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At the University of Cologne Hospital, 1062 kidney transplants in adults and 136 pediatric transplants were performed between 1990 and 2014. Immunosuppressive therapy was changed during this time period from a therapy with anti-lymphocyte globulin induction followed by a triple therapy to a period using induction (IL2 receptor antagonists) followed by low dose tacrolimus, mycophenolate mofetil and steroids. Antiviral therapy has been constant during the 25 years, consisting of ganciclovir or valganciclovir. Major change occurred in the age of donors and recipients, with more than a third of both now being older than 65 years. Living donation has increased in number and proportion, at the same time the number of deceased donors rapidly declined. Longer time periods on dialysis resulted not only in an increased risk profile of the recipients, but were also accompanied by a significantly higher number of mismatches for the allocated kidney, since the relative importance of waiting time in the allocation process increased. Multivariate analysis showed that immunological factors such as HLA-match and panel reactive antibody are relevant factors, even in a single center analysis.

Improved virtual crossmatch assessments following the implementation of solid phase HLA antibody immunoassays has significantly impacted transplantation of sensitized candidates, using either deceased or living donor organs. In deceased donor transplants, the virtual crossmatch has reduced the number of unexpected positive crossmatch tests resulting in improved organ allocation and reduced ischemia and wait times. The virtual crossmatch has also improved access to living donor transplantation by expediting donor evaluation by impacting clinical decisions regarding desensitization, and through implementation of successful kidney paired donation programs. However, continued improvements in predicting actual crossmatch outcomes are needed to further improve access to transplantation for sensitized candidates. Improved accuracy in HLA antibody strength assessments will allow for better correlations between transplant centers and the opportunity for collaborative trials to analyze transplant strategies and outcomes.

In 1980, when there was approximately a one-year wait for a standard criteria donor kidney (young trauma victim), there was little rationale for considering incentives for donation. Today, however, in the United States, there are over 100,000 candidates on the waiting list for a deceased donor kidney transplant. Yet, in spite of numerous attempts to increase the donation rate, there has not been an increase in the last seven years. As a result, the waiting list and the resultant waiting time continue to grow, leading to an increased number of deaths (or removals from the list because of development of comorbidity) while waiting. A number of concerns have been raised about incentives. However, the real question is that - on balance - do these concerns justify continuing a ban on incentives (and the resultant thousands of deaths per year) or should we develop trials of incentives to determine whether or not incentives increase donation while simultaneously not increasing short- and long-term donor or recipient risks over those seen with today's conventional donation?

Northwestern Memorial Hospital (NMH) has developed a single-center kidney paired donation (KPD) program that has resulted in 74 living donor kidney transplants in the 22 months since its inception. The NMH KPD program has increased access to transplantation among patients who are highly sensitized and has limited the amount of desensitization therapy used for incompatible recipients. Additionally, the incorporation of compatible pairs and non-directed donors into the KPD has allowed hard to match patients on the deceased donor waiting list the opportunity to receive living donor transplants. The number of donor-recipient pairs in the KPD pool has never exceeded forty and average time to transplant from entry into the KPD database until transplantation is less than four months. This demonstrates the capability of KPD to benefit challenging recipients and increase access to living donor transplantation in a timely manner. A multi-disciplinary approach is used to manage, review, and maintain the KPD database and resulting transplants.

