Chronic rejection: the next major challenge for pancreas transplant recipients

OBJECTIVE: With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. METHODS: We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. RESULTS: A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P=0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P<0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P=0.002), cytomegalovirus infection posttransplant (RR=2.41, P=0.001), a retransplant (versus primary transplant) (RR=2.27, P=0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P=0.04). CONCLUSIONS: As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.     

Combined kidney and pancreas transplantation. A 3-year experience.

Between May 1988 and September 1991, we performed 26 simultaneous kidney and pancreas transplants and one pancreas transplant after a kidney transplant. All transplants consisted of bladder drainage via a duodenal segment. Actuarial patient, kidney, and pancreas graft survival rates at 12 months were 96%, 88%, and 85%, respectively, and at 24 months were 96%, 88%, and 81%, respectively, and were not significantly different from those of diabetic recipients of cadaver kidney transplants alone. Excellent long-term glycemic control was obtained as monitored by fasting blood glucose and glycosylated hemoglobin levels and by oral glucose tolerance tests. The mean period of hospitalization and number of hospital admissions in the first year posttransplant were significantly greater for patients who received combined kidney and pancreas transplants than for those who received cadaver kidney transplants alone. Combined kidney and pancreas transplants can be performed with patient and graft survival comparable to those of kidney transplants alone, with excellent long-term glycemic control, but result in increased morbidity in the first postoperative year.     

Pancreas after kidney transplants

BACKGROUND: For certain uremic diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive alternative to a simultaneous transplant of both organs. The purpose of this study was to compare outcomes with simultaneous pancreas-kidney (SPK) versus pancreas after kidney (PAK) transplants to determine advantages and disadvantages of the two procedures. METHODS: Between January 1, 1994, and June 30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these, 193 were SPK transplants and 205 were PAK transplants. We compared these two groups with regard to several endpoints, including patient and graft survival rates, surgical complications, acute rejection rates, waiting times, length of hospital stay, and quality of life. RESULTS: Overall, surgical complications were more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK recipients versus 15.1% for PAK recipients (P = 0.006). Leaks, intraabdominal infections, and wound infections were all significantly more common in SPK recipients (P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK recipients). Short-term pancreas graft survival rates were similar between the two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK recipients (P = not significant). By 3 years, however, pancreas graft survival differed between the two groups (74.1% for SPK and 61.7% for PAK recipients), although this did not quite reach statistical significance (P = 0.15). This difference in graft survival seemed to be due to increased immunologic losses for PAK recipients: at 3 years posttransplant, the incidence of immunologic graft loss was 16.2% for PAK versus 5.2% for SPK recipients (P = 0.01). Kidney graft survival rates were, however, better for PAK recipients. At 3 years after their kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for PAK recipients (P = 0.001). The mean waiting time to receive the pancreas transplant was 244 days for SPK and 167 days for PAK recipients (P = 0.001). CONCLUSIONS: PAK transplants are a viable option for uremic diabetics. While long-term pancreas graft results are slightly inferior to SPK transplants, the advantages of PAK transplants include the possibility of a preemptive living donor kidney transplant, better long-term kidney graft survival, significantly decreased waiting times, and decreased surgical complication rates. Use of a living donor for the kidney transplant expands the donor pool. Improvements in immunosuppressive regimens will hopefully eliminate some of the difference in long-term pancreas graft survival between SPK and PAK transplants.     

