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PubMed2002

Immunology and failure of valved allografts in children.

Valved allografts are frequently used in the repair of congenital heart defects in children. Although the longevity of these grafts is generally very good, there continue to be ongoing problems with allograft stenosis, allograft valve insufficiency, and subsequent allograft failure, particularly in younger children. This review presents data on the immunologic and nonimmunologic risk factors implicated in valved allograft failure, in addition to ongoing investigation into the improvement of allograft function.

ABO Blood-Group System↗

PubMed1987

Occlusive coronary arteritis: a cause of early death in a cardiac transplant patient.

A patient died 5 months after undergoing cardiac transplantation. Endomyocardial biopsies performed prior to death showed no evidence of severe rejection. At autopsy, nonnecrotizing occlusive coronary arteritis was present. The intima of the coronary arteries contained numerous lymphocytes and plasma cells. Chronic rejection appeared to be responsible for the arteritis. The onset of coronary occlusive disease is insidious, and recognition depends on the performance of coronary arteriography, which is usually not done until the one-year follow-up. Early coronary arteriography is suggested to rule out occlusive coronary arteritis when cardiac allograft function is not satisfactory, even when the endomyocardial biopsy shows no evidence of rejection.

Arteritis↗

PubMed1997

Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation.

BACKGROUND: The development of obliterative bronchiolitis after lung transplantation portends a poor long-term outcome because of progressive decline in allograft function. There are currently no effective means of treating this condition. METHODS: Thirteen patients in whom obliterative bronchiolitis syndrome developed after lung transplantation were treated with mycophenolate mofetil, an antimetabolite immunosuppressant, at a dose of 1.5 g orally twice daily. Patients were followed up clinically and with pulmonary function testing. RESULTS: Duration of mycophenolate mofetil therapy ranged from 1 week to 24 months (mean duration, 11.4 months). Pulmonary function test results stabilized in the majority of patients with no significant further decline in forced expiratory volume in 1 second. Two patients died of progressive obliterative bronchiolitis, 1 patient is alive with progressive disease, and 1 patient died of an acute infection. The drug was discontinued in 2 additional patients. In no patient did severe leukopenia or cytomegalovirus infection develop; 1 patient had a fungal infection, and 7 patients experienced gastrointestinal side effects. CONCLUSIONS: In the setting of obliterative bronchiolitis syndrome, mycophenolate mofetil is generally well tolerated and is associated with stabilization of pulmonary function test results. These findings suggest that the otherwise progressive process of obliterative bronchiolitis can be slowed.

Adult↗

PubMed1995

The use of expandable metal stents in transplant renal artery stenosis.

The management of resistant transplant renal artery stenosis (TRAS) poses difficult problems. There is no consensus on the most appropriate course of action if severe stenosis recurs despite repeated percutaneous transluminal balloon angioplasty (PTA). Expandable metallic vascular stents have been increasingly successful as an adjunct to PTA in the coronary and peripheral circulation and more recently in the management of resistant native renal artery stenosis. We report four cases in which such stents were successfully used to treat resistant stenosis in transplant renal arteries. The cases illustrate the range of problems that may be caused by TRAS, from resistant hypertension to impending graft failure. The stents were successfully deployed in all four patients. One patient had an acute stent thrombosis successfully treated with immediate thrombolysis and two patients required repeat stenting. In all the cases there was arrest or slowing of previously aggressive recurrent TRAS and at the close of follow-up (4-24 months) all patients had adequate stable allograft function, and satisfactory blood pressure control including the one patient with a significant residual stenosis.

Acute Kidney Injury↗

PubMed1999

Prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease patients after fortification of cereal grain flour with folic acid.

