Efficient Utilization of the Expanded Criteria Donor (ECD) Deceased Donor Kidney Pool: An Analysis of the Effect of Labeling

We investigated the effect of the expanded criteria donor (ECD) label on (i) recovery of kidneys and (ii) acceptance for transplantation given recovery. An ECD is age ≥ 60, or age 50–59 with ≥ 2 of 3 specified comorbidities. Using data from the Scientific Registry of Transplant Recipients from 1999 to 2005, we modeled recovery rates through linear regression and transplantation probabilities via logistic regression, focusing on organs from donors just‐younger versus just‐older than the ECD age thresholds. We split the sample at July 1, 2002 to determine how decisions changed at the approximate time of implementation of the ECD definition. Before July 2002, the number of recovered kidneys with 0–1 comorbidities dropped at age 60, but transplantation probabilities given recovery did not. After July 2002, the number of recovered kidneys with 0–1 comorbidities rose at age 60, but transplantation probabilities contingent on recovery declined. No similar trends were observed at donor age 50 among donors with ≥ 2 comorbidities. Overall, implementation of the ECD definition coincided with a reversal of an apparent reluctance to recover kidneys from donors over age 59, but increased selectiveness on the part of surgeons/centers with respect to these kidneys.     

Renal transplantation from extended criteria cadaveric donors: problems and perspectives overview.

The critical shortage of organs available for renal transplantation has led to the consideration of alternative strategies for increasing the donor pool. Recently, the cadaveric kidney donor pool extended to donors who might have been deemed unsuitable in early times, leading to the concept of marginal donors and more recently to the notion of expanded criteria donors. Such organs are eligible for organ donation but, because of extreme age and other clinical characteristics, are expected to produce allograft at risk for diminished post-transplant function. Thus, the challenge is now to reduce the difference between graft outcome from patients grafted with marginal and 'optimal' donors. This implies appropriate transplantation strategies during pre-, peri- and post-transplantation phases including reduction of cold ischemia time, recipient selection, adaptation of immunosuppressive drug regimens, increase in nephron mass by dual kidney transplantation, and improvement in the graft selection process using histological criteria. This review summarizes current definition of a marginal donor and provides some guidance for clinical management of such transplant.     

Long-term outcomes of dual kidney transplantation—a single center experience

Abstract:  The shortage of kidney donors has led to broadening of the acceptance criteria for deceased donor organs beyond the traditional use of young donors. We determined long-term post-transplant outcomes in recipients of dual expanded criteria donor kidneys (dECD, n = 44) and compared them to recipients of standard criteria donor kidneys (SCD, n = 194) and single expanded criteria donor kidneys (sECD, n = 62). We retrospectively reviewed these 300 deceased donor kidney transplants without primary non-function (PNF) or death in the first two wk, at our center from 1996 to 2003. The three groups were similar in baseline characteristics. Kidney allograft survival and patient survival (nine yr) were similar in the three respective donor groups, SCD, sECD and dECD (60% vs. 59% vs. 64% and 82% vs. 73% vs. 73%). Acute rejection in the first three months was 23.2%, 16.1%, and 22.7% in SCD, sECD and dECD, respectively (p = 0.49) and delayed graft function was 25.2%, 31.9% and 17.1% in the three groups, respectively (p = 0.28). When PNF and death within the first two wk was included, there was no significant difference in graft survival between the three groups. In our population, recipients of dECD transplants have acceptable patient and graft survival with kidneys that would have usually been discarded.     

Histopathological evaluation of pretransplant donor biopsies in expanded criteria donors with high kidney donor profile index: a retrospective observational cohort study

There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5‐year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66–76) for KDPI <80% (n = 77), 86 (81–90) for KDPI 81–90% (n = 82), and 97 (94–100) for KDPI >91% (n = 205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and death‐censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.     

Technical Aspects of Unilateral Dual Kidney Transplantation from Expanded Criteria Donors: Experience of 100 Patients

One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety‐five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end‐to‐side. Surgical complications were comparable in both groups. At 3‐year follow‐up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3‐years follow‐up.     

How does age affect the outcome of kidney transplantation in elderly recipients?

The aging of the on‐dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aimed to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased‐donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient age with graft's and patient's survival, delayed graft function, acute cellular rejection (ACR), surgical complications, infections, and glomerular filtration rate. Four hundred and fifty‐two patients with a median age of 65 years were included in the study. One‐, 3‐, and 5‐year patient's and graft's survival were, respectively, of 98.7%, 93%, 89% and 94.4%, 87.9%, 81.4%. The increasing recipient age was an independent risk factor only for the patient's (P=.008) and graft's survival (P=.002). ACR and neoplasia were also associated to a worse graft survival. The reduced graft survival in elderly kidney recipients seems to be related more to the increasing recipient's age than to the donor's features. In this population, the optimization of organ allocation and immunosuppression may be the key factors to endorse improvements.     

