Tim E. Taber

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.

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

Mujtaba MA, Goggins W, Lobashevsky A, Sharfuddin AA, Yaqub MS, Mishler DP, Brahmi Z, Higgins N, Milgrom MM, Diez A, Taber T. The strength of donor‐specific antibody is a more reliable predictor of antibody‐mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.
Clin Transplant 2011: 25: E96–E102.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

Background Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. Methods In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%–99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti–human leukocyte antigen antibodies were analyzed before and after desensitization. Results Reduction of cPRA from 25% to 50% was noted for anti–class I (5 patients, within 20–60 days) and anti–class II (3 patients, within 10–20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti–class I antibodies at 350 days and anti–class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti–class II antibodies, and history of previous transplant. Conclusions The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Immediate Retransplantation for Pancreas Allograft Thrombosis

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1–16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin‐induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76–1137 days (mean 572 days). One‐year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first‐time pancreas transplantation.

Early reexploration for suspected thrombosis after pancreas transplantation

Background. Graft thrombosis is the most common cause of early graft loss after pancreas transplantation. Early reexploration may permit salvage or timely removal of the thrombosed graft. Methods. This was a retrospective review of 345 pancreas transplants performed at a single center between January 2003 and December 2009. Early reexploration was defined as within 1 week of pancreas transplantation. Results. Of the 345 transplants, there were 35 early reexplorations. The graft was compromised in 20 cases (57%): 10 venous thromboses, 3 arterial thromboses, 2 combined arterial and venous thrombosis, 2 thromboses secondary to allograft pancreatitis, and 3 cases of positional ischemia without thrombosis. Of these allografts, three reperfused once repositioned and six were successfully thrombectomized for a graft salvage rate of 45%. One of the thrombectomized grafts remained perfused but never functioned and was removed at retransplantation. The 10 remaining compromised grafts that were deemed unsalvageable and required allograft pancreatectomy. Nine of these recipients were retransplanted (eight within 2 weeks) and one was not a retransplantation candidate. Conclusions. Reexploration for suspected graft thrombosis after pancreas transplantation resulted in a negative laparotomy rate of 43%, but permitted graft salvage in 45% of compromised grafts.

No Difference in Transplant Outcomes for Local and Import Pancreas Allografts

Background. In the United States, pancreas allograft allocation is strictly regulated. Local centers have the first option to accept an organ, followed by regional and national allocation for those not accepted locally. For a pancreas to be imported, many centers must have previously rejected the organ for transplantation. This study reviews the outcomes of all pancreas allografts transplanted at a single center between January 2003 and November 2007. Early graft function and graft survival were stratified by geographic source of the donor pancreas. Methods. The records of 247 pancreas recipients and the donors of 11 imported and discarded pancreas allografts were reviewed. Pancreas allograft survival is represented using a Kaplan-Meier survival curve comparing (1) locally procured and imported pancreas grafts and (2) grafts procured by a team from our own center with the grafts procured by another team. Results. Of the 247 grafts, 184 (74%) were local and 63 (26%) were imported. There were no differences between the two geographic groups in 1-year graft survival (local 91%, import 90%, P=0.76). Similarly, graft survival was similar regardless of whether the organ was procured by our own team or by another center (local team 91%, another team 90%, P=0.96). Conclusions. Pancreas allografts refused by a large number of centers may still be imported and successfully transplanted without affecting survival results.

Impact of recipient age on whole organ pancreas transplantation

The goal of this study was to assess the impact of recipient age on post‐transplant outcome.

Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation

Fridell JA, Mangus RS, Taber TE, Goble ML, Milgrom ML, Good J, Vetor R, Powelson JA. Growth of a nation part II: impact of recipient obesity on whole‐organ pancreas transplantation.
Clin Transplant 2011: 25: E366–E374.

Risk factors for native kidney dysfunction in patients with abdominal multivisceral/small bowel transplantation

Kidney dysfunction is a recognized complication after non‐renal solid organ transplantation, particularly after intestinal transplant. In our study, we reviewed data on 33 multivisceral transplant (MVT)‐ and 15 isolated small bowel (ISB)‐transplant patients to determine risk factors for kidney dysfunction. Kidney function was estimated by modified diet in renal disease (MDRD) and Schwartz formula for adults and children, respectively. Acute kidney injury (AKI) was defined as an increase in the serum Cr (sCr) greater than twofold. Kidney function declined significantly at one yr after transplantation with 46% of subjects showing an estimated GFR (eGFR) <60 mL/min. Patients with an episode of AKI were more likely to have reduced eGFR than those without AKI (p < 0.025). In linear regression analyses, age, pre‐transplant sCr, eGFR at postoperative day (POD) 30, 90, 180, 270, and tacrolimus level at POD 7 showed significant correlation with one yr post‐transplant eGFR (p < 0.05). Pediatric patients and patients with MVT had lesser decline in kidney function compared with adults or patients with ISB. In conclusion, risk factors for post‐transplant kidney dysfunction in intestinal transplantation included age, pre‐transplant sCr, AKI episode, eGFR at POD 30, 90, 180, 270, and tacrolimus level at POD 7.

BK virus nephropathy in simultaneous pancreas kidney transplant: A potentially preventable cause of kidney allograft loss

More than half of the simultaneous pancreas kidney transplant (SPK) patients afflicted with BK virus nephropathy (BKVN) lose their kidney allograft. Fear of pancreatic rejection limits the ability to reduce immunosuppression; this may result in inadequate treatment of BKVN.