Cereal grain flour products fortified with 140 microg folic acid per 100 g flour became widely available in southeast New England by July 1997. We hypothesized that improved folate status secondary to this fortification policy would have a much more limited impact on the prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease patients. Between October 1997 and October 1998, fasting plasma total homocysteine (tHcy), folate and vitamin B12 levels were determined in a total of 86 renal transplant patients with stable allograft function, and 175 coronary artery disease patients whose serum creatinine was (1.4 mg/dl). All subjects lived in the Providence, RI, metropolitan area, and were either non-users of any supplements containing folic acid, vitamins B6 or B12, or had refrained from using such supplements for > or = 6 weeks. Geometric mean fasting tHcy levels were 88.0% higher (15.6 vs. 8.3 micromol/l; P < 0.001), and the prevalence of fasting tHcy levels > or = 12 microM (69.8% vs. 10.9%, P < 0.001) was markedly increased in the renal transplant patients, despite a much younger mean age and a relative preponderance of women. In the era of folic acid fortified flour, hyperhomocysteinemia is much more common in stable renal transplant versus coronary artery disease patients. As a result, renal transplant patients are a preferable high risk target population for controlled trials evaluating the tenable hypothesis that lowering total homocysteine levels will reduce cardiovascular disease outcomes.

Coronary Disease↗

PubMed1998

Total anatomic urinary tract replacement and renal transplantation: a surgical strategy to correct severe genitourinary anomalies.

During renal transplantation, the donor ureter is normally anastomosed to the recipient bladder. However, preexisting anomalies of the lower urinary tract or previous surgical interventions may render the recipient bladder unusable. Although in such situations urine may be externalized via cutaneous ureterostomy or an ileal conduit, both techniques are frequently complicated by bacterial colonization or chronic infection. To overcome these problems, the authors have been treating such children via extensive, staged, bladder reconstruction (augmentation) before transplantation. On rare occasions, however, the absence of a usable bladder necessitates the creation of a complete neobladder from other visceral tissues. The authors present two cases in which patients underwent complete anatomic reconstruction of the lower urinary tract before renal transplantation. This approach results in the optimal environment for allograft function and leads to a greater rehabilitation than that achieved with urinary diversion.

Female↗

PubMed1999

Long-term survival after liver transplantation.

BACKGROUND: Liver transplantation (LT) remains a high-risk operation, especially during the first months after LT when technical complications and preexisting illness exert their influence on survival. However, there are late deaths. The authors have reviewed their experience to identify factors impacting on long-term survival. METHODS: A total of 150 patients who had undergone liver transplantation over an 11-year period were reviewed. Thirty-three patients died after LT (22%). Of these, 18 of 33 (55%) died in the first 3 postoperative months. One hundred thirty-two patients survived beyond 3 months, and 15 patients (11%) suffered late deaths. This review concentrates on the latter group. RESULTS: The primary cause of death was sepsis in 11 of 15 (73%). In two, sepsis complicated retransplantation in chronically debilitated patients. Two additional patients had late-presenting postoperative complications (bile leak or abscess, intestinal obstruction with perforation). In two cases, pneumocystis carinii pneumonia occurred; noncompliance or unplanned discontinuation of prophylaxis was directly responsible. Multiple organ system failure from presumed immunoincompetence developed in four patients; one had undergone bone marrow transplantation for aplastic anemia (AA) after fulminant hepatic failure (FHF). Lymphoproliferative disease (LPD) was the cause of death in 3 of 15 cases (20%). In only three cases was the cause of death related to the patient's primary disease (chronic hepatitis, Alper's syndrome or seizures, and AA with FHF). Pretransplant diagnosis, and UNOS status at the time of LT did not influence the long-term survival. CONCLUSIONS: Long-term survival in patients who have undergone LT was compromised by immunosuppressive complications and sepsis. Early mortality factors, such as UNOS status, age at LT, primary diagnosis, and technical complications do not predict late deaths. In children who adhere to their medical regimen and have good initial allograft function, late postoperative infection, especially with Ebstein-Barr virus, accounts for most of the late mortality. Improved and decreased immunosuppression may further improve these long-term results.

Biliary Atresia↗

PubMed1997

Factors influencing short-term and long-term pediatric renal transplant survival.

