A novel organ donor facility: a decade of experience with liver donors.

Transplant surgeons have historically traveled to donor hospitals, performing complex, time-sensitive procedures with unfamiliar personnel. This often involves air travel, significant delays, and frequently occurs overnight.In 2001, we established the nation's first organ recovery center. The goal was to increase efficiency,reduce costs and reduce surgeon travel. Liver donors and recipients, donor costs, surgeon hours and travel time, from April 1,2001 through December 31,2011 were analyzed. Nine hundred and fifteen liver transplants performed at our center were analyzed based on procurement location (living donors and donation after cardiac death donors were excluded). In year 1, 36% (9/25) of donor procurements occurred at the organ procurement organization (OPO) facility, rising to 93%(56/60) in the last year of analysis. Travel time was reduced from 8 to 2.7 h (p<0.0001), with a reduction of surgeon fly outs by 93% (14/15) in 2011. Liver organ donor charges generated by the donor were reduced by37% overall for donors recovered at the OPO facility versus acute care hospital. Organs recovered in this novel facility resulted in significantly reduced surgeon hours, air travel and cost. This practice has major implications for cost containment and OPO national policy and could become the standard of care.

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Eicosanoid synthesis inhibition and renal allograft function during acute rejection.

The effects of the dual cyclooxygenase-lipoxygenase inhibitor 3-amino-1-(m[trifluoromethyl]phenyl)-2-pyrazoline (BW755C) (10 mg/kg, p.o., b.i.d.) on renal blood flow, glomerular filtration rate (GFR), and eicosanoid production were examined in anesthetized dogs that had undergone unilateral renal allotransplantation. Rejecting renal allograft blood flow significantly declined over a 5-day period compared to the nonrejecting native kidney. In animals treated with BW755C, renal allograft blood flow was maintained over the postoperative 5-day period at levels comparable to blood flow to the native kidneys. While GFR and urine flow progressively declined in the rejecting kidney, treatment with BW755C prevented the fall in GFR and even augmented urine flow. Allograft renal cortical production or thromboxane B2 (TXB2) and leukotriene B4 (LTB4) in animals treated with BW755C was not significantly different than production by the native contralateral kidneys. Furthermore, BW755C reduced cellular infiltration and tissue damage in allografts compared to nontreated renal allografts. The selective cyclooxygenase inhibitor, indomethacin (5 mg/kg, p.o., b.i.d.) exerted no effect on renal allograft GFR or urine output but reduced allograft blood flow after 4 days compared to nontreated allografts. In conclusion, inhibition of arachidonate cyclooxygenase and lipoxygenase metabolism improves renal allograft function and reduces tissue damage while selective inhibition of the cyclooxygenase pathway does not improve renal allograft function. These data indicate that products of arachidonate-lipoxygenase metabolism potentiate the loss of renal function and tissue destruction associated with renal allograft rejection.

Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial.