Hypertension in standard criteria deceased donors is associated with inferior outcomes following kidney transplantation

Singh RP, Farney AC, Rogers J, Gautreaux M, Reeves‐Daniel A, Hartmann E, Doares W, Iskandar S, Adams P, Stratta RJ. Hypertension in standard criteria deceased donors is associated with inferior outcomes following kidney transplantation.
Clin Transplant 2011: 25: E437–E446. © 2011 John Wiley & Sons A/S. Abstract: Background: Hypertension may be a either a cause or an effect of kidney disease. Although hypertension is an important component of the expanded criteria donor definition, risks of transplanting deceased donor kidneys from hypertensive standard criteria donors (SCD) are less well understood. Methods: Retrospective single‐center study in all adult patients who received a deceased donor kidney transplant from a SCD to evaluate the role of donor hypertension as a pre‐transplant risk factor for death‐censored graft loss (DCGL) and renal function. Results: From October 2001 through May 2008, 297 kidney transplants were performed from donation after brain death SCDs. A total of 47 (15.8%) grafts were lost, including 19 (6.4%) deaths with functioning grafts. Univariate analysis of death‐censored cases (n = 278) identified history of donor hypertension, cold ischemia time (CIT) >30 h, and African American (AA) recipients as significant pre‐transplant risk factors predictive for DCGL at five yr follow‐up (mean 38 months, all p < 0.02). Cox regression analysis showed donor hypertension (relative risk 2.2, p = 0.04) to be a significant risk factor for DCGL, whereas CIT >30 h and AA recipient ethnicity showed only trends toward DCGL. Renal function as determined by serum creatinine levels was significantly higher in recipients of hypertensive compared with non‐hypertensive SCD kidneys at all time points out to 48 months follow‐up and the disparity in renal function increased over time. Conclusions: Transplanting SCD kidneys from hypertensive donors is associated with worse graft function and an increased risk of graft loss.     

The aggressive phenotype: center-level patterns in the utilization of suboptimal kidneys

Despite the fact that suboptimal kidneys have worse outcomes, differences in waiting times and wait-list mortality have led to variations in the use of these kidneys. It is unknown whether aggressive center-level use of one type of suboptimal graft clusters with aggressive use of other types of suboptimal grafts, and what center characteristics are associated with an overall aggressive phenotype. United Network for Organ Sharing (UNOS) data from 2005 to 2009 for adult kidney transplant recipients was aggregated to the center level. An aggressiveness score was assigned to each center based on usage of suboptimal grafts. Deceased-donor transplant volume correlated with aggressiveness in lower volume, but not higher volume centers. Aggressive centers were mostly found in regions 2 and 9. Aggressiveness was associated with wait-list size (RR 1.69, 95% CI 1.20-2.34, p = 0.002), organ shortage (RR 2.30, 95% CI 1.57-3.37, p < 0.001) and waiting times (RR 1.75, 95% CI 1.20-2.57, p = 0.004). No centers in single-center OPOs were classified as aggressive. In cluster analysis, the most aggressive centers were aggressive in all metrics and vice versa; however, centers with intermediate aggressiveness had phenotypic patterns in their usage of suboptimal kidneys. In conclusion, wait-list size, waiting times, geographic region and OPO competition seem to be driving factors in center-level aggressiveness.     

Deceased Donor Kidney Transplantation from Donors with Acute Renal Failure due to Rhabdomyolysis

With the current shortage of solid organs for transplant, the transplant community continues to look for ways to increase the number of organ donors, including extending the criteria for donation. In rhabdomyolysis, the byproducts of skeletal muscle breakdown leak into the circulation resulting in acute renal failure in up to 30% of patients. In nonbrain dead patients, this condition is reversible and most patients recover full renal function. Seven potential donors had rhabdomyolysis with acute renal failure as evidenced by the presence of urine hemoglobin, plasma creatinine kinase levels of greater than five times the normal and elevated creatinine. One donor required dialysis. At our institution, 10 kidneys were transplanted from the seven donors. Two grafts had immediate function, five grafts experienced slow graft function and three grafts had delayed graft function requiring hemodialysis. At a mean of 8.7 months posttransplant (2.4–25.2 months), all patients have good graft function, are off dialysis and have a mean creatinine of 1.3 (0.7–1.8). In conclusion, our experience suggests that rhabdomyolysis with acute renal failure should not be a contraindication for donation, although recipients may experience slow or delayed graft function.     