OBJECTIVE: To determine the patient and donor characteristics important for short-term and long-term renal transplant survival at Cincinnati Children's Hospital Medical Center. METHODS: Cumulative transplant survival was calculated and univariate analysis of graft survival performed on 206 transplants done since 1970 in 148 pediatric patients. Grafts to black recipients were analyzed separately. Short-term graft survival is defined as 1-year allograft survival and long-term graft survival as graft half-life (t1/2) survival for allografts functioning after the first posttransplant year. RESULTS: One-year graft survival of living-related donor (LRD) and cadaver donor (CAD) transplants was 77% and 62%, respectively. Graft t1/2 was 11.2 years for LRD and 9.8 years for CAD grafts. The CAD 1-year graft survival when the recipient or donor was younger than 7 years was 36% and 41%, respectively. The LRD 1-year graft survival to children younger than 7 years was 88% versus 75% in older children. Graft survival at 1 year was similar for CAD primary and retransplants (60% vs 65%), but graft t1/2 better for CAD primary grafts (17.8 years vs 5.0 years, P < 0.001). Preemptive LRD grafts performed similarity at 1 year and better over the long term compared with patients who had long-term dialysis (85% vs 74%, P = NS; and 16.9 years vs 8.0 years, p < 0.001). Preemptive CAD grafts did poorly, with 1-year graft survival of 38%. Administration of Cyclosporine A (CsA) improved CAD 1-year graft survival (76% vs 54%, p < 0.001) but not long-term survival. Thirty grafts to 24 black children had a 1-year survival of 48%, with no graft surviving more than 5 years. CONCLUSIONS: Living-related donor transplantation should be aggressively pursued for young children. If a LRD is unavailable and the young child's medical condition is stable, delay in CAD transplantation should be considered, with dialysis before transplant. Use of CsA improves 1-year pediatric graft survival, but does not improve graft survival after 1 year at the Children's Hospital Medical Center. New strategies to improve graft survival in black children should be pursued.

Adolescent↗

PubMed2000

Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation.

OBJECTIVE: Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS: We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmenger's syndrome were excluded from analysis. RESULTS: Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION: We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.

Adult↗

PubMed1996

Human aortic valve allografts elicit a donor-specific immune response.

OBJECTIVE: The nature and magnitude of the immunologic response to implantation of human cryopreserved aortic valve allografts was investigated. METHODS: Twenty aortic valve allograft recipients were investigated for donor-specific antibody and T-cell-mediated responses with serial flow cytometric and microlymphocytotoxic crossmatch assays and one-way mixed lymphocyte cultures. RESULTS: Donor-specific immunoglobulin G antibodies to class I and II human leukocyte antigens were first detected in the serum of all aortic valve allograft recipients at 30 days after implantation and persisted in substantial amounts in all but one of the recipients at day 365. Recipient T-cell alloreactivity toward donor lymphocytes was significantly increased at day 30 compared with levels before and 10 days after operation. CONCLUSIONS: Cryopreserved aortic valve allografts elicit a substantial allogeneic response in recipients. This alloreactivity may contribute to the observed morphologic changes in aortic valve allografts and eventual long-term deterioration of allograft function.

Adult↗

PubMed1994

Use of a stockinette to minimize warm ischemia during renal transplant vascular anastomoses.

Prolonged warm ischemia during renal transplant vascular anastomosis may have a deleterious impact upon allograft function in the immediate post-transplant period. Placing the donor kidney and sterile ice slush in a cotton stockinette obviates renal rewarming during vascular anastomoses. We successfully used this technique in nearly 1,000 patients undergoing renal transplantation. The stockinette facilitates transplant vascular anastomoses by permitting easier handling of the kidney and eliminating warm ischemia during revascularization as documented by continuous core temperature monitoring.

Anastomosis, Surgical↗

PubMed1994

Renal transplantation into the dysfunctional bladder: the role of adjunctive bladder reconstruction.

A retrospective review of pediatric renal transplantation at 3 centers identified 9 patients who had undergone major bladder reconstruction. Seven patients underwent bladder augmentation (5 gastric, 1 colonic, 1 ureteral) and 2 received gastric neobladders. Six patients required Mitrofanoff neourethras. Patient survival was 100% with initial graft survival of 56% during a mean followup of 29.4 months. Eight patients (89%) are presently dialysis-free with functioning allografts and all 9 (100%) are continent of urine. We conclude that renal transplantation and reconstruction to ensure continence are justifiable in even the most anatomically compromised children with end stage renal disease. It is essential that the pediatric urologist should have an integral role in the management of such cases.

