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PubMed2001

Extraperitoneal placement of renal allografts in children weighing less than 15 kg.

PURPOSE: Extraperitoneal renal transplantation is not routine in small recipients, in whom transperitoneal engraftment is the norm. The outcome of extraperitoneal placement of renal allografts in children weighing less than 15 kg. was evaluated at 2 institutions. MATERIALS AND METHODS: We retrospectively reviewed all pediatric renal transplantations at 2 institutions from 1988 to 2000 and identified 29 children 14 to 72 months old (mean age 29.2) weighing less than 15 kg. (range 8 to 14.8, mean 11.2). All children underwent allograft placement extraperitoneally via a modified Gibson and low midline retroperitoneal incision in 27 and 2, respectively. A concurrent procedure was done via the same incision during 2 ipsilateral and 2 bilateral nephrectomies. RESULTS: Of the 29 patients 25 have a functioning renal allograft. In 2 cases the initial allograft was lost due to early postoperative thrombosis and acute rejection in 1 each. Two patients with a functioning allografts died of medical complications greater than 2 years after transplantation. One child required reexploration secondary to fascial dehiscence and an additional recipient required pyeloureterostomy due to ureteral necrosis after living related donor transplantation. CONCLUSIONS: Extraperitoneal renal transplantation is technically feasible in children who weigh less than 15 kg. This approach preserves the peritoneal cavity, limits potential gastrointestinal complications and allows the confinement of potential surgical complications, such as bleeding and urinary leakage. In addition, this approach provides complete access to the retroperitoneum to enable concurrent retroperitoneal surgery, such as nephrectomy, to be performed safely. We recommend that extraperitoneal renal engraftment should become routine in children weighing less than 15 kg. rather than using the more common transperitoneal approach for allograft placement.

Body Weight↗

PubMed1990

Image-guided 31P magnetic resonance spectroscopy of normal and transplanted human kidneys.

Image-guided 31-phosphorus magnetic resonance spectroscopy (MRS) was used to obtain spatially localized 31P spectra of good quality from healthy normal human kidneys and from well-functioning renal allografts. A surface coil of 14 cm diameter was used for acquiring phosphorus signals solely from a volume-of-interest located within the kidney. To determine the effects of kidney transplantation on renal metabolism, patients with well functioning allografts were studied. Little or no phosphocreatine in all spectra verifies the absence of muscle contamination, and is consistent with proper volume localization. The intensity ratio of phosphomonoesters (PME) to adenosine triphosphate (ATP) resonances in transplanted kidneys (PME/ATP = 1.1 +/- 0.4) was slightly elevated (P = 0.2) compared to that of healthy normal kidneys (PME/ATP = 0.8 +/- 0.3). The inorganic phosphate (Pi) to ATP ratio was similar in the two groups (Pi/ATP = 1.1 +/- 0.1 in transplanted kidneys vs. 1.2 +/- 0.6 in normal kidneys). Acid/base status, as evidenced from the chemical shift of Pi, was the same in both normal controls and transplanted kidneys. Despite the practical problems produced by organ depth, respiratory movement, and tissue heterogeneity, these results demonstrate that image-guided 31P MR spectra can reliably be obtained from human kidneys.

Adult↗

PubMed1975

Studies on the duct-ligated pancreas as allograft for islet cell function.

Twenty previously pancreatectomized dogs were heterotopically transplanted with duct-ligated allografts. Sixteen of the grafts were preserved for 24 hours, nine with continuous hypothermic albumin perfusion, seven with hypothermic storage. Five dogs died from early postoperative bleedings. Fifteen surviving dogs had a satisfying endocrine function assessed by blood glucose and serum insulin during fasting and after glucose load. In six dogs the glucagon release from the graft was investigated and significant release was evident in all dogs. A high release was found after L-arginine stimulation. The endocrine function was satisfying after 24 hour preservation both with hypothermic storage and continuous hypothermic albumin perfusion. During such perfusion the pancreas became very oedematous. This did not influence on the outcome of the transplantation. The grafts were enlarged four to eight days after transplantation. Oedema, fibrotic changes and collagen depositions in the interstitial tissue were observed in light microscopy. These changes seemed to come earlier in glands preserved for 24 hours. Islet cells were identified in all functioning grafts and seemed histopathologically and ultrastructurally unchanged. A duct-ligated pancreatic segment was allografted to one diabetic patient in a pilot experiment. There was a satisfying endocrine function for 40 days. After that the graft became necrotic due to thrombus formation.