Liver transplantation has been an accepted treatment for end-stage liver disease since the 1980s. The development of living donor liver transplantation (LDLT) was driven by limited deceased donor organ donation and a response to the growing demand for the option of liver replacement. LDLT is now performed with high rates of success due to judicious donor and recipient selection, careful preoperative planning, excellent anesthesia management, and prompt detection and treatment of complications. The first successful liver transplantation in Asia was performed in 1984, in Chang Gung Memorial Hospital in a Taiwanese adolescent with Wilson's disease, complicated by end-stage liver cirrhosis. The longest Asian liver transplant survivor has now been living for 26 years and that patient's transplant was also performed in Chang Gung Memorial Hospital. Through December 31, 2011, a total of 924 (783 living donor, 141 deceased donor) liver transplants have been performed at the Kaohsiung Chang Gung Memorial Hospital, where both graft and patient survivals are excellent. For biliary atresia, hepatitis B virus cirrhosis, and hepatocellular carcinoma recipients, our 5-year LDLT survival rates are 98%, 94%, and 90%, respectively. Our overall (deceased and living donor) actuarial 3-year survival rate is 91%. Innovative techniques in LDLT represent technical refinements in hepatic vein, portal vein, hepatic artery, and biliary reconstruction approaches. Hepatic vein reconstruction is highlighted by venoplasty reconstructions in both graft hepatic vein orifices and recipient hepatic veins, to ensure adequate outflow and decrease ischemia times during implantation. Vascular interposition to reconstruct middle hepatic vein tributaries with either fresh or cryopreserved vessels is used when the middle hepatic vein is not routinely harvested with the graft. We have extended the routine use of microsurgical techniques, initially for hepatic artery reconstruction, to biliary reconstruction where the possibility of duct-to-duct reconstruction is performed with accuracy and precision in pediatric non-biliary atresia and in multiple, small bile ducts. Long-term survival has always been related to the immunosuppression regimen, which influences outcome. Newer drugs do not equate to lesser complications. Rather, improvement in how we can find new uses for old drugs is now the norm. Less immunosuppression, as long as hepatic function is maintained at an acceptable level, decreases the chances of long-term complications related to immunosuppression use.

Since renal transplantation is the definitive therapy for most patients with end stage renal disease, we have the challenge of meeting the needs of this rapidly growing population. Currently greater than 1000 patients are waiting for kidney transplantation at the University of Michigan. To meet this demand we have aggressively expanded the donor pool from both deceased and living donors. The focus of this update has been the evolving living donor program at the University of Michigan. In light of the rising rates of obesity in America, we have developed a specialized evaluation to assess potential obese donors. Individuals with a history of hypertension and no other risk factors for kidney failure are screened according to a protocol seeking to identify patients with a low risk of developing chronic kidney disease. We have developed unique approaches to patients with anatomic anomalies as well as nephrolithiasis. Despite all of these progressive approaches, our living donor outcomes at the University of Michigan have remained excellent and we have continued to provide a high standard of care for our recipients suffering from end stage renal disease.

As with other programs across the country, at the University of Pittsburgh liver transplantation continues to evolve after three decades. The shortage of organs represents the biggest problem in the field, and in response there has been an increase in the number of expanded-criteria-donor transplants and other methods to expand the donor pool such as live-donor, domino, and split-liver transplants. As the program has matured, we have seen an increasing number of recipients needing re-transplantation because--unlike with kidney transplants--recurrence of disease represents a significantly greater problem than immunologic graft failure. Modern immunosuppression, especially with agents such as tacrolimus, have significantly reduced the immunologic problems associated with liver transplantation. But as survival rates have improved and patients are living longer after transplant, the problems associated with long-term immunosuppression have become increasingly important. Our program, along with others, continues to look at methods to minimize the overall amount of long-term immunosuppression to which patients are exposed.

The first case of kidney transplantation at our institution was carried out in 1971, and this first renal transplant recipient is still living with a functioning kidney. From 1971 through the end of 2011, more than 3000 cases of kidney transplantation have been carried out at our institution. Since 1983, cyclosporine-based immunosuppression has been employed at our center. During this period, most of the patients were treated with cyclosporine- or tacrolimus-based immunosuppression. The latest outcomes of kidney transplantation seem to have significantly improved compared to earlier periods. Since 2000, 10 year-graft survival is more than 90% in living donor kidney transplantation and 82% in deceased donor kidney transplantation. To resolve the serious problem of donor organ shortage, expansion of the donor pool by various options such as transplantation using extended criteria donation, donation after cardiac death, ABO-incompatible (ABO-ILKT) donors, or crossmatch-positive donors, has been carried out at our institution over the last decade. We performed the first case of ABO-ILKT in 1989, and have performed more than 400 cases at our institution as of 2011. We will describe our experience of kidney transplantation, including ABO-ILKT, sensitized recipients, pathological analysis, pediatric renal transplantation, laparoscopic donor nephrectomy, and recurrent glomerulonephritis. The data shows good outcomes, however, we still have many issues to resolve to improve long-term renal transplant outcome and to reduce complications.

