Surgical complications requiring early relaparotomy after pancreas transplantation: a multivariate risk factor and economic impact analysis of the cyclosporine era.

OBJECTIVES: To study significant surgical complications requiring early (< or = 3 months posttransplant) relaparotomy (relap) after pancreas transplants, and to develop clinically relevant surgical and peritransplant decision-making guidelines for preventing and managing such complications. SUMMARY BACKGROUND DATA: Pancreas grafts are still associated with the highest surgical complication rate of all routinely transplanted solid organs. However, the impact of surgical complications on morbidity, hospital costs, and graft and patient survival rates has not been analyzed in detail to date. METHODS: We retrospectively studied surgical complications requiring relap in 441 consecutive cadaver, bladder-drained pancreas transplants (54% simultaneous pancreas and kidney [SPK]; 22% pancreas after kidney [PAK]; 24% pancreas transplant alone [PTA]; 37% retransplant). Outcome and hospital charges were analyzed separately for recipients with versus without reoperation. RESULTS: The overall relap rate was 32% (SPK, 36%; PAK, 25%; PTA, 16%; p = 0.04). The most common causes were intraabdominal infection and graft pancreatitis (38%), pancreas graft thrombosis (27%), and anastomotic leak (15%). Perioperative relap mortality was 9%; transplant pancreatectomy was necessary in 57% of all recipients with one or more relaps. The pancreas graft was lost in 80% of recipients with versus 41% without relap (p < 0.0001). Patient survival rates were significantly lower (p < 0.05) for recipients with versus without relap. By multivariate analysis, significant risk factors for graft loss included older donor age (SPK, PAK), retransplant (PAK), relap for infection (SPK, PAK), and relap for leak or bleeding (PAK). For death, risk factors included older recipient age (SPK, PAK),retransplant (SPK, PAK), relap for thrombosis (PAK), relap for infection or leak (SPK), and relap for bleeding (PTA). CONCLUSIONS: Posttransplant surgical complications requiring relap were frequent, resulted in a high rate of pancreas (SPK, PAK, PTA) and kidney (SPK, PAK) graft loss, and had a major economic impact (p = 0.0001). Complications were associated with substantial perioperative mortality and decreased patient survival rates. The focus must therefore shift from graft salvage to preservation of the recipient's life once a pancreas graft-related complication requiring relap occurs. Thus, the threshold for pancreatectomy should be low. In this context, acceptance of older donors and recipients must be reconsidered.     

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation

BACKGROUND: Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. METHODS: The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. RESULTS: The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. CONCLUSIONS: Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.     

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.     

Lessons learned from more than 1,000 pancreas transplants at a single institution

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.     

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.     

A 10-year experience with 290 pancreas transplants at a single institution.

Since our report at the 1984 American Surgical Association meeting of 100 pancreas transplants from 1966 through 1983, another 190 have been performed. The current series, begun in 1978, now numbers 276 cases, and includes 133 nonuremic recipients of pancreas transplants alone (PTA), 46 simultaneous pancreas/kidney transplants (SPK), and 97 pancreas tranplants after a kidney transplant (PAK). Duct management techniques used were free intraperitoneal drainage in 44 cases, duct occlusion in 44, enteric drainage in 89, and bladder drainage in 128. The 1-year patient and graft survival rates in the entire cohort of 276 were 91% and 42%. One-year patient survival rates were 88% in the first 100, 91% in the second 100, and 92% in the last 76 cases; corresponding 1-year graft survival rates were 28%, 47%, and 56% (p less than 0.05). A prospective comparison of bladder drainage (n = 82) versus enteric drainage (n = 46) in PAK/PTA cases since November 1, 1984 favored bladder drainage (1-year graft survival rates of 52% vs. 41%) because of urinary amylase monitoring. The best results were in recipients of primary SPK bladder-drained transplants (n = 39), with a 1-year pancreas graft survival rate of 75%, kidney graft survival rate of 80%, and patient survival rate of 95%. Logistic regression analysis, with 1-year graft function as the independent variable, showed significant (p less than 0.05) predictors of success (odds ratio) to be technique: bladder drainage (5.8) versus enteric drainage (2.5) versus duct injection (1.0); category: SPK (6.0) versus PAK from same donor (3.2) versus PAK from different donor (1.2) versus PTA (1.0); and donor HLA DR mismatch: 0 (5.0) versus 1 (2.5) versus 2 (1.0) antigens. On April 1, 1989, 90 patients had functioning grafts (60 euglycemic and insulin-free for more than 1 year, 10 for 5 to 10 years); these, along with 24 others whose grafts functioned for 1 to 6 years before failing, are part of an expanding cohort in whom the influence of inducing a euglycemic state on pre-existing secondary complications of diabetes is being studied. Only preliminary data is available. In regard to neuropathy, at more than 1 year after transplant in patients with functioning grafts, conduction velocities in some nerves were increased over baseline. In regard to retinopathy, deterioration in grade occurred in approximately 30% of the recipients by 3 years, whether the graft functioned continuously or failed early, but thereafter retinopathy in the patients with functioning grafts remained stable.(ABSTRACT TRUNCATED AT 400 WORDS)     

