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PubMed1994

Liver transplantation for neonatal hepatitis as compared to the other two leading indications for liver transplantation in children.

Neonatal hepatitis is a syndrome of unknown etiology occurring in children with viral liver disease, as well as children with unidentified disorders of bile salt synthesis and other poorly understood metabolic diseases. It is characterized by jaundice, giant cell hepatitis and rare liver failure necessitating liver transplantation. In the present investigation, the outcome of liver transplantation performed in 16 children with neonatal hepatitis at the investigators' institution was determined from 1 January 1989 to 31 December 1991. The results were compared to those obtained in 288 children transplanted for biliary atresia and 66 children transplanted for recognized metabolic liver disease. The children transplanted for neonatal hepatitis (4.1 +/- 1.3 years) and metabolic liver disease (5.8 +/- 0.6 years) were older than those transplanted for biliary atresia (3.3 +/- 0.2 years) (p < 0.01), but did not differ in terms of sex, ABO type, UNOS status or year in which the transplant procedure was performed. Interestingly, first allograft survival was equal in the children with neonatal hepatitis (74%) and those with metabolic liver disease (74%), but was greater than that for children transplanted for biliary atresia (68%) (p < 0.01). Despite this significant difference in first graft survival, no differences in 5-year survival were seen for the three groups (81% for neonatal hepatitis, 68% for biliary atresia and 79% for metabolic liver disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Renal transplantation of the infant and young child and the use of pediatric cadaver kidneys for transplantation in pediatric and adult recipients.

Transplantation of infants less than 1 year of age with kidneys from live-related parental donors has recently led to good results, whereas cadaver donor renal transplantation in this recipient age group has led to a high mortality rate (11/13). Similarly, the results of cadaver donor renal transplantation in infants and young children less than 5 years of age has been suboptimal in the past, although recent data are more encouraging. With recent availability of long-term peritoneal dialysis for the infant and young child with end-stage renal disease (ESRD), it is possible to defer transplantation until an optimal donor becomes available. Because of the possible immunologic hyperactivity of such recipients, the immunosuppressive regimen may need to be modified if improved cadaver donor survival rates are to be obtained. The use of anencephalic kidneys for transplantation has been associated with a high incidence of primary nonfunction and few recipients with long-term functioning grafts. Harvesting of kidneys from anencephalic donors declared "brain-dead" at birth may reduce the incidence of primary nonfunction and increase the availability of anencephalic kidneys for transplantation. Reports of the use of pediatric cadaver kidneys for transplantation into pediatric and adult recipients yields discrepant results. Analysis of the data indicates that if pediatric cadaver kidneys from donors less than 6 years of age are used, the potential for decreased graft survival rates and an increased incidence of technical complications exists. However, the use of pediatric cadaver kidneys can provide adequate graft function in both pediatric and adult recipients and the use of such kidneys should increase the number of kidneys available for transplantation.

Adolescent↗
PubMed2003

Repeated intravascular ultrasound imaging in cardiac transplant recipients does not accelerate transplant coronary artery disease.

OBJECTIVES: This study was designed to examine the impact of repeated intravascular ultrasound (IVUS) examinations on transplant coronary artery disease (CAD). BACKGROUND: Serial IVUS is the most accurate method for early detection and surveillance of transplant CAD. However, the long-term safety of serial IVUS exams is not well described. Accordingly, we examined the impact of repeated IVUS examinations on transplant CAD. METHODS: We examined 226 transplant recipients who underwent one or more IVUS examinations and coronary angiography at least one year after the last IVUS exam. The coronary angiograms were analyzed using quantitative coronary angiography. Vessel diameters, frequency, and severity of stenoses in IVUS-imaged and nonimaged coronary arteries were compared. In a subgroup analysis of 31 patients, angiographic lumen diameters were measured at baseline (within eight weeks of transplantation) and during follow-up (after two, three, or four IVUS studies). RESULTS: In the 226 patients, 548 coronary arteries were previously imaged by IVUS and 130 arteries were not imaged by IVUS. On subsequent angiograms, stenoses were observed in 16.2% (21/130) of nonimaged arteries and 19.5% (107/548) of imaged arteries (p = 0.38). The arterial diameters of nonimaged and imaged arteries were not significantly different (p = 0.07), regardless of the number of IVUS exams and duration of follow-up. Subgroup analysis revealed a significant decrease in vessel lumen diameter over time in nonimaged as well as imaged arteries. The magnitude of the diameter decrease was not significantly different between the two groups. CONCLUSIONS: Repeated IVUS examinations following heart transplantation do not result in angiographically evident acceleration of transplant CAD. Therefore, serial IVUS imaging is a safe method for the detection and surveillance of transplant CAD.

