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.     

Half-life analysis of pancreas and kidney transplants

Although graft and patient survival data are available for pancreas and kidney transplants, they are rarely reported in terms of half-life. Our aim was to determine whether a more relevant measure of outcome is patient and allograft half-life. Using the data from the Organ Procurement and Transplantation Network Registry on kidney and pancreas transplants from January 1988 to December 1996, patient and graft half-life and 95% confidence intervals were calculated and demographic variables compared. No significant differences were found between demographic variables. Kidneys transplanted in diabetics as a simultaneous kidney-pancreas (SPK) fared better than diabetics receiving a kidney alone (9.6 vs. 6.3 years). Pancreatic graft survival in an SPK pair was better than pancreas after kidney transplant or pancreas transplant alone (11.2 vs. 2.5 years). Because kidney and pancreatic grafts have a longer half-life when transplanted with their mate grafts, we should consider the relative benefits of SPKs over pancreas after kidney transplant or pancreas transplant alone to limit the loss of precious resources.     

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.     

The effect of center volume on pancreas transplant outcomes

BACKGROUND: Caseload often correlates with improved outcomes for several surgical procedures, including solid organ transplantation. Given the unique nature of pancreas transplantation and large variation in transplant center volumes, this study aims to determine whether center volume affects patient and graft survival after pancreas transplantation. METHODS: Registry data on all forms of whole organ pancreas transplants performed between 1995 and 2000 were obtained from the United Network for Organ Sharing. Patient and graft survival rates were followed until 2002. Center volume then was categorized as: low (< 10/year), medium (10-20/year), high (21-50/year), and very high (< 50/year). Cox proportional hazard regression models were developed to evaluate factors affecting pancreas transplant outcomes. RESULTS: Very-high-volume centers were more likely to do pancreas after kidney transplant, pancreas transplant alone, pancreas with kidney transplant, and repeat transplants, while other centers more frequently performed simultaneous pancreas-kidney transplants (P < .001). Very-high-volume centers were more likely to transplant older recipients and less likely to transplant minority or Medicaid patients. Low-volume centers tended to accept pancreatic allografts from younger donors and had the longest waiting times. In models adjusting for differences in patient population, there were no differences in patient survival. However, low-volume centers had a slightly increased risk of graft loss compared to other centers. Early graft loss was similar among all centers, but medium-volume centers were at increased risk for late graft loss. CONCLUSIONS: Low center volume is not associated with increased mortality after pancreas transplantation. Other factors appear to be more important than center volume in determining pancreas transplant outcomes.     

Cyclosporine-based immunosuppressive strategies for kidney recipients: interim analysis of German data from the Multinational Observational Study (MOST)

INTRODUCTION: We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome. METHODS: As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002. RESULTS: Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.8 months posttransplant) and 821 patients on maintenance therapy (median 71 months posttransplant). Triple regimens with CsA + mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2 receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%), while mono and dual regimen use de novo is declining (de novo 4%, maintenance 20%). Among 689 patients transplanted between 1987 and 2002 with outcome data, the mean incidence of acute rejection during the first posttransplant year was 21.6%. Rejection rates on initial therapy with CsA + MMF + Ste +/- antibodies (n = 517) averaged 17.8%. CONCLUSIONS: Between 1987 and 2002, CsA-based immunosuppression combined with MMF and Ste became the most commonly used strategy for both initial and maintenance therapy after kidney transplantation in Germany, yielding the low acute rejection rates particularly when combined with IL-2Ra.     

Transplantation und Ergebnisqualität

Organ transplants are procedures which require intensive personal and material resources. The results of organ transplants have continuously improved during recent decades. International data bases (registries) have documented the continuous evolution of organ transplantation. On the basis of the German Transplant Law guidelines for “Requirements regarding quality control for procedures related to organ procurement and transplantation” have been formulated by the German Medical Chamber. Thus, monitoring of outcome quality will become a requirement for all German transplant centers. In this paper, the guidelines for the different organ transplants (kidney, pancreas, liver, heart, lung) are discussed as well as quality control for living donor transplantation. Studies from the USA and Europe demonstrated volume-outcome relationships in organ transplantation. In addition, in kidney transplantation a centre-effect could be demonstrated which influences outcome more than the immunological match between donor and recipient. The introduction of required quality control may have far reaching consequences for the future structure of organ transplantation in Germany.     

Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus.

Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown.     

Operative mortality after renal transplantation--does surgeon type matter?