Technical failures after pancreas transplants: why grafts fail and the risk factors--a multivariate analysis

BACKGROUND: Technical failure (TF) rates remain high after pancreas transplants; while rates have decreased over the last decade, more than 10% of all pancreas grafts continue to be lost due to technical reasons. We performed a multivariate analysis to determine causes and risk factors for TF of pancreas grafts. RESULTS: Between 1994 and 2003, 937 pancreas transplants were performed at our center in the following transplant categories: simultaneous pancreas-kidney (SPK) (n=327), pancreas after kidney (PAK) (n=399), and pancreas transplant alone (PTA) (n=211). Of these, 123 (13.1%) grafts were lost due to technical reasons (thrombosis, leaks, infections). TF rates were higher for SPK (15.3%) versus PAK (12.2%) or PTA (11.4%), though this was not statistically significant. Thrombosis accounted for 52.0% of all TFs. Other causes were infections (18.7%), pancreatitis (20.3%), leaks (6.5%), and bleeding (2.4%). Thrombosis was the most common cause for TF in all three transplant categories. By multivariate analysis, the following were significant risk factors for TF of the graft: recipient body mass index (BMI) >30 kg/m (relative risk [RR]=2.42, P=0.0003), preservation time >24 hr (1.87, P=0.04), cause of donor death other than trauma (RR=1.58, P=0.04), enteric versus bladder drainage (1.68, P=0.06), and donor BMI >30 kg/m (1.66, P=0.06). Not significant were donor or recipient age, a retransplant, and the category of transplant. CONCLUSIONS: TFs remain significant after pancreas transplants. In SPK recipients, TF represents the most common cause of pancreas graft loss. For isolated pancreas transplants, TF is second only to rejection as a cause of graft loss. Increased preservation times and donor or recipient obesity seem to be risk factors. Minimizing these risks factors would be important to try to decrease TF.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Risk Factors and Impact of Delayed Graft Function after Pancreas Transplants

Delayed graft function (DGF) occurs after many pancreas transplants (PTx), but is poorly characterized. We studied its incidence, course, and impact in a series of 531 pancreas transplants. Between January 1997 and September 2002, we performed 531 technically successful primary PTx. Of these 531 recipients, 176 (33%) had DGF, defined by their need for exogenous insulin at the time of hospital discharge. The incidence of DGF was roughly equivalent in the three transplant categories: SPK (36%), PAK (32%), and PTA (31%) (p = NS). By 3 months posttransplant, only 19 (3.5%) of all recipients remained on insulin. Only three recipients (0.56%) did not achieve insulin independence. The mean donor age of recipients with DGF was 35.1 years vs. 28.8 years without DGF (p = 0.003). By multivariate analysis, the most significant risk factor for DGF was donor age > 45 years (RR = 4.3, p = 0.0001). For SPK recipients with DGF, graft survival was 87% at 1 year and 82% at 3 years posttransplant; without DGF, 94% at 1 year and 87% at 3 years (p = 0.07). For PAK and PTA recipients, no difference was noted. Acute rejection rates were somewhat higher in recipients with DGF, but this did not reach statistical significance.     

