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Evidence-Based Nephrology
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Risks of Living Kidney Donation

Current State of Knowledge on Outcomes Important to Donors

Krista L. Lentine, Ngan N. Lam and Dorry L. Segev
CJASN April 2019, 14 (4) 597-608; DOI: https://doi.org/10.2215/CJN.11220918
Krista L. Lentine
1Saint Louis University Center for Abdominal Transplantation, St. Louis, Missouri;
2Department of Medicine, Saint Louis University School of Medicine, St. Louis, Missouri;
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Ngan N. Lam
3Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada; and
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Dorry L. Segev
4Department of Surgery and
5Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
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Abstract

In the past decade, there have been increasing efforts to better define and quantify the short- and long-term risks of living kidney donation. Recent studies have expanded upon the previous literature by focusing on outcomes that are important to potential and previous donors, applying unique databases and/or registries to follow large cohorts of donors for longer periods of time, and comparing outcomes with healthy nondonor controls to estimate attributable risks of donation. Leading outcomes important to living kidney donors include kidney health, surgical risks, and psychosocial effects of donation. Recent data support that living donors may experience a small increased risk of severe CKD and ESKD compared with healthy nondonors. For most donors, the 15-year risk of kidney failure is <1%, but for certain populations, such as young, black men, this risk may be higher. New risk prediction tools that combine the effects of demographic and health factors, and innovations in genetic risk markers are improving kidney risk stratification. Minor perioperative complications occur in 10%–20% of donor nephrectomy cases, but major complications occur in <3%, and the risk of perioperative death is <0.03%. Generally, living kidney donors have similar or improved psychosocial outcomes, such as quality of life, after donation compared with before donation and compared with nondonors. Although the donation process should be financially neutral, living kidney donors may experience out-of-pocket expenses and lost wages that may or may not be completely covered through regional or national reimbursement programs, and may face difficulties arranging subsequent life and health insurance. Living kidney donors should be fully informed of the perioperative and long-term risks before making their decision to donate. Follow-up care allows for preventative care measures to mitigate risk and ongoing surveillance and reporting of donor outcomes to inform prior and future living kidney donors.

  • Living donation
  • outcomes
  • Patient-centered care
  • Living Donors
  • Health Expenditures
  • Aftercare
  • quality of life
  • Kidney Failure, Chronic
  • kidney
  • Renal Insufficiency, Chronic
  • Insurance
  • Health
  • Registries
  • Nephrectomy
  • Salaries and Fringe Benefits

Introduction

Since the inception of the successful practice of living donor kidney transplantation in 1954, >150,000 living persons in the United States have donated a kidney to help a family member, a friend, or even a stranger (1). Worldwide, >35,000 living donor kidney transplants are performed each year (2). Living donors derive no medical benefit from donation, nor do they expect to, but living donors do deserve transparent information on the short- and long-term outcomes of donation to support informed decision-making, follow-up, and care (3). The risks of living donation are accepted as sufficiently low to justify the practice, but notably, much of the available evidence has been limited by short observation periods, a high proportion of donors lost to follow-up, insufficient power to quantify rare events, and limited racial diversity (4–6). Furthermore, until recently, most studies compared donors with the unscreened general population. Recognition of these deficiencies, and the vital need to address them, prompted a growing body of research over the past decade that has helped advance understanding of donor risks (7). The study methodologies include construction of multicenter cohorts (8,9), integration of national donor registries with other data sources to acquire longer-term information for a broader spectrum of outcomes (10–19), and assembly of healthy nondonor controls for estimation of donation-attributable risks (20–25). The resulting evidence suggests small donation-related increases in the risk of kidney failure that have affected policy requirements and guidelines for the informed consent and care of living donors (26,27). Efforts to establish larger living donor consortia and registries with long-term follow-up are also being planned and pilot-tested (28,29).

The recent 2017 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors focuses on risk assessment as a foundational theme. A central framework of the guideline is promotion of “consistent, transparent and defensible decision-making” on the basis of comparisons of individualized, quantitative estimates of donor risks “to a transplant program’s acceptable risk threshold” (Figure 1) (27). Although robust data necessary to ground risk thresholds for many outcomes are lacking, this conceptual framework provides a new structure for the consideration of available data by patients and providers, and a roadmap for design of future studies to address evidence gaps. Kidney donation is a decision with lifelong implications that can span dimensions of medical and psychosocial health. A new study found that “living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation” (30). In this review, we summarize the current state of evidence related to these outcomes important to donors, and suggest next steps to advance the evidence base for donor risk estimation and application with a transparent, consistent framework of shared decision-making.