Amylases↗

PubMed1997

Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation.

BACKGROUND: Lung function is altered by infection and rejection in patients who undergo heart-lung transplantation. The sensitivity, specificity, and positive/negative predictive values (PPV and NPV) of lung function for the detection of allograft dysfunction in these patients were measured. METHODS: Thirty three patients who underwent heart-lung transplantation were followed for a mean period of 16.3 months. On 123 occasions functional measurements were obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar lavage fluid was taken, which were used as gold standards. Optimal sensitivity (the value for which sensitivity equals specificity) was computed for each functional test from receiver-operator characteristic (ROC) curves. RESULTS: Acute rejection was present on 31 occasions and infection on 36 occasions; 56 samples were normal. Infection and rejection were accompanied by airflow obstruction, a rise in the slopes of the alveolar plateaus for nitrogen, hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%, 66%, and 60%, respectively; they were not different for infection and rejection and did not change over the study period. For infection and rejection together, PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional test and the postoperative period considered. CONCLUSIONS: Indices of ventilation distribution, FEF25-75, and TLC have the best optimal sensitivity for the diagnosis of infection and rejection after heart-lung transplantation. The high PPV of pulmonary function in detecting allograft dysfunction observed in this study suggests that a diagnostic procedure should be performed whenever one or more functional tests deteriorate; conversely, the low NPV indicates that a stable pulmonary function does not rule out allograft dysfunction.

Adolescent↗

PubMed1986

The diagnostic value of renal cortex-to-medulla contrast on magnetic resonance images.

The diagnostic value of magnetic resonance contrast between the renal cortex and renal medulla as an indicator of renal disease was retrospectively studied in 38 patients (ten patients with a variety of diseases affecting the renal parenchyma, nine with renal obstruction, four with diffusely infiltrating renal-cell carcinoma, one with renal hematoma, nine with normally functioning renal allograft, and five with renal allograft failure). Twelve normal volunteers served as controls. On spin-echo (SE) images (TR 0.5 sec, TE 28 msec), the cortex-to-medulla contrast was present in the kidneys of all the normal volunteers (19% contrast +/- 2% S.D.) and in all the normally functioning allografts (17% contrast +/- 2% S.D.). Decrease or absence of cortex-to-medulla contrast (SE image with TR 0.5 sec and TE 28 msec) was found to be a sensitive but nonspecific sign of renal disease. It occurred in renal diseases of various causes and was produced by different pathophysiologic mechanisms such as edema, scarring, and tissue replacement by neoplasm or hematoma. Of the calculated T1 and T2 relaxation times and spin density of the cortex and the medulla, the T1 changes most consistently reflected renal disease.

Adolescent↗

PubMed1985

Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy.