Adult↗

PubMed1994

Cyclosporine versus azathioprine: a 5-year followup of 200 consecutive cadaver renal transplant recipients.

When cyclosporine was introduced as an immunosuppressive agent, there was concern that cyclosporine could be detrimental to long-term renal allograft function and survival. In response to this concern, we report a 5-year followup of 200 consecutive renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. The azathioprine and cyclosporine groups had similar 1-year (89% versus 91%) and 5-year (74% versus 80%) patient survival rates. Cyclosporine treated patients had superior 1-year (83% versus 58%) and 5-year (61% versus 29%) graft survival rates. At the 5-year interval, cyclosporine treated grafts had an elevated, yet stable, mean serum creatinine level compared to azathioprine treated grafts. Despite ongoing mild renal dysfunction in cyclosporine treated grafts, cyclosporine does not induce an inexorable decrease in graft function and continues to provide long-term graft survival superior to azathioprine.

Azathioprine↗

PubMed1992

Therapeutic use of ganciclovir for invasive cytomegalovirus infection in cadaveric renal allograft recipients.

Between November 1987 and September 1989, 419 cadaveric renal transplants were performed at our university. Of the patients 36 (8.6%) had invasive cytomegalovirus infection documented by gastric or duodenal mucosal biopsy in 23 (64%), bronchoalveolar lavage in 12 (33%), allograft biopsy or nephrectomy specimen in 5 (14%) and/or liver biopsy in 1 (3%). Cytomegalovirus severity was defined as mild in 27 patients, moderate in 6 and severe in 3. Ganciclovir [9-(1,3-dihydroxy-2-propoxymethyl)-guanine] was begun once the diagnosis was confirmed by histology or culture at a median of 56 days from transplantation (range 28 to 133 days). Duration of ganciclovir therapy was a minimum of 7 days or until fever was absent for 5 consecutive days (mean 12.2 +/- 3.5 days, range 4 to 21). Ganciclovir was well tolerated and side effects were limited to de novo neutropenia (7 patients), thrombocytopenia (2) and rash (1). Initial clinical improvement was observed in all patients. Two patients had recurrent cytomegalovirus infections that responded to a second course of ganciclovir. The 1-year actuarial patient survival was 100%. At a mean followup of 12.7 +/- 6.2 months 19 patients retained allograft function with a mean serum creatinine of 2.5 mg./dl. (range 1.2 to 4.6). Ganciclovir appears to be a safe and effective drug for the treatment of tissue invasive cytomegalovirus infection in cadaver renal transplant recipients. Prompt institution of this drug at diagnosis of invasive cytomegalovirus may lower the mortality rate formerly associated with this disease.

Adolescent↗

PubMed1988

Surgical treatment of localized renal cell carcinoma in von Hippel-Lindau's disease.

From 1981 to 1986, 10 patients with von Hippel-Lindau's disease underwent an operation for bilateral nonmetastatic renal cell carcinoma. Of the patients 9 underwent unilateral partial nephrectomy and contralateral radical nephrectomy, and 1 underwent bilateral nephrectomy with subsequent hemodialysis and cadaver renal transplantation. Pathologically, the tumor was stage I in 9 patients and stage III in 1. Currently, 8 patients are alive after partial nephrectomy (5 to 56 months) with good renal function (mean serum creatinine 2.0 mg. per dl.) and no evidence of malignancy; 1 of these patients underwent excision of a cerebral metastasis 2 years after partial nephrectomy. One patient is alive on dialysis after removal of the renal remnant for local tumor recurrence. The patient who underwent transplantation is free of tumor with a well functioning allograft. The distinctive features of renal cell carcinoma in von Hippel-Lindau's disease that influence the management of these patients are reviewed.

Adult↗

PubMed1990

Pancreas transplantation at Mayo: III. Multidisciplinary management.

