Increased T cell immunosenescence and accelerated maturation phenotypes in older kidney transplant recipients.

Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens. We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping. Older kidney transplant recipients demonstrated decreased frequency of naïve CD4+ and CD8+ T cells, and increased frequency of terminally differentiated, immune senescent, and NK T cells expressing KLRG1. There was a trend towards increased frequency of T cell immune senescence in patients experiencing infection in the first year after transplantation, which reached statistical significance in a multivariate analysis. This pilot study reveals immune dysfunction in older compared with younger transplant recipients, and suggests a likely mechanism for increased vulnerability to infection. The ability to assess T cell maturation and immune senescence in transplant recipients offers the potential for risk stratification and customization of immune suppression to prevent infection and rejection after transplantation.

Financial Neutrality for Living Organ Donors: Reasoning, Rationale, Definitions, and Implementation Strategies.

In the United States, live organ donation can be a costly and burdensome undertaking for donors. While most donation-related medical expenses are covered, many donors still face lost wages, travel expenses, incidentals, and potential for future insurability problems. Despite widespread consensus that live donors (LD) should not be responsible for the costs associated with donation, little has changed to alleviate financial burdens for LDs in the last decade. To achieve this goal, the transplant community must actively pursue strategies and policies to eliminate unreimbursed out-of-pocket costs to LDs. Costs should be more appropriately distributed across all stakeholders; this will also make live donation possible for people who, in the current system, cannot afford to proceed. We propose the goal of LD "financial neutrality," offer an operational definition to include the coverage/reimbursement of all medical, travel, and lodging costs, along with lost wages, related to the act of donating an organ, and guidance for consideration of medical care coverage, and wage and other expense reimbursement. The intent of this report is to provide a foundation to inform discussion within the transplant community and to advance initiatives for policy and resource allocation.

Living and deceased organ donation should be financially neutral acts.

The supply of organs­particularly kidneys­donated by living and deceased donors falls short of the number of patients added annually to transplant waiting lists in the United States. To remedy this problem, a number of prominent physicians, ethicists, economists and others have mounted a campaign to suspend the prohibitions in the National Organ Transplant Act of 1984 (NOTA) on the buying and selling of organs. The argument that providing financial benefits would incentivize enough people to part with a kidney (or a portion of a liver) to clear the waiting lists is flawed. This commentary marshals arguments against the claim that the shortage of donor organs would best be overcome by providing financial incentives for donation. We can increase the number of organs available for transplantation by removing all financial disincentives that deter unpaid living or deceased kidney donation. These disincentives include a range of burdens, such as the costs of travel and lodging for medical evaluation and surgery, lost wages, and the expense of dependent care during the period of organ removal and recuperation. Organ donation should remain an act that is financially neutral for donors, neither imposing financial burdens nor enriching them monetarily.

Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Organ transplantation for nonresidents of the United States: a policy for transparency.

A policy proposal relating to transplantation of deceased donor organs into nonresidents of the United States was jointly sponsored by the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) International Relations and Ethics Committees and approved by the OPTN/UNOS Board in June 2012. The proposal followed prior acceptance by the Board of the definitions of "travel for transplantation" and "transplant tourism" and the introduction in March 2012 of revised data collection categories for transplant candidates who are neither citizens nor residents. The most important aspect of the new policy concerns replacement of the previous so-called "5% rule" with the review of all residency and citizenship data and the preparation of a public annual report. The new policy does not prohibit organ transplantation in nonresidents. However, the policy and public data report will ensure transparency and support transplant center responsibility to account for their practices. Since the adoption of the policy, the first 19 months of data show that less than 1% of new deceased donor waitlist additions and less than 1% of transplantation recipients were non-US citizen/nonresidents candidates who traveled to the United States for purposes of transplantation. By adopting this policy, the US transplant community promotes public trust and serves as an example to the international transplant community.

Simultaneous liver-kidney transplantation summit: current state and future directions.

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

Chain transplantation: initial experience of a large multicenter program.

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

The use of executed prisoners as a source of organ transplants in China must stop.

