Showing papers in "Clinical Transplantation in 2000"

Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity.

Abstract: UNLABELLED We sought to examine the potential benefits of therapeutic drug monitoring of sirolimus, a potent immunosuppressive agent that displays a pleiotropic array of side effects. METHODS A high-performance liquid chromatography (LC) procedure combined with ultraviolet detection (UV) was used to measure serial concentrations of parent compound sirolimus in 150 renal transplant recipients over a period of 4 yr. Drug concentrations in whole blood at trough time, as well as within pharmacokinetic profiles, were correlated with clinical events using contingency tables, logistic regression analysis, and receiver operating characteristic (ROC) curves. RESULTS The LC/UV method showed an excellent correlation with detection of LC-resolved components by tandem mass spectrometry, demonstrating that the LC/UV method selectively detected parent compound. Sirolimus displayed the characteristics of a critical-dose drug: Its concentration could not be predicted by a standard body or demographic measure, or by dose, and it showed high degrees of intra- and inter-individual variability. However, there was a good correlation between trough and area-under-the-curve measurements. There was a significant association between trough values expressed as either observed ( < 5 ng/mL) or dose-corrected parameter ( < 1.7 ng/mL per mg administered drug) and the occurrence and severity of acute rejection episodes - despite the low overall incidence of 23 episodes among the cohort of 150 patients. Similarly, ROC functions showed a correlation of the occurrence of hypertriglyceridemia, thrombocytopenia, and leukopenia, but not hypercholesterolemia, with trough concentrations above 15 ng/mL. CONCLUSION Due to its behavior as a critical-dose drug, therapeutic monitoring to measure sirolimus concentrations by a LC/UV method may provide clinicians with a tool to optimize outcomes.

Central nervous system complications in liver transplant recipients--incidence, timing, and long-term follow-up.

Abstract: Background Neurological impairment is a major source of morbidity and mortality following orthotopic liver transplantation (OLT). We reviewed our experience with neurologic complications among our first 463 consecutive adult OLT recipients. Methods Between September 1988 and October 1993, 463 adult patients underwent OLT. Data on incidence, time of onset, and outcome of central nervous system (CNS) complications was obtained from patient charts, including autopsy results when available. CNS complications were classified by clinical presentation and by etiology. Results 93 patients (20.1%) had CNS complications following OLT. Encephalopathy (11.8%) and seizure (8.2%) were the leading complications. The incidence of immunosuppressive drug-related complications was 5.6%; coma, 1.7%; cerebral hemorrhage, 1.5%; central pontine myelinolysis (CPM), 1.2%; stroke, 0.6%; and primary CNS lymphoma, 0.2%. Most CNS events (80%) were encountered in the first month after OLT. In the majority of cases, encephalopathy (70%) and seizure (50%) presented in the first 2 wk. Although most CNS infections occurred early, 2 patients developed tuberculous meningitis more than 1 yr post-OLT. In 12 patients, death was directly related to CNS complications (2.6%). Conclusions Most CNS complications occur early following OLT but may be seen even after 1 yr. Patients may survive serious neurologic events, such as cerebral hemorrhage, CPM, and meningitis.

Venous complications after orthotopic liver transplantation

Abstract: Complications involving the portal vein or the vena cava, are rare after orthotopic liver transplantation. We report on the incidence and treatment of venous complications following 1000 orthotopic liver transplantations in 911 patients. Twenty-six of the adult patients (2.7%) suffered from portal complications after transplantation, whereas complications of the vena cava were observed in only 17 patients (1.8%). Technical problems or recurrence of the underlying disease (e.g. Budd-Chiari syndrome) accounted for the majority of complications of the vena cava, whereas alteration of the vessel wall or splenectomy during transplantation could be identified as important risk factors for portal vein complications. In patients undergoing modification of the standard end-to-end veno-venous anastomosis of the portal vein due to pathological changes of the vessel wall, complications occurred in 8.3%, whereas only 2.4% of patients who received a standard anastomosis of the portal vein experienced complications of the portal vein. Furthermore, splenectomy during transplantation was also associated with an increased incidence of portal vein complications (10.5 vs. 2.2% in patients without splenectomy). Treatment was dependent on the signs and symptoms of the patients, and varied considerably between patients with portal vein complications and patients suffering from complications of the vena cava. Complications of the vena cava led to retransplantation in about one-third of the patients, whereas in patients with occlusion of the portal vein, retransplantation was necessary in only 15%, and more than half of the patients suffering from portal vein complications did not require any treatment at all. Usually, treatment of patients with portal vein complications only became necessary when additional complications such as arterial occlusion or bile duct injuries occurred.

