Towards Improving the Transfer of Care of Kidney Transplant Recipients.

Kidney transplant recipients require specialized medical care and may be at risk for adverse health outcomes when their care is transferred. This document provides opinion-based recommendations to facilitate safe and efficient transfers of care for kidney transplant recipients including minimizing the risk of rejection, avoidance of medication errors, ensuring patient access to immunosuppressant medications, avoidance of lapses in health insurance coverage, and communication of risks of donor disease transmission. The document summarizes information to be included in a medical transfer document and includes suggestions to help the patient establish an optimal therapeutic relationship with their new transplant care team. The document is intended as a starting point towards standardization of transfers of care involving kidney transplant recipients.

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.

Socioeconomic status and ethnicity of deceased donor kidney recipients compared to their donors.

Public perception and misperceptions of socioeconomic disparities affect the willingness to donate organs. To improve our understanding of the flow of deceased donor kidneys, we analyzed socioeconomic status (SES) and racial/ethnic gradients between donors and recipients. In a retrospective cohort study, traditional demographic and socioeconomic factors, as well as an SES index, were compared in 56,697 deceased kidney donor and recipient pairs transplanted between 2007 and 2012. Kidneys were more likely to be transplanted in recipients of the same racial/ethnic group as the donor (p < 0.001). Kidneys tended to go to recipients of lower SES index (50.5% of the time, p < 0.001), a relationship that remained after adjusting for other available markers of donor organ quality and SES (p < 0.001). Deceased donor kidneys do not appear to be transplanted from donors of lower SES to recipients of higher SES; this information may be useful in counseling potential donors and their families regarding the distribution of their organ gifts.

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.

Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

Investigating geographic variation in mortality in the context of organ donation.

Organ procurement organizations (OPOs) report a nearly fourfold difference in donor availability as measured by eligible deaths per million population (PMP) based on hospital referrals. We analyzed whether mortality data help explain geographic variation in organ supply as measured by the number of eligible deaths for organ donation. Using the 2007 National Center for Health Statistics' mortality data, we analyzed deaths occurring in acute care hospitals, aged ≤ 70 years from cerebrovascular accidents and trauma. These deaths were mapped at the county level and compared to eligible deaths reported by OPOs. In 2007, there were 2 428 343 deaths reported in the United States with 42 339 in-hospital deaths ≤ 70 years from cerebrovascular accidents (CVA) or trauma that were correlated with eligible deaths PMP (r(2) = 0.79.) Analysis revealed a broad range in the death rate across OPOs: trauma deaths: 44-118 PMP; deaths from CVA: 34-118 PMP; and combined CVA and trauma: 91-229 PMP. Mortality data demonstrate that deaths by neurologic criteria of people who are likely to be suitable deceased donors are not evenly distributed across the nation. These deaths are correlated with eligible deaths for organ donation. Regional availability of organs is affected by deaths which should be accounted for in the organ allocation system.

International practices of organ donation.

Organ donation and transplant rates vary widely across the globe, but there remains an almost universal shortage of deceased donors. The unmet need for transplants has resulted in many systematic approaches to increase donor rates, but there have also been practices that have crossed the boundaries of legal and ethical acceptability. Recent years have seen intense interest from international political organizations, led by the World Health Organization, and professional bodies, led by The Transplantation Society. Their efforts have focused on the development of a series of legal and ethical frameworks, designed to encourage all countries to eradicate unacceptable practices while introducing programmes that strive to achieve national or regional self-sufficiency in meeting the need for organ transplants. These programmes should seek to reduce both the need for transplantation and also develop deceased donation to its maximum potential. Living donation remains the mainstay of transplantation in many parts of the world, and many of the controversial--and unacceptable--areas of practice are found in the exploitation of living donors. However, until lessons are learnt, and applied, from countries with highly developed deceased donor programmes, these abuses of human rights will be difficult to eradicate. A clear international framework is now in place to achieve this.

The impact of variation in donation after cardiac death policies among donor hospitals: a regional analysis.

The Joint Commission requires all hospitals have a policy regarding donation after cardiac death. To this date however, a quantitative analysis of adult hospital donation after cardiac death (DCD) policies and its impact on transplantation outcomes has not been reported. Specific characteristics for DCD polices were identified from 90 of the 164 (54.9%) hospitals within the New England Organ Bank's donor service area. Forty-five policies (50.0%) allow family members to be present during withdrawal of life-sustaining therapy (WLST) whereas eight (8.9%) prohibit this. Seventeen policies (18.9%) require WLST to occur in the operating room (OR); 20 (22.2%) specify a location outside of the OR. Fifty-six (62.2%) policies fail to state the method of determining death; however, some require arterial line (15 policies, 16.6%) and/or EKG (10 policies, 11.1%). These variables were not associated with organ recovery, utilization or donor ischemia time. Our regional analysis highlights the high degree of variability of hospital DCD policies, which may contribute to misunderstanding and confusion among providers and patients that may influence acceptance of this mode of donation.