Living donor kidney exchange, also referred to as kidney paired donation (KPD), is a relatively new transplant modality that is growing by leaps and bounds in the U.S. From its first realization as an exchange of kidneys between two incompatible donor/recipient pairs, KPD has expanded to include compatible pairs, nondirected donors, three-way and larger exchanges, and living/deceased donor exchanges. Innovations both clinical (transporting organs instead of donors, and improved HLA screening) and mathematical (simulation to test policies, optimization to find better and more matches) have made this modality even more useful and accessible. There are several independent multi-center paired donation registries and many more single-center registries operating in the U.S., but incompatible pairs are most likely to match when they participate in the largest possible paired exchange pool; a single, unified KPD program in the United States would likely best serve patients in search of matches.

This study began with the 2010 UNOS data-set of 181,653 deceased donor kidney transplant cases and 92,577 living donor cases. Cases with ambiguous or missing HLA typing were excluded, and the remaining cases were split into subgroups by the number of previous transplants and ethnic groups of donor-patient pairs. 41,128 Caucasian donor-patient pairs that were primary living-donor transplant cases were used as the pilot population to identify potential epitope groups that have a negative effect on graft outcome. Sixty four of the most common HLA-A and -B antigens were selected. Amino acid sequences of the most frequently corresponding allele in the Caucasian population were used to build the starting theoretical epitope table. Amino acids of the 115 polymorphic positions, analyzed in one, two or three positions, resulted in 15,801,920 combinations. After eliminating combinations shared by no allele or by all 64 alleles, the table was trimmed to 1,635,044. Grouping combinations according to their antigen list (antigens that share the combinations/epitopes), 40,830 epitope groups were left. Based on the distances between amino acid positions of each epitope, and the requirement that each epitope must be shared by at least one allele, but not all 64, the number of theoretical epitopes was reduced to 39,670 and 3,703 epitope groups of unique antigen lists. The pilot population was composed of 41,128 primary living-donor transplants with Caucasian donor-patient pairs. For each of the 40,830 epitope groups in the non-distance-restricted table, 15-year death-censored graft survival was computed for epitope-group mismatches--i.e., cases with a BMQ0001 mismatch, with a BMQ0002 mismatch, etc.. Results were compared, using the log rank test, with average graft survival. Of the 3,703 epitope groups, 2,487 appeared in over 1000 cases, but only 88 of them had significant p-values, which ranged from 0.006 to 0.049, with 76 of the 88 significantly below average, 12 above average (Fig. 1). We then ran survival analyses taking the 76 epitope groups that were below average two at a time--i.e., cases with mismatches of the first and second epitope group, the first and third, first and fourth, etc. Of more than 2,500 pairs, 148 resulted in significantly (p < 0.01) lower than average survival in those primary living-donor cases. The effect of the 76 epitope-group mismatches that showed below-average results was then analyzed for other transplant populations--Caucasian donor-patient pair cases with deceased donors , Caucasian donor-patient pair cases with re-transplant living donors, Caucasian donor-patient pair cases with re-transplant deceased donors, and African-American donor-patient pair cases with primary living donors. None of these four populations exhibited any significant effect due to the 76 epitope- group mismatches. Likewise, the effect of the 148 epitope-group combination mismatches detailed in paragraph 5, above, was analyzed for the other four other transplant populations, detailed in paragraph 6. That significant effect was absent in all four. The analyses were repeated on the 40,830 epitope groups without the 27 angstrom distance constraint. Of the 40,830 epitope groups, 439 exhibited a significantly lower 15-year graft survival, with p-value ranging from 0.0053 to 0.0498. Again, none of these had any negatively significant effects on graft survival for the other four transplant populations. In the pilot population, the negative effect of the epitope group mismatches was clearly seen, but the significant differences did not carry across to the other four populations. That absence may be partially explained by the allele level differences in the HLA-A and -B typing of the donors and patients. Past studies indicate that the appearance of DSA has a negative effect on the graft outcome, so the mismatch of epitopes recognized by these DSA could also have similar negative effects. With the data available at present, and with the currently available assays for antibody detection, we are not able to analyze the impact of specific epitope mismatches. We will need the development of new methods of antibody detection that specifically indicate the exact epitope to which an antibody binds before we can continue this effort to determine the negative impact on graft survival due to epitope mismatches.

