Article
Reference
Are criteria for islet and pancreas donors sufficiently different to minimize competition?
RIS, Frédéric, et al.
Abstract
Islet and pancreas transplantation may compete for a limited number of organs. We analyzed records from the national Swiss transplant registry during a 4-year period to investigate the proportion of donors that are suitable for islet and pancreas transplantation. Suitability for pancreas transplantation was mainly defined as: age 10-45 years; weight
RIS, Frédéric, et al . Are criteria for islet and pancreas donors sufficiently different to minimize competition? American Journal of Transplantation , 2004, vol. 4, no. 5, p. 763-6
DOI : 10.1111/j.1600-6143.2004.00409.x PMID : 15084172
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Blackwell Munksgaard
Copyright Blackwell Munksgaard 2004 doi: 10.1111/j.1600-6143.2004.00409.x
Are Criteria for Islet and Pancreas Donors Sufficiently Different to Minimize Competition?
Fr ´ed ´eric Ris, Christian Toso, Florence Unno Veith, Pietro Majno, Philippe Morel
and Jos ´e Oberholzer∗
Clinic for Digestive and Transplant Surgery, Department of Surgery, University Hospital, Geneva, Switzerland
∗Corresponding author: Jos ´e Oberholzer, jober@uic.edu
Islet and pancreas transplantation may compete for a limited number of organs. We analyzed records from the national Swiss transplant registry during a 4-year period to investigate the proportion of donors that are suitable for islet and pancreas transplantation.
Suitability for pancreas transplantation was mainly defined as: age 10–45 years; weight ≤ 80 kg; BMI
≤ 25 kg/m2; amylasemia ≤ 150 U/l; ICU stay ≤ 3 days and absence of severe hypotension (MAP≤60 mmHG). Between 1.1.1997 and 31.12.2000, data of 407 donors were collected, from which 321 donors were included in the study. Thirty-three (10%), 143 (45%), and 23 (7%) donors fulfilled the criteria for pancreas, islet transplantation, and both procedures, respectively. Giving priority to pancreas transplanta- tion and accepting the absence of one selection cri- terion, 90 (28%) pancreas and 100 (31%) islet donors were identified. We conclude that with current alloca- tion policies prioritizing pancreas transplantation, pan- creas and islet transplantation may coexist with little competition.
Key words: Donor selection criteria, islet transplan- tation, organ donation, pancreas transplantation Received 24 July 2003, revised and accepted for publi- cation 22 December 2003
Introduction
Thanks to improved surgical techniques, refined per- operative management and new immunosuppression protocols, the results of pancreas transplantation have steadily improved over the last two decades (1). One- year pancreas graft survival is now close to 80% for pancreas-after kidney and pancreas alone transplanta- tion and greater than 80% in the setting of simultane- ous pancreas and kidney transplantation (2). The num- ber of pancreas transplantations performed each year and reported to the International Pancreas Transplant Reg-
istry (http://www.iptr.umn.edu/annualreports.htm) is in- creasing. During the year 2002, 6186 cadaveric organ donors were identified in the USA; during the same pe- riod 1485 pancreas transplants were performed (based on the organ procurement and transplantation network data since February 28, 2003;www.optn.org). The number of islet transplants performed during this period is not avail- able yet, but was probably less than 100 for the year 2002.
Different figures are reported from Europe, where pan- creas transplantation is performed less frequently (3). For instance, the French organ procurement agency (Etablisse- ment Fran ¸cais des Greffes) reported an average of 1000 cadaveric donors and only 50 combined kidney-pancreas transplants and less than 10 islet transplants per year (4).
The results of islet transplantation have recently improved, reaching 80% 1-year insulin-independence, as reported by the Edmonton group (5,6). Although still requiring multiple donors, these cellular grafts are in the process of entering clinical reality.
New islet transplant programs are starting worldwide, and the question of whether islet and pancreas transplantation compete for cadaveric donor pancreases arises accord- ingly. The present study investigates which proportion of donors could be considered for islet or pancreas transplan- tation according to current selection criteria, and to what extent these donor populations overlap.