Immunologic and nonimmunologic factors: different risks for cadaver and living donor transplantation

BACKGROUND: There is a debate about the relative contribution of immunologic (rejection) and nonimmunologic (limited nephron mass) factors in long-term graft survival. METHODS: Using multivariate analysis, we studied the association of the following variables with outcome: delayed graft function (DGF), acute rejection, recipient race (black vs. nonblack), donor age (<50 vs. > or =50), donor race, and donor and recipient gender. Because of the association between DGF and rejection, recipients were grouped as follows: DGF, rejection; DGF, no rejection; no DGF, rejection; no DGF, no rejection. Data were analyzed on 1199 first kidney transplants in adults (752 living donor, 447 cadaver donor) done between January 1, 1985 and December 31, 1996. Two analyses were done: first, all transplants; second, only those with > or =1 year survival. For both, there was no difference in risk factors if death with function was or was not censored. RESULTS: For all cadaver transplant recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50. For living donor recipients, only acute rejection was a risk factor. When only 1-year graft survivors were considered, risk factors were the same: for cadaver recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50; for living donor recipients the risk factor was rejection. CONCLUSION: We found immunologic factors (rejection with or without DGF) to be significant in both living donor and cadaver donor transplants. Nonim. munologic factors (donor age, recipient race) were significant only in cadaver donor transplants.     

Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months

BACKGROUND: The aim of the present study was to assess long-term survival of cadaveric second kidney allografts performed in our center and to determine risk factors predictive of long-term graft outcome. METHODS: Of 1704 kidney transplantations performed between January 1985 and March 1998, 233 were second grafts. The majority of the recipients were sensitized. All patients were treated with the same quadruple immunosuppressive regimen. RESULTS: Kaplan-Meier analysis documented graft survival of 89% at 1 year, 76% at 5 years, and 53% at 10 years. Graft survival was similar for second and primary kidney transplants performed during the same period of time. When long-term second graft survival was examined, only two risk factors were found to be significant: (1) the degree of human leukocyte antigen (HLA) DR mismatch (MM) and (2) the number of acute rejection episodes. Multivariate analysis of several pre- and posttransplant variables also confirmed the importance of HLA MM (DR> A), but also, identified serum creatinine at 12 months as the most significant predictor of graft survival. In addition, the Cox proportional hazards model revealed that only the year of transplantation had an independent significant effect on acute rejection occurrence (RR = 0.591, 95%CI 0.437 to 0.801, P < 0.0007). Indeed, the incidence of acute rejection was found to decrease over time (44% of patients experienced at least one episode of acute rejection before 1990 vs. 17% after 1990). CONCLUSION: Finally, second graft long-term outcome shows an improved evolution according to the time period resulting from a strong decrease in acute rejection incidence and the impact of creatinine at 12 months.     

Superior results with combined kidney-pancreas transplants.

From February of 1987 to February of 1991 the authors performed 23 pancreas transplants for Type I diabetes mellitus. Eight of the pancreas transplants were in patients who had a previous kidney transplant, 14 were simultaneous kidney and pancreas transplants, and 1 was in a pre-uremic diabetic. Two patients have been retransplanted after losing first grafts. All pancreata were retrieved from heart-beating cadaver donors. Pancreata were transplanted into the iliac fossa of the recipient using the iliac artery and vein as arterial inflow and venous outflow, respectively. Drainage of the pancreatic ductal system was accomplished by anastomosing either a patch or segment of duodenum surrounding the ampulla of Vater to the urinary bladder. All pancreata functioned initially with no patient requiring insulin 6 hours after surgery. Two grafts were lost early due to thrombosis of the venous drainage of the transplant; 4 grafts were lost to acute rejection; 3 were lost to chronic rejection; and 1 patient died with a functioning pancreas. One-year graft survival for all pancreatic grafts is 62 per cent. One-year patient survival is 96 per cent. One-year pancreatic graft and patient survival for the 14 combined kidney-pancreas transplants is 88 per cent and 100 per cent, respectively. Two kidneys transplanted with pancreata also were lost to acute rejection. Pancreas transplantation has proven to be a viable treatment alternative for selected patients with Type I diabetes mellitus. Long-term results are best when pancreas transplantation is done in combination with renal transplantation.     

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.     