Organ trafficking and transplant tourism: a commentary on the global realities.

The extent of organ sales from commercial living donors (CLDs) or vendors has now become evident. At the Second Global Consultation on Human Transplantation of the World Health Organization's (WHO) in March 2007, it was estimated that organ trafficking accounts for 5-10% of the kidney transplants performed annually throughout the world. Patients with sufficient resources in need of organs may travel from one country to another to purchase a kidney (or liver) mainly from a poor person. Transplant centers in 'destination' countries have been well known to encourage the sale of organs to 'tourist' recipients from the 'client' countries.

Should pediatric patients wait for HLA-DR-matched renal transplants?

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA-DR mismatches on graft survival. Zero HLA-DR-mismatched kidneys had statistically comparable 5-year graft survival (71%), to 1-DR-mismatched kidneys (69%) and 2-DR-mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel-reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA-A, -B or -DR mismatch of the first transplant, nor was there a 'dose effect' when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN)allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA-DR-matched kidney.

Determinants of discard of expanded criteria donor kidneys: impact of biopsy and machine perfusion.

We examined factors associated with expanded criteria donor (ECD) kidney discard. Scientific Registry of Transplant Recipients (SRTR)/Organ Procurement and Transplantation Network (OPTN) data were examined for donor factors using logistic regression to determine the adjusted odds ratio (AOR) of discard of kidneys recovered between October 1999 and June 2005. Logistic and Cox regression models were used to determine associations with delayed graft function (DGF) and graft failure. Of the 12,536 recovered ECD kidneys, 5139 (41%) were discarded. Both the performance of a biopsy (AOR = 1.21, p = 0.02) and the degree of glomerulosclerosis (GS) on biopsy were significantly associated with increased odds of discard. GS was not consistently associated with DGF or graft failure. The discard rate of pumped ECD kidneys was 29.7% versus 43.6% for unpumped (AOR = 0.52, p < 0.0001). Among pumped kidneys, those with resistances of 0.26-0.38 and >0.38 mmHg/mL/min were discarded more than those with resistances of 0.18-0.25 mmHg/mL/min (AOR = 2.5 and 7.9, respectively). Among ECD kidneys, pumped kidneys were less likely to have DGF (AOR = 0.59, p < 0.0001) but not graft failure (RR = 0.9, p = 0.27). Biopsy findings and machine perfusion are important correlates of ECD kidney discard; corresponding associations with graft failure require further study.

Impact of donor kidney recovery method on lymphatic complications in kidney transplantation.

INTRODUCTION: Prolonged lymphatic drainage and lymphocele are undesirable complications following kidney transplantation. We evaluated the impact of kidney recovery methods (deceased donor vs laparoscopic nephrectomy) on the lymphatic complications of the kidney transplant recipients. METHOD: The incidence of lymphatic complications was retrospectively analyzed in recipients of deceased donor kidneys (DD, n = 62) versus laparoscopically procured kidneys from living donors (LP, n = 61). A drain was placed in the retroperitoneal space in all recipients. The drain was maintained until the output became less than 30 mL/d with no evidence of fluid collection by ultrasound examination. RESULTS: There was no statistically significant difference in the patient demographics (age, gender, and original disease and procedure time) between two groups. The incidence of lymphocele that required therapeutic intervention was comparable in both groups (3.2%). However, the duration of drain placement was significantly longer in the LP group than in the DD group, 8.6 +/- 2.5 days versus 5.4 +/- 2.5 day, respectively (P < .05). CONCLUSION: The recipients of laparoscopically removed kidneys had a higher incidence of prolonged lymphatic leakage. More meticulous back table preparation may be required in LP kidneys to prevent prolonged lymphatic drainage after kidney transplantation. These observations may indicate that the major source of persistent lymphatic leakage is lymphatics of the allograft rather than severed recipient lymphatics.

Managing the highly sensitized transplant recipient and B cell tolerance.

The detection of anti-donor-HLA antibodies in a renal allograft recipient's serum, either at the time of or after transplantation, is usually associated with specific antibody-mediated clinical syndromes. These can be divided temporally into three categories: hyperacute rejection, acute humoral rejection and chronic humoral rejection. With the identification of new immunosuppressive drug combinations, more-effective control of alloantibody production has been recently achieved in humans. Thus, prevention and/or treatment of antibody-mediated allograft injury are now possible. Ultimately, the induction of mixed hematopoietic chimerism may allow us to overcome the problem of allosensitization and accept an allograft without chronic immunosuppression.

The use of local allograft irradiation following renal transplantation.