Pancreas after kidney transplants in posturemic patients with type I diabetes mellitus.

Pancreas after previous kidney (PAK) transplants are an attractive option for type 1 diabetic patients because of the short waiting time and use of living kidney donors. Factors associated with the increased success rate of PAK transplants in four immunosuppressive eras were analyzed. Between July 1, 1978, and April 30, 2000, 406 PAK transplants were performed in posturemic patients. Four immunosuppressive eras were analyzed: (1) the precyclosporine era, era 1 (n = 65; 16%); (2) the cyclosporine era, era 2 (n = 109; 27%); (3) the tacrolimus era with monoclonal or polyclonal antibody induction therapy, era 3 (n = 104; 26%); and (4) the tacrolimus era with monoclonal and polyclonal antibody induction therapy, era 4 (n = 128; 31%). Patient and graft survival, rejection, and technical failure rates were calculated. Patient survival rates have remained high over time, from 91% (era 1) to 96% (era 4) at 1 yr posttransplant. Pancreas graft survival rates with primary cadaver transplants have significantly increased, from 17% (era 1) to 81% (era 4) at 1 yr. The rate of graft loss from rejection has significantly decreased, from 78% (era 1) to 9% (era 4) at 1 yr. Results were best when donors and recipients were matched for at least one antigen per HLA locus. Kidney graft survival was higher in PAK transplant recipients compared with diabetic recipients of kidney transplants alone from the time of the kidney as well as the pancreas transplants. PAK recipients now enjoy >80% graft survival at 1 yr. This improvement in outcome results from better immunosuppression, good matching, and close posttransplant monitoring for rejection.     

The survival advantage of pancreas after kidney transplant

Patient survival after pancreas after kidney transplant ( PAK) has been reported to be inferior to patient survival after simultaneous pancreas–kidney transplant (SPK). The authors examine national data to further explore allograft (kidney and pancreas) and patient survival after PAK. Kaplan–Meier and Cox proportional hazard models were used to analyze Organ Procurement and Transplantation Network data from 1995 to 2010. The analysis compared PAK and SPK candidates and recipients. Kaplan–Meier analysis results showed that PAK after either a living or a deceased donor kidney transplant is associated with increased kidney graft survival compared with recipients with type 1 diabetes who received only a kidney. The best kidney allograft survival was for patients who received a living donor kidney followed by PAK. Receiving a living donor kidney was associated with increased pancreas allograft survival compared with receiving a deceased donor kidney. PAK transplant recipients who receive both organs have a survival advantage compared with uremic candidates who receive neither (SPK waitlist). Compared with uremic diabetic waitlist patients, SPK and PAK recipients showed similar overall patient survival. Successful PAK offers a survival advantage compared with receiving neither a kidney nor a pancreas transplant. These data also suggest that receiving a pancreas (after kidney) transplant may have a protective effect on the kidney allograft.     

The case for pancreas after kidney transplantation

Abstract:  Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.     

Systematic Evaluation of Pancreas Allograft Quality,Outcomes and Geographic Variation in Utilization

Pancreas allograft acceptance is markedly more selective than other solid organs. The number of pancreata recovered is insufficient to meet the demand for pancreas transplants (PTx), particularly for patients awaiting simultaneous kidney‐pancreas (SPK) transplant. Development of a pancreas donor risk index (PDRI) to identify factors associated with an increased risk of allograft failure in the context of SPK, pancreas after kidney (PAK) or pancreas transplant alone (PTA), and to assess variation in allograft utilization by geography and center volume was undertaken. Retrospective analysis of all PTx performed from 2000 to 2006 (n = 9401) was performed using Cox regression controlling for donor and recipient characteristics. Ten donor variables and one transplant factor (ischemia time) were subsequently combined into the PDRI. Increased PDRI was associated with a significant, graded reduction in 1‐year pancreas graft survival. Recipients of PTAs or PAKs whose organs came from donors with an elevated PDRI (1.57–2.11) experienced a lower rate of 1‐year graft survival (77%) compared with SPK transplant recipients (88%). Pancreas allograft acceptance varied significantly by region particularly for PAK/PTA transplants (p < 0.0001). This analysis demonstrates the potential value of the PDRI to inform organ acceptance and potentially improve the utilization of higher risk organs in appropriate clinical settings.     

Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004

As of December 31, 2004, more than 23,000 pancreas transplant had been reported to the IPTR, >17,000 in the US and almost 6000 from outside the US. An analysis of US pancreas transplants performed between 1988 and 2003 showed a progressive improvement in outcome, with pancreas transplant graft survival rates (GSRs) going from 75% at 1 yr for 1988/1989 to 85% for 2002/2003 simultaneous pancreas-kidney (SPK) cases, from 55 to 78% for pancreas after kidney (PAK) cases, and from 45 to 77% for pancreas transplants alone (PTA) cases. The improvements were due both to decreases in technical failure (TF) rates (from 12 to 6% in SPK, 13-8% in PAK, and 24-7% in PTA) and immunological failure rates (going from 7 to 2% for SPK, from 28 to 7% for PAK, and from 38 to 8% for PTA cases). These results are even more impressive under the aspect that during the same time the rate of potential risk factors increased and the duct management techniques changed from bladder to enteric drainage. The improvement in outcome allowed also an increase in the number of solitary pancreas transplants from initially 12% to now 35%. Contemporary primary deceased donor pancreas transplant outcomes were calculated separately for 2000-2004 US and non-US cases. The US patient survival rates at 1 yr were >95% in each recipient category, with 1 yr primary pancreas GSRs of 85% for SPK, 78% for PAK, and 76% for PTA (p < 0.0001). The immunological graft failure rates for 2000-2004 technically successful (TS) SPK, PAK, and PTA cases were 2, 8, and 10% at 1 yr (p = 0.0001). In the majority of all transplants ED was used for duct management (81% of SPK, 67% of PAK, and 56% for PTA cases). Of the ED transplants, venous drainage via the portal system was used for 20% of SPK, 23% of PAK, and 35% of PTA cases. Duct management technique did not have a significant impact on overall pancreas graft function in the univariate or the multivariate model. The outcomes of ED and BD transplants are comparable with 85 vs. 87% at 1 yr for SPK, 77 vs. 80% for PAK, and 72 vs. 79% for PTA. The overall TF rate was higher in ED pancreas transplants but this difference did reach significance only in SPK. In addition, in technically successful PTA the immunological graft loss rate was higher in ED vs. BD transplants (15 vs. 5% at 1 yr). The different vascular management techniques did not seem to have an impact on the outcome of the pancreas transplants. Kidney GSRs were not significantly different for ED vs. BD SPK cases, 93 and 91% at 1 yr (p = 0.24). The overall conversion rate from BD to ED was 9% at 1 yr and 17% at 3 yr post-transplant. The most influential factor for patient survival in SPK and PAK in the multivariate and the univariate models was the status of the transplanted organ. The hazard ratio (HR) for a failed kidney was 14.99 in SPK and 9.17 in PAK (p = 0.0001). The HR for a failed pancreas graft was 3.51 in SPK and 4.17 for PAK (p = 0.0001). In PTA a failed pancreas graft did not have a direct impact on patient survival. SPK and PAK patients older than 44 yr at the time of transplants also showed an increased mortality risk, but at the same time the risk of immunological graft loss was significantly decreased for those patients. TAC&MMF remained the dominant maintenance immunosuppressant for 2000-2004 US cases (approximately two-third) in all three categories and with this regime 1-year GSRs were > or =80% in all three recipient categories. The results were comparable (> or =83% 1-year GSR) for patients (approximately 10%) treated with Sirolimus (SIR) under various protocols. In regard to non-US pancreas transplants, even for 2000-2004 the overwhelming majority continued to be in the SPK category (91%), with 1-year patient, kidney and pancreas survival rates of 94, 92, and 87%. Solitary transplants are still very rarely done outside the US. Non-US PAK GSR at 1 yr was 85%, non-US PTA GSR at 1 yr was 76%. In summary, with the new advancements in immunosuppression and changes in surgical techniques the outcomes in patient survival and pancreas transplant graft function continue to improve even with an increasing proportion of high risk patients in all three categories.     