Coronary Angiography↗
PubMed2000

De novo cancers in paediatric renal transplant recipients: a multicentre analysis within the North Italy Transplant programme (NITp), Italy.

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein-Barr virus (EBV)--associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantation, but developed EBV primary infection after transplantation. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.

Adolescent↗
PubMed2001

Quality of life outcomes after heart transplantation in individuals bridged to transplant with ventricular assist devices.

BACKGROUND: Increasing numbers of individuals receive ventricular assist devices (VADs) as bridges to heart transplantation. Physical morbidity risks and benefits, and quality of life (QOL) during VAD support have been documented. Effects of pre-transplant VAD support on functional and QOL outcomes after transplantation have received no empirical attention. METHODS: Sixty-three VAD patients who received heart transplants underwent QOL evaluations of physical functioning, emotional and cognitive well-being, and social functioning at 2, 7, and 12 months after transplant (response rate = 95%). Ninety patients who had not received VADs--matched to the VAD group on cardiac-related and sociodemographic characteristics--served as longitudinal controls. RESULTS: Both VAD and non-VAD groups showed similar levels and similar, statistically significant (p < 0.05) improvement in physical functioning (sleep, body care, mobility, ambulation, overall functional status, number of somatic complaints) across the study period. Emotional well-being (elevated depressive, anxiety, and anger symptoms; post-traumatic stress disorder rate) was stable or improved in both groups, and VAD patients showed significantly lower anxiety rates. The VAD patients' post-transplant cognitive status was significantly poorer. The VAD patients were significantly less likely to return to employment; other social functioning measurers (daily concerns, interpersonal activities/involvement, role function) showed mixed effects. Cognitive impairment explained much of the association between VAD support and post-transplant employment. CONCLUSIONS: Although post-transplant physical and emotional recovery is similar in VAD and non-VAD patients, VAD patients retain more cognitive impairment and show mixed changes in social functioning. Increased attention to strategies to maximize VAD patients' cognitive capacity is required to facilitate social reintegration.

Cognition↗
PubMed2003

Sequential big endothelin plasma levels in heart transplant recipients during bridging therapy and after successful heart transplantation.