Figure 1.
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Figure 1.

The KDIGO framework to accept or decline donor candidates compares projected lifetime risk of kidney (quantified as the aggregate of risk related to demographic and health profile and donation-attributable risks) to a transplant program's threshold of acceptable risk. Reproduced from reference 27, with permission.

Kidney Health

Assessment of living kidney donor values and perceptions at three centers in Australia and Canada by Hanson et al. (30) identified kidney function as the highest ranked outcome important to living donors, underpinned by fear of developing kidney failure. Although many donors felt they had ruled out the risk of kidney failure during evaluation, some were uncertain whether their glomerular filtration rate (GFR) after donation was “normal” and how to protect their long-term kidney function (e.g., by lifestyle or dietary modifications) (30). Similarly, a new study of 193 living kidney donors in the United States, assessed at 1, 6, 12, and 24 months postdonation, found that 21% (n=32) reported an emergence of anxiety about kidney injury or loss at one or more postdonation assessments, but this anxiety dissipated in 35% (11 out of 32) (31). In an interview-based study of 50 living donors at one center (assessed at a median 9 years after donation), 22% reported concern for failure of the remaining kidney before donation, whereas 12% endorsed this concern postdonation (32).

After donor nephrectomy there is compensatory hyperfiltration in the remaining kidney, such that the net reduction in GFR early after donation is only approximately 30% (25%–40%; i.e., decrement in GFR of 25–40 ml/min per 1.73 m2) (33–36). One long-term study of glomerular hemodynamics after kidney donation observed that the adaptive hyperfiltration mostly resulted from compensatory glomerular hypertrophy and hyperperfusion in the remaining kidney, rather than pathologic glomerular hypertension (37). In a prospective study of 182 predominantly (94.6%) white kidney donors and paired healthy nondonors, GFR measured by iohexol clearance declined 0.36 ml/min per year in nondonor controls but increased 1.47 ml/min per year in donors between 6 and 36 months of follow-up (33,35). The trajectory of change in GFR beyond 36 months postdonation, and associations with risk for ESKD, requires examination in larger, demographically diverse samples. A recent study of 2002 predominantly white living donors followed for up to 20 years at one center did not support an association of postdonation estimated glomerular filtration rate (eGFR) trajectory and ESKD risk (38). Nevertheless, there is concern that adaptive hyperfiltration might result in faster progression of de novo kidney disease that could accelerate deterioration to low levels of kidney function or kidney failure (39).

Clinically important kidney end points include progression to advanced stages of CKD, injury markers such as proteinuria, and most importantly, ESKD. One study of 3956 predominantly white kidney donors found that 36% had eGFR<60 ml/min per 1.73 m2 (corresponding to CKD stage 3 or higher) at a median time of 9.2 years postdonation, and 2.6% had eGFR<30 ml/min per 1.73 m2 (corresponding to CKD stage 4 or higher) at a median of 23.9 years (40). Postdonation proteinuria was higher in men (adjusted hazard ratio [aHR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) and those with higher body mass index (BMI) (aHR, 1.10 per unit; P<0.001) (40). A meta-analysis found that after an average of 10 years of follow-up, 12% of donors had a GFR in the 30–59 ml/min range whereas only 0.2% had a GFR in the <30 ml/min range; further, most donors did not have a progressive GFR loss after the initial reduction postdonation (36). As in the general population, risk of kidney complications varies by baseline donor traits, such as race. For example, a study of 4650 donors in the United States found that by 7 years postdonation, after adjustment for age and sex, a greater proportion of black donors compared with white donors had kidney-related diagnoses: CKD (12.6% versus 5.6%; aHR, 2.32), proteinuria (5.7% versus 2.6%; aHR, 2.27; 95% CI, 1.48 to 3.62), and nephrotic syndrome (1.3% versus 0.1%; aHR, 15.7; 95% CI, 2.97 to 83.0) (17).

