David N. Landsberg, MD, FRCPC, R. Jean Shapiro, MD, FRCPC




                                           Kidney, pancreas,...
Kidney, pancreas, and pancreatic islet transplantation




                                                               ...
Kidney, pancreas, and pancreatic islet transplantation




immunosuppressive therapy, HLA
matching is less important and t...
Kidney, pancreas, and pancreatic islet transplantation




                                                               ...
Kidney, pancreas, and pancreatic islet transplantation




the longest. Candidates for PAK, in            Pancreas transpl...
Kidney, pancreas, and pancreatic islet transplantation




                                                               ...
Kidney, pancreas, and pancreatic islet transplantation




inopathy has stabilized in transplant
recipients compared with ...
Kidney, pancreas, and pancreatic islet transplantation




      5. Bray R, Nolen J, Larsen C, et al. Trans-              ...
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British Columbia Medical Journal - May 2010: Kidney, pancreas, and pancreatic islet transplantation

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British Columbia Medical Journal, May 2010 issue.

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British Columbia Medical Journal - May 2010: Kidney, pancreas, and pancreatic islet transplantation

  1. 1. David N. Landsberg, MD, FRCPC, R. Jean Shapiro, MD, FRCPC Kidney, pancreas, and pancreatic islet transplantation Many patients with end-stage renal disease are now being helped with improved transplantation techniques and immunosuppressive regimens. ABSTRACT: Kidney transplantation Kidney transplantation ing donor kidneys have steadily im- is the treatment of choice for many The first kidney transplant in BC was proved. This is mainly due to refine- patients with kidney failure, and out- performed in 1968. With the dramatic ments in immunosuppressive thera- comes in BC are excellent. Because improvement in graft and patient sur- pies. Today tacrolimus has largely donor organ shortage remains a vival, transplantation has become the replaced cyclosporine; mycopheno- major challenge, BC has developed treatment of choice for many patients late mofetil has replaced azathioprine; innovative programs to expand the with end-stage kidney disease. How- and the use of steroids is no longer pool of both living and deceased ever, significant challenges remain. routine. Biological agents such as donors, and allocation policies for Although immunosuppressive agents basiliximab (an interleukin-2 receptor deceased donor kidneys have evolv- are effective, they have significant blocker) or antithymocyte globulin ed to improve utility while maintain- toxicity and individualized therapy is (ATG) are now commonly used at the ing equity. Other improvements in required to optimize function while time of transplant.1,2 The immunosup- kidney transplantation have been limiting complications. There are also pressive regimen is determined by a made by individualizing immunosup- too few deceased donor kidneys to patient’s immunological risk of expe- pressive therapy to maximize effica- meet patient needs, and waiting times riencing rejection. Low-risk patients cy while minimizing toxicity. are in excess of 5 years after starting are recipients of first transplants with- Pancreas and pancreatic islet dialysis. This leads to morbidity in out evidence of antibodies to HLA transplantation are reserved for patients waiting for transplantation antigens. Patients with detectable those with type 1 diabetes. Because and affects survival after transplanta- anti-HLA antibodies and those who of the very limited number of suit- tion. More living kidney donation and have previously rejected a transplant able organ donors, whole pancreas expansion of the deceased donor pool are high-risk and receive more aggres- transplantation is restricted to in- are needed to address the deceased sive immunosuppression. Low-risk dividuals with end-stage renal dis- donor kidney shortage. It is critical ease who have otherwise limited with deceased donor kidneys to max- Dr Landsberg is the medical director of comorbidities and who are already imize their utility by appropriate allo- renal transplantation at St. Paul’s Hospital, on immunosuppressive medication. cation so that potential kidney life Vancouver, BC. He is also a clinical profes- Successful pancreas transplanta- years are not lost when patients die sor in the Department of Medicine at the tion can