A review of utility-based allocation strategies to maximize graft years of deceased donor kidneys

With the continuing shortage of deceased donor kidneys coupled with a growing number of older potential recipients, there has been a greater acceptance of using older donor kidneys, including increased utility of expanded criteria donor (ECD) kidneys. In this review, we will look at the impact of using ECD kidneys on graft and patient survival, and to identify modifiable factors that may improve transplant outcomes in recipients receiving ECD kidneys. In addition, we will discuss whether the implementation of utility-based allocation strategies to maximize graft outcomes is an appropriate way forward to provide a better balance between utility and equity in the distribution of deceased donor kidneys.     

Clinico-anatomical evaluation of donor kidneys unsuitable for transplantation

The authors conducted clinicoanatomical analysis of 112 donor kidneys which clinicians found to be unfit for transplantation. The procedure of preparing the donors in these cases did not differ from that commonly accepted. An essential moment was prolonged arterial hypotension (6.0 +/- 0.8 hours), in donors whose kidneys were used for transplantation it lasted 2.0 +/- 0.2 hours. Examination showed that in 90% of cases the kidneys were unfit because of congenital or acquired diseases. It is concluded that the existing clinical methods for appraising the fitness of donor kidneys are adequate.     

Non-heart-beating donor kidneys in the Netherlands: allocation and outcome of transplantation

BACKGROUND: Since February 1, 2001, kidneys from both heart-beating (HB) and non-heart-beating (NHB) donors in The Netherlands have been indiscriminately allocated through the standard renal-allocation system. METHODS: Renal function and allograft-survival rate for kidneys from NHB and HB donors were compared at 3 and 12 months. RESULTS: The outcomes of 276 renal transplants, 176 from HB donors and 100 from NHB III donors, allocated through the standard renal allocation system, Eurotransplant Kidney Allocation System, and performed between February 1, 2001 and March 1, 2002 were compared. Three months after transplantation, graft survival was 93.7% for HB kidneys and 85.0% for NHB kidneys (P<0.05). At 12 months, graft survival was 92.0% and 83.0%, respectively (P<0.03). Serum creatinine levels in the two groups were comparable at both 3 and 12 months. Multivariate analysis identified previous kidney transplantation (relative risk [RR] 3.33; P<0.005), donor creatinine (RR 1.01; P<0.005), and NHB (RR 2.38; P<0.05) as independent risk factors for transplant failure within 12 months. In multivariate analysis of NHB data, a warm ischemia time (WIT) of 30 minutes or longer (P<0.005; RR 6.16, 95% confidence interval 2.11-18.00) was associated with early graft failure. No difference in 12-month graft survival was seen between HB and NHB kidneys after excluding the kidneys that failed in the first 3 months. CONCLUSION: Early graft failure was significantly more likely in recipients of kidneys from NHB donors. A prolonged WIT was strongly associated with this failure. Standard allocation procedures do not have a negative effect on outcome, and there is no reason to allocate NHB kidneys differently from HB kidneys.     

Balancing organ quality, HLA-matching, and waiting times: impact of a pediatric priority allocation policy for deceased donor kidneys in Quebec

Deceased donor kidney allocation policy must balance the desire for high-quality organs, good human leukocyte antigen (HLA) matching, and minimal waiting times. We describe a 10-fold reduction in waiting times and an improvement in nonimmunologic indices of organ quality for child recipients after a change in organ allocation policy in Quebec, Canada. The new policy gives first priority to children (<18 yr) irrespective of HLA matching or waiting time. HLA matching after the policy change was predictably much worse. This study highlights the trade-offs that must be considered both in setting allocation policy and in decisions for individual recipients. We also consider potential unintended negative effects of such a policy change.     

The discard of deceased donor kidneys in the UK

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002‐3 to 12% in 2011‐12. A national offering system for hard‐to‐place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31–80) yr. Kidneys had been offered to a median of 3 (1–12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard‐to‐place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.     

The rationale for the new deceased donor pancreas allocation schema

BACKGROUND: To ensure the continued success of whole organ pancreas and islet transplantation, deceased donor pancreas allocation policy must continue to evolve. METHODS: To assess the existing system, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing Kidney and Pancreas Transplant Committee retrospectively analyzed the disposition and outcomes of deceased donor pancreata in the United States between January 1, 2000 and December 31, 2003. RESULTS: During the time period studied, consent was obtained but the pancreas was not recovered in 48% (11,820) of organ donors. The most common reasons given for nonrecovery were poor quality of the pancreas and difficulty in placement. Of whole organ pancreata that were transplanted, 90% were from donors with a body mass index (BMI) 50 years (P=0.04), and there were trends toward lower graft survival with donor BMI >30 (P=0.06) and increasing cold-ischemia time. CONCLUSIONS: Based on these data, the OPTN adopted a new allocation algorithm in which pancreata from donors >30 kg/m or >50 years of age are, unless accepted for a local whole organ pancreas transplant candidate, preferentially allocated for islet transplantation. These data also suggest that many good quality pancreata are not procured, emphasizing the need for improved communication and cooperation between organ procurement organizations and pancreas and islet transplant programs.     