Objective: We analyzed a single center's experience during 16 years of living-donor liver transplantation (LDLT). The impacts of HLA mismatches and positive crossmatches on long term outcomes and tolerance were evaluated., Methods: This study was of primary LDLTs of consecutive patients from January 1996 to December 2011; re-transplants were not included. Long-term survival was compared by primary disease, number of HLA mismatches, and crossmatches. Demographics and complications after transplantation between pediatric recipients who achieved clinical operational tolerance and those who did not were compared., Results: One-year liver graft survival rates for adult and pediatric cases were 90.4% and 91.9%, respectively; the 5-year rates were 83.1% and 89.2%, respectively; the 10-year rates were 79.7% and 89.2%, respectively; and 15-year rates were 65.9% and 83.8%, respectively. For the grafts that survived more than one year, the 10-year rates for adult and pediatric cases were 88.2% and 97.0%, respectively. The 10-year rates for adult LDLT in 0 mismatches, 1-2 mismatches, 3-4 mismatches, and 5-6 mismatches were 79.2%, 86.8%, 77.4%, and 69.4%, respectively. Although the survival rates were not significantly different, the survival rates were lowest in LDLT recipients with 5-6 HLA mismatches. Ten-year liver graft survival rates for adult LDLT with negative T-cell crossmatch, and positive T-cell crossmatch were 80.0% and 71.1%, respectively. The 1-year liver graft survival rates for adult LDLT with negative B-cell crossmatch, and positive B-cell crossmatch were 90.6% and 88.2%, respectively. None of the factors--age of recipients and donors, primary disease, donor gender, relationship of donors to recipients, positive crossmatches, or number of HLA mismatches--was significantly different between COT and non-COT recipients, except for recipient gender (p = 0.01); in COT cases, there were more female recipients (88.9%) than male (11.1%). Post-transplant complications--acute rejection rate in one year post-transplant, biliary complications rate, and vascular complication rate--were not significantly different between COT and non-COT recipients., Conclusions: High long-term survival was achieved by both adult and pediatric recipients. Even higher survival can be achieved by improving early graft loss. Further studies are necessary to determine the impact of HLA mismatches and positive crossmatches on long-term outcomes and tolerance.

It is possible to achieve better results after liver transplantation in adult and pediatric patients. An approach driven by multidisciplinary protocol is the most important factor, along with excellent communication skills, technical expertise, application of new technologies such as MARS and Arctic-Sun for ALF, and new knowledge/treatment protocols such as escalating-dose interferon ribavirin treatment, protocol biopsies, routine use of IL28B gene mutation and new protease inhibitors as part of antiviral therapy for hepatitis C.

In January 2004, the Dutch transplant centers agreed on a protocol for a national Living Donor Kidney Exchange Program for ABO blood type incompatible and positive cross match donor-recipient pairs. Here, we report the results of that program. All transplants performed within the Living Donor Kidney Exchange Program between January 2004 and December 2011 were analysed. We collected demographic data of recipients and donors. Univariate and multivariate Cox proportional hazard analyses were performed, including recipient age, donor age, and reason for participation in the exchange program. We studied overall uncensored survival and graft survival censored for death in both ABO blood type incompatible and positive cross match groups. We enrolled 472 donor-recipient combinations, consisting of 269 ABO blood type incompatible pairs and 203 positive cross match pairs. In the end, we performed 187 kidney transplants (40% of those enrolled) with 83 ABO blood type incompatible and 104 positive cross match pairs. Most of the transplanted recipients (119/187, 64%) had an age difference of less than 5 years with their original incompatible donors. The age differences with their actual donors varied widely, but the number of recipients with a donor > 5 years older was comparable to the number of recipients with a donor > 5 years younger. In the multivariate Cox analysis, age as a continuous variable was found to have a significant influence on graft failure. Nevertheless, the 5-year uncensored survival (85%) and the graft survival censored for death (89%) were excellent and comparable to the results of direct living donation. No differences were found between the ABO incompatible and the positive cross match groups. The Dutch Living Donor Kidney Exchange Program has a high transplant rate of 40%, with excellent 5 year graft survival.