BACKGROUND: The purpose of this study was to investigate the impact of successful heart transplantation in patients with refractory heart failure receiving bridging therapy on sequential plasma levels of big endothelin, norepinephrine, atrial natriuretic peptide and aldosterone. METHODS: Fourteen patients (2 women, 12 men) accepted for heart transplantation were studied. All had severe chronic heart failure refractory to optimized oral therapy with angiotensin-converting enzyme inhibitors and furosemide, were in New York Heart Association functional Class IV, and had a left ventricular ejection fraction of <15%, Right heart catheterization was performed in all patients (cardiac index 1.9 +/- 0.1 liters/min. m(2), pulmonary capillary wedge pressure 30 +/- 2 mmHg, systemic vascular resistance index 2,827 +/- 253 dyn. s/cm(5). m(2)). As bridging therapy, patients received either prostaglandin E(1), prostaglandin E(1) and dobutamine or dobutamine alone as a continuous infusion. Neurohumoral variables were measured prior to bridging therapy and 3.5 months before and 7 and 10 months after successful heart transplantation. RESULTS: Big endothelin, norepinephrine and atrial natriuretic peptide plasma levels decreased from 7.4 +/- 2.9 fmol/ml, 1112 +/- 686 pg/ml and 366 +/- 312 pg/ml to 6.0 +/- 4.5 fmol/ml, 720 +/- 503 pg/ml and 198 +/- 160 pg/ml, respectively, after bridging therapy, and further to 2.1 +/- 0.9 fmol/ml (p < 0.00001 vs baseline), 527 +/- 31 pg/ml (p < 0.02 vs baseline) and 115 +/- 70 pg/ml (p < 0.03 vs baseline), respectively, after cardiac transplantation. Aldosterone plasma levels decreased from 242 +/- 220 pg/ml to 183 +/- 142 pg/ml during bridging therapy and increased after heart transplantation to 252 +/- 189 pg/ml. Plasma creatinine levels increased from 1.2 +/- 0.4 mg/dl at baseline to 1.4 +/- 0.2 mg/dl after transplantation (NS). CONCLUSIONS: The study suggests that excessive overproduction of big endothelin, atrial natriuretic peptide and norepinephrine is predominantly related to pump failure and, after cardiac transplantation, a moderate spillover of big endothelin persists. Its specific origin, however, remains to be elucidated. Furthermore, our data suggest a protective effect of prostaglandin E(1) on kidney function after heart transplantation.

Aged↗
PubMed2000

Transplant coronary artery disease in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary artery disease (TxCAD) contributes to a large percentage of late morbidity and mortality among adult heart transplant recipients. Intracoronary ultrasound (ICUS) is a sensitive tool in the diagnosis of TxCAD in adult patients and has allowed analysis of factors contributing to disease development. Experience with ICUS in pediatrics, however, has been limited. By using ICUS we sought to determine the overall prevalence of TxCAD in pediatrics and to characterize factors associated with its development in this population. METHODS: Eighty-six studies were performed in 51 pediatric patients a median of 3.4 years after heart transplantation. Evaluation included angiography and ICUS in 83 and angiography alone in 3 studies. Donor and recipient characteristics were obtained. The ICUS images were analyzed for intimal thickening and compared with coronary angiograms. The presence of any intimal thickening on ICUS was considered TxCAD. An intimal index and point of maximal intimal thickening (MIT) were measured. Vessel disease was graded 0 to 4 based on these results. Four patients had evidence of vasculopathy by angiography, whereas 32 patients (63%) had evidence of intimal proliferation by ICUS. Grade 2 or greater disease was present in 19 (37%) patients. A positive correlation was found when comparing time from transplant with intimal index and MIT (p < 0.001). No other factors were found to predict the development of disease. The overall prevalence of disease was 74% in patients studied at least 5 years after transplant. Intracoronary ultrasound can be performed safely in pediatric patients. Transplant coronary artery disease is common in infants and children after heart transplantation, although its prevalence appears to be less than in adult recipients at similar time intervals. We found no factor other than time from transplant was associated with development of disease.

Adolescent↗
PubMed1999

Follow-up experience in pediatric liver transplantation in an academic, non-transplant-based gastroenterology group.

As pediatric liver transplantation has become relatively common since the early 1980s, most long-term follow-up care has shifted from transplant centers to the pediatric gastroenterologists at referring institutions. We reviewed our experience with 16 patients who have undergone liver transplantation at eight institutions from 1987 to 1996. Our initial follow-up visit took place at an average 4.1 months after the transplant. The mean duration of follow-up was 41 months. During this period 11 hospitalizations at the transplant center occured, including five that were to rule out lymphoma or post-transplant lymphoproliferative disease. At the Schneider Children's Hospital, NY, USA, 158 outpatient visits were recorded. Forty-two hospitalizations occurred. Twenty of the hospital admissions were accounted for by two patients. Forty-nine outpatient/inpatient surgical or diagnostic procedures were performed, including 15 percutaneous liver biopsies. In only one biopsy was there a disagreement in the histologic diagnosis between our pathologist and the pathologist at the transplant center. In conclusion, comprehensive follow-up care can be provided by an academic hospital-based gastroenterology group in conjunction with a transplant center.