Health related quality of life (HRQOL) of kidney transplanted patients : Variables that influence it

Abstract: The incidence and prevalence of patients on renal replacement therapy (RRT) who receive a renal transplant are continuously increasing in Spain. At the moment, they are the main group of end-stage renal disease (ESRD) patients in our region (60% of total RRT patients). The aim of the present study was to assess the health related quality of life (HRQOL) of kidney transplanted patients of our region, and to identify socio-demographic and clinical variables that influence it. The intention was also to compare the HRQOL of these patients with that of chronic haemodialysis (HD) patients and of the general population. Methods. Two hundred and ten kidney transplanted patients and 170 HD patients were evaluated using the Karnofsky performance scale (KPS), sickness impact profile (SIP), and SF-36 Health Survey (SF-36). Socio-demographic and clinical data, including a comorbidity index (CI), were also collected. To compare our patients with the general population we used SF-36 mean scores from an aleatory sample taken from our region. Results. Transplant patients had lower mean scores on SIP dimensions and higher scores on SF-36 dimensions than chronic HD patients. In transplant patients, we found significant differences on SIP and SF-36 scores in gender, educational level, haematocrite and haemoglobin, CI, time since transplantation, and KPS. Conclusions. The HRQOL of transplant patients is clearly better than that of chronic HD patients and similar to that of the general population. Differences in the HRQOL within transplant patients did not appear to be as a result of patient's age, but rather it would appear to be a consequence of gender, analytic figures, CI, KPS score, time with transplant, and educational level.

Influence of religious and spiritual values on the willingness of Chinese–Americans to donate organs for transplantation

Abstract: The rate of organ donation among minority groups in the United States, including Chinese-Americans, is very low. There is currently very little data in the biomedical literature that builds on qualitative research to quantify the attitudes of Chinese Americans toward organ donation. The present study quantitatively assesses the religious and cultural reasons that Chinese-Americans appear to be less willing to donate their organs than other populations. It also seeks to determine whether Confucian, Buddhist, or Daoist ideals are a significant factor in their overall reluctance to donate organs among respondents in this sample. A questionnaire distributed to Chinese American adults asked about general feelings toward organ donation and Buddhist, Confucian, Christian, Daoist, and other spiritual objections. The results suggest that Chinese-Americans are indeed influenced by Confucian values, and to a lesser extent, Buddhist, Daoist, and other spiritual beliefs, that associate an intact body with respect for ancestors or nature. Another significant finding is that the subjects were most willing to donate their organs after their deaths, to close relatives, and then in descending order, distant relatives, people from their home country, and strangers. This 'negotiable' willingness has enormous implications for clinicians, who may be able to increase organ donation rates among Chinese-Americans by, first, recognizing their diverse spiritual beliefs, and, second, offering a variety of possibilities for the organ procurement and allocation.

Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients.

Abstract: The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.

Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature.

Abstract: Human Parvovirus B19 (PV B19) is one of the several recently described ‘emerging viruses’ and has been identified as the etiological agent of ‘fifth disease’ in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19-induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine-based immunosuppression and 14 had tacrolimus-based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self-limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.

Bone loss after renal transplantation: role of hyperparathyroidism, acidosis, cyclosporine and systemic disease.

Abstract: UNLABELLED In order to determine risk factors for bone loss after renal transplantation, dual energy X-ray absorptiometry was performed in 125 renal transplant patients. The bone mineral density (BMD) was expressed as a percentage of the normal population (BMD%) and Z-score (SD from normal). The whole body, lumbar spine and femoral neck BMD% (Z-score) values were 93.9 +/- 8.9 (-0.90 SD), 91.6 +/- 14.9 (-0.98 SD) and 87 +/- 15.3 (-1.0 SD)%, respectively. Low BMD% was associated with low creatinine clearance ( 40 mL/min: 95.6 +/- 8.0, p 1: 87.4 +/- 9.3, p 5: 90.1 +/- 10.6, p 27: 96.7 +/- 7.2, p 200: 87.7 +/- 5.0, p 300: 85.6 +/- 13.2, p 100: 89.3 +/- 7.6, p 10: 82.1 +/- 20.1, p 20: 96.9 +/- 7.4, p 150: 92.1 +/- 9.3, p 550: 94.2 +/- 7.8, p 3 microg/wk: 97.3 +/- 6.9, p < 0.05). No relationships with transplantation duration, 1,25-OH-vitamin D, aluminium, calcium or steroid dose were found. No involutional changes in tertiary hyperparathyroidism could be discerned. CONCLUSION The major threats to bone mass after renal transplantation appear to be ongoing hyperparathyroid bone disease, low renal function, acidosis, systemic disease and hypo-vitaminosis D.