Improved cadaver kidney allograft survival rates, shorter duration of acute tubular necrosis, and a reduction in the incidence of rejection have been achieved using "quadruple sequential therapy"--AZA, prednisone, and antilymphocyte globulin (ALG) induction followed by the delayed addition of CsA. OKT3 has been shown to be effective in preventing and treating rejection, including steroid- and ALG-resistant rejection episodes. A single institution prospective randomized trial comparing ALG and OKT3 prophylaxis in first cadaver kidney allograft recipients was performed to assess their relative advantages and disadvantages. First cadaver kidney allograft recipients were prospectively randomized to receive 7 days of either ALG (n = 58) or OKT3 (n = 59) as part of a quadruple therapy protocol that included AZA, prednisone, and oral CsA. Patient characteristics, patient survival and causes of death, graft survival and causes of graft loss, incidence of and time to rejection and response to treatment, incidence of infections and their type, renal function, and antibody formation to ALG and OKT3 were examined. The 1-, 2-, and 3-year actuarial patient survival rates were 96% in the ALG group and 98% in the OKT3 group. The graft survival rates were 81.1%, 78.4%, and 78.4% in the ALG group and 84.1%, 78.7%, and 78.7% in the OKT3 group. In ALG-treated patients, 63% never had rejection, compared with 49% in the OKT3 patients (P = NS). In the ALG group 31% had a single rejection, 6% had 2 rejections, and none had 3 rejections, compared with 37%, 12%, and 2% in the OKT3 group. In the ALG group, 43% were steroid responsive compared with 65% in the OKT3 group (P = 0.08). There were 1.44 infections per patient in the ALG group compared with 0.76 in the OKT3 group (P = 0.0004). In the ALG group, 37% of patients developed CMV disease compared with 10% in the OKT3 group (P = 0.001). In donor-positive/recipient-negative patients, 8/10 (80%) in the ALG group developed CMV infection, of which 6 (75%) had severe or moderate CMV disease, compared with 2/15 (13%) patients in the OKT3 group (P = 0.002), of whom only one (6.7%) developed moderate disease. In donor-positive/recipient-positive patients, 8/23 (35%) in the ALG group developed CMV infection, of whom 5/8 (62.5%) developed severe or moderate disease compared with 1/21 (4.8%) in the OKT3 group (P = 0.02). Antibody formation to ALG and OKT3 occurred in 11% and 8% of patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal transplantation for systemic lupus erythematosus and recurrent lupus nephritis. A single-center experience and a review of the literature.

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Cytolytic T lymphocytes from human renal allograft biopsies are tissue specific.

The cytolytic activity of T lymphocytes infiltrating renal allografts from recipients undergoing episodes of acute cellular rejection was studied. These T-cell populations, composed of both CD4+ and CD8+ cells, demonstrated significant cytolytic activity against both donor-derived KCLs and B-LCLs. In five of 21 biopsy-derived lines greater cytolytic activity was measured against donor KCLs compared to donor B-LCLs, suggesting the presence of kidney antigen-specific, MHC-restricted clones. Clones developed by stimulation with donor B-LCLs lysed both donor B-LCLs and KCLs while clones developed on donor KCLs as stimulator cells showed tissue specificity. Three of 26 clones recognized tissue-specific antigens in the context of donor MHC class I antigens lysing donor KCLs but not B-LCLs. These data demonstrate that a subpopulation of T cells recognizing kidney-specific antigens are present in biopsies of renal allograft recipients undergoing acute cellular rejection. This subpopulation of tissue-specific cytotoxic T lymphocytes may prove to contribute significantly to the pathology of allograft rejection.

Spontaneous abdominal aortic rupture from erosion by a lumbar spine fixation device: a case report.

Spontaneous retroperitoneal hemorrhage is an uncommon event. A case of delayed postoperative aortic rupture from erosion by a spinal fixation device, heretofore not previously described, is presented to call attention to this potential catastrophe. Appropriate management includes aggressive patient resuscitation and early surgical intervention with initial proximal and distal control of the aorta, removal of the offending prosthetic appliance, and repair of the vascular injury. Prevention of this complication of vascular erosion by an implanted foreign body requires absolute avoidance of impingement on any medium or large artery.

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.

Intrahepatic portosystemic vascular stents: a bridge to hepatic transplantation.

Refractory esophageal variceal hemorrhage (EVH) remains a formidable problem in patients awaiting liver transplantations. Transjugular intrahepatic portosystemic shunts (TIPS) have provided an alternative approach for managing EVH that may obviate the need for portosystemic shunt surgery. Experience with TIPS placement and subsequent successful hepatic transplantation in patients without previous portosystemic shunt surgery has not been previously reported. Two patients are reported who underwent TIPS placement and subsequent successful hepatic transplantation without previous portosystemic shunt surgery. This experience indicates that (1) TIPS can provide effective control of EVH for at least several weeks, (2) TIPS placement decreases portal hypertension, thus facilitating technical performance of the transplant procedure and minimizing blood loss, (3) TIPS may undergo vascular incorporation, thus requiring that they be accurately positioned so that the lengths of suprahepatic inferior vena cava and portal vein are not compromised at the time of transplantation, (4) TIPS thrombosis can be effectively treated and prolonged patency may be observed, and (5) deterioration in hepatic function and exacerbation of hepatic encephalopathy were not observed after TIPS placement. In summary, TIPS provide an attractive, effective means for managing refractory EVH in patients awaiting liver transplantation.