We assessed the structural and functional evolution of small intestinal transplant rejection in a rat model by use of 1-micron section, electron microscopic, and in vitro electrophysiologic techniques to study jejunal mucosa 3, 6, and 9 d posttransplantation. The earliest structural abnormalities detected in jejunal loops transplanted from Lewis X Brown Norway F1 hybrids into Lewis rats occurred within 3 d posttransplantation and consisted of focal endothelial cell injury of the microvasculature and focal injury of crypt epithelial cells. Both alterations were associated with adjacent infiltration of large lymphoid cells, and both markedly progressed and became rather diffuse over the following 6 d. In contrast, villus absorptive cells were not markedly altered in structure until the 9th postoperative day. As compared with host jejuna, allograft jejunal epithelium demonstrated multiple functional abnormalities. Transepithelial resistance declined progressively by days 6 and 9 (both P less than 0.05), although baseline transepithelial spontaneous potential difference was only affected at day 9 (P less than 0.01). Stimulated absorption by allograft jejuna, as assessed by measuring electrical response to mucosal glucose, was not significantly diminished until day 9 (P less than 0.05). In contrast, stimulated secretion assessed by measurement of electrical response to serosal theophylline was diminished by day 6 (P less than .01). These data suggest that the earliest epithelial injury during rejection, as judged both structurally and functionally, occurs in the crypt and is paralleled by endothelial injury at the level of the microvasculature. Thus, the primary targets for rejection are most likely endothelial cells and crypt epithelial cells. In contrast, structural and functional impairment of villus epithelium is detectable only at substantially later times during rejection and are most likely secondary processes related to either ischemia produced by microvascular injury or decreased epithelial regenerative ability secondary to crypt injury. Last, we show that the detrimental structural and functional sequellae of jejunal transplantation across the major histocompatibility complex in this model is strikingly ameliorated with cyclosporine therapy.

Animals↗

PubMed1998

Effect of lung allograft ischaemia duration on postreperfusion graft function and postoperative course.

Lung transplantation is limited by the effects of ischaemia. Previous clinical studies related graft ischaemia duration to post-operative pulmonary function in the ICU, morbidity, and overall survival. This report describes the intraoperative pulmonary allograft function immediately after reperfusion. 23 lung transplantations (15 bilateral, 8 single) were analysed. Donor selection and organ procurement were identical. After pulmonary vasodilation with prostacyclin, allografts were flush-perfused with cold modified Euro-Collins solution. Mean duration of lung ischaemia was 255.1 +/- 35.1 min (190-314 min). Ischaemia times did not differ with respect to the recipient's disease or the use of extracorporeal circulation. After reperfusion, oxygenation indices deteriorated in 73.9% of patients compared with the native lungs (313.4 +/- 163.5 vs 427.2 +/- 96.1, p = 0.006). Linear regression analysis and subgroup analysis both revealed a significant influence of the duration of allograft ischaemia on early transplant function. Ischaemia of more than 4 hours resulted in an acceptable but significantly lower PaO2 (254.9 +/- 143.3 mmHg vs 463.0 +/- 149.2 mmHg, p = 0.011). However, mean time until extubation and time spent in the ICU were not affected. It is concluded that flush-perfusion of the lung with modified Euro-Collins solution provides reliable preservation of lung function up to four hours. Longer ischaemia, up to six hours, is followed by an acceptable but progressively reduced early transplant function.

Adult↗

PubMed1978

Studies of renin-aldosterone axis in stable normotensive and hypertensive renal allograft recipients.

Functional aspects of the renin-aldosterone axis were investigated in long-term normotensive and hypertensive renal allograft recipients. Unstimulated plasma renin and aldosterone levels were within control range in all patients and rose significantly in response to sodium depletion. However, no difference in the stimulated renin and aldosterone values between normotensive and hypertensive patients was noted. Baseline aldosterone secretory rates were elevated in all patients, but were higher in hypertensive patients than in normotensive patients. In both groups sodium depletion failed to augment this already elevated aldosterone secretion rate. Possibly, changes in the body pool and/or metabolic clearance rate of aldosterone account for elevations in plasma levels despite a relatively fixed secretory rate, though the role played by the lack of normal innervation of the kidneys cannot be ignored. It is unknown whether these observations may be causal or affected by other presently unknown or unmonitored factors. This in part may reflect unfolding problems in the understanding of nonrenal transplant hypertension.

Adult↗

PubMed2001

Expression of endomyocardial nitric oxide synthase and coronary endothelial function in human cardiac allografts.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts. METHODS AND RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.

Acetylcholine↗

PubMed2006

FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function.

Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.

Animals↗

PubMedDate not supplied

Functional integrity of vascular allografts after endothelial removal.

