Moving closer to understanding the risks of living kidney donation

Recent studies from the United States and Norway have suggested an unexpected 8‐ to 11‐fold relative risk of ESRD after kidney donation, but a low long‐term absolute risk. Abundant renal epidemiologic data predict that these studies have underestimated long‐term risk. The 1% lifetime post‐donation risk in the US study requires medical screening to predict ESRD in 96 of 100 candidates. This is particularly unlikely in the 30–35% of candidates under age 35, half of whose lifetime ESRD will occur after age 64. Many experts have attributed the increased relative risks in these studies to loss of GFR at donation, which ultimately means that high–normal pre‐donation GFRs will reduce absolute post‐donation risks. The 8‐ to 11‐fold relative risks predict implausible risks of uninephrectomy in the general population, but lower estimates still result in very high risks for black donors. Young vs. older age, low vs. high–normal pre‐donation GFRs, black race, and an increased relative risk of donation all predict highly variable individual risks, not a single “low” or “1%” risk as these studies suggest. A uniform, ethically defensible donor selection protocol would accept older donors with many minor medical abnormalities but protect from donation many currently acceptable younger, black, and/or low GFR candidates.     

Associations of perceived information adequacy and knowledge with pursuit of live donor kidney transplants and living donor inquiries among African American transplant candidates

We studied associations between perceived adequacy of live donor kidney transplant (LDKT) information or knowledge with pursuit of LDKT or receipt of live donor inquiries among 300 African American kidney transplant candidates. Participants reported via questionnaire how informed or knowledgeable they felt regarding LDKT. Participants also reported their pursuit of LDKT, categorized as “low” (no discussion with family or friends about LDKT and no identified donor), “intermediate” (discussed LDKT with family but no identified donor) or “high” (discussed LDKT with family and identified a potential donor). We reviewed participants' electronic health records to identify potential donors' transplant center inquiries on participants' behalves. A minority of participants reported they felt “very” or “extremely” well informed about LDKT (39%) or had “a great deal” of LDKT knowledge (38%). Participants perceiving themselves as “very” or “extremely” (vs “not” or “slightly”) well informed about LDKT had statistically significantly greater odds of intermediate or high (vs low) pursuit of LDKT (odds ratio [95% confidence interval] 2.71 [1.02-7.17]). Perceived LDKT knowledge was not associated with pursuit of LDKT. Neither perceived information adequacy nor knowledge was associated with living donor inquiries. Efforts to better understand the role of education in the pursuit of LDKT among African American transplant candidates are needed.     

Evaluation and care of international living kidney donor candidates: Strategies for addressing common considerations and challenges

End-stage kidney disease patients in the United States may have family members or friends who are not US citizens or residents but are willing to serve as their living kidney donor in the United States (“international donors”). In July 2017, the American Society for Transplantation (AST) Live Donor Community of Practice (LDCOP) convened a multidisciplinary workgroup of experts in living donation care, including coordinators, social workers, donor advocates, administrators, and physicians, to evaluate educational gaps related to the evaluation and care of international donors. The evaluation of international living donor candidates is a resource-intensive process that raises key considerations for assessing risk of exploitation/inducement and addressing communication barriers, logistics barriers, and access to care in their home country. Through consensus-building discussions, we developed recommendations related to: (a) establishing program guidelines for international donor candidate evaluation and selection; (b) initial screening; (c) logistics planning; (d) comprehensive evaluation; and (e) postdonation care and follow-up. These recommendations are not intended to direct formal policy, but rather as guidance to help programs more efficiently and effectively structure and execute evaluations and care coordination. We also offer recommendations for research and advocacy to optimize the care of this unique group of living donors.     

Paired kidney donation by shipment of living donor kidneys

It is apparent from calculations that for paired kidney donation programs, a national program will provide optimum benefit. To obviate major problems associated with donors traveling long distances, we propose shipping donor kidneys. Evidence is provided from the United Network for Organ Sharing (UNOS) Kidney Transplant Registry, that 14,873 immediate functioning kidneys from deceased head-trauma donors with an average cold ischemia time of 18.3 h had 85.7% three-yr graft survival compared with 87.8% survival of 23 369 transplants from living donors with 2.4 h of ischemia. Grafts from 10,368 deceased donors with 13-24 h cold ischemia time had three-yr graft survival of 82.6% compared with 84.2% for 1153 transplants with up to six h cold ischemia time. After adjusting for major confounding factors, cold ischemia does not significantly influence graft survival. We conclude that shipment of donor kidneys can be performed safely and will significantly increase paired donor transplants.     