Methods
We analyzed the records of 407 consecutive donors registered in the Swiss national organ sharing organization (Swiss Transplant) in the 4-year period from 1.1.1997 to 31.12.2000. Swiss Transplant coordinates all organ do- nations in Switzerland, a country of 7.5 million inhabitants. Twenty-eight nonheart beating donors and 58 donors for whom only incomplete data were available because the pancreas was not procured, e.g. owing to fam- ily restricting the donation to kidneys or liver, were excluded. The remaining 321 donors constituted the study population.
We considered that a pancreas was suitable for whole organ transplantation or for an islet isolation/transplantation when the criteria of Table 1 were met. These criteria were defined according to our current practice and to the international literature (1,5,7–9).
We applied the criteria to the study population and we calculated the number of potential pancreas transplantation and islets isolations. We then loosened the criteria for pancreas procurement by accepting donors with one criterion missing (excluding diabetes and/or alcohol abuse), or by extending the limits
Ris et al.
Table 1: Criteria for the selection of pancreas and islet donors Criteria Pancreas selection Islets
Age ≥10 and≤45 years ≥20 and≤70 years
Weight ≤80 kg –
BMI ≤25 kg/m2 –
Amylasemia ≤150 U/l –
ICU stay ≤3 days –
Hypotension∗ No –
Glycemia ≤11 mmol/L 11 mmol/L
Cardiac arrest No No
History of diabetes No No
Alcohol abuse No No
∗Mean arterial pressure<60 mmHg at any time since potential donor was announced to the organ sharing organization. BMI= body mass index, ICU=intensive care unit.
of some criteria. We finally investigated the overlap of donors being suitable for both pancreas and islet transplantation.
Results
From 1.1.1997 to 31.12.2000, 407 organ donors were reg- istered in the Swiss Transplant files (13.6 donors per million inhabitants per year). The characteristics of the donors are summarized in Table 2, and were described in greater detail elsewhere (10). Donors were located in 30 different hos- pitals, with the longest distance between them being 300 km. Thirty percent (122/407) of the donors were registered in the two University Hospitals performing pancreas trans- plantation in Switzerland (Geneva and Zurich). Pancreata were harvested and grafted as whole organ in 4% of the donors (17/407). Islets were isolated in 25% of the donors (101/407). In the remaining cases, the organs were not harvested because of nonheart beating donor procedure (27 cases), specific family refusal to harvest the pancreas (25 cases), various pancreas abnormalities in 55 cases (including diabetes and alcoholic disease), lack of appro- priate recipient, logistical reasons or medical contraindica- tions for pancreas donation (182 cases).
Potential number of pancreas donors available Of the 321 donors studied, 33 fulfilled all the criteria for pancreas transplantation (10%, 1.4 donors/million inhabi- tants/year) and 143 donors fulfilled all the criteria for islet transplantation (45%, 6 donors/million inhabitants/year).
Twenty-three donors fulfilled all criteria for both whole pan- creas and islet transplantation (7%, 0.95 donors/million in- habitants year) and were included in these numbers; allo- cating these donors to pancreas transplantation (prioritized in most programs) would still have left 38% of donors avail- able for islet transplantation. The mean age of whole pan- creas donors was 28.1±10 years and of islet donors was 43.3±13 years.