Implication of advanced donor age on the outcome of liver transplantation

Abstract: Historically, age has been considered to be a relative contraindication for organ donors. The use of elderly donors for liver transplantation remains controversial due to the fear of inferior outcome. According to United Network for Organ Sharing (UNOS) data, the proportion of older donors has been increasing annually. This study describes the short- and long-term outcomes for transplantation of elderly donor livers. Three hundred and seventy-four primary liver transplantations, which had been performed at the University of Virginia Health System from 7 February 1988 to 31 December 1998, were included. Graft survival, incidence of primary non-function, and hepatic artery thrombosis (HAT) after transplantation according to the different age groups of liver donors were analyzed. Cases were analyzed by donor age (group I, n = 106: aged 5 yr younger than their age; group VI, n = 43: recipients from donors > 5 yr older than their age). Group III or VI (group of advanced donor age) and group II or V (control group) were compared by age, gender, race, body weight, height, pre-transplantation cytomegalovirus (CMV) status of the recipients donors, cause of brain death of donors, total or warm ischemic time, ABO matching, and degree of human leucocyte antigen (HLA) mismatching. No significant difference in 5 yr graft survival was found between the groups by donor age (p = 0.604) and by donor age compared with recipient age (p = 0.567). Moreover, no significant differences in the incidence of primary non-function and HAT after transplantation were found between the groups by donor age and by donor age compared with recipient age. Older donors were more likely to be women and to have antibodies to CMV, as well as to have died by cerebrovascular causes. Race, body weight, height of both recipients and donors, total or warm ischemic time of grafts, ABO matching, and degree of HLA mismatching were not significantly different between the groups. We conclude from this study that advanced donor age is not a contraindication to liver transplantation if careful assessment of donors is made on a case-by-case basis. There is a need to maintain an open mind with regard to the use of livers from older donors due to the current situation of serious organ shortages.

Prophylactic photopheresis and chronic rejection: effects on graft intimal hyperplasia in cardiac transplantation.

Abstract: Background: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti-HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia. Methods: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy. Results: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1-yr (0.23 vs. 0.49 mm, p < 0.04) and 2-yr (0.28 vs. 0.46 mm, p < 0.02) follow-up compared with the control group. Conclusion: In this small pilot study, photopheresis is a safe, well-tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post-transplant graft intimal hyperplasia.

Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors

Abstract: Introduction. The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV ) or hepatitis C virus seronegative (HCV ) donors into HCV recipients; and 2) to determine whether HCV patients with end-stage renal disease (ESRD) might benefit from receiving renal allografts from HCV donors.

Improved outcomes in cadaveric renal allografts with pulsatile preservation.

Abstract: Background: Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation - pulsatile perfusion (PP) versus cold storage (CS) - is debated. Methods: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( 40 min) and total ischemic time (TIT) ( 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. Results: There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). Conclusions: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

Abstract: An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

A calcineurin inhibitor-sparing regimen with sirolimus, mycophenolate mofetil, and anti-CD25 mAb provides effective immunosuppression in kidney transplant recipients with delayed or impaired graft function.

Abstract: Delayed graft function (DGF) after renal transplantation is a significant risk factor for early acute rejection and graft loss. Sirolimus (SRL) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. We examined a calcineurin-sparing regimen using SRL during the early post-operative period in renal transplant patients with delayed or impaired graft function. A retrospective review of 14 consecutive kidney transplant recipients with delayed or impaired graft function who received SRL was performed. The immunosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5-15 mg load followed by 2 5 mg daily maintenance therapy), corticosteroids, and mycophenolate mofetil (MMF, 1.5-3 g/d). Patients were monitored for allograft function, acute rejection, graft survival, thrombocytopenia, and leukopenia. Serum levels of SRL were determined by high-performance liquid chromatography performed at an independent commercial laboratory. Donors were cadaveric in 13 cases and living related in one. The duration of follow-up was 0.5-5.2 months. Nine patients required hemodialysis after transplantation. The mean time to initiation of calcineurin inhibitors was 21 +/- 13 d. Average serum creatinine levels at the initiation of SRL and at 1 month after transplantation were 8.4 +/- 2.7 and 2.1 +/- 1.2 mg/dL, respectively. There were 2 patients (14%) who experienced acute rejection within the first month after transplantation -1 with type I (steroid therapy) and 1 with type II (anti-thymocyte therapy). Serum levels of SRL were initially undetectable in the 2 patients with acute rejection. No grafts were lost during the period of follow-up. Three patients developed thrombocytopenia (platelets < 100 x 10(9)) and no patients developed leukopenia. The combination of SRL with anti-CD25 mAb, MMF, and corticosteroids appears to provide effective non-nephrotoxic immunosuppression for kidney transplantation without the need for a lymphocyte-depleting regimen. However, it is important to monitor serum SRL levels to determine the optimal dosing regimen. Furthermore, long-term follow-up of these patients will be helpful to determine whether improved immunosuppression can be achieved with a fully calcineurin-sparing regimen using SRL.