Academic Medical Centers↗
PubMed2000

Sirolimus in pediatric gastrointestinal transplantation: the use of sirolimus for pediatric transplant patients with tacrolimus-related cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) associated with the use of tacrolimus is a rare complication of liver and intestinal transplantation seen almost exclusively among pediatric patients. Reduction of tacrolimus dosage or conversion to cyclosporin A (CsA) has been used as an effective treatment in reviewed cases. We present three pediatric transplant recipients who developed hypertrophic obstructive cardiomyopathy while under tacrolimus immunosuppression and were treated with conversion to sirolimus (Rapamycin). The patients (ages 6 yr, 12 yr and 11 months) were transplant recipients (liver, n = 2; liver and intestine, n = 1) who developed significant cardiomyopathy 15 and 96 months post-transplant. One patient died of post-transplant lymphoproliferative disorder 21 days after starting sirolimus. One patient had received two liver transplants and had been on CsA for 12 yr before conversion to tacrolimus at 60 months post-transplant for acute and chronic rejection. The surviving patients were receiving mycophenolate mofetil, tacrolimus and steroids at the time of diagnosis. Dose reduction of tacrolimus and treatment with beta blockers failed to alleviate the hemodynamic changes. The patients were converted to sirolimus 1.6, 37 and 148 months post-transplant and maintained a whole-blood trough level of 15-20 ng/mL 21 days after starting sirolimus. Repeat echocardiograms in the surviving patients showed improvement in cardiomyopathy. One patient had one rejection episode (intestinal biopsy, mild acute cellular rejection) after starting sirolimus that responded to a transient increase in steroids. The early demise of the third patient after sirolimus conversion prevented an adequate assessment of cardiomyopathy. Conversion to sirolimus was associated with a reduction in the cardiomyopathy of the two surviving patients while still providing effective immunosuppression. To our knowledge this observation has not been previously reported.

Acute Disease↗
PubMed2000

Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon?

BACKGROUND: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. METHODS: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. RESULTS: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717-1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. CONCLUSION: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.

Acinetobacter Infections↗
PubMed1998

Outcome of acute lymphoblastic leukaemia in Danish children after allogeneic bone marrow transplantation. Superior survival following transplantation with matched unrelated donor grafts.

Outcome of allogeneic BMT for childhood ALL performed at a national centre was evaluated for the period between 1985 and 1996. Sixty-seven patients representing all Danish children and adolescents (1-19 years) transplanted for ALL, were evaluated. Patients transplanted with a family donor (n = 51) had a 3-year probability of leukaemia-free survival (P-LFS) of 56% (95% confidence limits 41-69%) and patients receiving marrow from a matched unrelated donor (MUD) (n = 16) had a 3-year P-LFS of 67% (34-86%) (P = 0.38). Relapse was responsible for 48% of the deaths and occurred with increasing frequency among children transplanted with marrow from HLA-identical siblings. Patients transplanted with family donors from 1985-1989 had P-LFS of 72% (54-84%) compared to patients transplanted after 1990 who revealed a significantly reduced P-LFS of 28% (10-49%, P = 0.01). Furthermore, the risk of relapse was increased (65% (24-88%)) (P = 0.02) in the later period. In contrast, patients transplanted with marrow from a MUD (1990-1996) had a lower risk of relapse (11%, 5-20%) (P = 0.002) but a comparable risk of transplant-related mortality. Children who experience relapse after modern, intensive treatment for ALL may have an increased propensity for relapse even after BMT. Therefore, when performing BMT for childhood ALL, there may be a benefit in overall survival from the increased graft-versus-leukaemia effect that follows less intensive GVHD prophylaxis or transplantation with a MUD.

Adolescent↗
PubMed1997

Kidney transplant candidates' views of the transplant allocation system.