The liver transplant program at the transplant center of Tianjin First Center Hospital opened in 1994 and has become a leading center for academic research and development in clinical liver transplantation during the past 18 years. As of Nov 30, 2011, we had performed 4,103 liver transplantations in patients ranging from 6 months to 79 years old. Since 1998, the program has ranked first in mainland China in the annual number of liver transplants performed, the cumulative total liver transplants and the number of long-surviving patients. We've accomplished a number of "firsts" among the Chinese liver transplant centers, including: the first split liver transplantation, the first pediatric liver transplant, the first living donor simultaneous liver-kidney transplant, the first dual-graft liver transplant using a domino right lobe and a living donor left lobe, the first laparoscopic assisted live donor right hepatectomy including the middle hepatic vein and we have assembled the first liver transplant chain comprising multiple donors and recipients. We have performed the largest number of living related and split liver transplantations in mainland China. The combined prophylactic protocol of "Lamivudine and HBIG" to prevent HBV recurrence post transplantation was first used by our center in China and now is utilized by most of the domestic transplant centers. We have begun using livers from donors after cardiac death (DCD) during the past 2 years, with careful donor selection and recipient management. All the approaches and techniques we've developed are aimed at the utilization of all types of available grafts. However, increasing the rate of transplantation with excellent graft and recipient survival are still the challenges facing us.

There continues to be an increasing disparity between organ supply and demand in kidney transplantation with over 87,000 patients currently on the waiting list. Prolonged waiting times on dialysis is associated with significant morbidity and mortality rates. At Columbia University Medical Center/New York-Presbyterian Hospital we have implemented several strategies to improve access to transplantation. Here we present these key steps that have resulted in a significant reduction in our median waiting times and successfully increased the rate of transplantation at our center.

Methodist Specialty and Transplant Hospital has performed a total of 125 KPD transplants from the onset of the program in Dec. 2007. With the addition of the KPD program, live donor transplants have increased annually by 35% demonstrating the ability to substantially increase access to transplantation utilizing this modality. Furthermore, KPD combined with selective desensitization has provided a means for individualized assessment and management of the highly sensitized patient.

With 37-years of experience, a total of 801 kidney transplantations (59.4% were deceased donors and 40.6% were living donors) performed at Siriraj hospital were reported. The point system parallel to OPTN/UNOS for waitlists was utilized. Most of the recipients of deceased donor kidney transplantations had 3 HLA mismatches. Due to the point allocation system, none of them had 6 HLA mismatches. Extended criteria donor comprised 7.8% of all deceased donors. Mean duration of dialysis prior to deceased donor transplant was 53 +/- 34 months. Delayed graft function (DGF) was found in 54% of deceased donor kidney transplantation and resulted in significantly higher rate of 1 year biopsy-proven acute rejection, longer duration of kidney transplant admission, higher admission cost and lower patient survival compared to those with immediate graft function. Most of living donor kidney transplant recipient had 1 haplotype match. Mean donor age was 35.9 +/- 9.8 years. 95.6% of the recipients were on hemodialysis prior to transplantation. The current standard regimen includes calcineurin inhibitor, Mycophenolic acid and prednisolone. Interleukin-2 receptor monoclonal antibody has been used in the high immunological risk or high risk for DGF recipients that were 50% of the recipients. There was no statistically significant difference in the biopsy-proven acute rejection (BPAR) free survival between deceased and living donor transplantation. Proportion of cases with the diagnosis of acute rejection according to Banff 2007 classification is as follows: 32.4% acute cellular rejection (ACR), 39.4% antibody-mediated rejection (AMR) and 21.1% mixed cellular and antibody-mediated rejection. Seventy two patients, 35 deceased donor and 37 living donor kidney transplant recipients, had biopsy-proven glomerular disease after transplantation which IgA nephropathy is the most common form of glomerulonephritis. Median graft survival was 7.6 and 13.2 years and median patient survival was 12.1 and 15.5 years for recipient of deceased and living donor transplant respectively. The follow up program of living donors was introduced in 2003 and there were not any donors who required renal replacement therapy.