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)     

A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus

BACKGROUND: We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. METHODS: Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids. RESULTS: Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups. CONCLUSIONS: We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.     

Kidney and Pancreas Transplantation in the United States, 1998–2007: Access for Patients with Diabetes and End-Stage Renal Disease

Although the number of candidates on the kidney transplant waiting list at year-end rose from 40 825 to 76 070 (86%) between 1998 and 2007, recent growth principally reflects increases in the number of patients in inactive status. The number of active patients increased by 'only' 4510 between 2002 and 2007, from 44 263 to 48 773. There were 6037 living donor and 10 082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD deceased donor kidneys. The total number of pancreas transplants peaked at 1484 in 2004 and has since declined to 1331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at 1 year and 53% at 10 years. Between 1998 and 2006, among diabetic patients with end-stage renal disease (ESRD) who were under the age of 50 years, 23% of all and 62% of those waitlisted received a kidney-alone or SPK transplant. In contrast, 6% of diabetic patients aged 50–75 years with ESRD were transplanted, representing 46% of those waitlisted from this cohort. Access to kidney-alone or SPK transplantation varies widely by state.     

Technical failure of the pancreas after SPK transplant: are these patients good candidates for later pancreas retransplant?

Abstract:  Technical failure of the pancreas graft after a simultaneous pancreas–kidney (SPK) transplant is not uncommon, affecting roughly 10% of SPK recipients. These patients often recover with good kidney function, but have persistent issues related to their diabetes. The aim of this study was to determine if these patients were good candidates for a later pancreas retransplant. Outcomes were compared between 21 PASPK (pancreas after SPK) recipients and 361 recipients of a primary pancreas after kidney (PAK) transplant. Except for kidney graft source, there was no significant difference in the demographic characteristics between these two groups. In general, early surgical complications were more common in PASPK than PAK recipients (47.6% vs. 35.5%, p = 0.15), although the difference was not statistically significant. The incidence of acute rejection was no different between these two groups (28% vs. 33%, p = NS). At three yr post-transplant, patient and pancreas graft survival rates were also no different between the two groups (p = NS). The most common cause for graft loss in both groups was acute or chronic rejection. In conclusion, pancreas retransplant is a viable option for SPK recipients experiencing early technical failure of the pancreas graft. These recipients are not at higher immunologic risk vs. primary PAK recipients.     

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function

Abstract:  In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 ± 20 mL/min (PAK) vs. 43 ± 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.     

Optimal timing for a pancreas transplant after a successful kidney transplant

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 option. But how long to wait after the kidney transplant before proceeding with a pancreas transplant is unclear. We studied outcomes in recipients of a pancreas at varying times after a kidney to determine the optimal timing for the second transplant. METHODS: We compared pancreas after kidney (PAK) transplants performed early (< or =4 months) and late (>4 months) after the kidney transplant to determine any significant differences in surgical complications or outcomes between the two groups. RESULTS: Between January 1, 1994, and September 30, 1998, we performed 123 cadaver PAK transplants. Of these, 25 (20%) were early and 98 (80%) were late. Characteristics of the two recipient groups were similar. We found no significant differences in outcome between the two groups. The incidence of surgical complications (bleeding, leaks, thrombosis, infections) and of opportunistic infections (such as cytomegalovirus) did not significantly differ between the two groups. Graft and patient survival rates were also equivalent (P=NS). The incidence of acute rejection by 3 months posttransplant was 20% in both groups. CONCLUSION: The timing of the pancreas transplant for PAK recipients does not seem to influence outcome. As long as an acceptable organ is available and the recipient is clinically stable, a PAK transplant can be performed relatively soon after the kidney transplant.