PURPOSE: Currently there are 64 accredited renal transplantation fellowships in Canada and the United States. Only 27% are limited in scope to kidney transplants. In the remaining fellowships the trainee learns to transplant multiple abdominal organs. Given this evolution to the multiorgan transplant surgeon, we evaluated the effect of the current training paradigm on practice patterns and outcomes for kidney transplants. MATERIALS AND METHODS: Using data from the Nationwide Inpatient Sample, discharge records for kidney transplants (6,674) were abstracted (1993 to 2003). Through the Nationwide Inpatient Sample unique surgeon identifier we determined the proportion of kidney transplants performed by multiorgan and kidney only transplant surgeons. We fit multilevel regression models to examine the relationship between surgeon type and transplant outcome. RESULTS: We identified 99 multiorgan and 196 kidney only transplant surgeons who performed 3,255 and 3,419 kidney transplants, respectively. Kidney only transplant surgeons were more likely than multiorgan surgeons to practice in nonteaching, private, for-profit hospitals (p <0.05). Unadjusted operative mortality was higher in patients treated by kidney only vs multiorgan transplant surgeons (1.7% vs 0.9%, p = 0.002). After adjusting for patient and hospital factors, those who underwent renal transplantation performed by multiorgan transplant surgeons had 55% lower odds of inpatient death (OR 0.45, 95% CI 0.26-0.76) vs kidney only transplant surgeons. CONCLUSIONS: Despite the current training paradigm, kidney only transplant surgeons have a prominent role in renal transplantation. However, given the current donor organ shortage and the implications for quality, the observed mortality difference suggests that additional investigation is needed to determine whether this role should be decreased.     

Metabolic Surgery for the Treatment of Type 2 Diabetes in Pancreas After Kidney Transplant Candidates

Metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM) in patients not morbidly obese (BMI <35) has been widely studied. Taking into account that ∼12% of pancreas transplants are performed in patients with T2DM, our goal was to evaluate the impact of metabolic surgery on the management of obese patients with T2DM on waiting lists for a pancreas transplant. We performed a Roux-en-Y gastrointestinal bypass in 5 patients with insulin-dependent T2DM who were candidates for pancreas after kidney transplant and with a BMI <35. Three patients became insulin independent by the end of the first year while the other 2 reduced their insulin requirements by 70%. Furthermore, all patients achieved improved control of lipid levels. We concluded that the surgery was effective in controlling blood glucose and lipid metabolism in these obese T2DM kidney transplant recipients. In this population, a pancreas transplant, along with its associated morbidity, may be avoided.     

Diagnosis, Management, and Outcome of Late Duodenal Complications in Portal–Enteric Pancreas Transplantation: Case Reports

Background: Enteric drainage (ED) of pancreas allografts is an alternative to the bladder drainage (BD) technique and eliminates unique metabolic complications seen in the BD pancreas transplant recipients. Little longterm data has been reported in ED pancreas transplants.

Study Design: Of 53 patients who underwent pancreas transplantations performed with ED drainage of the exocrine secretion to a Roux-en-Y limb, who had more than 6 months graft function, four patients were identified with late duodenal segment complications (more than 6 months after transplantation) and are presented as case reports.

Results: The duodenal segment complications occurred between 8 and 48 months after simultaneous pancreas–kidney transplantation. Three patients were diagnosed with leakage from the duodenal segment. All were managed operatively. The fourth patient developed a distal stricture of the transplant duodenum occluding the anastomosis between the duodenum and the Roux-en-Y limb and also had a pancreatic pseudocyst. Drainage via a cyst-jejunostomy resulted in graft salvage. The mean followup after operative management of the duodenal-related complications was 15 months (range, 3–24 months). The patient, pancreas and kidney graft survival are 100%.

Conclusions: Late duodenal complications occurred in 8% of pancreas transplant recipients with ED. Operative intervention in all four patients resulted in excellent graft and patient outcome and is recommended for these complications.     

Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987–2014

Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987–2014, CF patients (N = 4600) underwent 17 liver–pancreas, three lung–pancreas, one liver–lung pancreas, four kidney–pancreas, and three pancreas‐only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF‐related diabetes (CFRD) before transplantation, and nine of those received a liver–pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver–lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two‐year posttransplantation survival was 88% after liver–pancreas transplant, 33% after lung–pancreas transplant, and 100% after pancreas–kidney and pancreas‐only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted.     

The 2022 International Pancreas Transplant Registry Report—A Review

Over the last decades, the number of pancreas transplants has increased all over the world. Since the first pancreas transplant in 1966, patient and graft survival after simultaneous pancreas and kidney as well as after solitary pancreas transplantation have improved significantly. Patient survival at 1 year is >96% in all 3 recipient categories and pancreas graft survival is >90% for simultaneous pancreas and kidney and >86% for solitary transplants. For transplants performed between 2001 and 2010, with >10 years’ follow-up time, the half-life (50% graft function) was 13 years for simultaneous pancreas and kidney, almost 10 years for a pancreas after kidney transplant, and >6 years for a pancreas transplant alone. These excellent results are even more astonishing because more high-risk patients were transplanted. The main reasons for improvement in outcome were reductions in technical failures and immunologic graft losses. These decreases were due to better patient and donor selection, standardization of surgical techniques, and superior immunosuppressive protocols.     

胰腺、肾脏在单独和联合移植中排斥反应的差异

目的 比较胰腺、肾脏在单独和联合移植中排斥反应的差异。方法 在大鼠同种异体单独胰腺移植、单独肾脏移植和肺肾联合移植基础上,对胰腺、肾脏在单独和联合移植中的排斥瓜反应分别进行了比较。结果 （１）胰腺在联合肾脏移植中受到肾脏保护,与单独上比,功能与形态不者到显著改观;（２）肾脏在联合胰腺移植时未受到胰腺保护,与单独移植比较,各项指标未得到显著改善。结论 胰腺与肾脏联合移植的结局优于单独胰腺移植,而肾脏     

The time interval between kidney and pancreas transplantation and the clinical outcomes of pancreas after kidney transplantation

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008. Kaplan-Meier survival and multivariate Cox regression analyses were performed using the time interval between kidney and pancreas transplantation either as a categorical (less than one yr, between one and less than three yr, and greater than or equal to three yr) or as a continuous variable (months) to assess kidney graft and patient survival. Patients who received a pancreas transplant three yr or later after kidney transplantation had higher risk of death-censored kidney graft loss (HR 1.56, 95% CI 1.04, 2.32, p = 0.03). Each month beyond three yr between kidney and pancreas transplantation incurred 1% higher risk of subsequent death-censored kidney graft loss (HR 1.01, 95% CI 1.001, 1.02, p = 0.03). In conclusion, time interval between pancreas and kidney transplantation is an independent risk factor of kidney graft loss following pancreas transplantation. Shortening the time interval between pancreas and kidney transplantation to less than three yr may reduce the risk of kidney graft loss in qualified PAK transplant candidates.     

Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole‐organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10‐year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1‐ and 5‐year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft‐function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.     

Long-term outcome of simultaneous kidney-pancreas transplantation: analysis of 61 patients with more than 5 years follow-up

BACKGROUND: The long-term outcome of simultaneous kidney pancreas transplant recipients is not well established. METHODS: We retrospectively reviewed all patients who underwent simultaneous kidney-pancreas transplantation with bladder drainage at our center between January 1989 and December 1991. A total of 57 patients (93%) were alive with functioning grafts 1 year after transplantation and were followed for a minimum of 5 years. These patients formed the study group. RESULTS: Five-year actual patient, kidney and pancreas survival rates were 95%, 85%, and 88%, respectively. Fasting serum glucose fell from 198 mg/dL preoperatively to 94 mg/dL and remained stable thereafter. Glycohemoglobin levels decreased from 9.8% preoperatively to 4.8% 1 year after transplantation and remained normal thereafter. Kidney function remained good, with mean serum creatinine of 2.0 and creatinine clearance of 56 ml/min throughout the follow-up period. Hospital admissions decreased significantly with increasing time after transplantation from a mean of 1.2 admissions per patient in the 1st year to a mean of 0.2 admissions per patient 6 years after transplantation. Of the readmissions, 42% were for <48 hr and the most common reasons for readmission were infection, surgery, and dehydration. Mean systolic blood pressure decreased from 166 mm Hg before the transplant to 142 mm Hg 1 year after the transplant. CONCLUSIONS: Simultaneous kidney pancreas transplantation is a safe and effective method to treat advanced diabetic nephropathy and is associated with stable metabolic function, decreased cholesterol, improved hypertension control, improved rehabilitation over time, and little morbidity or mortality after the 1st year.     

OPTN/SRTR 2018 Annual Data Report: Pancreas

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.     

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.     

Simultaneous pancreas-kidney transplant: a single-center long-term outcome

BACKGROUND: In patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney transplantation is associated with increased survival when compared with solitary deceased kidney transplant or dialysis. We consider that the analysis of our long-term program (based in a single center) of simultaneous pancreas-kidney transplantation would provide valuable information for this therapeutic approach regarding patient and organ survival. METHODS: The outcome of 57 consecutive pancreas-kidney transplants patients was analyzed. The analysis included characteristics of the donor and recipient and survival rates of patients and both grafts. We also analyzed age and modality of renal replacement treatment as possible mortality risk factors. RESULTS: Ten-year patient, kidney and pancreas graft survival rates were 75.8%, 57.2% and 42.7%, respectively. Censoring for patient death, the results for 10-year kidney and pancreas survival were 78.5% and 58%, respectively. CONCLUSION: Our results add evidence to support the notion that the double and simultaneous pancreas-kidney transplantation is in fact the treatment of choice in selected patients with end-stage renal failure due to type 1 diabetes mellitus.