Piggyback technique and selective use of veno-venous bypass in adult orthotopic liver transplantation.

Abstract: Background. The piggyback technique (PT), with preservation of the cava, is being used more frequently in adult orthotopic liver transplantation (OLT). The advantages of PT include hemodynamic stability during the anhepatic phase without a large-volume fluid infusion and obviating the need for veno-venous bypass (VVB). At our center, we changed our practice in July 1997 from the standard technique (ST) of OLT with routine use of VVB to PT and selective use of VVB. The purpose of the present study was to analyze the results with the two different practices, ST-routine VVB versus PT-selective VVB. Methods. Forty OLTs were performed during the period July 1995-July 1997 using ST-routine VVB (group I) and 36 during August 1997--December 1998 using PT-selective VVB (group II). The etiology of liver disease was similar in the two groups, with hepatitis C and alcoholic liver disease accounting for half of the patients in each group. The UNOS status, age, sex, and percentage of patients with previous upper abdominal surgery were also similar between the two groups. Results. In the PT-selective VVB era (group II), 34/36 patients (94%) underwent OLT with PT and VVB was used for 8 (22%) patients. The decision to use VVB was elective for 3 patients (fulminant hepatic failure, 2; severe portal hypertension, 1) and urgent for 5 patients (hemodynamic instability during hepatectomy). The intraoperative use of packed red blood cells (PRBC) (mean ± SD) was 15 ± 12 units for group I and 9 ± 8 units for group Il (p = 0.023). Anastomosis time and total operating time (mean ± SD) were 91 ± 30 min and 9.5 ± 3.2 h, respectively, for group I patients compared with 52 ± 28 min and 7.6 ± 1.6 h, respectively, for group II patients (p 90%) undergoing OLT. With the routine application of the piggyback procedure, the use of VVB has been reduced to 20% of OLTs at our center. The practice of piggyback technique with the selective use of VVB is associated with shorter anhepatic phase and total operating time, lower blood product use, a trend towards shorter hospital length of stay, and reduced hospital charges compared with standard technique of OLT with routine use of VVB.

The use of contaminated donor organs in transplantation.

Abstract: Introduction. Organ transplantation has become an accepted means of treating end-stage organ disease in recent years with acceptable patient and graft survival. Transplant recipients have an increased risk of infectious complications due to multiple factors including decreased host resistance from chronic end-stage organ failure as well as from the immunosuppression required to prevent graft rejection. Hypothesis. Therefore, the use of contaminated allografts could result in life-threatening infections in organ recipients. Method. In this study, transplant patients receiving organs from donors with positive blood or urine cultures, from 1993 to 1997, were retrospectively reviewed. Results. There was a total of 599 organ donors in our state. Forty-six (7.5%) had positive blood cultures and 25 (4.5%) had positive urine cultures. A total of 179 patients received organs from these contaminated donors, 36 of which were transplanted at our center. In this group, there were 16 kidney, 9 liver, and 11 heart transplants. Both donors and recipients received prophylactic broad-spectrum antibiotics, which were adjusted based on culture and sensitivity results. The most common organisms isolated from the blood were staphylococci followed by streptococci and Gram-negative organisms. Three of the 9 liver transplant patients in the series died with a mortality of 33%. Two of the 3 patients who died had sepsis but the responsible organisms were different from those recovered from the donor. The rest (66%) did well and have acceptable liver function. None of the 16 renal transplant recipients developed an infection and all survived. One patient developed acute irreversible rejection requiring transplant nephrectomy. There was one death in the heart transplant group resulting in a mortality of 9%. This death was not attributed to infectious processes. Three of 11 heart transplant patients grew organisms in the post-operative period that were similar to those found in the corresponding donors. However, no patient suffered significant morbidity or mortality from these infections and all recovered. The recipients of contaminated organs had levels of organ function similar to those of randomly chosen recipients of non-contaminated organs, and both groups had similar lengths of hospital stay. Conclusion. Only 3 of 36 organ recipients had infections caused by organisms found in the contaminated donor organs for a rate of 8%. Contaminated donor organs seem to fare as well as non-contaminated donor organs and there was no increase in morbidity or mortality. Contamination of organs should not be an absolute contraindication to the use of these organs in transplantation.