Grandparent donors in paediatric renal transplantation

The outcome of transplantation from grandparent donors in comparison with parental donors in paediatric renal transplantation was evaluated in 53 living related donor (LRD) transplantations performed between January 1996 and August 2003. The donor in 13 cases (25%) was a grandparent (Gpar group), and the remaining donors formed the parent group (Par group). The median age of recipients in the Gpar group was 2.75 (1.7–10.6) years and in the Par group was 12.75 (2.4–22) years (P<0.0001). There was no evidence of a difference in patient and graft survival, glomerular filtration rate (GFR) after transplantation, or the number of biopsy proven episodes of rejection between the groups. Doses of prednisolone in the first year following transplantation were greater in recipients from Gpar donors, but the other immunosuppression doses were similar. The median age of donors in the Gpar group was 56 (50–67) years and in the Par group was 41 (27–58) years (P<0.0001). There was no evidence of a difference between the two donor groups in mean creatinine clearance at last follow-up. There were two major donor complications in the Gpar group and one in the Par group. There was no evidence that the length of stay differed between the two groups in either the donors or recipients. These results support the use of carefully selected healthy grandparents as LRDs in children. This option potentially allows for the use of parent donors for a subsequent transplantation.     

Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.     

Expanding the donor pool to increase renal transplantation.

INTRODUCTION: The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. METHODS: Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. RESULTS: Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P = 0.4). CONCLUSION: Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.     

Enhancing the Expanded Criteria Donor Policy as an Intervention to Improve Kidney Allocation: Is It Actually a ’Net‐Zero’ Model?

In the United States, relatively little progress has been made in recent years to improve the efficiency and effectiveness of deceased donor kidney allocation. Despite enactment of the Expanded Criteria Donor (ECD) Policy in 2002, known inequities and suboptimal utility of donated kidneys persist. In contrast with dialysis patients with shorter predicted life expectancies, those with longer predicted lifetimes can often improve their survival by waiting longer for a Standard Criteria Donor (SCD) kidney. Yet, a substantial fraction of these candidates accept ECD kidneys, often poorly HLA matched. Meanwhile, waitlist mortality continues to rise, particularly among older transplant candidates. Despite required consent processes for candidates to list for ECD kidneys, centers appear to interpret and implement ECD policy differently—some list candidates selectively while others list nearly their entire candidate pool. To ensure more efficient and effective implementation of ECD policy across centers, we advocate for (1) more oversight and guidance in directing patients to the ECD list who stand to benefit the most from receipt of an ECD kidney; and (2) enhanced transparency of center‐level ECD consent and listing practices. More uniform implementation of ECD policy could improve efficiency and effectiveness of deceased donor kidney allocation without deleteriously impacting equity.     

Centers for Disease Control ‘High‐Risk’ Donors and Kidney Utilization

The aims of this study were to determine whether Centers for Disease Control high risk (CDCHR) status of organ donors affects kidney utilization and recipient survival. Data from the Scientific Registry of Transplant Recipients were used to examine utilization rates of 45 112 standard criteria donor (SCD) deceased donor kidneys from January 1, 2005, and February 2, 2009. Utilization rates for transplantation were compared between CDCHR and non‐CDCHR kidneys, using logistic regression to control for possible confounders. Cox regression was used to determine whether CDCHR status independently affected posttransplant survival among 25 158 recipients of SCD deceased donor kidneys between January 1, 2005, and February 1, 2008. CDCHR kidneys were 8.2% (95% CI 6.9–9.5) less likely to be used for transplantation than non‐CDCHR kidneys; after adjusting for other factors, CDCHR was associated with an odds ratio of utilization of 0.67 (95% CI 0.61–0.74). After a median 2 years follow‐up, recipients of CDCHR kidneys had similar posttransplant survival compared to recipients of non‐CDCHR kidneys (hazard ratio 1.06, 95% CI 0.89–1.26). These findings suggest that labeling donor organs as ‘high risk’ may result in wastage of approximately 41 otherwise standard kidneys per year.     

Kidney transplantation from related and unrelated living donors in a single German centre.