Since its establishment in 2008, the National Kidney Registry has facilitated 213 kidney transplants between unrelated living donors and recipients at 28 transplant centers. Rapid innovations in matching strategies, advanced computer technologies, good communication and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 91% as a result of changes to the HLA typing requirements for potential donors and improved mechanisms to list unacceptable HLA antigens for sensitized patients. A uniform financial agreement among participating centers eliminated a major roadblock to facilitate unbalanced donor kidney exchanges among centers. The NKR transplanted 64% of the patients registered since 2008 and the average waiting time for those transplanted in 2010 was 11 months.

In summary, the analysis of more than 270,000 kidney transplants recipients who were transplanted between January 1988 and August 2010 showed the following important points: Despite enormous progress in short-term graft survival in the last decades, long-term graft survival remained largely unchanged over the period from 1988 to 2010. The marked decline in acute rejection episodes in the early transplantation period mainly contributed to the improvement of shortterm graft survival. The immunosuppressive agents that were introduced in the past 3 decades have not improved long-term graft survival. Therefore, new treatment approaches are strongly required to prevent and treat chronic allograft injury especially caused by immunologic factors. Avoiding and controlling risk factors that are responsible for cardiovascular diseases are the sine qua non for increased long-term graft survival.

The annual number of liver transplants increased from 1,678 in 1988 to 6,139 in 2006 and appeared to decline slightly in 2007. Living donor (LD) liver transplants (most from biologically unrelated donors) increased from less than 100 each year prior to 1999 to 522 in 2001 and have slowly declined since. In 2007, 265 LD liver transplants were performed. Most of the increased activity in liver transplantation has been in the adult population. About 500 pediatric liver transplants are performed each year and the number has remained roughly constant since 1990. Pediatric LD liver recipients were significantly younger than deceased donor (DD) liver recipients. Unadjusted graft and patient survival rates were 61% and 71% at 7 years, respectively, for 2,375 LD recipients and 58% and 66%, respectively, for 71,686 DD recipients during 1988-2007. Five-year graft survival rates improved by 9% comparing transplants done in 1988-1993 to those done in 2002-2004. Adult female patients and recipients of a male donor graft had better survival rates, whereas recipient and donor gender in the pediatric age group showed no significant association with survival rates. Implementation of the MELD/PELD scoring system resulted in more patients with severe liver failure receiving DD grafts. Nevertheless, recipients transplanted from 2002 onwards showed improved graft survival. Comparing patients with different levels of MELD/PELD scores however, showed that the cohort with the highest score (> 30) had the worst survival, suggesting that improved survival rates since 2002 would be more likely attributed to the great progress in medical science.

This study indicates that intentional portal pressure control under 20 mmHg can improve patient survival not only for recipients of small-for-size grafts but also in classically appropriately sized grafts undergoing A-LDLT. In a retrospective analysis of 100 transplants with intentional portal pressure control, we found that patient survival was significantly better at an even lower final portal pressure of 15 mmHg. As a result, we have adjusted our target portal pressure control protocol, targeting a final portal pressure below 15 mmHg. Portal pressure control allows living donors to donate the smaller left lobe in many cases, which is safer in terms of living donors' post-operative morbidity. As intentional portal pressure control can overcome size-mismatching between the donor and recipient, we propose that it may also be applied to deceased donor liver grafts and in the split-liver transplant setting when the graft size is considered small for the recipient. Intentional portal pressure control can be applied in many liver transplantation situations to overcome small-for-size problems.