Extracorporeal membrane oxygenation support of donor abdominal organs in non-heart-beating donors.

Abstract: Both family consent and legal consent were required for organ/tissue donation from non-heart-beating donors (NHBD) in Taiwan. A district attorney had to come to the bedside to confirm the donor's asystole, confirm the family consent, and complete some legal documents before a legal consent was issued for organ donation. The resultant warm ischemic time would be unpredictably long and in fact precluded the organ donation from NHBD in Taiwan. We developed a method of using extracorporeal membrane oxygenation (ECMO) to maintain NHBD for a longer time and prevent warm ischemic injury of the donor abdominal organs. After ventilator disconnection in NHBD, phentolamine and heparin were injected and mannitol infusion was given. After the donor's asystole was confirmed by the electrocardiogram (EKG) strip recording, the ECMO support was set up through the right femoral veno-arterial route, an occlusion balloon catheter was inserted through the left femoral artery to occlude the thoracic aorta, and bilateral femoral arteries were ligated. Usually, the ECMO could begin within 10 min after the donor's asystole. The ECMO, combined with a cooler, provided cold oxygenated blood to the abdominal visceral organs, and prevented their warm ischemic injuries. Under the ECMO support (range: 45-70 min), eight renal grafts were procured from 4 NHBD. With the exception of the first two renal grafts with delayed function, all others had immediate function postoperatively and dialysis was no longer needed. In conclusion, by our ECMO technique, NHBD could be maintained for a longer time and the renal grafts had better immediate postoperative function than those reported by other methods.

Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants

Abstract: Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.

Nonoperative management of bile leaks following liver transplantation.

Abstract: The biliary anastomosis has been called the Achilles heel' of liver transplantation (RABKIN JM, ORLOFF SL, REED MH. Transplantation 1998: 65 [2]: 193; DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447). Biliary complications after liver transplantation reportedly occur at an incidence of 20-30%, 10-15% as bile leaks. The management of bile leaks, especially early bile leaks, is controversial. In the present study, we report our experience with the management of bile leaks after liver transplantation. In this retrospective study, we reviewed 85 liver transplants over a 3-yr period. In 79, the biliary anastomosis was choledochocholedochostomy (CDCD) over a small-caliber T-tube, while choledochojejunostomy (CDJ) was used in 7. Over a mean follow up period of 13.5 months (median 10 months), 10 patients (12%) experienced a clinically significant bile leak within the first 3 months after liver transplantation. The early leaks, occurring within 1 month of transplant, were successfully managed by observation (DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447) or endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a biliary stent for a duration of 6-12 wk (RANDALL HB, WACHS ME, SOMBERG KA. Transplantation 1996: 61 [2]: 258). One of these resulted from accidental dislodgement of the T-tube on postoperative day 1; one resulted from necrosis at the CDCD anastomosis and required CDJ; the remaining four resulted from leaks along the T-tube track. One of the late leaks occurred following the planned removal of the T-tube at 3 months after liver transplantation; the other two were leaks along the T-tube track. All were successfully treated by ERCP and stent placement, though in one case, ERCP was initially unsuccessful because of the inability to advance a guidewire, necessitating a fluoroscopically aided guide wire placement during a mini laparotomy. ERCP was then successfully performed with the placement of a stent. Tab. Conclusions: Our experience indicates that most bile leaks after liver transplantation, including early leaks, can be successfully managed non-operatively. Most will require intervention, but ERCP and stent placement are usually sufficient.

Knowledge and opinions about organ donation among urban high school students: pilot test of a health education program.

Abstract: Background: Increasing the diversity of the organ donor pool might improve the opportunities for people of color on organ transplant waiting lists to receive donated organs. We report on the results of a pilot classroom health education program to improve knowledge about organ donation and transplantation among a diverse student body at an urban high school. Methods: The effectiveness of the educational program was evaluated with baseline and follow-up questionnaires which examined: 1) whether the program increased knowledge about organ donation; 2) whether the students’ opinions about organ donation changed; and 3) whether the program was related to any changes in opinion. Results: On the follow-up questionnaire, correct answers on 15 factual questions increased by 18% for the treatment group, compared to 5% for the control group (p=0.00). Regarding opinions, at baseline 92% of white students had positive opinions about donation, compared to 48% of the students of color (p=0.00). In the follow-up survey, the increase in positive opinions among the students of color was significantly greater than among white students (p=0.04). In this pilot study, however, changes in opinions occurred with equal frequency among students in the treatment and control groups. In regression analysis, both knowledge of the subject and discussing donation with one's family were significantly associated with positive opinions about donation. Conclusions: Overall, this pilot study provided encouraging evidence that the classroom health education program affected knowledge about organ donation, and that opinions about organ donation are responsive to increases in knowledge.

