Actual Graft Survival Rates Research Articles

Renal Transplantation With Final Allocation Based onthe Virtual Crossmatch.

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1year (AR<1year) for FCXM+ (n=54) and FCXM- (n=454) recipients. Median follow-up is 7.1years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p=0.03), duration of dialysis (31.0months vs. 13.5months, p=0.008), retransplants (17% vs. 7.3%, p=0.04), % sensitized (63% vs. 19%, p=0.001), and PRA>80% (20% vs. 4.8%, p=0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR<1year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility.

Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Type 1 Receptor Antagonist Therapy Is Associated with Prolonged Patient and Graft Survival after Renal Transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.

Pediatric Transplantation: The Hamburg Experience

Since starting our program in 1989, 455 pediatric orthotopic liver transplantations have been performed using all techniques. In April 2001, we experienced our last in-hospital death of a pediatric liver-transplant recipient. Since then, all our liver-transplant children (n=170) were able to be discharged from the hospital. The aim of this study is to analyze the actual status of pediatric liver transplantation at the University of Hamburg and to find future perspectives to improve the results after pediatric liver transplantation. From May 4, 2001 until September 8, 2004, 22 (13%) whole organs, 18 (11%) reduced-size organs, 79 (47%) split organs, and 51 (30%) organs from living donors were transplanted into 142 patients. One hundred forty-one were primary liver transplants, 25 retransplants, 3 third, and 1 fourth liver transplants. Of the 170 orthotopic liver transplantations (OLT), 31 (18%) were highly urgent (United Network of Organ Sharing [UNOS] I). After 170 consecutive pediatric liver transplants, no patients died during the hospital course (100% patient survival<3 months), but overall, 5 (2.9%) recipients died during further follow-up. The 3-month and actual graft survival rates are 93% and 85%, respectively. Twenty (11.8%) children had to undergo retransplantation. However, patient survival was not sustained by longer graft survival. Analyzing our series, we see that graft survival after reduced-size liver transplantation showed a significantly lower rate versus living-donor liver transplantation. The learning curve in pediatric liver transplantation has reached a turning point where immediate patient survival is considered the rule. The challenge is to increase graft survival to the same level. The long-term management of the transplant patients, with the aim of avoiding late graft loss and achieving excellent quality of life, will become the center of the debate.

One Hundred Thirty-Two Consecutive Pediatric Liver Transplants Without Hospital Mortality

Orthotopic liver transplantation (OLT) has become an established procedure for the treatment of pediatric patients with end-stage liver disease. Since starting our program in 1989, 422 pediatric OLTs have been performed using all techniques presently available. Analyzing our series, we have concluded that the year of transplantation is the most important prognostic factor in patient and graft survival in a multivariate analysis. From April 2001 to December 1, 2003, 18 whole organs (14%), 17 reduced-size organs (13%), 53 split organs (42%; 46 ex situ, 7 in situ), and 44 organs from living donors (33%) were transplanted into 115 patients (62 male and 53 female). One hundred twelve were primary liver transplants, 18 were retransplants, one third and one fourth liver transplants. Of the 132 OLTs, 26 were highly urgent (19.7%). The outcome of these 132 OLTs was retrospectively analyzed. Of 132 consecutive pediatric liver transplants, no patients died within the 6 months posttransplantation. Overall, 3 recipients (2%) died during further follow-up, 1 child because of severe pneumonia 13 months after transplantation and the second recipient with unknown cause 7 months postoperatively, both with good functioning grafts after uneventful transplantation. The third had a recurrence of an unknown liver disease 9 months after transplantation. The 3-month and actual graft survival rates are 92% and 86%, respectively. Sixteen children (12%) had to undergo retransplantation, the causes of which were chronic rejection (3.8%), primary nonfunction (3.8%), primary poor function (PPF; 1.5%), and arterial thrombosis (3%). The biliary complication rate was 6%; arterial complications occurred in 8.3%; intestinal perforation was observed in 3%; and in 5%, postoperative bleeding required reoperation. The portal vein complication rate was 2%. Progress during the past 15 years has enabled us to perform pediatric liver transplantation with near perfect patient survival. Advances in posttransplant care of the recipients, technical refinements, standardization of surgery and monitoring, and adequate choice of the donor organ and transplantation technique enable these results, which mark a turning point at which immediate survival after transplantation will be considered the norm. The long-term treatment of the transplanted patient, with the aim of avoiding late graft loss and achieving optimal quality of life, will become the center of debate.