The shortage of deceased donor kidneys for transplantation has resulted in the expansion of living donation programs. A number of possibilities have been explored, since it became clear that donors do not need to be genetically related to their recipients. Apart from classical direct donation, other options such as paired exchange, list exchange, altruistic donation and domino paired exchange programs have been implemented. In the Netherlands, patients who cannot be transplanted with their potential living donor because of ABO blood group incompatibility or a positive crossmatch, have the option to participate in a national paired kidney exchange program. The practical issues related to this program are described. The 5-years experience with the Dutch kidney exchange program is very positive as, so far, 42% of the recipients included have been transplanted. Recommendations are given for a successful implementation of a common kidney exchange program of different transplantation centers focusing on the advantage of a central histocompatibility laboratory.

There are many changes happening in donation and transplantation in the UK and this review provides a baseline against which the success of future developments can be assessed. There has been a decrease in donation after brain death over the 10-year review period, but increases in both donation after cardiac death and living kidney donation. Antibody incompatible transplantation and paired and altruistic donation programmes are starting to have an impact on the number of living donor transplants carried out and are expected to make a more marked impact in the years ahead. A new national Kidney Allocation Scheme for deceased donors after brain death was introduced in 2006 to replace the previous scheme implemented in 1998. The 2006 scheme aims to improve equity of access to transplant and is showing significant benefits for long-waiting patients. To ensure that all UK transplant centres continue to achieve high standards, both within- and across-centre monitoring of graft and patient outcomes is routinely undertaken and reported. The most important factor in increasing organ donation and transplantation in the UK is the government funding that has been provided to develop national organ donation infrastructures. These major changes are expected to have a significant impact on numbers of donors and transplants in the next 5 years.

This chapter summarizes data on 159,119 deceased donor (DD) and 83,471 living donor (LD) kidney transplants reported to the OPTN/ UNOS registry during the 20-year period between 1988 and 2007. The 15-year graft survival rates for transplants performed during 1991-1995 were 25% for 32,327 DD and 40% for 13,992 LD recipients. Graft survival rates improved modestly (4% for DD and 2% for LD) transplants performed during 1996-2005. Graft half-lives rose from 8 to 10 years for DD and from 12 to 18 years for LD transplant recipients during the study period. The number of DD kidney recipients over age 50 increased from 1,620 in 1988 to 4,492 in 2007 with no corresponding increase in the number of younger transplants. Annual LD kidney transplants increased from 1,816 in 1988 to 6,273 in 2004, but the rapid growth in LD transplants leveled off in 2001-2002 and may be falling in more recent years. The growth and slowdown of LD transplants occurred at different times for different groups of LD according to their relationship to the patient. Parent donor transplants have not increased substantially, whereas offspring-to-parent graft, spouse and sibling transplants increased rapidly in the early to mid-1990's donors and leveled off in 2001-2002. Other unrelated LD transplants began to rise in 1995 and continued to increase until 2005. Parent-to-child transplants have declined 33% since the new UNOS prioritization of pediatric recipients for young adult DD kidneys in 2005. The difference in 10-year DD kidney survival between the best and worst HLA-matched combinations was 10%, with halflives ranging from 11.6 years to 8.6 years. Nearly one-third of DD transplants performed during 1996-2005 were completely HLA mismatched (5-6 HLA-A,B,DR mismatches) compared with 15% of transplants with no HLA antigens mismatched. About 11% of LD transplants were HLA-matched (most HLA-identical siblings) and 10-year graft survival was 74% compared with 58% for HLA mismatched transplants. There was no survival difference associated with increasing HLA mismatches among LD kidney recipients. The graft half-lives were 27 years for HLA-matched and 15 years for HLA-mismatched LD transplants The increasing use of newer solid-phase tests for HLA-antibodies appears to have inflated recent PRA estimates for sensitized patients as suggested by the increasing percentage of highly sensitized (80+% PRA) patients transplanted since 2003 (from 25 to 40% of retransplanted patients). Three-year graft survival rates for broadly sensitized recipients during 2004-2007 was 77% (vs 79% for less sensitized) compared with 74% (vs 80% for less sensitized) during 1999-2003, which was more similar to the less sensitized patients in either period. There was considerable variability among centers in the percentage of broadly sensitized patients that were transplanted during each period, but most centers reported transplanting more sensitized patients between 2004-2007. Cold ischemia times (CIT) for DD kidney transplants have been reduced over the past 20 years from an average of 24 hours during 1988-1992 to 18 hours in 2003-2007. Despite this reduction in CIT, the incidence of delayed graft function has remained at 25% each year since 1990. The effect of prolonged CIT (> 30 hours) on graft survival was a 1% reduction over 10 years for DD kidneys under age 35 and a 4% reduction for DD kidneys over age 55 compared with the graft survival results for DD kidneys in either age group transplanted within 18 hours.