Improving equity of access to deceased donor kidneys in New Zealand

Before 1999, deceased donor kidneys in New Zealand were allocated by local nephrologists on the basis of local needs and factors thought to be beneficial to graft outcome-in particular, matching tissue type. Waiting times were much longer for patients whose tissue type was different from that of our mainly white population of deceased donors. A National Kidney Allocation System was developed that improved equity of access for our unique population base in New Zealand, taking into account not only tissue-type matching but time spent waiting.     

Gene expression patterns in deceased donor kidneys developing delayed graft function after kidney transplantation

BACKGROUND: Delayed graft function (DGF) after kidney transplantation (KTx) ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest because DGF exerts negative influences on long-term outcomes. We studied gene expression profiles in deceased donor kidney (DDK) biopsies with and without DGF. METHODS: Gene expression profiling was performed on donor kidney tissues from 33 DDK with the use of microarrays. DDK were classified as grafts with immediate function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a dialysis requirement in the first week after transplantation. Demographic donor and recipient information was collected. The robust-multiarray average method was used to estimate probe set expression summaries. Logistic regression was used to identify genes significantly associated with DGF development. RESULTS: Patients were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were univariably differentially expressed in DDK with DGF when compared with DDK with non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for cold ischemia time (alpha=0.001). Gene ontology terms classified the overexpressed genes in DDK with DGF as principally related to cell cycle/growth (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was overexpressed in DDK with DGF. CONCLUSIONS: Cold ischemia time was a predictor of DGF independently of the preservation method. We identified a set of 36 genes candidates of DGF in DDK, with genes involved in the inflammatory response being the more important.     

Regional differences in deceased donor liver transplantation and their implications for organ utilization and allocation

Hayashi PH, Axelrod DA, Galanko J, Salvalaggio PR, Schnitzler M. Regional differences in deceased donor liver transplantation and their implications for organ utilization and allocation.
Clin Transplant 2011: 25: 156–163. © 2010 John Wiley & Sons A/S. Abstract: We examined the UNOS database from 7/15/00‐7/17/05 for Regional deceased donor liver utilization. For each region, we performed logistic regression and derived odds ratios (OR) for donor characteristics associated with livers being transplanted outside of the region or not transplanted at all. Regions with smallest and least significant OR were considered aggressive users of suboptimal organs. We estimated how many untransplanted livers from less aggressive regions might be used by more aggressive regions. Only Region 9 was significantly more aggressive than others (median OR: 6 vs. 16; p < 0.01; median OR size: 1.4 vs. 3.6; p < 0.01). Region 9 transplanted at higher median Model for End‐stage Liver Disease (MELD) score (20.4 [6–73] vs. 18.3 [6–70], p < 0.01), but had the lowest one‐ and five‐yr graft survival (p < 0.01). Of 30 474 livers, 5056 were not transplanted, of which 3690 were procured outside Region 9 but met Region 9 use criteria. Of these, 1488 and 1807 livers had donor risk indices ≤ 2, for hypothetical 12 and 8 h cold ischemia time (CIT), respectively. Regional differences in liver utilization are profound. Region 9 is significantly more aggressive. At the most, 297–361 organs per year may have been used under Region 9’s use criteria but overall graft survival may have declined.     

Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system

Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99‐100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long‐distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99‐100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015. All patients had at least 6 months post‐transplant follow‐up. The mean follow‐up was 13.9±3 months in cPRA ≥99% and 12.3±3.5 months in cPRA ≤98%. There was a total of 152 transplants, 25 study patients, and 127 controls. No statistically significant differences were found between the two groups in delayed graft function, rejection, kidney function, graft and patient survival, or infections. We conclude that transplanting the most highly sensitized patients with kidneys shared outside their local donation service areas is associated with excellent short‐term outcomes that are comparable to controls.     

Allocation of deceased donor kidneys: A review of international practices

The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.     

Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation

The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n = 59 328 allografts, 2014‐2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI). Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [_95%LCLaOR_95%UCL], _3.293.51_3.76). This association was most pronounced for low‐risk (KDPI <20) kidneys (aOR, _5.456.47_7.69), with minimal impact at KDPI >85 (aOR, _0.881.15_1.51). Adjusted MORs for kidney discard and biopsy were greatest for low‐risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates.     