Potential number of pancreas available with extended criteria
A less restrictive policy to pancreas harvesting, including donors with one of the above-mentioned criteria missing,
Table 2: Repartition of the donors according to the criteria for pancreas transplantation or islet transplantation
Donor criteria [number (%) of donors excluded
because of missing data] % of donors
Age; 1 (0.2%) <10 years 3.2% (13/406)
≥10;<20 years 9.4% (38/406)
≥20;<45 years 37% (150/406)
≥45;<50 years 9.6% (39/406)
≥50;<60 years 37.9% (154/406)
≥60;<70 years 13.4% (45/406)
≥70 years 3.2% (13/406)
Weight; 20 (4.9%) ≤80 kg 81.4% (315/387)
>80 kg 18.6% (72/387) BMI; 20 (4.9%) <25 kg/m2 65.1% (252/387)
≥25;<27 kg/m2 22.0% (85/387)
≥27 kg/m2 12.9% (50/387) Duration of ICU stay; 0 ≤3 days 82.0% (334/407)
>3;≤5 days 8.6% (35/407)
>5 days 9.4% (38/407) Minimal mean arterial
pressure; 15 (3.6%) <60 mmHg 24.0% (94/392)
≥60 mmHg 76.0% (298/392) Glycemia; 17 (4.2%) <11 mmol/L 42.3% (165/390)
≥11 mmol/L 57.7% (225/390) Amylasemia; 77 (18.9%) <150 U/l 73% (243/330)
≥150 U/l 27% (99/330)
Cardiac arrest; 0 No 76.0% (309/407)
Yes 24.0% (98/407)
Diabetes; 0 No 96.9% (395/407)
Yes 3.1% (12/407)
Alcohol abuse; 11 (2.7%) No 89.1% (353/396)
Yes 10.9% (43/396)
BMI=body mass index, ICU: intensive care unit.
would have increased the percentage of potential pancreas transplantations from 10% to 28% (3.9 donors/million in- habitants/year). Giving priority to pancreas transplantation, 31% of all donors (four donors/million inhabitants year) would be available for islet procedures (Figure 1). Alto- gether, loosening the selection by one criterion would al- low for procuring the pancreas as a whole organ or islets in 59% of the donor population.
Age, BMI, glycemia, amylasemia and mean arterial pres- sure were the criteria that excluded the highest proportion of donors (Table 2).
The consequences of omitting or extending the selection criteria for age, glycemia, amylasemia, ICU stay and BMI on the numbers of pancreas and islet donors are illustrated in Figure 1.
Impact of selection criteria on the competition for donors between pancreas and islet transplantation According to whether the policy of accepting whole pan- creas is restrictive (all criteria fulfilled) or liberal (up to one criteria missing), respectively, 10% or 28% of the donors qualified for pancreas transplantation and 45% for islet
764 American Journal of Transplantation2004; 4: 763–766
all criteria
omitting one criterion
age≤
50 y age≤
60 y any glycemia
any amylase
ICU≤
5 d BMI≤
27 0
5 10 15 20 25 30 35 40
Percentage of donors (%)
Selection criteria 38
31 35
33 34 36 37 37
3 7
14 14
3 10
3 12
3 11
3 9
3 8
4 8 Islet Pancreas Overlap
Figure 1: Percentages of donor pancreases available for pan- creas, islet or both procedures (overlap) according to the se- lection criteria.BMI=body mass index (kg/m2); ICU=intensive care unit.
transplantation. Loosening the donor acceptability criteria increased the overlap between both procedures from 7%
to 14%, and giving priority to pancreas transplantation, the number of pancreas donors increased, and the number of islet donors diminished.
Discussion
This study shows that with stringent selection criteria only 10% of cadaveric multiorgan donors qualify for pan- creas donation. Our analysis further showed that an ad- ditional 38% of the donors were suitable for islet isola- tion/transplantation. By omitting one selection criterion, the pancreas donor rate could be increased from 10% to 28%, and 31% of donors remained available for islet trans- plantation.
Selection of donors for pancreas transplantation aims at reducing the risk of graft related postoperative morbidity and mortality in recipients often suffering from advanced chronic diabetic complications. Selection of donors for islet isolation is more of economical value, to reduce the num- ber of islet isolation failing to deliver sufficient islets for clinical use.
Limiting the donor age to less than 45 years may be con- sidered as too a restrictive age limit, but is current practice in many centers. Some experienced teams have extended the upper age limit and still obtained good results with donors between 55 and 60 years, and even beyond 60 years as reported by the Pittsburgh group (11). However, the series reported by the University of Wisconsin indi- cates that grafts from donors 45 years of age or older have significantly lower 1- and 5-year graft survival rates (12).
