency should be ruled out. This benign phenomenon usually occurs in younger age groups and does not necessarily preclude donation. Borderline high proteinuria can be further evaluated for microalbuminuria, a more reliable marker of intrinsic renal disease. The presence of microalbuminuria in such cases should preclude kidney donation.

Hematuria.

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