Prostanoids and hypothermic renal preservation injury.

The effect of 48 hours of hypothermic renal ischemia utilizing Euro-Collins flush and short term reperfusion on renal prostaglandin synthesis was studied in dogs. Hypothermic ischemia followed by 60 minutes of reperfusion in-vivo resulted in significant elevations in renal Thromboxane B2 (TXB2) production in the outer cortex, inner cortex, and medulla, relative to non-ischemic kidneys. Prostaglandin E2 (PGE2) and 6-keto Prostaglandin F1 alpha (6-K PGF1 alpha) production were not significantly affected by ischemia and reperfusion. Enhanced TXB2 production was not seen with ischemia alone (without reperfusion) or with reperfusion with O2 saturated buffer, indicating a blood born source or stimuli. Early postreperfusion renal blood flow after hypothermic ischemia followed a biphasic pattern; blood flow increased for the first 10 minutes of reperfusion to achieve normal values, and then steadily declined over the next 20 minutes. This pattern was not altered by the cyclooxygenase inhibitors Idomethacin (5 mg/kg, P.O.) or Mefenamic acid (10 mg/kg, I.V.). Administration of the TXA2 synthesis inhibitor CGS-12970 (3 mg/kg, I.V.) or the TXA2/endoperoxide receptor antagonist SQ-29548 (80 micrograms/min, I.A.) significantly increased renal blood flow during reperfusion but neither agent altered the basic time dependent pattern observed in the control group. These data indicate that 48 hours of hypothermic renal ischemia results in dramatic changes in intrarenal TXA2 synthesis at the time of reperfusion. Enhanced TXA2 production is not dependent on reoxygenation per se, but rather requires reperfusion with blood suggesting a circulatory source.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal allograft recipient immunomodulation by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. One hundred thirty-five of 140 nonsensitized patients underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at 2 years (93%) and 7 years (87%) is significantly better (P less than .01) than our historical experience with one-haplotype living-related transplants at 2 years (68%) and 7 years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argue for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting-out process as the mechanism for improved allograft survival.

Preoperative immunomodulation of renal allograft recipients by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 113 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor/recipient combinations were at least 1-haplotype disparate and 17 were 2-haplotype disparate. Presensitization, defined as a positive Amos or antiglobulin T cell CM or a positive high-titer (greater than or equal to 1:8) B cell CM was present in 10 patients and not present in 103 patients. Attempts at desensitization of the already sensitized group were uniformly unsuccessful. Treatment of the 103 nonpresensitized patients resulted in transient sensitization in 3 patients, permanent sensitization in 8, and no evidence of sensitization in 92. Ninety-one nonsensitized patients underwent renal transplantation from the specific blood donor, and only 5 have experienced renal allograft rejection loss during a mean follow-up period of 26 months (6 to 70 months). Fifty-four percent have never experienced a rejection episode. The allograft survival rate at 2 years (91%) and 5 years (89%) is significantly better (P less than .01) than our historical experience with 1-haplotype living-related transplants at 2 years (66%) and 5 years (64%). The low rate of sensitization (8%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of rejection (5%) argues for a modification of the immunologic response rather than a selecting out process as the mechanism for improved allograft survival.

Concomitant immunosuppression and donor-specific transfusions prior to renal transplantation.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. Of 140 nonsensitized patients, 135 underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at two years (93%) and seven years (87%) is significantly better (p less than .01) than our historical experience with one-haplotype living-related transplants at two years (68%) and seven years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argues for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting out process as the mechanism for improved allograft survival.