Although the risk of ESKD after kidney donation does not exceed ESKD rates in the general population (41–43), two recent studies comparing donors with healthy nondonors for estimation of donation-attributable risk found that donation is associated with a small but significant increase in the risk of ESKD. In comparing 1901 kidney donors with 32,621 healthy, demographically matched controls in Norway, Mjøen et al. (22) found that nine donors (0.47%) developed ESKD versus 22 healthy nondonors (0.07%) (aHR, 11.9; 95% confidence interval [95% CI], 4.4 to 29.6). On the basis of linking data for 96,217 living donors from the United States donor registry and healthy participants drawn from National Health and Nutrition Examination Survey III to national ESKD reporting forms, Muzaale et al. (21) reported that the cumulative incidence of ESKD at 15 years was 30.8 per 10,000 in donors compared with 3.9 per 10,000 in matched donors (risk attributable to donation of 26.9 per 10,000). Considered by race, black living donors had the highest absolute risk of ESKD postdonation as well as the highest risk attributable to donation. Although the risk increase is small, details have been debated (44), and absolute postdonation risk is low overall, these data have appropriately shaped informed consent policies in the interest of transparent disclosure, such that United States transplant programs are now required to disclose the possibility of donation-attributable increase in ESKD risk (26), and similar disclosure is recommended for international practice by the 2017 KDIGO guideline (27).

Some information is available on ESKD causes after donation. A linkage of national donor registry data to ESKD registry data for 125,427 living donors found that early postdonation ESKD was predominantly reported as due to glomerulnephritis (GN), whereas late postdonation ESKD was more frequently reported as due to diabetes or hypertensive kidney disease, the latter two consistent with the leading causes of ESKD in the United States general population (45). In a single-center study of 3956 predominantly white living donors, 48% of ESKD events with known causes (n=12 out of 25) were related to hypertension or diabetes (46). Although the pathways from predonation metabolic and genetic risk factors to postdonation ESKD are not yet well defined, these data emphasize the importance of careful evaluation to identify kidney risk factors, counseling regarding known and unknown risks, and engagement in postdonation follow-up, especially for higher-risk groups, so that any signs of early postdonation kidney problems can be recognized and managed.

To help ground a quantitative framework for living donor candidate evaluation, the 2017 KDIGO guideline development methodology included collaboration with the CKD Prognosis Consortium to develop a tool to project the 15-year and lifetime incidence of kidney failure in the absence of donation on the basis of demographic and health characteristics at the time of evaluation (47). The risk model uses meta-analysis of data from nearly 5,000,000 healthy persons identified from seven general population cohorts who are similar to kidney donor candidates, calibrated to annual ESKD incidence in the United States healthy population (47), and the resulting online tool is available online (www.transplantmodels.com). Projected ESKD risk was higher in the presence of a lower estimated GFR, higher albuminuria, hypertension, current or former smoking history, diabetes mellitus, and obesity. In the model-based lifetime projections, the risk of ESKD in the absence of donation was highest among persons in the youngest age group, particularly among young black men. Importantly, a central principle of the approach and tool is risk assessment on the basis of simultaneous consideration of a profile of demographic and clinical characteristics, rather than individual factors in isolation (e.g., risk related to high BP or BMI alone), and comparison of integrated risk to a threshold of acceptable risk (Figure 1).

Other tools are available. Using a cohort of 3956 white donors, Ibrahim et al. (40) developed a calculator for eGFR<30 ml/min per 1.73 m2 or ESKD on the basis of risk relationships for older age (hazard ratio [HR], 1.07; 95% CI, 1.05 to 1.09 P<0.001), higher BMI (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01). Another recent tool estimates postdonation risk on the basis of national United States registry and ESKD data for 133,824 living donors. ESKD risk after donation in this model is higher with male sex, black race, higher BMI, and biologic relationship to recipient (48). Because of the lack of available data, the model does not incorporate clinical or laboratory variables, such as the use of antihypertensive medications and urine albumin excretion. A key finding in this study was that although the 20-year predicted ESKD risk was very small in the average (median) donor (34 in 10,000), in a small subgroup of donors (1%) the risk was substantially higher than the median (256 in 10,000) (48). Recent studies of kidney outcomes in living donors, including ESKD, reduced GFR/CKD, and proteinuria, are summarized in Table 1.

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Table 1.

Summary of recent studies of kidney outcomes in living donors, according to risk perspective

Surgical Risks

In the study by Hanson et al. (30), avoiding catastrophic consequences such as surgical mortality and morbidity was important to donors, particularly during decision-making, because they were the “most serious” outcomes and would also affect their family. Some participants ranked time to recovery, surgical complications, and pain highly because they felt “deeply disappointed” and “resentful” about enduring a more debilitating and protracted recovery than they had been “led to expect.” (30) In a multicenter, prospective study of 228 living donors, perioperative complications, not surprisingly, were associated with clinically and statically significant reductions in measures of health-related quality of life (49). Other studies have noted that a minority of donors have reported slower than expected recovery (50). However, aside from capture of length of initial hospital stay and time to return to work in some clinical trials (typically comparisons of different operative techniques) (51,52) and single-center reports, data on postdonation recovery are not systematically captured.