Several studies have indicated that antigen-presenting endothelial cells represent the primary initiator of acute arterial graft rejection, leading to decreased arterial patency rates. Patency rates dramatically increase upon endothelial removal (denudation) prior to orthotopic transplantation into antigenically disparate hosts. Although patent, the biomechanical and functional changes seen in these allograft vessels (ACI rats to Lewis rats) have not been described. The present investigation examined functional differences between these allograft arteries and normal rat femoral arteries. Moreover, endothelial removal may also alter function; thus, an autograft injury model (Lewis to Lewis) was employed to discern the differences between injury and rejection. The results indicate that denudation injury alone caused no change in the passive stress-strain curve, the muscle length at which stress was maximum (Lo), or in phenylephrine- or nitroglycerin-induced concentration-response curves. Similarly, concentration-response curves were not affected by allograft transplantation; however, both the passive stress-strain curve and Lo values were shifted to significantly longer lengths (0.25 and 0.20 mm, respectively), suggesting an increase in arterial plasticity but not compliance. Furthermore, allografts produced significantly weaker KCl-induced contractions than did autografts (22 vs. 66% of control values, p < 0.05). Acetylcholine maximally relaxed phenylephrine-contracted arteries in the following descending order. ACI > Lewis > autograft > allograft. In conclusion, these data suggest that vascular rejection involves subendothelial tissues, is distinct from vascular injury, and that the denudation allograft transplantation model can be employed to examine this process.

Acetylcholine↗

PubMed1985

Functional capacity of solid tissue transplants in the brain: evidence for immunological privilege.

The capacity of the mammalian brain to support the physiological function of allografts was assessed in parathyroidectomized Fischer strain rats bearing either isografts or immunogenic DA allografts of parathyroid glands implanted in their cerebral cortices. Established isografts and allografts survived indefinitely in the brain, maintaining normal serum calcium levels, with equal numbers of spontaneous failures (18-21%) in each group. Similarly, both MHC-compatible and incompatible skin allografts survived and were 'functional' at 40-50 days postgrafting as assessed by: continued formation of keratin; the presence of differentiated hair follicles and sebaceous glands; and frequent mitotic figures. No serum alloantibodies were induced by either MHC-incompatible parathyroid glands or skin in this site. However, both types of allografts were promptly rejected or failed to become established in the brains of specifically presensitized hosts. Furthermore, when Fischer hosts with long-established intracerebral DA parathyroid grafts received orthotopic DA skin grafts, their parathyroid grafts were rejected along with first-set rejection of the skin grafts. The tempo of this cellular immune response and the primary alloantibody response that accompanied it indicate that although the intracerebral grafts failed to induce detectable host sensitization or suppression, they remained susceptible to immune effectors. Thus, by using strongly immunogenic, adult tissues, we have established that the rat cerebral cortex is an immunologically privileged site, and the privilege is not dependent on lack of graft immunogenicity or alterations in host responsiveness. Furthermore, Ia+ (possible antigen-presenting) cells were rare in the cortical parenchyma sites used for transplantation though numerous in the choroid plexus of the ventricles and in certain areas of white matter. Therefore, privilege probably reflects deficient graft antigen presentation related to the paucity of Ia+ cells as well as to the brain's poor lymphatic drainage.

Animals↗

PubMed2006

Cardiac surgery in kidney and liver transplant recipients.

OBJECTIVE: To evaluate operative management, outcome, and long-term survival in patients with functioning renal and hepatic allografts who underwent cardiac surgery. PATIENTS AND METHODS: We studied all patients who had previously undergone either renal or hepatic transplantation and who subsequently (1986-2001) underwent cardiac surgery at our institution. Data were obtained by retrospective medical record analysis. RESULTS: The study comprised 47 patients with renal (n=34) and hepatic (n=13) functioning allografts. Median time to cardiac surgery from transplantation was 79 months. The most common procedures were as follows: coronary artery bypass grafting, 22 (47%); aortic valve procedures, 11 (23%); and mitral valve procedures, 5 (11%). One patient (2%) died within 30 days of surgery. Renal allograft dysfunction was noted in 5 renal patients (15%) immediately after surgery. Two patients required dialysis postoperatively, 1 of whom required continued dialysis on dismissal. Transient allograft dysfunction, as determined by elevated liver enzyme levels, occurred in 6 hepatic patients (46%). However, all hepatic patients had functional allografts on dismissal. Two patients (4%) developed leg wound infections, and 9 (19%) had respiratory complications. No sternal or mediastinal infection occurred. One- and 5-year survival rates (mean +/- SEM) for all patients were 93%+/-4% and 76%+/-8%, respectively. Of the renal patients, 1- and 5-year survival rates (mean +/- SEM) were 97%+/-3% and 82%+/-8%, respectively. One- and 5-year survival rates (mean +/- SEM) for hepatic patients were 77%+/-12% and 69%+/-13%, respectively. CONCLUSION: Cardiac surgery can be performed safely in kidney and liver transplant recipients, with low early mortality and excellent medium-term survival. In almost all instances, allograft function is well preserved.