significantly improve both with functioning kidneys. University of British Columbia. Dr Shapiro quality and quantity of life. Islet is the medical director of Renal Transplan- transplantation is still in its infancy, Individualizing tation and the medical manager of Solid but has been shown to improve gly- immunosuppressive therapy Organ Transplantation at Vancouver Gener- cemic control and stabilize retinopa- Graft survival rates ( Figure 1 ) and pa- al Hospital. She is also a clinical associate thy and nephropathy. tient survival rates ( Figure 2 ) for BC professor in the Department of Medicine recipients of deceased donor and liv- at UBC. www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 189
  2. 2. Kidney, pancreas, and pancreatic islet transplantation BC protocols were derived from our local experience and confirmed by 100% results of international large-scale tri- 90% als.3 Results in low-risk patients have 80% been excellent, with 1- and 10-year 70% graft survival at 96.4% and 77.7%. Survival rate 60% Results in high-risk patients have 50% also improved. This is in part through 40% 2000–2007 first transplant laboratory tests that can detect anti- 1990–1999 first transplant donor antibodies and hence avoid sit- 30% 1968–1989 first transplant 20% 2000–2007 re-transplant uations in which the likelihood of 1990–1999 re-transplant rejection is very high.4,5 In addition to 10% 1968–1989 re-transplant the introduction of potent antirejec- 0% tion drugs, there has been improve- 0 1 2 3 4 5 6 7 8 9 10 ment in the use of antiviral agents Years post-transplant and screening for viral infections, reducing the risk of severe or even Figure 1. Graft survival for kidney transplants by graft number and year of transplant, fatal complications.6 1968–2007. Source: BC Transplant Promoting and expanding living donation In BC there has been a decrease in the 100% number of deceased donor kidney 90% transplants performed since 1990, but 80% this has been offset by an increase in 70% the number of living donor transplants Survival rate 60% ( Figure 3 ). Today the BC program 50% promotes pre-emptive living donor 2000–2007 first transplant kidney transplant, whereby transplan- 40% 1990–1999 first transplant 1968–1989 first transplant tation occurs before the initiation of 30% 2000–2007 re-transplant dialysis, as the treatment of choice for 20% 1990–1999 re-transplant most patients with kidney failure. This 10% 1968–1989 re-transplant approach allows for better outcomes.7 0% Living donation has grown because 0 1 2 3 4 5 6 7 8 9 10 of a number of factors. These include Years post-transplant the development of programs that help recipients reach out to identify and request living donors, the acceptance Figure 2. Patient survival for kidney transplants by graft number and year of transplant, 1968–2007. of genetically unrelated living donors, Source: BC Transplant the anonymous living donor program, the donor exchange program, and pro- patients receive a protocol consist- exposure. Of these low-risk patients, tocols to desensitize recipients to their ing of basiliximab, tacrolimus, myco- only those who experience acute living donors. It should be emphasized phenolate, and rapid steroid elimina- rejection episodes are treated with that living donors undergo rigorous tion, while high-risk patients receive steroids, and less than 20% of low- medical and psychological testing ATG, tacrolimus, mycophenolate, and risk patients required steroids over the before being accepted into the pro- steroids. past 5 years. The steroid-free regimen gram, and are followed lifelong. In BC approximately 80% of has contributed to reduced morbidity Historically, living donors were transplant recipients are low-risk and and weight gain, better bone density, close family members, such as parents, thus receive minimal corticosteroid and improved patient satisfaction. The children, or siblings. With improved 190 BC MEDICAL JOURNAL VOL. 52 NO. 4, MAY 2010 www.bcmj.org