HBsAg(+) donor as a kidney transplantation deceased donor

Background

The organ shortage and high prevalence of hepatitis B (HB) infection in the general population are important issues in Taiwan. It is difficult for us to abandon HBsAg(+) donors. Hereby we present our experience transplanting kidneys from deceased donors with HB virus infection.

Methods

From November 1977 to March 2007, 21 patients with end-stage renal disease received kidney grafts from 12 HBsAg(+) deceased donors (3.92% of 306 donors). One of the 12 donors was hepatitis Be antigen (HBeAg) (+), and 5 displayed antibody to hepatitis core antigen (anti-HBc) (+). Four of the 21 recipients were HBsAg(+) before transplantation.

Results

Four HBsAg(+) recipients remained surface antigen positive after transplantation. One of them died of an intracranial hemorrhage. Two (11.76%) of the other 17 HBsAg(−) recipients became HBsAg(+), 1 of whom died of hepatic failure and the other of sepsis. The other 15 HBsAg(−) recipients (88.23%) remained HBsAg(−) after transplantation. They displayed normal serum levels of aspartate aminotransferase/alanine aminotransferase during the follow-up period. The 5-year patient and graft survivals were 85.15% and 61.14%, respectively.

Conclusion

Although the number of patients is relatively small, it does suggest that a kidney allograft from an HBsAg(+) deceased donor transplanted to an HBsAg(+) or (−) recipient is safe. This strategy shortens the waiting time. Additional prophylactic HB immunoglobulin and antiviral medications are also suggested. Frequent surveillance after transplantation is essential.     

Maximizing the donor pool: use of right kidneys and kidneys with multiple arteries for live donor transplantation

Background

Studies have shown donor and recipient outcomes to be equivalent for laparoscopic donor nephrectomy (LDN) and open donor nephrectomy. In the past, LDN has been avoided in the procurement of the right kidney or organs with multiple arteries. This study compares procurement of right and left kidneys as well as procurement of single- and multiple artery organs.

Methods

A review of all LDNs at a single institution between August 2000 and December 2007 was performed. The data included estimated blood loss (EBL), need for transfusion, operative time, warm ischemia time, length of hospital stay (LOS), and delayed graft function. Arterial supply was assessed using renal arteriogram or computed tomographic (CT) angiography. Outcomes for multiple versus single artery and left versus right LDN were compared. Student’s t-test and chi-square test were used for statistical comparison.

Results

A total of 230 LDNs were performed. Multiple arteries were present in 37 donors. The right kidney was procured from 36 donors. No significant difference in EBL, transfusions, operative time, or LOS was noted between multiple and single or right and left LDNs. Warm ischemia time was significantly longer for multiple arteries (mean, 83 s) than for single arteries (mean, 63 s; p = 0.007), and for right kidneys (mean, 86 s) than for left kidneys (mean, 62 s; p = 0.001). No significant difference in delayed graft function was seen in the comparison of multiple (21.6%) and single (11.4%) artery organs (p = 0.11) or of right (13.9%) and left (12.9%) kidneys (p = 0.79).

Conclusions

The presence of multiple arteries or the need to procure the right kidney does not affect the operative outcome of laparoscopic donor nephrectomy. Warm ischemia time may be greater for these groups, but this does not result in delayed allograft function. The laparoscopic approach should be the standard of care even when expansion of the donor pool includes organs with multiple arteries and procurement of the right kidney.     

Excellent outcomes after transplantation of deceased donor kidneys with high terminal creatinine and mild pathologic lesions

BACKGROUND: Outcomes after kidney transplantation using deceased donors with high terminal creatinine are not well described but potentially represent an underutilized source of renal allografts. Utility of renal biopsy of these kidneys is similarly not well established. METHODS: To better understand the posttransplant function of kidneys from donors with high terminal creatinine, we reviewed our database of almost 500 cadaveric kidney transplants. We compared the 65 nonexpanded criteria donors with a final donor creatinine > or = 2.0 mg/dl (range 2.0-4.9 mg/dl) with kidneys procured from donors with terminal creatinine of <1.5. Biopsy results were correlated with graft function. RESULTS: Kidneys from deceased donors with high terminal creatinine performed as well as kidneys from donors with a normal terminal creatinine with respect to primary non-function, acute rejection, 6-year graft and patient survival, and function over the first 48 months. High creatinine kidneys with moderate or severe lesions on biopsy demonstrated poorer function at 6 months and 1 year as compared to those with mild or no histological lesions. CONCLUSIONS: Under select conditions, kidneys from donors with high terminal creatinine can be used safely with excellent results.