Pancreas transplant outcomes for United States (US) cases reported to the United Network for Organ Sharing (UNOS) and non-US cases reported to the International Pancreas Transplant Registry (IPTR) as of October, 2000.

Abstract: As of October 2000, > 15,000 pancreas transplant had been reported to the IPTR, > 11,000 in the US and > 4,000 outside the US. An era analysis of US cases from 1987-2000 showed a progressive improvement in outcome (p 45 years old increased from 5% to 25%, and the improved outcomes encompassed the older patients as well. In patients > 45 years old, SPK pancreas GSRs at one year increased from 62% to 78% (p or = 94% in each recipient category, with one-year pancreas GSRs of 84% for SPK (n = 3,697), 76% for PAK (n = 696), and 71% for PTA (n = 300) (p = 0.0001). The immunological graft failure rates for 1996-2000 US SPK, PAK and PTA cases were 2%, 6%, and 8% at one year (p = 0.001). There was a progressive increase in the use of ED (as opposed to BD) for duct management, to > 50% for 1996-2000 US SPK transplants. Approximately 20% of US SPK ED transplants had venous drainage via the portal system. Pancreas GSRs were not significantly different for 1996-2000 ED (n = 1,940) and BD (n = 1,541) US SPK transplants (83% and 84%, respectively, at one year), nor was there a difference in pancreas GSRs for systemic (n = 1,509) versus portal (n = 411) venous drained ED SPK transplants (83% for both at one year). Kidney GSRs were also not significantly different for ED versus BD US SPK cases, 93% versus 91% at one year (p = 0.13). Duct management did matter for solitary (PAK and PTA) pancreas transplants (P 0.08). In regard to non-US cases, the overwhelming majority were in the SPK category (n = 676 for 1996-2000), with a one-year pancreas GSR of 84%, not significantly different than for US cases. In summary, pancreas transplant graft survival rates were > 70% in the solitary (PAK and PTA) and > 80% in SPK recipients during the last 4 years of the 20th century. These outcomes culminate a third of a century of application for the treatment of diabetes mellitus.

Quality of life in long-term survivors after liver transplantation: impact of recurrent viral hepatitis C virus hepatitis.

Abstract: Post liver transplant recurrence of infection with hepatitis C virus (HCV) occurs in approximately 50 of patients transplanted because of HCV-related liver disease. The aim of this study was to assess long-term quality of life, psychologic distress, and coping in patients with recurrent HCV after liver transplantation in comparison to patients transplanted for other etiologies of underlying liver disease. All liver transplant recipients transplanted at a University affiliated Veterans Affairs Medical Center who had greater than 6 months follow-up were sent a questionnaire investigating quality of life (assessed by Medical Outcomes study health survey SF-36), depression (assessed by Beck Depression Inventory), total mood disturbance (assessed by Profile of Mood States scale), coping (assessed by Billing and Moos Inventory of coping with illnesses), and employment status. Lower Beck Depression Inventory score (p = 0.001), lower mood disturbance score (p = 0.0001), overall satisfaction with present work (p = 0.0001), and lesser use of avoidant coping (p = 0.06) were predictors of better quality of life in long-term survivors of liver transplantation. At a mean follow-up of 4 yr after liver transplantation, patients with histopathologically diagnosed recurrent viral HCV hepatitis had significantly lower global quality of life score (mean score of 76.4 versus 86.2, p = 0.011) and physical functioning score (mean score 20 versus 25, p = 0.015), as compared to all other patients. In summary, quality of life and physical functioning were significantly impaired in liver transplant recipients with histopathologically diagnosed recurrent HCV hepatitis, as compared to those whose HCV hepatitis had not recurred or those transplanted for other reasons.

Efficacy and safety of amphotericin B lipid complex injection (ABLC) in solid-organ transplant recipients with invasive fungal infections.

Abstract: Background Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients. Methods Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease. Results The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n = 39); candidiasis (n = 20); zygomycosis (n = 8); cryptococcosis and histoplasmosis (n = 3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis, Dactylaria gallopava, and an unspecified fungal infection (n = 1 each). The median duration of ABLC therapy was 28 d (1-178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n = 37) or improved (n = 27) serum creatinine at the end of treatment. Conclusions ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.