  3. 3. Kidney, pancreas, and pancreatic islet transplantation immunosuppressive therapy, HLA matching is less important and trans- plants from living unrelated donors 200 DD transplants LD transplants are as successful as those from living 180 Total transplants related donors.8 Today in BC more 160 than 50% of transplants come from 140 ABO compatible living unrelated 120 donors, such as spouses, friends, in- 100 laws, and coworkers. Part of our pre- 80 transplant assessment involves coun- 60 seling patients on ways to reach out 40 for living donors. 20 The BC Transplant kidney trans- 0 plantation program was the first in 90 991 992 993 994 995 996 997 998 999 000 001 002 003 004 005 006 007 008 19 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 Canada to utilize living anonymous donors (LAD). After initial research Figure 3: Living (LD) and deceased (DD) donor transplants in BC by year, 1990–2008. probing societal views on this issue,9 Source: BC Transplant the first LAD transplant was perform- ed in 2005. In this program, indivi- duals who have undergone rigorous medical and psychological testing donate their kidney to a recipient who LAD D1 D2 D3 D4 Group 0 Group A Group B Group C Group D is unknown to them. This is done anonymously to protect both the re- cipient and the donor. LAD kidneys ABO ABO Positive ABO incompatible incompatible crossmatch incompatible may be given to a patient at the top of the wait list, or used in the donor x x x x exchange program. Up to 30% of donor and recipient R1 R2 R3 R4 Deceased pairs may be incompatible because of donor Group 0 Group A Group B Group C wait list ABO blood group mismatch or the presence of donor-specific anti-HLA antibodies. In paired exchange, ap- D = Donor R = Recipient proved donor and recipient pairs are registered into a database where suit- Figure 4. Four-pair transplant chain triggered by a living anonymous donor (LAD) and resulting in one kidney going to a recipient on the deceased donor wait list. able combinations are identified. In the simplest example, pair 1 has a donor who is blood group A and a paired donor exchange registry, which Expanding the deceased recipient who is blood group B. Pair 2 will facilitate matches. The use of donor pool has a blood group B donor and a blood LADs in the exchange program great- Historically, organ donation has group A recipient. The exchange oc- ly enhances the number of possible occurred when donors have been curs by the A donor from pair 1 donat- matches, as the LAD is not tied to a declared brain dead but have main- ing to the A recipient from pair 2, and recipient who must receive a trans- tained circulation and hence organ vice versa. In more complicated situ- plant and thus can act as a key to perfusion. Until recently, donors who ations, chains are established to allow unlock a chain of transplants. In the suffered cardiac death have not been multiple transplants. The success of example shown in Figure 4 , the use of used because of concerns that irre- the paired donor exchange program is the LAD kidney allows a four-way versible organ damage will have fol- based on the number of donor and exchange to take place and still gener- lowed circulatory collapse. However, recipient pairs who are entered into ates a kidney for the deceased donor in controlled situations, organ dam- the exchange. There is now a national wait list. age, especially kidney damage, can be www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 191
  4. 4. Kidney, pancreas, and pancreatic islet transplantation over the age of 60 has recently been implemented and will be carefully monitored to ensure that it is achiev- Pancreas-kidney transplants 12 Pancreas-after-kidney transplants ing the desired results and maintain- ing fairness for all patient groups. 10 Pancreas transplantation 8 As is the case for kidney transplanta- tion, demand is far greater than supply 6 for pancreas transplantation and this disparity appears to be increasing.13 4 The goals of pancreas transplantation 2 are to provide sustained normogly- cemia without insulin and, over time, 0 to reverse or minimize microvascular 86 88 90 92 94 96 98 00 02 04 06 08 and macrovascular complications. 19 19 19 19 19 19 19 20 20 20 20 20 With whole pancreas transplantation, Figure 5. Simultaneous pancreas-kidney (SPK) and pancreas-after-kidney (PAK) transplants unlike pancreatic islet transplantation, in BC, 1986–2008. the counter-regulatory axes are also Source: BC Transplant restored. Most centres have found that successful pancreas transplantation significantly improves both quality reduced to the point where the organs kidney damage, such as hypertension, and quantity of life.14,15 can be effectively utilized for trans- have traditionally not been used for Pancreas transplantation is reserv- plantation. This process is referred to transplantation. However, there has ed for those with insulinopenic type 1 as donation after cardiac death (DCD). been increased utilization of such diabetes. There are only six to eight In this case family may consent or donors, termed expanded criteria don- suitable pancreas donors annually in request that