BACKGROUND: Organ transplantation began in 1954 with living related donation (LRD). Because of organ shortage from cadavers, unrelated kidney donation (LURD) has been proposed and shown to have good results despite complete HLA mismatching. This study aims to look at differences and similarities comparing LRD and LURD performed in our centre since the implementation of the German transplant law in 1997. METHODS: Between January 1997 and July 2001, 62 out of 112 potential living donors and their recipients were accepted. Immunosuppression consisted of triple therapy (steroids, cyclosporin, mycophenolate) in patients with three or fewer mismatches, or quadruple therapy including mono- or polyclonal antibody treatment in patients with four or more mismatches or cytotoxic antibodies. LRD and LURD groups were compared for number and type of rejections, complications and kidney function at the end of observation (median 15.5 months, range 1-50 months). RESULTS: Out of 112 pairs presenting, transplantation was performed in only 62 cases (55.4%). Reasons to deny transplantation were medical problems of the potential donors in 19, psychological problems in 13, recipient problems in seven and other reasons in 11 pairs. In 38 cases LRD transplantation and in 24 cases LURD transplantation was carried out. Recipient age was significantly lower in the LRD group (37.7+/-12.1 years) compared with the LURD group (53.6+/-7.8 years). Mean donor age was 49.7+/-9.2 years in the LRD group and 50.3+/-9.1 years in the LURD group (ns). The number of mismatches was lower in LRD (2.1+/-1) than in LURD (4.4+/-0.9) (P=0.001) transplantation. The acute rejection rate was similar in both groups (52.2 vs 54.2%). OKT3 and tacrolimus rescue therapy for more severe rejections was more often applied in the LRD group but the difference did not reach the level of significance. There were more infectious complications in LURD transplantation (66.7 vs 36.4%, P=0.036) and a trend towards more surgical complications in LRD transplantation (28.9 vs 8.3%, P=0.062). One graft was lost due to transplant artery thrombosis and one recipient died 4 months after transplantation subsequent to cerebral ischaemia. Both patients belonged to the LRD group. Creatinine values at the end of observation time were 1.76+/-0.6 mg/dl in the LRD group and 1.62+/-0.5 mg/dl in the LURD group (ns). CONCLUSION: Although kidney transplantation from unrelated donors was performed with a lower HLA match and although the recipients were older, the results are equivalent to living related transplantation. Therefore, kidney transplantation from emotionally related living donors represents a valuable option for patients with end-stage renal disease. Careful selection of donors and recipients is a prerequisite of success.     

The use of elderly living donors in renal transplantation

The safety and the results of using living donors above the age of 60 years were studied. In 235 consecutive donors the complications were not different in elderly (n=70) compared to younger donors. Graft survival and function were studied in 232 consecutive 1-HLA-haplotype mismatched grafts. Graft survival at 1 year was equivalent (87% vs. 92%), but after 2–6 years graft survival was inferior in recipients of older grafts (n=62). The recipients of older grafts were 10 years older, and patient death with functioning graft was a more frequent cause of graft loss. Up to 4 years serum creatinine levels were significantly higher, but stable, in recipients of older grafts; at 5 years the difference was not significant. It is concluded that the use of elderly living donors is safe. Taking recipient age into consideration, graft survival is not different in the two groups. Graft function in older grafts is some what inferior, but stable.     

The Effects of Donor and Recipient Practices on Transplant Center Finances

Over the past several years we have noted a marked decrease in this profitability of our kidney transplant program. Our hypothesis is that this reduction in kidney transplant institutional profitability is related to aggressive donor and recipient practices. The study population included all adults with Medicare insurance who received a kidney transplant at our center between 1999 and 2005. Adopting the hospital perspective, multi-variate linear regression models to determine the independent effects of donor and recipient characteristics and era effects on total reimbursements and total hospital margin. We note statistically significant decreased medical center incremental margins in cases with ECDs (−$5887) and in cases of DGF (−4937). We also note an annual change in the medical center margin is independently associated with year and changes at a rate of −$5278 per year, related to both increasing costs and decreasing Medicare reimbursements. The financial loss associated with patient DGF and the use of ECD kidneys may resonate with other centers, and could hinder efforts to expand kidney transplantation within the United States. The Centers for Medicare and Medicaid Services (CMS) should consider risk-adjusted reimbursement for kidney transplantation.     

Evaluation and selection of potential live kidney donors

PURPOSE: Renal transplantation is an optimal therapy for patients with end stage kidney disease. A thorough evaluation of potential donors is necessary to provide the best functional outcome for recipients and ensure no or minimal morbidity for donors. MATERIALS AND METHODS: Between 1992 and 2001, 1661 ABO compatible potential living donors were evaluated clinically as well as by laboratory and imaging studies. RESULTS: Of 1661 potential donors 814 (49%) were excluded. The reasons for elimination were general medical reasons in 34.4% of cases, nephrological disorders in 25.6%, urological diseases in 11.7% and immunological causes in 16.2%. Exclusion on an ethical basis accounted for 12.2% of cases. CONCLUSIONS: Although kidneys from living donors provide the best functional outcome, 50% of potential candidates must be excluded.