Simultaneous cadaver pancreas living-donor kidney transplantation: a new approach for the type 1 diabetic uremic patient

OBJECTIVE: To review the authors' experience with a new approach for type I diabetic uremic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplant (SPLK). SUMMARY BACKGROUND DATA: Simultaneous cadaver kidney and pancreas transplantation (SPK) and living-donor kidney transplantation alone followed by a solitary cadaver-donor pancreas transplant (PAK) have been the transplant options for type I diabetic uremic patients. SPK pancreas graft survival has historically exceeded that of solitary pancreas transplantation. Recent improvement in solitary pancreas transplant survival rates has narrowed the advantage seen with SPK. PAK, however, requires sequential transplant operations. In contrast to PAK and SPK, SPLK is a single operation that offers the potential benefits of living kidney donation: shorter waiting time, expansion of the organ donor pool, and improved short-term and long-term renal graft function. METHODS: Between May 1998 and September 1999, the authors performed 30 SPLK procedures, coordinating the cadaver pancreas transplant with simultaneous transplantation of a laparoscopically removed living-donor kidney. Of the 30 SPLKs, 28 (93%) were portally and enterically drained. During the same period, the authors also performed 19 primary SPK and 17 primary PAK transplants. RESULTS: One-year pancreas, kidney, and patient survival rates were 88%, 95%, and 95% for SPLK recipients. One-year pancreas graft survival rates in SPK and PAK recipients were 84% and 71%. Of 30 SPLK transplants, 29 (97%) had immediate renal graft function, whereas 79% of SPK kidneys had immediate function. Reoperative rates, early readmission to the hospital, and initial length of stay were similar between SPLK and SPK recipients. SPLK recipients had a shorter wait time for transplantation. CONCLUSIONS: Early pancreas, kidney, and patient survival rates after SPLK are similar to those for SPK. Waiting time was significantly shortened. SPLK recipients had lower rates of delayed renal graft function than SPK recipients. Combining cadaver pancreas transplantation with living-donor kidney transplantation does not harm renal graft outcome. Given the advantages of living-donor kidney transplant, SPLK should be considered for all uremic type I diabetic patients with living donors.     

Pancreas transplantation with pancreaticocystostomy and quadruple immunosuppression

Forty-three whole-pancreas transplantations with pancreaticocystostomy were performed. Eighteen patients received pancreas transplants after previously receiving living-related kidney transplants, 18 patients received simultaneous kidney and pancreas transplants, and seven patients received pancreas transplants after previously receiving cadaver kidney transplants. All patients were immunosuppressed with quadruple immunosuppression including antilymphocyte globulin, prednisone, cyclosporine, and azathioprine. Overall graft survival for pancreas transplants is 73.1%. In the group with pancreas after living-related kidney, 1-year graft survival was 50% for the pancreas and 95.4% for the kidney. In the pancreas after cadaver kidney group, pancreas and kidney survival rates were 100% at 1 year, and in the simultaneous pancreas and kidney group, pancreas 1-year graft survival was 87.5% and kidney transplant survival was 93.8%. Overall patient survival at 1-year is 95.6%. Technical complications occurred in 21 patients. These included wound infections, intra-abdominal abscess formation, bleeding, and disruption of the pancreaticocystostomy. We believe that pancreas transplantation can now be performed with acceptable graft and patient survival.     

Risk factors for slow graft function after kidney transplants: a multivariate analysis

BACKGROUND: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long-term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF). METHODS: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post-operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post-transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups. RESULTS: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel-reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post-transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5-yr death-censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF). CONCLUSIONS: SGF represents part of the spectrum of graft injury and post-transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post-transplant can have a negative impact on long-term graft survival.     