organ retrieval occur after ors (ECD), as long as renal function is BC, and hence eligibility criteria are the heart has stopped and death has adequate. Older recipients who receive fairly strict to maximize the likelihood been declared. Withdrawal of life sup- ECD kidneys benefit because of of successful outcomes. Individuals port occurs in the operating room or reduced time on the wait list.10,11,12 In being considered for simultaneous an adjacent area, with the retrieval BC the ECD program allows recipi- pancreas-kidney transplantation (SPK) team on standby. The patient is moni- ents who have received the appropri- must have end-stage renal disease, tored but there are no interventions. If ate information and consented to this good cardiac function, minimal peri- cardiac standstill ensues quickly with- procedure to receive these kidneys. pheral vascular disease, be nonsmok- out a prolonged period of hypoten- ing, and have few other significant sion, the organs are still viable and Kidney allocation comorbidities. SPK in BC did not organ retrieval commences 5 minutes Transplant recipients may die with really begin to flourish until the after the heart stops. If cardiac arrest their transplant still functioning well, mid-1990s ( Figure 5 ).15 SPK with both does not occur within 2 hours of an event termed “death with a func- grafts from a common deceased donor removal of life support, organ dona- tioning graft.” It would be optimal to was the usual form of transplantation. tion does not occur and the patient direct kidneys with shorter expected However, because the waiting time for receives the same palliative care that duration of function into older recipi- SPK is now so prolonged, prospective would have occurred after life support ents who have shorter life expectan- recipients are encouraged to identify withdrawal. The first DCD in BC cies, and kidneys from younger donors potential live kidney donors, and wait occurred in November 2008. We into younger recipients.12 In BC a sys- for pancreas-after-kidney transplanta- believe that this donor source will tem preferentially allocating kidneys tion (PAK). The usual waiting time increase the donor pool by 20%. from donors under the age of 35 to between kidney transplantation and Donors over the age of 60 or recipients under 55, and kidneys from PAK is in the order of several years, younger donors with risk factors for donors over the age of 60 to recipients with blood groups O and B waiting 192 BC MEDICAL JOURNAL VOL. 52 NO. 4, MAY 2010 www.bcmj.org
  5. 5. Kidney, pancreas, and pancreatic islet transplantation the longest. Candidates for PAK, in Pancreas transplantation requires more reliable indicator of acute rejec- addition to the requirements for SPK, more intensive immunosuppression tion and should prompt pancreas bi- must have achieved good renal graft than kidney transplantation alone. For opsy. By the time impaired glucose function and be free of severe im- SPK, patients receive induction ther- levels are established, pancreatic munological or infectious disease risk. apy with an interleukin-2 receptor rejection has probably been present Recipients opting for PAK have sig- antibody and methylprednisolone; for some time, and the pancreatic allo- nificantly enhanced long-term patient maintenance therapy consists of myco- graft may be difficult to salvage. Loss survival compared with those who phenolate, tacrolimus, and steroids. of pancreas function can also occur wait for deceased donor kidneys.14 The standard protocol differs from from recurrence of type 1 diabetes This has been attributed to lessening that in renal transplant recipients in (autoimmune loss versus alloimmune the morbidity and mortality from that steroids are continued. For those loss). These two entities can be reliably excessive amounts of urea, which ac- undergoing PAK, the induction regi- distinguished by pancreas biopsy.17 cumulates while the recipient waits. Recipients with good kidney function at the time of PAK experience fewer perioperative complications and shor- ter hospital stays compared with those with renal failure. Pancreas transplant alone (PTA) is an option that has been offered to individuals with brittle dia- Active pancreas rejection rates are betes but no end-stage renal disease. However, patient selection is prob- difficult to quantify, as pancreatic lematic, and there are higher than biopsies are not performed as expected rates of graft failure and development of renal failure.15 routinely as kidney biopsies. Initial surgical approaches in the 1970s and 1980s