Liver transplantation remains the only definitive therapy for patients with decompensated liver disease. Significant advances over the past 20 years in surgical technique, immunosuppressive agents, patient selection, and infection prophylaxis and treatment have led to improved patient and graft survival. The success of liver transplantation coupled with expanding indications has resulted in a marked shortage of donor organs. Our approach at the University of Wisconsin to address the shortage of liver allografts is to maximize organ donation and recovery, include the use of liver allografts from donation after cardiac death, the use of split liver transplant, and the use of living-donor liver transplant when necessary. Split-liver transplantation is an effective technique to expand the number of organs available for transplantation. Continued improvements in organ preservation remain a priority to maximize outcomes, especially when the use of marginal donors or split-liver transplantation is planned. Recipient selection criteria have been expanded to include older recipients as well as previous recipients of multiple allografts. Over time it has become clear that less intensive immunosuppression is required since many patients can be maintained on tacrolimus monotherapy. We remain committed to a continued evaluation of donor and recipient factors in order to maximize outcomes of liver transplantation, as well as a critical appraisal of current and newer immunosuppressive agents and their effects on long-term outcome and recurrent disease.

The worldwide search for unrelated stem cell donors (now over 6 million) is one of the great success stories of international cooperation in the medical field. The initial search report from Bone Marrow Donors Worldwide estimates the chance of finding a suitably matched donor for a given patient. Registries whose donors are HLA-A, -B and -DR typed present the optimal prerequisite to identify a suitable donor for most patients. High-resolution matching HLA class I and class II alleles of the donor and recipient improves clinical outcome after unrelated donor transplantation. The clinical results of unrelated donor bone marrow transplantation are continually improving reflecting improvements in HLA matching, GvHD prophylaxis and transplantation in a favourable phase of disease. However, matching each HLA allele may or may not be critical for successful stem cell transplantation. Some degree of HLA mismatch ("permissible" mismatches) may be tolerated, especially in children. Cord blood banks provide a supplementary source of unrelated stem cell donors, in particular to patients from ethnic minority groups.

Aside from HLA identical sibling donors, spousal donor transplants are the best living donors because their 3-year graft survival is comparable to that of all other living donors--with the exception of HLA identical siblings. Interestingly, the 14.5 year half-life of spousal donor kidneys was superior to the 10.8 year half-life of other living donor transplants. Better quality kidneys is the principal explanation for higher spousal donor graft survival rates when compared with cadaver donors. This was evident from the 2% anuria rate in the first post-operative day for spouse donor compared with 10% of cadaver donor transplants. Moreover, the requirement for dialysis was 6% for spouse donor grafts compared with 22% of cadaver donor transplants. The damage is not attributable to cold ischemia time but rather to agonal events and shock prior to kidney harvesting. In a survey of 176 spousal renal transplant donors, 175 of 176 said they would advise others to donate a kidney to a spouse--and only one donor advised against it. Of the "yes" responses, 28% provided additional comments enthusiastically recommending it. About 47% reported improvements in the marital relationship, 29% in the sexual relationship, and 25% described improved relations with their children. The fact that the donor reaps many direct personal benefits should make spousal donation the first consideration for living-donation (after the HLA-identical sibling donor).