Causes of long-term graft failure in renal transplantation

Summary A single-center experience of 980 consecutive renal transplant recipients treated with cyclosporine (CyA) was reviewed to analyze the causes of renal allograft loss and the factors affecting long-term renal survival in CyA-treated kidney transplants. In all, 217 grafts were lost during the observation period, with the most common causes of graft loss being chronic rejection (96 cases, 44%), death with a functioning graft (52 cases, 24%), glomerulonephritis (28 cases, 13%), and acute rejection (20 cases, 8%). The actuarial 10-year survival of patients with living and cadaveric grafts was 93% and 91%, respectively. The actuarial 10-year survival of living and cadaveric grafts was 70% and 63%, respectively. Patients were divided into two groups, namely a graft-survival group (n=763) and a graft-loss group (n=217). There was no significant difference between the two groups in terms of sex, donor source, donor age, recipient age, duration of hemodialysis, retransplants, transfusions, presensitization, of HLA match. There was no difference between the graft-survival group and the graft-loss group in the mean CyA dose given or the mean CyA trough level measured at any time following transplantation. Acute rejection episodes occurred in patients from the graft-survival group (55%) as compared with those from the graft-loss group (83%; P<0.00001). These data suggest that long-term graft survival in CyA-treated kidney transplant patients is primarily influenced by the occurrence of rejection episodes rather than by the drug dose or the duration of CyA administration. CyA nephrotoxicity was not the major risk factor for long-term graft survival in CyA-treated renal transplants.     

Kidney Retransplantation Outcomes: A Paired Recipient Control Study

BackgroundDespite progressive improvements in graft and patient survival after kidney transplantation over the last decades, an increasing number of patients are waitlisted for retransplantation. Identifying the risk factors for second graft failure can help us improve management for such patients. The aim of this study was to compare the outcomes of kidney retransplantation with those of first transplantation.MethodsThis retrospective study included all the recipients of a second kidney transplant between January 2008 and December 2019. For each patient with a second kidney transplant, we selected the paired recipient from the same donor. We excluded recipients of donations from living donors, patient-and-donor pairs with more than 1 transplant, and patients without a pair. The follow-up took place December 31, 2020. We included 152 patients, corresponding to 76 pairs of recipients.ResultsPatients who underwent a second transplant had significantly higher panel reactive antibody values and longer waiting time for retransplantation. Biopsy-proven acute rejection episodes were doubled in patients undergoing a second transplant (P = .12). There was a lower survival of second grafts at the first, fifth, and 10th year (P < .05). The main factor influencing graft loss for both groups was acute rejection, and, in patients, with a second transplant, acute rejection increased the risk of graft loss by 17 times (odds ratio, 17.5; 95% confidence interval, 4.19-98).ConclusionsThe clinical results of second kidney transplants still fall short of first transplants, with the main factor of poor prognosis being acute rejection. In young patients, allocation and immunosuppression management should consider this risk to improve long-term outcomes.     

Risk factors on graft survival of living donor kidney transplantation

Living donors have always been the basic resources of transplantation in our country, where cadaveric harvesting is still hampered for various reasons. OBJECTIVE: The aim of this study was to compare graft survival rates between living unrelated donor (LURD) and living related donor (LRD), to assess the potential risk factors for the graft survival, and to discuss the role of LURD. METHOD: From October 1991 to February 2003, 77 living donor renal transplants were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables were donor relationship, recipient age and sex, donor age and sex, HLA-DR mismatching, nonspecific blood transfusion history of donor, acute rejection episodes, repeated rejection episode (more than 3 times), delayed graft function, recurred primary disease, and immunosuppressive regimen. Graft survival rate was assessed with the Kaplan-Meier method and the significance of possible variables with the Cox proportional hazard model. RESULTS: Eleven recipients lost their grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%, and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%, and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05). Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1) and preoperative multiple transfusion history (RR = 4.2) were significant factors on graft survival in our series. CONCLUSION: Acute rejection episodes markedly decreased the long-term graft survival in live donor renal transplants. The use of LURD transplants provides graft survival comparable with LRD transplants and proper management to acute rejection is essential for long-term graft survival.     