Fortunately, the risk of morbidity and mortality after living donor nephrectomy is low. A United States study linking the national donor registry for 80,347 donors to the Social Security Death Master Index reported the 90-day mortality to be 3.1 per 10,000 (20). Consistent rates have also been reported in other studies (53). Administrative data have been used to identify perioperative complications in large samples of living kidney donors, independent of center or surgeon reporting. Using a composite outcome of cardiac, respiratory, digestive, urinary, procedural, hemorrhage, or infectious complications, one United States study estimated the incidence of perioperative complications as 7.9% and noted a decrease over time, from 10.1% in 1998 to 7.6% in 2010 (54). Limitations of this study include the lack of confirmation of donor status through patient-level linkages to the national registry, and use of weighting schemes to draw inferences for a “represented” sample of all United States donors on the basis of a stratified sample of 20% of acute care hospitalizations (55). A subsequent study integrated national United States donor registry data as a source of verified living donor status with administrative records from a consortium of 98 academic hospitals (2008–2012, n=14,964). In this study, 16.8% of donors experienced any perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), and surgical/anesthesia-related injuries (2.4%) (18). Major complications, defined as Clavien grading system for surgical complications level 4 or 5 (56), affected 2.5% of donors. Similarly, a Norwegian registry-based study of 1022 living kidney donations performed between 1997 and 2008 reported 18% minor and 2.9% major complications by Clavien grading (57). The 2017 KDIGO guideline and the European Association of Urology Guidelines on Renal Transplantation: Update 2018 present these estimates as information for donor counseling (27,58). Given the low incidence of major perioperative complications, estimates for predonation characteristics that alter the risk are imprecise. Efforts to capture granular complications data, such as through large, national registries, including development and validation of patient-centered recovery measures, are needed to support contemporary estimates of the risk of perinephrectomy complications according to an individualized profile of predonation characteristics (27).

Psychosocial Outcomes

Quality of Life

Although living donors derive no personal medical benefit from donation, they may experience psychosocial benefits related to the altruistic act of improving the health and wellbeing of another person. A systematic review assessing psychosocial health in living kidney donors found that the majority of donors scored high on health-related quality-of-life measurements (59). Psychosocial health was unchanged or improved after donation and overall, and was similar or better than the general population. A minority of donors experienced negative psychosocial outcomes such as depression, anxiety, stress, and lower-quality relationships. Reassuringly, most donors did not regret their decision to donate and would undergo the process again, even in the rare circumstances when the recipient experiences a poor outcome (9). However, recipient graft loss and death have been associated with increased risk of depression treatment after donation in some studies (12).

Recently, Rodrigue et al. (31) reported on psychosocial measures assessed pre- and postdonation among 193 living kidney donors and 20 healthy controls. Donors experience minimal to no dysfunction in mood, body image, fear of kidney failure, life satisfaction, and decisional stability up to 2 years postdonation, and their outcomes did not differ significantly from the healthy nondonor controls. The overall incidence of new-onset mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%) after donation was low. Donors with preexisting concerns were at the highest risk of the same outcomes postdonation. Thus, although donors have generally favorable psychosocial outcomes postdonation, the small risk of adverse psychosocial functioning should be discussed with all living kidney donor candidates.

Financial Risks

Although the study by Hanson et al. (30) found that some donors had financial assistance to help them absorb out-of-pocket expenses and replace lost income as a result of donation, other participants ranked financial concerns highly because they believed that lost income and out-of-pocket expenses were unfair barriers to donors. For younger donors, single parents, and one donor who was not a resident and uninsured, the costs were “a big hit” and, for one, “an absolute destruction.” (30) The leave required for recovery caused some donors to lose their jobs (30). A recent survey of 51 United States donors found that perceived financial burden was highest among those with predonation cost concerns and with an income <$60,000 (60).

Although it is widely accepted that living donation should be a financially neutral act, unfortunately, financial risks are a reality in current practice. Even in countries where the donation-related medical expenses are paid by the recipient’s insurance or the health care system, it has been documented that donor candidates may incur many types of direct and indirect costs in the donation process, including for travel, medications, lost time from work, and dependent care (61–63). In one United States study, 92% of living kidney donors incurred direct costs (median $433, range $6–$10,240) and more than one third (36%) reported lost wages in the first year after donation (median $2712, range $546–$19,728) (62). Similarly, a multicenter, Canadian cohort found that 98% of living kidney donors incurred donation-related costs, with median (seventh percentile) out-of-pocket costs of $1254 ($2598) (Canadian dollars); among 30% who experienced unpaid time off work, median lost income was $5534, and total costs exceeded $5500 in 25% of the cohort (64). A single-center, retrospective survey of living donors who were working for compensation at the time of donation (2005–2015) found that increased length of time to return to work was a significant predictor of financial burden, and that donors in manual/skilled trade occupations experienced greatest financial burden for each week away from work (65). Older age at donation and nondirected (versus directed) donation were associated with significantly decreased financial burden (65). Living donation may also affect ability to obtain life, disability, and health insurance (66–68).