utilizing a form of enteric drainage were abandoned because of surgical complications. Exocrine pancreas drainage was redi- rected to the bladder, which allowed monitoring of pancreas rejection by urinary amylase. However, bladder men consists of a T-cell depleting For patients with type 1 diabetes drainage posed its own problems, agent (antithymocyte globulin) and and end-stage renal disease, timely mainly from the exocrine secretions methylprednisolone, with maintenance transplantation is particularly impor- (metabolic acidosis from loss of uri- treatment the same as for SPK. It is tant. Death on the wait list for SPK nary bicarbonate, chronic bladder controversial whether the two grafts candidates is very common, with a inflammation, bladder stones) and in are independent in terms of develop- reported 4-year mortality of 41.3% the mid-1990s most pancreas pro- ing rejection or if rejection in one graft compared with 18.3% for those wait- grams switched back to a simplified is always concordant with simultane- ing for PAK.14,18 This underscores the version of enteric drainage. In this ous rejection in the other graft.16 Acute significant mortality attached to ure- operation, the donor duodenum with pancreas rejection rates are difficult to mia and highlights the reason we the attached pancreas is anastomosed quantify, as pancreatic biopsies are not advise patients to seek live donor kid- end-to-side to the recipient small performed as routinely as kidney ney transplant while they wait for a bowel and placed in the pelvis in a biopsies. Deteriorating renal function, pancreas. way similar to kidney transplantation. reflected by a rise in serum creatinine, Patient and graft survival for pan- The arterial anastomosis is to the is sometimes used as an indicator of creas transplantation in BC are good. recipient’s iliac artery and either sys- pancreas rejection, although it is rec- In patients with SPK, cumulative 5- temic or portal venous drainage can ognized that this is an insensitive year kidney graft survival in BC over be used. marker. Rising serum amylase is a several different transplant eras is www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 193
  6. 6. Kidney, pancreas, and pancreatic islet transplantation Islet transplantation Despite the initial success of islet trans- 100% plantation reported from Edmonton in 95% 2000,19 this therapy is still considered 90% experimental and offered only to those who have refractory hypoglycemia Survival rate 85% or who are being treated in experienc- 80% ed centres undertaking research.20,21 The goals of islet transplantation are 75% Kidney graft to decrease or eliminate the need for 70% Pancreas graft insulin, to improve HbA1c readings, and to minimize or prevent diabetes 65% complications in patients with type 1 60% diabetes. 0 1 2 3 4 5 There are significant technical and Years post-transplant medical challenges with islet trans- plantation. Islet isolation requires ex- Figure 6. Graft survival for the first simultaneous pancreas-kidney (SPK) transplants in BC pertise, and the quality and quantity by organ, 1986–2008. of islets must be assessed before being Source: BC Transplant deemed suitable for donation. Most individuals require multiple islet transplants in order to achieve suffi- cient functioning islet mass. Place- 100% ment of islets is also problematic, and 95% although current practice relies on 90% portal venous embolization, this site is probably not optimal.22 At the time Survival rate 85% of transplantation, the immediate 80% problems include an acute intrahepat- ic coagulation reaction, and promo- 75% tion of cell viability and engraftment. 70% Over time, the potential for alloim- 65% mune and autoimmune destruction becomes apparent. 60% 0 1 2 3 4 5 In BC the islet program began in Years post-transplant the context of research, comparing islet transplantation with intensive insulin Figure 7. Patient survival for the first simultaneous pancreas-kidney (SPK) transplants in therapy. Candidates had to have nor- BC, 1986–2008. mal renal function, minimal albumin- Source: BC Transplant uria, and minimal retinopathy. The first islet transplantation occurred in 2003, and since then 70 islet trans- 87.5%, while the rate for pancreas mortality in the first 90 days follow- plantations have been performed in 31 graft survival is 80.5% ( Figure 6 ). ing SPK,14,18 successful SPK confers a patients.23 Our results have demon- Patient survival for this same time significant survival advantage, with strated stable and improved metabol- span is 94.5% ( Figure 7 ), comparable more than 20 life years gained over ic control, with significantly lower to US registry data with 5-year patient those on a wait list.14 Failure of the HbA1c values in islet transplant recip- survival reported at 83% to 87% for pancreatic graft leads to increased ients compared with those on inten- SPK13,14 and pancreas graft survival at mortality,18 the most important contrib- sive medical therapy. As well, renal 73%.13 While there is an initial excess utor being cardiovascular disease.14,15,18 function has not declined, and ret- 194 BC MEDICAL JOURNAL VOL. 52 NO. 4, MAY 2010 www.bcmj.org