We explored the impact of extending the age limit to 50 and 60 years. This increased the proportion of donors po- tentially suitable for whole pancreas transplantation from 10 to 13% when accepting donor up to 50 years of age and to 15% when the upper age limit was extended to 60 years. This finding indicates that even a marginal age extension can increase the pancreas donor pool.
The importance of normoglycemia in the donor is still controversial. While some groups do not consider high donor blood glucose as a contraindication for pancreas transplantation (13,14) other groups have reported that hy- perglycemia is a risk factor for poor pancreas graft out- come (15,16). Accepting peak blood glucose level up to 11 mmol/L would have increased the percentage of pan- creas donors from 10 to 14%. When evaluating glucose levels as donor selection criterion, other parameters, which may influence glycemia or insulin-sensitivity in the donor, e.g. glucose infusion or doses of catecholamines have to be considered.
Relaxing other criteria such as amylase levels, extending intensive care stay from 3 to 5 days or accepting donors with a BMI up to 27 kg/m increased the pancreas donor pool only marginally.
Hemodynamic stability has been considered a prerequi- site for good organ function when using cadaveric organs for transplantation. In our population, one in four donor was excluded because of episodes of marked hypotension.
This high proportion identifies hemodynamic instability as a relevant exclusion criterion, which may be questioned if the pancreas donor pool is to be increased. In a recent report, delayed graft function was more common in pan- creas transplants originating from hemodynamically unsta- ble donors, but long-term graft outcome was not different from organs coming from stable donors (11). The use of pancreata from unstable donors for islet isolation has been addressed (17), but needs further analysis.
Although this study is based on the donor population of a whole country, and as such it is freer from selection bi- ases owing to different attitudes towards pancreas and islet donations in specific centers, it presents some limi- tations. First, we could not analyze the intraoperative find- ings during the procurement and the evaluation by the sur- geon as a selection criterion. Second, the above-presented donor population may differ from the population in coun- tries with different donation rates. Countries with a higher donation rate may have more marginal donors and coun- tries with a higher incidence of traumatic brain deaths may have a younger donor population. However, our registry data match the figures reported by most European and North-American countries (18). With a donation rate of 13.6 donors per million inhabitants per year, our results are likely to apply to most organ-sharing regions. It is remarkable that the calculated 28% rate of donors suitable for pancreas transplantation using the liberal criteria was very close to
Ris et al.
the 24% pancreas utilization rate in the USA for the year 2002 (1485 pancreata were transplanted from 6168 cadav- eric donors,www.optn.org).
In our analysis, we gave priority to pancreas transplanta- tion, considering that at the present time islet transplan- tation is still an experimental procedure and clearly less efficacious in terms of pancreas utilization. The process for islet isolation is still somewhat unreliable, depending on the quality of the pancreas, degree of cold storage, and digestion characteristics of the lot of enzyme used (19).
Currently, to achieve insulin-independence, islet prepa- rations from often two, and occasionally three, donors are required. Once islet transplantation is more reliable and consistently achieves insulin-independence with a single donor at the same rate as pancreas transplanta- tion, current allocation policies may be revised. Then a common allocation scheme could be used for a com- mon list of recipients, and the choice of how the or- gan is used would be purely technically based on the recipient’s characteristics (e.g. recipients with high body weight and high insulin requirements would qualify for a pancreas rather than an islet transplant). Our analysis indicates that in the mean time, using the specified se- lection criteria, allocation for islets can be made from a sufficient number of donors for the field to progress even while allowing all cadaveric donor organs meeting both pancreas and islet criteria to be used for pancreas transplants.
Acknowledgments
The authors thank A. Haessig, D. Moretti, I. Van-Hollebeke and C. Zimmer- mann for their help in collecting the donor data in the Swiss Transplant Registry.
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