OBJECTIVES: The point system used to distribute scarce transplantable kidneys places great emphasis on antigen matching. This contributes to increased waiting times for African Americans, who have a disproportionate share of rare antigens. We conducted a pilot study to explore the understanding and attitudes of kidney transplant candidates toward the way the transplant allocation system trades off between antigen matching and waiting time. MEASUREMENTS AND MAIN RESULTS: We performed semi-structured interviews of a convenience sample of 33 patients awaiting transplants in Philadelphia and its surrounding suburbs. Patients had a number of misconceptions about the transplant allocation system. Many incorrectly thought, for example, that quality of life and financial status influence which patients on the waiting list receive available organs. Despite these and other misconceptions, the majority of patients thought the allocation system was fair. However, many African Americans thought the system was biased against them because of their race. After hearing about how the transplant system factors antigen matching and waiting time into organ allocation, the majority of subjects still felt the system was fair. After hearing that the emphasis on antigen matching causes African Americans to wait twice as long as whites, a larger number of subjects thought the system was unfair. Nevertheless, few thought the system should be changed. Even African American patients who felt the system was unfair still approved of the emphasis on antigen matching out of a desire to have a successful kidney transplant. CONCLUSIONS: We found that most of the interviewed patients awaiting kidney transplant thought the system should continue to emphasize antigen matching. Although attitudes toward the allocation system differed by race, with African American patients more suspicious of the system, the importance patients placed on antigen matching did not appear to differ by race.

Adult↗
PubMed2004

Advanced glycation end products in kidney transplant patients: a putative role in the development of chronic renal transplant dysfunction.

Chronic renal transplant dysfunction is one of the leading causes of graft failure in kidney transplantation. A complex interplay of both alloantigen-related and alloantigen-unrelated risk factors is believed to underlie its development. We propose that advanced glycation end products (AGEs) are involved in the development of chronic renal transplant dysfunction. AGE formation is associated with different alloantigen-unrelated risk factors for chronic renal transplant dysfunction, such as recipient age, diabetes, proteinuria, hypertension, and hyperlipidemia. In vitro studies have shown that AGEs induce the expression of various mediators associated with chronic renal transplant dysfunction. Furthermore, AGE-induced renal damage has been found in multiple experimental studies. This renal damage shows similarity to the damage found in chronic renal transplant dysfunction. Together, several lines of evidence support a role of AGEs in the development of chronic renal transplant dysfunction and suggest that preventive therapy with AGE inhibitors may be helpful in preserving renal function in transplant recipients.

Animals↗
PubMed2002

Recipient-derived hepatocytes in liver transplants: a rare event in sex-mismatched transplants.

Bone marrow-derived stem cells have been shown to engraft and populate native tissues during repair and in transplanted animal tissues. Very few studies have been performed in humans to evaluate the possibility of stem cell engraftment in transplanted tissues. In human renal transplants, recipient cells have been demonstrated within vascular and interstitial structures. In a previous study of patients with hepatic transplants, hepatocytes with XY chromosome patterns have been detected in sex-mismatched female to male transplanted livers in a small number of cases. Because of the possibility of Y chromosome microchimerism of females with male offspring, we analyzed the presence of X and Y chromosomes in liver biopsies of 13 patients with sex-mismatched liver transplants (8 female to male, 5 male to female) and long transplant to biopsy intervals (1.2 to 12 years; mean, 4.5 years). We were able to detect recipient-specific sex chromosomal patterns in inflammatory cells by fluorescent in situ hybridization/immunohistochemistry combination within the liver parenchyma but not within hepatocytes. In conclusion, recipient engraftment of stem cells may be an early feature in liver transplant but may be an infrequent persistent feature in long-term grafts.

Adult↗
PubMed2003

Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons.