  7. 7. Kidney, pancreas, and pancreatic islet transplantation inopathy has stabilized in transplant recipients compared with medical controls.23 Renal transplant recipients in BC enjoy Immunosuppressive regimens excellent success rates, but there remains continue to be refined. The original Edmonton protocol relied on a combi- the ongoing challenge of the shortage of nation of sirolimus and tacrolimus, but donor organs for transplantation. this combination proved more nephro- toxic than anticipated. In BC we use induction with antithymocyte globu- lin for the first transplant and mainte- nance with tacrolimus and mycophe- risk of immune sensitization, particu- after-kidney transplantation with nolate in a steroid-free regimen. For larly as multiple donors are required, preceding live donor kidney trans- subsequent transplants, induction is which may significantly limit access plantation offers superior long-term with basiliximab. Other centres use a to future renal transplantation should graft and patient survival compared variety of induction agents and main- that be required.21,27 Unlike whole pan- with either kidney transplant alone tenance regimens.24 There is also a creas transplantation, islet transplan- from a deceased donor or remaining nonimmunological component in the tation does not have a durable response, on the wait list.14 therapy of islet transplantation, with with less than 50% of patients remain- Pancreatic islet transplantation drugs directed at the coagulation cas- ing insulin-independent at 3 years.28 holds promise for individuals with cade, and antiapoptotic strategies uti- type 1 diabetes. However, there are lizing incretin-based therapies.25,26 Conclusions still significant technical and medical The advantages and disadvantages Kidney transplantation has been one hurdles to overcome. Newer treatment of islet transplantation are summa- of the true medical miracles of the past strategies include refining immuno- rized in the accompanying Table . A 50 years. Renal transplant recipients suppressive protocols and developing sufficient functioning islet mass must in BC enjoy excellent success rates, agents that will improve islet viability be obtained to achieve the principal but there remains the ongoing chal- and function. advantages—freedom from or reduc- lenge of the shortage of donor organs tion in insulin requirements, improved for transplantation. The BC renal Competing interests metabolic profile, and stabilization of transplant program has developed and None declared. diabetic complications. However, these implemented innovative strategies to benefits come with the cost of lifelong deal with these issues. References immunosuppression and its attendant For those with type 1 diabetes, 1. Halloran PF. Immunosuppressive drugs risks, including infection and malig- successful simultaneous pancreas- for kidney transplantation. N Engl J Med nancy. In addition, there is also the kidney transplantation or pancreas- 2004;351:2715-2729. 2. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin Table. Advantages and disadvantages of pancreatic islet transplantation. inhibitors in renal transplantation. N Engl J Med 2007;357:2562-2575. Advantages Disadvantages 3. Vincenti F, Schena FP, Paraskevas S, et al. Freedom from insulin injections Not a durable transplant, with more than 50% returning to A randomized, multicenter study of over the short term some insulin use after 3 years steroid avoidance, early steroid with- Improved glycemic control, Requires lifelong immunosuppression with attendant risks drawal or standard steroid therapy in kid- with less hypoglycemia, better (infection and malignancy) ney transplant recipients. Am J Trans- HbA1c, measurable C-peptide plant 2008;8:307-316. Stability or improvement in May need multiple classes of drugs: oral hypoglycemic agents; 4. Gebel H, Bray R, Nickerson P. Pre-trans- nephropathy, retinopathy glucagon-like peptide-1 agonists (exenatide) or dipeptidyl-4 inhibitors (januvia) for successful long-term results plant assessment of donor-reactive, HLA-specific antibodies in renal trans- Risk of sensitization, jeopardizing future renal transplant opportunities plantation: Contraindication vs. risk. Am J Transplant 2003;3:1488-1500. www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 195