The use of daclizumab as induction therapy in combination with tacrolimus and mycophenolate mofetil in recipients with previous transplants

Clinical trials using daclizumab as induction therapy in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in solid organ transplantation. In an attempt to obtain a low rejection rate we proceeded with the use of daclizumab as induction therapy, in combination with TAC and MMF for recipients with previous transplants. In this study, we analyzed patients who received previous transplants, treated with the above immunosuppressive regimen. Group A consisted of four patients with previous liver transplants, group B consisted of 16 recipients with previous kidney transplants and group C consisted of three patients with previous simultaneous pancreas-kidney transplants. All patients underwent cadaveric kidney transplants except one patient in group B, who underwent a pancreas transplant. At 12 months, patient and graft survival for all groups was 100 and 100%, respectively. Acute rejection rate was 0% for group A, 12.5% for group B, and 0% for group C. Daclizumab induction therapy is effective for patients with previous transplants and does not appear to increase the risk of acute rejection.     

Long term results of living donor kidney transplantation: graft and patient survival

Donor kidney transplantation's graft and patient survivals are better than cadaver donor's. In Spain, living donor kidney transplantation hardly accounts for 1% of transplant activity in comparison to 60% in United States. Accordingly to bibliography, the experience of the Renal Transplant Unit of the Hospital Clinic de Barcelona has demonstrated better graft and receptor survival for living donor recipients. The analysis of 184 living donor kidney transplants and 1678 cadaver donor transplants performed between 1978 and 2002 showed that graft survival was higher in the group of living donors (p < 0.01). At the same time, graft survival was clearly better in receptors of HLA haploidentical grafts (n=142) (p < 0.05). The introduction of new and better immunosuppressive drugs, as well as better diagnostic and therapeutic management of acute rejection, prophylaxis for infections, and control of complications have contributed to better results. The absence of acute rejection between 1978 and 1983 was 45.1%, between 1984 and 1998 was 57.3% and 84.7% between 1999 and 2003. In conclusion, these results demonstrate better graft and patient survival for living donor kidney transplants in comparison with cadaver donor receptors. Altogether with the low risk involved for donors should incentivate authorities, professionals, and patients to promote these therapeutic option by means of adequate information and wider diffusion. Living donor kidney transplantation should contribute together with cadaver kidney transplantation to lessen our long waiting lists, because they are not excluding options.     

Increasing the donor pool using en bloc pediatric kidneys for transplant

OBJECTIVES: En bloc pediatric kidney transplants (EBPKT) are still a subject of controversy. The aim of this study was to determine whether acceptable long-term graft survival and function can be achieved in EBPKT compared with the transplant of single, cadaveric, adult donor kidneys. METHODS: A retrospective review was conducted of 66 recipients of en bloc kidneys from cadaveric pediatric donors and 434 patients who underwent transplantation with a single kidney from an adult donor between January 1990 and May 2002 at the authors' hospital. The recipients were well-matched demographically. Both transplant groups were analyzed for short- and long-term performance in terms of transplant outcome and quality of graft function. RESULTS: Overall death-censored actuarial graft survival rates at 1 and 5 years were 89.2% and 84.6% in the adult kidney transplants (AKT) and 83.3% and 81.1% in EBPKT, respectively (P=0.56). In the EBPKT group, graft function was improved over that observed in AKT. Vascular thrombosis was the most common cause of graft loss in EBPKT. Acute rejection occurred more frequently in AKT and Cox's regression analysis indicated that undergoing an AKT was a predictive factor for acute vascular rejection (adjusted risk ratio, 3.8; 95% confidence interval, 1.4-10.2; P=0.001). CONCLUSIONS: Overall graft survival was similar in both groups, vascular complications were the main cause of graft loss in EBPKT, and the EBPKT showed excellent long-term graft function and a low incidence of acute rejection.     

2,500 living donor kidney transplants: a single-center experience

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.     