Is there still a need for living-related liver transplantation in children?

To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

Strategies to expand the donor pool for pancreas transplantation.

Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.

Chronic renal allograft rejection in the first 6 months posttransplant.

Between May 1, 1986 and May 31, 1992 at the University of Minnesota, we interpreted 129 renal allograft biopsy specimens (done in 48 grafts during the first 6 months posttransplant) as showing changes consistent with chronic rejection. For this retrospective analysis, we reexamined these biopsies together with clinical information to determine: (a) whether a diagnosis other than chronic rejection would have been more appropriate, (b) how early posttransplant any chronic rejection changes occurred, and (c) if the diagnosis correlated with outcome. We found that (1) chronic rejection is uncommon in the first 6 months posttransplant; it was documented in only 27 (2.4%) of 1117 renal allografts and was preceded by acute rejection in all but 3 recipients (for these 3, the first biopsy specimen showed both acute and chronic rejection). (2) Chronic vascular rejection was seen in 1 recipient as early as 1 month posttransplant; the incidence increased over time and was associated with an actual graft survival rate of only 35%. (3) The most frequent cause of arterial intimal fibrosis in the first 6 months posttransplant was arteriosclerotic nephrosclerosis (ASNS) of donor origin. Long-term graft function for recipients with ASNS was 67%. (4) Early-onset ischemia or thrombosis was seen in 14 recipients and predicted poor outcome: only 35.7% of these recipients had long-term graft function. (5) Cyclosporine (CsA) toxicity was implicated in only 3 recipients, who had mild diffuse interstitial fibrosis in association with elevated CsA levels. Other variables (including systemic hypertension, urinary tract infection, obstructive uropathy, neurogenic bladder, cobalt therapy, and recurrent disease) were not significantly associated with chronic renal lesions in the first 6 months posttransplant. A significant number of biopsies were originally interpreted as showing chronic rejection, but the diagnosis was changed upon reevaluation in conjunction with clinical data. We conclude that many factors coexist to produce chronic lesions in biopsies during the first 6 months posttransplant, so clinical correlation is needed before establishing a diagnosis of chronic rejection.

Standardized quick en bloc technique for procurement of cadaveric liver grafts for pediatric liver transplantation.

This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine).

THE IMPACT OF AZATHIOPRINE AND CYCLOSPORINE ON LONG-TERM FUNCTION IN KIDNEY TRANSPLANTATION

To assess the impact of cyclosporine on long-term kidney function in transplant patients, we retrospectively analyzed 273 patients on azathioprine and 308 on CsA with graft functioning at 1 year. To balance the length of follow-ups, the observation of patients was cut at 5 years. Actual graft survival rate at 5 years was similar in Aza and CsA (88% vs. 90%). Multivariate analysis in Aza pts showed that proteinuria (P = 0.006) and hypertension at 1 year (P = 0.002) increased the probability of irreversible graft failure by 2.47 and 2.85, respectively. In CsA patients, proteinuria (P = 0.007) and plasma creatinine higher than 2.5 mg/dl (P = 0.006) increased the probability of graft failure by 5.12 and 6.48, respectively. In both Aza and CsA patients with a follow-up of at least 5 years, plasma creatinine levels were significantly worse at 5 years vs. 1 year (P = 0.004). The slopes of plasma creatinine values plotted vs time were not different between the two groups. Chronic graft dysfunction (CGD) was defined as a stable increase of plasma creatinine of at least 50% above stable values at 1 year. The probability of remaining without CGD at 5 years was 75% for CsA and 80% for Aza patients (P = N.S.). Multivariate analysis of factors influencing the development of CGD showed that hypertension (P = 0.003) and proteinuria at 1 year (P = 0.081) increased the probability of developing CGD by 2.19 and 1.76, respectively, in Aza, while in CsA patients proteinuria only (P = 0.063) increased the probability of developing CGD by 2.29. Graft survival at 5 years after development of CGD was 34% in Aza and 53% in CsA-treated patients. These data confirm that in the long-term CsA does not cause a higher prevalence of CGD and show that, in the presence of CGD, CsA has a superior protective effect than Aza.