Care of international living kidney donor candidates in the United States: A survey of contemporary experience,practice, and challenges

The evaluation and care of non-US citizen, non-US residents who wish to come to the United States to serve as international living kidney donors (ILKDs) can pose unique challenges. We surveyed US transplant programs to better understand practices related to ILKD care. We distributed the survey by email and professional society list-servs (Fall 2018, assessing 2017 experience). Eighty-five programs responded (36.8% program response rate), of which 80 considered ILKD candidates. Only 18 programs had written protocols for ILKD evaluation. Programs had a median of 3 (range: 0,75) ILKD candidates who initiated contact during the year, from origin countries spanning 6 continents. Fewer (median: 1, range: 0,25) were approved for donation. Program-reported reasons for not completing ILKD evaluations included visa barriers (58.6%), inability to complete evaluation (34.3%), concerns regarding follow-up (31.4%) or other healthcare access (28.6%), and financial impacts (21.4%). Programs that did not evaluate ILKDs reported similar concerns. Staff time required to evaluate ILKDs was estimated as 1.5-to-3-times (47.9%) or >3-times (32.9%) that needed for domestic candidates. Among programs accepting ILKDs, on average 55% reported successful completion of 1-year follow-up. ILKD evaluation is a resource-intensive process with variable outcomes. Planning and commitment are necessary to care for this unique candidate group.     

Predonation psychosocial evaluation of living kidney and liver donor candidates: a systematic literature review

Evaluating a person's suitability for living organ donation is crucial, consisting not only of a medical but also of a thorough psychosocial screening. We performed a systematic literature review of guidelines, consensus statements, and protocols on the content and process of psychosocial screening of living kidney and liver donor candidates. We searched PubMed, Embase, CINAHL, and PsycINFO until June 22, 2011, following the PRISMA guidelines, complemented by scrutinizing guidelines databases and references of identified publications. Thirty‐four publications were identified, including seven guidelines, six consensus statements, and 21 protocols or programs. Guidelines and consensus statements were inconsistent and lacked concreteness for both their content and process, possibly explaining the observed variability in center‐specific evaluation protocols and programs. Overall, recommended screening criteria are not evidence‐based and an operational definition of the concept “psychosocial” is missing, causing heterogeneity in terminology. Variation also exists on methods used to psychosocially evaluate potential donors. The scientific basis of predonation psychosocial evaluation needs to be strengthened. There is a need for high‐quality prospective psychosocial outcome studies in living donors, a uniform terminology to label psychosocial screening criteria, and validated instruments to identify risk factors.     

Better graft outcomes from offspring donor kidneys among living donor kidney transplant recipients in the United States

A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001‐2016 to evaluate death‐censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15‐year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] = _0.730.77_0.82, P < .001), and was attenuated among African American donors (aHR _0.770.85_0.95; interaction: P = .01) and female recipients (aHR _0.770.84_0.91, P < .001). Although offspring kidney recipients had higher mortality (15‐year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR = _1.021.06_1.10, P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR = _0.930.97_1.01, P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.     

Australian nephrologists' attitudes towards living kidney donation.

BACKGROUND: The demand for deceased donor kidneys far outweighs the supply. The rate of living kidney donation (LKD) has been steadily increasing world-wide and is associated with excellent outcomes for the recipient. With respect to donors' outcomes, however, a strong evidence base is lacking. This study explores the attitudes and perceptions of Australian nephrologists towards LKD, specifically regarding donor risk, their willingness to recommend LKD and their own preparedness to become a live donor. METHODS: A postal survey of Australian nephrologists was conducted. Responses to six multiple choice questions about LKD were collected as a separate focus of a larger study. RESULTS: We achieved a survey response rate of 52.4% and analysed responses from 184 practicing nephrologists and trainees. Australian nephrologists and trainees were generally supportive of LKD. The vast majority (95%) of respondents indicated that they would recommend it to a suitable donor or would themselves (97%) donate a kidney to an immediate family member. However, fewer than half (43%) would recommend LKD to a potential donor, where their relative's end-stage kidney disease (ESKD) had been attributed to diabetes and where there was a strong family history of diabetes. A minority thought that LKD increased the donor's risk of mortality (12%) or of ESKD (25%). Few nephrologists (4%) indicated their preparedness to be an altruistic donor--to a recipient unknown to them. CONCLUSIONS: Although LKD is clearly supported by the nephrologists, the increasing incidence of ESKD attributable to diabetes, now the leading cause of ESKD in Australia, might, however, progressively limit its use. Meeting the growing demand for kidney transplantation will require an increased supply of both live and deceased donor kidneys. We should develop, evaluate and implement best-practice approaches to achieve this.     