Evolution of the renal function is a better predictor of long-term survival than serum creatinine

BACKGROUND: In recent years acute rejection has decreased to 10% to 20%. Therefore it is necessary to look for new endpoints in renal transplantation. Serum creatinine and changes in creatinine have been reported to be powerful predictors of long-term kidney transplant survival. Chronic renal allograft nephropathy is the primary cause of long-term graft failure but may appear at any stage in the evolution. METHODS: Data from 315 patients receiving cadaver donor renal transplants between February 1987 and March 2001 that functioned for 1 year were examined for the influence of demographic characteristics and transplant variables. Creatinine clearance was estimated using the Cockroft-Gault formula. Survival was assessed with the actuarial method. The multivariate analyses were performed using Cox proportional hazard models. RESULTS: The 10-year graft survival showed a relative risk of 2.5 in the univariate analysis when there was more than 10% decrease in renal function at 3 months compared with nadir values. When the decrease was more than 25% of creatinine clearance at the third month, during the evolution and serum creatinine at 3 months introduced in the multivariate model, the latter was not significant, while the other variables had a RR of 4.4 and 10, respectively. CONCLUSION: The evolution of renal function at 3 months and throughout the evolution were better predictors of graft failure than an isolated serum creatinine value.     

Effect of splenectomy on first cadaver kidney transplants.

A prospective study was begun in January 1975 to evaluate the effect of splenectomy on graft and patient survival in recipients of first cadaver kidney transplants. Ninety-two cases were evaluated. Splenectomy increased the survival of both grafts and recipients. The benefit from splenectomy compensated readily for the perioperative morbidity of splenectomy and the long-term increased risk of sepsis from certain bacteria for the asplenic patient. Splenectomy exerted its effect by reducing the incidence and intensity of rejection episodes. It was not clear whether the observation resulted from a direct immunosuppressive effect of splenectomy or from the increased tolerance to azathioprine observed in asplenic recipients. Finally, splenectomy negated an effect of race that had been observed earlier for survival of cadaver transplants and recipients.     

Increased immunogenicity and cause of graft loss of old donor kidneys.

Donor age was identified recently as a major factor that determines long-term outcome after transplantation, but the mechanism that is responsible for increased graft loss of old donor kidneys is unknown. The influence of donor age on graft survival was assessed retrospectively in 514 consecutive first cadaveric transplants that were treated with cyclosporine maintenance immunosuppression. Donor age > or =50 yr (relative risk [RR] = 1.7; 95% confidence interval [CI], 1.2 to 2.6), acute rejection (RR = 2.0; 95% CI, 1.3 to 3.0), and type of rejection (RR = 3.3; 95% CI, 2.0 to 5.3) had a significant impact on graft survival. However, when subsets of patients who entered subsequent intervals after transplantation were analyzed, donor age was not an independent predictive factor of graft loss. Donor age (RR = 1.53; 95% CI, 1.19 to 1.98), human leukocyte antigen-DR mismatch (RR = 2.28; 95% CI, 1.78 to 2.92), and recipient age (RR = 1.34; 95% CI, 1.05 to 1.72) were associated significantly with acute rejection episodes. Delayed graft function alone was not associated independently with the occurrence of early acute rejection (RR = 1.24; 95% CI, 0.96 to 1.61). The timing of the rejection episodes of old donor kidneys was not different, and the excess rejection prevalence was attributable entirely to interstitial (grade I) types of rejection. Interstitial rejection episodes in kidneys from old donors had a significant (P < 0.05) negative impact on graft survival. Beyond the first year, poor renal function and proteinuria were significant risk factors for graft loss, regardless of rejection. Our data fit best the hypothesis that increased graft loss of older donor kidneys results from an increased incidence of acute interstitial rejection episodes in the early posttransplantation months. It is proposed that kidneys from older donors are more immunogenic than kidneys from young donors and that acute rejection episodes result in functional deterioration. Contrary to interstitial rejection in kidneys from younger donors, kidneys from old donors seem to have an impaired ability to restore tissue.