Internationally accepted ethical standards are unequivocal in their prohibition of the use of organs recovered from executed prisoners: yet this practice continues in China despite indications that Ministry of Health officials intend to end this abhorrent practice. Recently published articles on this topic emphasize the medical complications that result from liver transplantation from executed 'donors' but scant attention is given to the source of the organs, raising concern that the transplant community may be becoming inured to unacceptable practice. Strategies to influence positive change in organ donation practice in China by the international transplant community are discussed. They include an absolutist policy whereby no clinical data from China is deemed acceptable until unacceptable donation practices end, and an incremental policy whereby clinical data is carefully evaluated for acceptability. The relative advantages and drawbacks of these strategies are discussed together with some practical suggestions for response available to individuals and the transplant community.

Asynchronous, out-of-sequence, transcontinental chain kidney transplantation: a novel concept.

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

Disparities in the utilization of live donor renal transplantation.

Despite universal payer coverage with Medicare, sociodemographic disparities confound the care of patients with renal failure. We sought to determine whether adults who realize access to kidney transplantation suffer inequities in the utilization of live donor renal transplantation (LDRT). We identified adults undergoing primary renal transplantation in 2004-2006 from the United Network for Organ Sharing (UNOS). We modeled receipt of live versus deceased donor renal transplant on multilevel multivariate models that examined recipient, center and UNOS region-specific covariates. Among 41 090 adult recipients identified, 39% underwent LDRT. On multivariate analysis, older recipients (OR 0.62, 95% CI 0.56-0.68 for 50-59 year-olds vs. 18-39 year-old recipients), those of African American ethnicity (OR 0.54, 95% CI 0.50-0.59 vs. whites) and of lower socioeconomic status (OR 0.72, 95% CI 0.67-0.79 for high school-educated vs. college-educated recipients; OR 0.78, 95% CI 0.71-0.87 for lowest vs. highest income quartile) had lower odds of LDRT. These characteristics accounted for 14.2% of the variation in LDRT, more than recipient clinical variables, transplant center characteristics and UNOS region level variation. We identified significant racial and socioeconomic disparities in the utilization of LDRT. Educational initiatives and dissemination of processes that enable increased utilization of LDRT may address these disparities.

Evaluating living kidney donors: relationship types, psychosocial criteria, and consent processes at US transplant programs.

We conducted a survey of 132 US kidney transplant programs to examine how they evaluate and select potential living kidney donors, focusing on donor-recipient relationships, psychosocial criteria, and consent processes. There is heterogeneity in donor-recipient relationships that are considered acceptable, although most programs (70%) will not consider publicly solicited donors. Most programs (75%) require a psychosocial evaluation for all potential living donors. Most programs agree that knowledge of financial reward (90%), active substance abuse (86%), and active mental health problems (76%) are absolute contraindications to donation. However, there is greater variability in how other psychosocial issues are considered in the selection process. Consent processes are highly variable across programs: donor and recipient consent for the donor evaluation is presumed in 57% and 76% of programs, respectively. The use of 13 different informed consent elements varied from 65% (alternative donation procedures) to 86% (description of evaluation, surgery and recuperative period) of programs. Forty-three percent use a 'cooling off' period. Findings demonstrate high variability in current practice regarding acceptable donor-recipient relationships, psychosocial criteria, and consent processes. Whether greater consensus should be reached on these donor evaluation practices, especially in the context of more expansive use of living donor kidney transplantation, is discussed.

The medical evaluation of living kidney donors: a survey of US transplant centers.

The use of living donors for kidney transplantation in the United States is common, and long-term studies have demonstrated the safety of donation by young, healthy individuals. However, transplant programs have little data to guide them in deciding which donors are unacceptable, and which characteristics are associated with kidney disease or poor psychosocial outcomes after donation. To document current practices in evaluating potential donors, we surveyed all US kidney transplant programs. Compared to a survey 12 years ago, medical criteria for donation are more inclusive in several areas. All responding programs now accept living unrelated donors. Most programs no longer have an upper age limit to be eligible. Programs are now more likely to accept donors with treated hypertension, or a history of kidney stones, provided that certain additional criteria are met. In contrast, medical criteria for donation are more restrictive in other areas, such as younger donor age and low creatinine clearance. Overall, significant variability remains among transplant programs in the criteria used to evaluate donors. These findings highlight the need for more data on long-term outcomes in various types of donors with potential morbidities related to donation.