Over a 10 year period, 67 recipients of 71 renal allografts received graft irradiation following the diagnosis of rejection. The majority of kidneys were treated with a total dose of 600 rad, 150 rad per fraction, in 4 daily fractions. Fifty-three kidneys were irradiated following the failure of standard systemic immunosuppression and maximally tolerated antirejection measures (pulse high dose steroids, Actinomycin, ATG) to reverse an episode of acute rejection. Seven of these patients (13%) had greater than a 50% improvement in serum creatinine (Cr) 1 week following completion of the irradiation. Twenty-two (42%) of these allografts were noted to have stable (i.e. no deterioration) or improved function 1 month following the treatment with irradiation. Eleven (21%) of these allografts maintained function 1 year following transplantation. There were 10 patients whose allografts were irradiated because of renal dysfunction in a clinical setting which did not permit the administration of further immunosuppression, i.e., infection or hematologic dyscrasias. Three of these patients (30%) had greater than a 50% improvement in serum Cr 1 week following completion of the irradiation. Nine (90%) of these allografts had stable or improved function 1 month following the treatment with irradiation. Biopsies were obtained of 41 allografts. Of the 24 renal allografts with predominantly cellular rejection, 10 (42%) had the process reversed or stabilized at 1 month following irradiation. Five (21%) of these allografts were functioning at 1 year following irradiation. Rejection was reversed or stabilized in 6 of 17 (35%) allografts at 1 month when the histologic features of renal biopsy suggested predominantly vascular rejection. One (6%) of these allografts was functioning at 1 year following transplantation. Local graft irradiation has helped maintain a limited number of allografts in patients whose rejection has failed to respond to systemic immunosuppression. Irradiation may also benefit patients with ongoing rejection in whom further systemic immunosuppression is contra-indicated.

First report of the United Network for Organ Sharing Transplant Tumor Registry: donors with a history of cancer.

BACKGROUND: Severe organ shortages have led to donor pool expansion to include older individuals, patients with hypertension, diabetes, and a past history of cancer. Transmission of cancer from cadaveric donors is a risk of transplantation and carries a high mortality rate. METHODS: During a 33 month period, UNOS recorded 14,705 cadaveric donors of which 257 had a past history of cancer (PHC). A total of 650 organs (397 kidneys, 178 livers, and 75 hearts) were transplanted from these 257 donors. Type of cancer, tumor-free interval at organ procurement, and whether any PHC donor transmitted a tumor to the recipient were analyzed. RESULTS: Three PHC donor tumor types (skin, brain, genitourinary) were associated with 549 of the transplanted organs (85%). Twenty-eight recipients of PHC donor organs developed posttransplantation tumors (18 skin, 2 PTLD, 8 solid cancers). During a mean follow-up of 45 months (range 30-61 months), no recipients of organs from PHC donors developed a donor derived cancer. The majority (71.5%) of all non-skin and non-CNS system cancer donors had a cancer-free interval of greater than five years. CONCLUSIONS: Risks of cancer transmission from donors with a history of non-melanoma skin cancer and selected cancers of the CNS appear to be small. Risks of tumor transmission with certain other types of cancer may be acceptable, particularly if the donor has a long cancer-free interval prior to organ procurement while certain other cancers pose a high transmission risk. Selective use of PHC donors may permit expansion of the donor pool.

Variation in patient response associated with different preparations of murine monoclonal antibody therapy.

The sera of 37 renal and 12 liver allograft recipients treated with OKT3 (42), Leu2a (7), or both (2) monoclonal antibodies were serially analyzed by an enzyme-linked immunosorbent assay to determine the humoral response (IgG) to mAb. Anti-mAb IgG to the treatment mAb was detected in the serum of 23 (76%) renal and 6 (50%) liver OKT3 recipients, and all 7 Leu2a renal recipients, usually within 14 days of mAb completion, but never during the first week of Rx. Each of the 7 Leu2a recipients developed reactivity not only to Leu2a isotype (IgG1), but also to OKT3 isotype (IgG2a). In contrast, only 1 of the 42 renal and liver allograft recipients treated with OKT3 developed reactivity to the Leu2a isotype. Blocking studies indicated that the specificity of the response to the treatment mAb was directed at the idiotype--and, in some patients, to the constant domain (isotype) of the mAb administered. The antibody response to an alternate isotype (IgG2a) observed in Leu2a (IgG1)-treated patients most likely resulted from irrelevant immunoglobulin (IgG2a) in the Leu2a preparation. This reactivity appeared to be specific for the IgG2a subclass. Clinicians administering mAb therapy should be aware that various mAb preparations may contain immunoglobulin isotypes unrelated to the therapeutic mAb. Crossimmunization to the irrelevant immunoglobulins may occur, precluding subsequent use of other mAbs sharing similar isotype.

Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus.

Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown.