Chain transplantation: initial experience of a large multicenter program.

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

Transporting live donor kidneys for kidney paired donation: initial national results.

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

Steroid avoidance in two-haplotype-matched living donor renal transplants with basiliximab induction therapy.

BACKGROUND: Induction therapy and haplotype matching are utilized to mitigate immunologic risk in renal transplantation. The incidence of acute rejection (AR) of renal allografts has been reported to be as low as 9.3% within the first year among two-haplotype-matched siblings with no induction and triple-drug maintenance immunosuppression. We report our use of basiliximab induction in a series of two-haplotype-matched living donor renal transplants (LDRT). METHODS: We retrospectively reviewed 25 patients who received a two-haplotype-matched LDRT with basiliximab induction therapy. The primary endpoints were acute rejection (AR) episodes at 6 and 12 months and 1-year patient and graft survival rates. The secondary endpoints were the incidence of delayed graft function (DGF), cytomegalovirus (CMV), and BK virus (BKV). RESULTS: The rate of AR at 6 months was 0% (0/25) and 4% (1/25) at 12 months. The 1-year graft and patient survival rates were 100%. The incidence of DGF was 4% (1/25), while the incidences of CMV and BKV were 0%. CONCLUSION: Basiliximab induction therapy with a steroid-sparing regimen yields favorable results in two-haplotype-matched LDRT, including a notable reduction in the rates of AR as compared to triple-drug maintenance immunosuppression without induction. These patients have excellent graft survival with no increased incidences of secondary infections.

Room temperature pulsatile perfusion of renal allografts with Lifor compared with hypothermic machine pump solution.

This pilot study compared the use of the Lifor Organ Preservation Medium (RTLF) at room temperature with hypothermic Belzer machine preservation solution (CMPS) and room in vitro temperature Belzer machine preservation solution (RTMPS) in a porcine model of uncontrolled donation after cardiac death (DCD). In this study, 5 porcine kidneys for each perfusate group were recovered under a DCD protocol. The kidneys were recovered, flushed, and placed onto a renal preservation system following standard perfusion procedures. The average flow rate for CMPS was 36.2 +/- 7.2549 mL/min, RTMPS was 90.2 +/- 9.7159 mL/min, and RTLF was 103.1 +/- 5.1108 mL/min. The average intrarenal resistance for CMPS was 1.33 +/- 0.1709 mm Hg/mL per minute, RTMPS was 0.84 +/- 0.3586 and RTLF was 0.39 +/- 0.04. All perfusion parameters were statistically significant (P < .05) at all time points for the CMPS when compared with both RTMPS and RTLF. All perfusion parameters for RTMPS and RTLF were equivalent for the first 12 hours; thereafter, RTLF became significantly better than RTMPS at 18 and 24 hours. It appears that both RTMPS and RTLF have equivalent perfusion characteristic for the initial 12 hours of perfusion, but LF continues to maintain a low resistance and high flow up to 24 hours. The results of this pilot study indicate that RTLF may represent a better alternative to pulsatile perfusion with CMPS and requires validation in an in vivo large animal transplant model.

Generation and functional capacity of polyclonal alloantigen-specific memory CD4 T cells.

Alloreactive memory T cells can significantly impact graft survival due to their enhanced functional capacities, diverse tissue distribution and resistance to tolerance induction and depletional strategies. However, their role in allograft rejection is not well understood primarily due to the lack of suitable in vivo models. In this study, we use a novel approach to generate long-lived polyclonal alloreactive memory CD4 T cells from adoptive transfer of alloantigen-activated precursors into mouse hosts. We demonstrate that CD25 upregulation is a marker for precursors to alloantigen-specific memory and have created a new mouse model that features an expanded population of polyclonal alloreactive memory T cells that is distinguishable from the naive T-cell population. Furthermore, we show that alloreactive memory T cells exhibit rapid recall effector responses with predominant IFN-gamma and IL-2 production, and mediate vigorous allograft rejection. Interestingly, while we found a heterogeneous distribution of allomemory T cells in lymphoid and nonlymphoid tissues, they were all predominantly of the effector-memory (CD62Llo) phenotype. Our results present a unique model for the generation and tracking of polyclonal allospecific memory CD4 T cells in vivo and reveal insights into the distinct and robust nature of alloreactive T-cell memory.

Pulsatile pump perfusion of pancreata before human islet cell isolation.

Machine pulsatile perfusion for whole pancreas preservation might improve yield, viability, and function of human islets recovered after prolonged cold ischemia times. Four human pancreata were procured from cadaver donors (1 non-heart-beating donor) and stored in cold University of Wisconsin (UW) solution for a mean 13 hours prior to placement on a machine pulsatile perfusion device. The four pancreata were perfused for 4 hours with UW solution before undergoing islet isolation. Islets were quantified, viability was assessed, and insulin secretion was measured. Results were compared with nonpumped islet isolations stratified for cold ischemia time (CIT) <8 hours or cold ischemia time >8 hours. The islet yield for the four pumped pancreata was 3435 (+/-1951) islet equivalents/gram pancreas tissue (IEQ/g), compared with a mean yield of 5134 (+/-2700) IEQ/g and 2640 (+/-1000) IEQ/g from pancreas with <8 hours and >8 hours CIT, respectively. The mean viability after machine pulsatile perfusion was 86% (vs 74% and 74% for the <8 hour and >8 hour CIT groups). The mean viable yield (total yield x viability) was 2937 IEQ/g for machine perfusion, compared with 3799 IEQ/g and 1937 IEQ/g from pancreata with <8 hours and >8 hours CIT, respectively. The insulin secretion index of islets after machine perfusion was 6.4, compared with indices of 1.9 and 1.8 for the <8 hour and >8 hour CIT groups. This preliminary data indicates that low-flow machine pulsatile perfusion of pancreata with prolonged cold ischemia time can result in excellent yield, viability, and function.

Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.

Combined simultaneous organ transplantation has become more common as selection criteria for transplantation have broadened. Broadening selection criteria is secondary to improved immunosuppression and surgical techniques. The kidney is the most common extrathoracic organ to be simultaneously transplanted with the heart. A series of 13 patients suffering from both end-stage heart and renal failure underwent 14 simultaneous heart and kidney transplantations at Temple University Hospital between 1990 and 1999. This is the largest series reported from a single center. Three patients died during the initial hospitalization for an in-hospital mortality of 21%. Of 10 patients who left the hospital, 1-year survival was 100% and 2-year survival 75%. One patient required retransplant for rejection within the first year. Overall mortality at 1 and 2 years was 25 and 41%, respectively. Four out of nine (44%) patients greater than 5 years post-transplant were alive. Of the 10 patients who left the hospital, 66% were alive at 5 years. One patient succumbed to primary nonfunction of the cardiac allograft, while the four other deaths were secondary to bacterial or fungal sepsis. The patient's racial backgrounds were equally divided between African-American and white. These results are similar to those reported in a United Network of Organ Sharing Database (UNOS) registry analysis of 84 simultaneous heart and kidney transplants that found 1- and 2-year survival to be 76 and 67%, respectively. Simultaneous heart and kidney transplantation continues to be a viable option for patients suffering from failure of these two organ systems, although the results do not match those of heart transplant alone.