Limiting financial disincentives in live organ donation: a rational solution to the kidney shortage.

Availability of kidney transplantation is limited by an inadequate supply of organs, with no apparent remedy on the immediate horizon and increasing reliance on living donors (LDs). While some have advocated financial remuneration to stimulate donation, the National Organ Transplant Act (NOTA) of 1984 expressly forbids the offer of 'valuable consideration.' However, recent developments indicate some fluidity in the definition of valuable consideration while evolving international standards highlight deficiencies (particularly regarding long-term care and follow-up) in the current American system. Recognizing that substantial financial and physical disincentives exist for LDs, we propose a policy change that offers the potential to enhance organ availability as well as address concerns regarding long-term care. Donors assume much greater risk than is widely acknowledged, risk that can be approximated for the purpose of determining appropriate compensation. Our proposal offsets donor risk via a package of specific benefits (life insurance, health insurance and a small amount of cash) to minimize hazard and ensure donor interests are protected after as well as before nephrectomy. It will fund medical follow-up and enable data collection so that long-term risk can be accurately assessed. The proposal should be cost effective with only a small increase in the number of LDs, and the net benefit will become greater if removal of disincentives stimulates even further growth. As importantly, by directly linking compensation to risk, we believe it preserves the essence of kidney donation as a gift, consistent with NOTA and implementable in the United States without altering current legal statutes.

Obesity and outcome following renal transplantation.

Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to determine whether obesity affects outcome following renal transplantation. From the UNOS database, we identified patients who underwent primary kidney-only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI < 18.5), normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9) or morbidly obese (BMI > or = 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success. The study sample comprised 27,377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p < 0.001). Compared with normal weight patients, morbid obesity was independently associated with an increased risk of DGF (p < 0.001), prolonged hospitalization (p < 0.001), acute rejection (p = 0.006) and decreased overall graft survival (p = 0.001). Donor BMI did not affect overall graft survival (p > or = 0.07). Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.

Recurrent and de novo diabetic nephropathy in renal allografts.

BACKGROUND: Histologic findings of diabetic nephropathy (DN) are observed in allografts of patients with pretransplant (PreTx) diabetes mellitus (DM) and in patients who develop DM posttransplant (PostTx). Patients with allograft biopsies (Bx) were retrospectively studied to determine the incidence of recurrent and de novo DN and to ascertain what, if any, risk factors predispose to histologic DN in either patient population. METHODS: From the renal transplant services at four hospitals from 1992 to 2000, the authors identified all patients with PreTxDM and PostTxDM (n=81). Those with renal biopsies performed >/=18 months PostTx were classified according to the presence or absence of histologic DN (Bx-positive, n=23; Bx-negative, n=35). Patients were then subdivided into four categories-recurrent DN (n=16), de novo DN (n=7), no recurrent DN (n=27), and no de novo DN (n=8)-for analyses. RESULTS: Among these 58 patients, 74.1% had PreTx and 25.9% had PostTx diabetes. Of those with histologic DN, 69.6% were recurrent DN and 30.4% were de novo DN, making de novo DN at least as likely to develop as recurrent DN. After the onset of diabetes in the de novo population, the time to development of histologic DN was similar in the recurrent and the de novo patients (6.68+/-3.86 years vs. 5.90+/-3.13 years, P=0.66) and more rapid than previously reported. Apart from a more frequent family history of hypertension in patients with allograft DN compared with those without allograft DN, known risk factors for the development of native DN did not significantly differ among patients in the four cohorts. Proposed risk factors related to transplantation did not correlate with the development of recurrent or de novo DN. CONCLUSION: Among patients with histologic DN, de novo DN occurred at least as frequently as recurrent DN, and the time to onset of histologically apparent DN was more rapid than previously reported. Neither the usual clinical predictors of DN nor clinical variables related to transplantation clearly distinguished the group with DN from the group without it, potentially implicating novel mechanisms in its pathogenesis.