Peripheral endothelial dysfunction in heart transplant recipients: possible role of proinflammatory cytokines.

Abstract: Endothelium-dependent vasodilation in the peripheral circulation may be impaired in heart transplant recipients (HTx rec). Conflicting results have been obtained and the mechanisms involved have not been examined. In the present study, we examined whether long-time survivors of heart transplantation (Tx) show signs of endothelial dysfunction in the peripheral microcirculation, and further investigated the possible role of endothelium-related markers and proinflammatory cytokines in this process. The vasodilatory responses to acetylcholine (Ach) (endothelium-dependent) and sodium nitroprusside (SNP) (endothelium-independent) were evaluated by skin laser-Doppler perfusion measurements in 63 clinically stable HTx rec 6 yr (range 1-13 yr) after Tx, and compared with 20 healthy controls. Ten HTx rec were also followed prospectively with three repeated measurements during the first year after Tx. Plasma von Willebrand factor, big-endothelin (b-ET), and proinflammatory cytokines were measured by enzyme immunoassays. Vascular responses to both Ach and SNP were significantly attenuated in the HTx rec compared with controls. In longitudinal testing, there was a significant reduction in endothelium-dependent vasodilation, but not independent vasodilation from 1 to 12 months after Tx. Plasma levels of vWF and b-ET, as well as levels of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta, were all markedly increased in HTx rec. HTx rec responses to Ach were negatively correlated to TNF-alpha levels in plasma (r = -0.39, p < 0.01). Moreover, there was also a significant positive correlation between plasma b-ET and TNF-alpha (r = 0.34, p < 0.01). In the long-term follow-up of HTx rec, endothelial dysfunction is demonstrated by both regulation of blood flow in the skin microcirculation and by raised markers of endothelial activation in plasma. This endothelial dysfunction may be related to enhanced levels of proinflammatory cytokines in these patients.

Immunization of renal transplant recipients with pneumococcal polysaccharide vaccine.

Abstract: Background: Streptococcus pneumoniae, a common pathogen leading to pneumonia, is a cause of morbidity and mortality in immunosuppressed patients. Vaccination against this agent can be recommended for immunosuppressed patients, including those with chronic renal failure, nephrotic syndrome and renal transplant recipients: however, a diminished immune response and loss of protective antibodies have been observed. Patients and methods: In our prospective study, the efficacy and side effects of polyvalent pneumococcal vaccination were investigated in renal transplant recipients. A total of 21 patients (6 female. 15 male) with well-functioning renal allografts, who had transplant surgery at least 2 months before, were included in the study. The patients were stratified according to the immunosuppressive protocol and 8 received double, while 13 received triple, immunosuppresive agents. After obtaining basal serum samples, all cases were vaccinated with the 0.5 mL intramuscular administration of polyvalent polysaccharide pneumococcal vaccine (Pneumo 23 Pasteur Merieux. lot No: K 1131). Results: Following a mean of 6 wk in all patients and also a mean of 12 wk in 12 patients, serum samples were again obtained to measure pneumococcal antibodies. Antibody titers following 6 and 12 wk of vaccination were significantly higher, as compared with basal values in all patients, except one. These titers did not show any statistically significant difference between double and triple therapies. There was no significant difference between the 12th and 6th wk postvaccination antibody titers. No systemic or local adverse effects were observed Conclusion: Pneumococcal vaccination is safe and effective in patients with well-functioning renal allografts, at least in the short term. This vaccination policy may be useful for preventing invasive pneumococcal disease in immunosuppressed patients.

Simultaneous pancreas-kidney transplantation: portal versus systemic venous drainage of the pancreas allografts.

Abstract: Simultaneous pancreas-kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end-stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group = 17) received SPK transplantation with systemic venous drainage, and the second group (PV group = 17) received pancreas allograft with portal drainage. A Roux-en-Y loop was performed in all the patients. Patient follow-up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.