The involvement of healthy living donors and the degree of technical difficulty make adult living donor liver transplantation (LDLT) different from any other surgical procedure. We surveyed 100 liver transplant surgeons to assess their views on the complex issues raised by LDLT. Data were collected at meetings on LDLT and by electronic mail. The study instrument was divided into general, donor, surgeon, recipient, and donor and recipient issues. Subjects provided the projected 1-year survival threshold that they would require for the recipient before they would perform LDLT. They listed the three topics that they thought were most critical for transplant fellows to know about LDLT. A majority agreed that transplant programs have a duty to their patients to offer LDLT, that the increasing success of the procedure will expand indications for liver transplantation, and that the risk to the donor causes them a moral dilemma. There was more divergence of opinion regarding who should have the final say about a potential donor's candidacy, whether it is difficult for donors to comprehend the risks of the procedure, and whether repeat cadaveric transplantations should be offered for failed LDLT performed for extended indications. Surgeons' median recipient survival threshold was a conservative 79%. Priorities for educating trainees focused on understanding complications and risks, technical factors, and ethical concerns such as putting the donor first. In conclusion, the findings of this survey indicate that transplant surgeons are working to balance their moral imperative to provide life-saving therapy for transplantation candidates with the risks posed to living donors.

Adult↗
PubMed1986

Are there indications for heterotopic heart transplantation in 1986? A 2- to 11-year follow-up of 49 consecutive patients undergoing heterotopic heart transplantation.

In the 9-year period between November 1974 and December 1983, 49 patients underwent heterotopic heart transplantation at Groote Schuur Hospital. Eight patients subsequently underwent a further transplant procedure, and one of these a third transplant (58 transplants in 49 patients). Conventional immunosuppressive therapy (azathioprine, corticosteroids, and rabbit antithymocyte globulin) was used in 47 cases (81%), and cyclosporine and conventional immunosuppression in 11 (19%). Follow-up (to 1st January 1986) has been for a minimum of 2 and a possible maximum of 11 years. Forty-one of the 49 patients (85%) have subsequently died, mean survival of this group being 18.5 months. Mean survival of the 8 patients alive is 74 months. One-year survival has been 55% and 5-year survival 22%. In light of this experience, it would seem to us that the indications for heterotopic transplantation have now greatly diminished. There would still appear to be a place for it, however, when the donor heart is small in relation to the mass of the recipient, when there is a possibility of myocardial recovery following the resolution of a myocarditis, and when there is an elevated pulmonary vascular resistance which may make orthotopic transplantation hazardous. Heterotopic heart transplantation may also be indicated when the recipient circulation is failing rapidly despite maximal medical support, and therefore transplantation is urgent.

Adolescent↗
PubMed1998

Plasma leptin concentration in kidney transplant patients during the early post-transplant period.

BACKGROUND: Leptin, is produced by adipose tissue and is presumed to be involved in the regulation of appetite and energy balance. The kidneys are involved in the inactivation of circulating leptin, and elevated plasma leptin concentrations were reported in uraemic patients. Finally, glucocorticosteroids as used in transplanted patients stimulate leptin secretion. METHODS: The present study aimed to asses the relationship between plasma leptin concentration and kidney graft function in the early post-transplant period. We studied 40 successfully transplanted haemodialysed uraemic patients (27 males, 13 females, mean age 34.3 +/- 1.6 years, mean body mass index 22.5 +/- 0.5 kg/m2). The circadian rhythm of leptinaemia and insulinaemia was assessed twice: 2-4 days after kidney transplantation and 1 day before discharge from the hospital when graft function was good. Plasma leptin concentration was measured at 8 am, 4 pm, and 12 pm. The control group consisted of 21 healthy subjects (13 males, 8 females, mean age 39.4+/-2.5 years, mean body mass index 24.1 +/-0.7 kg/m2). RESULTS: Before kidney transplantation, patients had elevated plasma leptin and insulin levels. A positive correlation was found between BMI and leptinaemia and BMI and insulinaemia, respectively. An inverse relationship was found between leptinaemia and age. Successful kidney transplantation was followed by a significant decline of leptinaemia i.e. from 21.5 +/- 0.1 vs 7.1 +/- 1.3 ng/ml. Kidney transplantation did not influence the circadian rhythm of leptinaemia. CONCLUSION: Leptinaemia was not related to the excretory graft function or immunosuppression. In addition to renal excretory function, other factors must be involved in the post-transplant decline of leptinaemia.

Adult↗
PubMed2000

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