The National Organ Transplant Act has been clarified, to explicitly state that “reasonable payments associated with… the expenses of travel, housing, and lost wages incurred by the donor” are legal (69). Many states have enacted legislation to offer tax deductions or credits, or other benefits, to living organ donors (70). These programs vary state by state, are underused, and have not been studied with regard to effect on financial burden of donation. Trials of replacement of lost wages in the donation process are being pilot-tested (71,72).

A 2016 convenience sample of informed consent forms for living donor and transplant candidate evaluation from nine geographically diverse programs in the United States identified misconceptions about defraying donation-related costs, reinforced by ambiguous language or omissions in the donor informed consent documents (73). Living donor candidates should receive counseling about financial costs and risks before donation, information about the availability of legal cost replacement programs, and assistance in accessing legitimate cost replacement programs. In 2016, the American Society of Transplantation launched an online financial toolkit to help donor candidates learn about the finances of being a living organ donor; this dynamic resource will be expanded and updated over time (74). An American Society of Transplantation Living Donor Community of Practice work group has developed guidance to help transplant centers maximize donor coverage and minimize financial consequences to donors (75).

Summary and Future Directions

The practice of living donation relies on the ethical principles of beneficence and nonmaleficence (where the benefits to the recipient are great whereas the risks to the donor are justifiably low) as well as donor autonomy after informed consent (where risks and uncertainties are fully disclosed) (76). Understanding risks related to kidney health, surgical complications, and psychosocial outcomes is vital for donors and their care providers, and defining knowns and unknowns can inform future research and policy development priorities (Figure 2). However, focus on these key outcomes important to donors is not intended to be comprehensive, and other outcomes (e.g., pregnancy risks, hypertension, metabolic conditions, and effect on relationships, family dynamics, and lifestyle) are discussed elsewhere (13,14,19,24,77–85). Some adverse outcomes may only be fully appreciated after decades of follow-up of large cohorts of donors with diverse demographic characteristics. Ongoing commitment to strengthen the evidence base for donor candidate evaluation, selection, and counseling, including longer follow-up in representative cohorts, well designed use of integrated data sources (55), long-term registries (28), and advancement of tools for tailored risk estimation (7,47,76,86,49), should remain a leading priority for researchers, practitioners, and policymakers.

Figure 2.
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Figure 2.

Applying knowledge on outcomes important to donors can inform current counseling and next steps for research and policy. Infographic prepared for this perspective by Heather Hunt, JD, in collaboration with Alvin Thomas, MSPH.

Disclosures

None.

Acknowledgments

Heather Hunt, JD, and Alvin Thomas, MSPH, collaborated in preparing the original infographic for this article and grant permission for its use. Ms. Hunt is president of LIVE ON Organ Donation, Inc., a nonprofit organization that raises money to support living organ donors’ nonmedical expenses, and is vice chair of the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) Living Donor Committee. Mr. Thomas is a student in the Department of Epidemiology at the University of North Carolina at Chapel Hill.

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

  • See related Commentary, “Commentary on Risks of Living Kidney Donation: Current State of Knowledge on Core Outcomes Important to Donors,” on pages 609–610.

  • Copyright © 2019 by the American Society of Nephrology

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Clinical Journal of the American Society of Nephrology: 14 (4)
Clinical Journal of the American Society of Nephrology
Vol. 14, Issue 4
April 05, 2019
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Risks of Living Kidney Donation
Krista L. Lentine, Ngan N. Lam, Dorry L. Segev
CJASN Apr 2019, 14 (4) 597-608; DOI: 10.2215/CJN.11220918

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Risks of Living Kidney Donation
Krista L. Lentine, Ngan N. Lam, Dorry L. Segev
CJASN Apr 2019, 14 (4) 597-608; DOI: 10.2215/CJN.11220918
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  • Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney Disease
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Keywords

  • Living donation
  • outcomes
  • Patient-Centered Care
  • Living Donors
  • health expenditures
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  • quality of life
  • Kidney Failure, Chronic
  • kidney
  • Renal Insufficiency, Chronic
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