Specificity of preformed alloantibodies causing B cell positive flow crossmatch in renal transplantation

Abstract: The specificity of alloantibodies (alloAb) and their clinical significance in association with T-/B+ flow cytometry crossmatch (FCXM) in kidney transplantation are not clearly defined. This study was undertaken to examine the HLA specificity and clinical relevance of Ab causing B+ FCXM in pre-transplant (final XM) recipients' serum samples. Final FCXM serum samples were analyzed from 457 renal transplant patients followed for 10 months post-transplantation. Two hundred and sixty patients had T-/B+ final FCXM. The control group included 197 recipients with T-/B- FCXM at time of transplantation. Class I/class II PRA and specificity of anti-HLA class I and class II Ab in final FCXM serum samples were analyzed by FlowPRA Class I Screening Test and FlowPRA Class II Screening Test. We found no correlation between graft outcome and pre-transplant T-/B- and T-/B+ FCXM status. Additionally, we observed no clinical relevance of B+ FCXM in retransplant patients. However, MCS > or =200 in B+ FCXM retransplant recipients was associated with anti-class II Ab to previous mismatches in regrafted patients (n = 46). This finding was confirmed by specificity analysis of anti-DR/DQ Ab in patients with high ( > or =15%) class II PRA. In 63% (12 of 19) of retransplants having T-/B+ FCXM, we defined the specificity of alloAb to first graft mismatched class II antigens. In contrast, anti-class II Ab was detected in only 5.7% (2 of 35) of single-graft recipients with different PRA values. Significantly greater MCS (240 +/- 61 vs. 163 +/- 48; p = 0.022) was observed in retransplant patients having short ( or =5 m). Only 2% of retransplant recipients with B + FCXM had non-HLA Ab. In contrast, the overwhelming majority of primary recipients had no detectable alloAbs. No significant difference in class I PRA was found between B- and B+ FCXM recipients. However, class II PRA was significantly higher in patients having B + FCXM (p = 0.028). Collectively, these data show that MCS intensity is not always a reliable criterion for anti-HLA Ab detection because of the presence of non-HLA Ab. These results can be explained by low titers of anti-class II Ab, at which concentration these Ab cannot produce a deleterious effect. FlowPRA and Flow screen beads appeared to be reliable and sensitive methods for detection and specificity analysis of anti-class II alloAb.

Influence of anti-rejection therapy on the timing of cytomegalovirus disease and other infections in renal transplant recipients.

Abstract: Orthotopic liver transplantation is used for treatment of liver cirrhosis and organ failure due to chronic hepatitis B infection. However, in the absence of effective antiviral therapy, patients can develop recurrent hepatitis B leading to graft failure. In this report, a review is presented of several European studies that have demonstrated the efficacy of hepatitis B immunoglobulin (HBIg) in lowering the rate of recurrence or the severity of the recurrent infection. Clinical protocols and results of these studies are described in detail. Several important conclusions can be derived from the clinical results. HBIg is most effective when administered in high doses for a long time. Characteristics of the recipients, such as the presence or absence of viral DNA, can also affect the rate of recurrence. Intramuscular injection of HBIg has minimal side effects and results in reduced cost relative to intravenous injection.

Cost-benefit analysis of a clinical pharmacist-managed medication assistance program in a renal transplant clinic

Abstract: UNLABELLED Medicare pays for 80% of the cost of immunosuppressant agents needed within the first 3 years of solid organ transplantation; however, many patients cannot afford the remaining 20%. Furthermore, many patients who are beyond 3 years post-transplantation and have prescription coverage cannot afford the co-payment for these medications. Other patients may not be able to afford their medications due to limited or no insurance coverage. The Medical College of Georgia (MCG) has been giving immunosuppressant medications to renal transplant patients if they cannot afford to pay for them. To assist MCG with drug cost for medications and maintain quality care for renal transplant patients, a clinical pharmacist-managed medication assistance program was implemented to procure immunosuppressants from pharmaceutical manufacturers. METHODS All patients enrolled in medication assistance programs from 1 January 1998 through 31 December 1998 were included in this analysis. Medication acquisition costs with and without Medicare reimbursement and the cost of implementing the clinical pharmacist-managed medication assistance program were used to determine the value of implementing this service. RESULTS Sixty-one patients were enrolled in manufacturers' assistance programs and a net cost avoidance of $124,793 was realized for the year of the program (benefit-to-cost ratio of 7.5:1). Assuming that the hospital collected the maximum amount allowed for patients receiving Medicare benefits, a cost avoidance of $69,233 was calculated (benefit-to-cost ratio of 4.16:1). CONCLUSIONS A clinical pharmacist-managed medication assistance program in a renal transplant clinic produced substantial cost savings over this 1-year study period. For each dollar spent in pharmacist's time, a minimum of $4 was returned to the institution.

Graft-versus-host disease after liver transplantation: documentation by fluorescent in situ hybridisation and human leucocyte antigen typing.

Abstract: Graft-versus-host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. Skin biopsy showed characteristic changes of GVHD. Using Y-chromosome-specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti-thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA-identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.