The relative importance of donor age in deceased and living donor kidney transplantation

In deceased donor kidney transplantation donor age is known to influence graft survival. The influence of living donor age on graft survival is questioned. We compared the influence of living and deceased donor age on the outcome of renal transplantation. All 1821 transplants performed in our center between 1990 and 2009 were included in the analysis. Observation was until April 2012. A total of 941 patients received a deceased donor kidney and 880 a living donor kidney. In multivariate Cox analysis, recipient age, maximum and current panel reactive antibodies, transplant year, HLA‐mismatches, donor age, donor gender, donor type, delayed graft function, and calcineurin inhibitor (CNI) and prednisone as initial immunosuppression were found to have a significant influence on death‐censored graft failure. The influence of both living and deceased donor age followed a J‐shaped curve, above 30 years the risk increased with increasing age. Donor type and donor age had an independent influence. The graft failure risk of deceased donor transplantation is almost twice that of living donor transplantation so that a 60‐year‐old living donor kidney has the same graft failure risk as a 20‐year‐old deceased donor kidney.     

Persistent regional and racial disparities in nondirected living kidney donation

Nondirected living donors (NDLDs) are an important and growing source of kidneys to help reduce the organ shortage. In its infancy, NDLD transplantation was clustered at a few transplant centers and rarely benefited African American (AA) recipients. However, NDLDs have increased 9.4‐fold since 2000, and now are often used to initiate kidney paired donation chains. Therefore, we hypothesized that the initial geographic clustering and racial disparities may have improved. We used Scientific Registry of Transplant Recipients data to compare NDLDs and their recipients between 2008‐2015 and 2000‐2007. We found that NDLD increased an average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11‐1.13, P < .001). In 2000‐2007, 18.3% of recipients of NDLD kidneys were AA; this decreased in 2008‐2015 to 15.7%. NDLD transplants initially became more evenly distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite the increased number of NDLDs, racial disparities have worsened and the center‐level distribution of NDLD transplants has narrowed in recent years.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Transplant social worker and donor financial assistance to increase living donor kidney transplants among African Americans: The TALKS Study,a randomized comparative effectiveness trial

Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans’ potential living kidney donors. African Americans (N = 300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants’ mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n = 39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51–2.30] for TALK SWI and 0.92 [0.42–2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p = 91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).     

Successful three-way kidney paired donation with compatible pairs to increase donor pool

Despite heightened international interest in performing living donor kidney paired donation (KPD) transplantation after the publication of a research protocol by Ross and colleagues in 1997, only a few hundred have been performed worldwide. The major obstacle is that many individuals in end-stage renal disease are of blood type O and can only receive an organ from a donor of blood type O, whereas blood type O donors are “universal donors” and will be able to donate directly with an intended recipient of any blood type unless there is a positive crossmatch. To overcome this, patients with compatible but non-HLA identical donors over 45 years of age should be approached for inclusion in KPD program especially O blood group donors. Inclusion of all these additional pairs into the algorithm greatly increases chances of possible matches for O blood group recipients. We report successful three-way KPD transplantation resulting in transplantation of O blood group patient using compatible O blood group donor from India. None of the patients had delayed graft function or rejection and all had stable graft function on discharge without any medical and surgical complications. We need to allocate O blood group kidneys from compatible donors to overcome the barrier of HLA, non-HLA antibodies and other donor related factors to improve transplant quality and long term outcomes. This will increase transplantation of O blood group patients.     

Motives for becoming a living kidney donor.

BACKGROUND: Recruitment of living donors represents a medical and moral responsibility. Their motives are often complex. Categories of motives and factors causing concern were identified from a previous in-depth interview study and from the literature. The aim of the present study was to evaluate these motives. METHODS: A questionnaire was sent to 207 potential kidney donors undergoing evaluation for donation in Norway and Sweden. They were asked to mark on a visual analogue scale, 0-10, the importance given to each of nine motives and five factors of concern. Questions were also asked about who took the initiative and the source of information. RESULTS: The response rate was 74%; 154 questionnaires were returned. The strongest motives to become a donor were a wish to help (median 9.3), self-benefit from the recipient's improved health (median 9.2) and identification with the recipient (median 9.1). In contrast, a sense of guilt regarding past relationships (median 0.9), pressure from others (median 0.8), a religious motive (median 0.8) and increased self-esteem (median 0.7) were rare or weak incentives for donation. There were large individual variations in the mix, particularly regarding moral duty (5.6, range 0.1-10.0). Most potential donors (64%) had taken the initiative for the assessment themselves, but in 22% it was the recipient's physician. Physicians were the dominant source of information. The potential donors expressed much more concern for the recipient than for themselves. CONCLUSIONS: Living kidney donor assessment includes an exploration of the individuals' mixed feelings. An analysis of the motive enables individualized treatment and support for non-donors.