  8. 8. Kidney, pancreas, and pancreatic islet transplantation 5. Bray R, Nolen J, Larsen C, et al. Trans- creas transplantation. Lancet 2009;373 al. Effect of glucagon-like peptide-1 (7- planting the highly sensitized patient: The (9677):1808-1817. 37) on beta-cell function after islet trans- emory algorithm. Am J Transplant 16. Kaplan B, West-Thielke PM, Herren H, et plantation in type 1 diabetes. Diabetes 2006;6:2307-2315. al. Reported isolated pancreas rejection Res Clin Pract 2006;74:189-193. 6. Asberg A, Humar A, Rollag H, et al. Oral is associated with poor kidney outcomes 27. Campbell PM, Senior PA, Salam A, et al. valganciclovir is noninferior to intra- in recipients of a simultaneous pancreas High risk of sensitization after failed islet venous ganciclovir for the treatment of kidney transplant. Transplantation 2008; transplantation. Am J Transplant 2007; cytomegalovirus disease in solid organ 86:1229-1233. 7:2311-2317. transplant recipients. Am J Transplant 17. Drachenberg CB, Odorico J, Demetris 28. Alejandro R, Barton FB, Hering BJ, et al. 2007;7:2106-2113. AJ, et al. Banff schema for grading pan- 2008 Update from the Collaborative Islet 7. Weir M. Preemptive kidney transplanta- creas allograft rejection: Working pro- Transplant Registry. Transplantation tion: Why not? Am J Transplant 2003;3: posal by a multi-disciplinary international 2008;86:1783-1788. 1336-1340. consensus panel. Am J Transplant 2008; 8. Chkhotua AB, Klein T, Shabtai E, et al. 8:1237-1249. Kidney transplantation from living-unre- 18. Gruessner RW, Sutherland DE, Gruess- lated donors: Comparison of outcome ner AC. Mortality assessment for pan- with living-related and cadaveric trans- creas transplants. Am J Transplant 2004; plants under current immunosuppres- 4:2018-2026. sive protocols. Urology 2003;62:1002- 19. Shapiro AMJ, Lakey JR, Ryan EA, et al. 1006. Islet transplantation in seven patients 9. Henderson AJZ, Landolt MA, McDonald with type 1 diabetes mellitus using a glu- MF, et al. The living anonymous kidney cocorticoid-free immunosuppressive donor: Lunatic or saint? Am J Transplant regimen. N Engl J Med 2000;343:230- 2003;3:203-213. 238. 10. Schold JD, Meier-Kriesche HU. Which 20. Robertson RP, Davis C, Larsen J, et al. renal transplant candidates should Pancreas and islet transplantation in type accept marginal kidneys in exchange for 1 diabetes. Diabetes Care 2006;29:935. a shorter waiting time on dialysis? Clin J 21. Bromberg JS, Kaplan B, Halloran PF, et al. Am Soc Nephrol 2006;1:532-538. The islet transplant experiment: Time for 11. Merion RM, Ashby VB, Wolfe RA, et al. a reassessment. Am J Transplant 2007; Deceased-donor characteristics and the 7:2217-2218. survival benefit of kidney transplantation. 22. Merani S, Toso C, Emamaullee J, et al. JAMA 2005;294:2726-2733. Optimal implantation site for pancreatic 12. Wolfe R, McCullough K, Schaubel D, et islet transplantation. Br J Surgery 2008; al. Calculating life years from transplant 95:1449-1461. (LYFT): Methods for kidney and kidney- 23. Warnock GL, Thompson DM, Meloche pancreas candidates. Am J Transplant RM, et al. A multiyear analysis of islet 2008;8:987-1011. transplantation compared with intensive 13. McCullough KP, Keith DS, Meyer KH, et medical therapy on progression of com- al. Kidney and pancreas transplantation plications in type 1 diabetes. Transplan- in the United States, 1998-2007: Access tation 2008;86:1762-1766. for patients with diabetes and end-stage 24. Fiorina P, Shapiro AM, Ricordi C, et al. renal disease. Am J Transplant 2009;9: The clinical impact of islet transplanta- 894-906. tion. Am J Transplant 2008;8:1990-1997. 14. Ojo AO, Meier-Kriesche HU, Hanson JA, 25. Froud T, Faradji RN, Pileggi A, et al. The et al. The impact of simultaneous pan- use of exenatide in islet transplant recip- creas-kidney transplantation on long- ients with chronic allograft dysfunction: term patient survival. Transplantation Safety, efficacy, and metabolic effects. 2001;71:82-90. Transplantation 2008;86:36-45. 15. White SA, Shaw JA, Sutherland DE. Pan- 26. Fung M, Thompson DM, Shapiro RJ, et 196 BC MEDICAL JOURNAL VOL. 52 NO. 4, MAY 2010 www.bcmj.org

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