Although pancreas transplantation is a complicated procedure, a good level of success has been achieved because of the introduction of cyclosporine for immunosuppression, improved methods for diagnosing rejection, and a multidisciplinary approach to management. Our immunosuppressive regimen was quadruple therapy with induction by using Minnesota antilymphoblastic globulin. A biopsy technique was instituted in which the pancreas specimens were obtained under cystoscopic direction during episodes of hypoamylasuria. The criteria for rejection episodes were not only biochemical abnormalities but also histologic confirmation and a follow-up to exclude other causes of graft dysfunction. Infectious disease management included use of oral selective bowel decontamination for 3 weeks after transplantation. At the Mayo Clinic between October 1987 and December 1988, 16 patients received pancreaticoduodenal allografts (both kidney and pancreas in 13 and pancreas only in 3 after a prior successful kidney transplantation). In two pancreas and one kidney allograft, function was lost. One patient died of multiorgan failure. The cystoscopically directed biopsy technique was performed 23 times with minimal complications and a 93% success rate. The metabolic results have been excellent; the glycosylated hemoglobulin level was normal 3 to 6 months after transplantation. The quality of life was significantly improved in almost all patients. Nutritional assessment revealed little deterioration after transplantation. With a multidisciplinary approach, the needed answers about the effect of pancreas transplantation on the degenerative complications of diabetes should be forthcoming.

Adult↗

PubMed1995

Corticosteroid withdrawal after liver transplantation.

BACKGROUND: Long-term side effects of corticosteroids (CSs) result in > major morbidity for recipients of orthotopic liver transplants (OLT). We instituted a program of CS withdrawal among OLT recipients to quantify the contribution of CS to adverse clinical sequelae and to determine whether long-term CS administration is necessary to avoid rejection. METHODS: Recipients who had normal allograft function on CS, cyclosporine, and azathioprine more than 1 year after OLT were offered CS withdrawal during 12 to 22 weeks. Patients underwent routine clinical monitoring and laboratory studies. Continuous variables were compared by paired t test analysis. RESULTS: CSs were discontinued in 51 recipients; 45 (88%) of 51 patients remain steroid-free after a mean follow-up of 13.8 months (range, 4 to 36). CS therapy was reinstituted in 6 patients who had abnormal transaminase levels during routine follow-up. Among the patients who remain off CS, there were no significant changes in blood pressure, transaminase, alkaline phosphatase, bilirubin, or glucose levels during the study period. Mean number of blood pressure medications decreased from 0.7 +/- 0.1 to 0.4 +/- 0.1 (p = 0.007). Cholesterol decreased from 217 +/- 8 mg/dl on CS to 204 +/- 9 mg/dl at 1 month (p = 0.0001), 183 +/- 10 mg/dl at 3 months (p = 0.0001), 198 +/- 8 mg/dl at 6 months (p = 0.04), 213 +/- 11 mg/dl at 12 months (p = 0.01), 209 mg/dl +/- 16 at 18 months (p = 0.02), and 183 +/- 19 mg/dl at 24 months (p = 0.2) off CS. Weight loss occurred in 88% of patients and averaged 9.5 pounds. CONCLUSIONS: CS therapy can be successfully withdrawn without precipitating rejection in liver transplant recipients who have stable graft function 1 year after OLT. The incidence and severity of hypertension and hypercholesterolemia are reduced in patients whose CSs have been withdrawn.

Adrenal Cortex Hormones↗

PubMed1978

Pancreatic whole organ transplantation.

Transplantation of the whole pancreas can produce normal glucose homeostasis and there is evidence that a functioning allograft is capable of arresting or even perhaps reversing the vascular changes of diabetes. The technical complications of necrosis, bleeding, and perforation of the transplanted duodenum and disruption of the duodenalenteric anastomosis can all be managed by immediate removal of the allograft at the first sign of rejection. While there is increasing evidence that islet cells are more violently rejectedly in the human than are some other transplanted tissues, it is not clear whether this is true with the organ pancreas transplant. The four relatively long-term successes of organ pancreas transplants in the human would suggest that the organ transplant may act more like a kidney transplant than do islet cells. In the author's opinion, many of the problems may be technical, and carefully controlled, staged whole or partial pancreas allografts in the human still hold promise for ultimate better long-term success.

Animals↗