Adolescent↗

PubMed2002

Cardiac surgery after renal transplantation.

Renal transplantation remains a mainstay of therapy for end-stage renal disease. Cardiac disease has a high prevalence in this patient population. This study reviews the factors and outcomes associated with cardiac surgery in renal transplant recipients. We performed a retrospective review of all patients at our institution with a functioning renal allograft at the time of their cardiac surgical procedure. Between June 1971 and April 2000, 2343 patients underwent renal transplantation at Vanderbilt University Medical Center. Twenty-six patients with a functioning renal allograft subsequently underwent a cardiac procedure requiring cardiopulmonary bypass. There were 11 women and 15 men. Twenty-four patients underwent coronary bypass, one had a double valve replacement, and one had a combined coronary bypass/valve replacement. The interval from renal transplant to heart surgery ranged between 0.6 and 227 months (mean 79.1). Operative mortality was zero but there were two hospital deaths: one due to multisystem organ failure and one due to pulmonary embolism. Six additional patients died late with only one due to heart disease. Four patients required perioperative dialysis, and one of these went on to require permanent dialysis. Two additional patients returned to dialysis late postoperatively. The requirement for acute perioperative dialysis was predicted by preoperative creatinine, hematocrit, and intraoperative urine output. The overall survival is 69 per cent (18 of 26) with a median follow-up of 38 months. The majority of long-term survivors have minimal cardiac symptoms. Standard cardiac surgery procedures can be performed with relative safety in patients with functioning renal allografts. The incidence of perioperative and late development of renal failure requiring dialysis is low. The long-term survival and symptomatic improvement achieved are favorable and warrant continued performance of cardiac surgery in patients with functioning renal allografts.

Adult↗

PubMed2004

Inhibition of inducible nitric oxide synthase and superoxide production reduces matrix metalloproteinase-9 activity and restores coronary vasomotor function in rat cardiac allografts.

OBJECTIVE: Oxidants such as nitric oxide (NO) and superoxide are involved in coronary endothelial dysfunction, an early event in the process of allograft coronary atherogenesis, possibly by activation of matrix metalloproteinases (MMPs) and extracellular matrix proteins. We investigated the contribution of inducible nitric oxide synthase (iNOS) derived NO and superoxide on (MMP)-9 activity and to changes in coronary vasomotor function in rat cardiac allografts. METHODS AND RESULTS: An allogenic (Brown Norway to Lewis rats) heterotopic cardiac transplantation model was used to study the effect of continuous treatment with a selective iNOS inhibitor; N-(3-(aminomethyl) benzyl) acetamidine (1400W), and polyethylene glycol conjugated superoxide dismutase (SOD) either alone or in combination on coronary vasomotor dysfunction. 1400W or SOD 24 h alone or their combination improved endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) coronary flow reserve and inhibited enhanced MMP-9 protein and activity. In addition, histopathological study revealed that either 1400W or SOD or their combination reduced superoxide production and nitrotyrosine protein. CONCLUSION: The present study demonstrates for the first time that selective iNOS inhibition or SOD treatment reduces enhanced MMP-9 protein and activity associated with improvement of both, endothelium-dependent and -independent coronary vasomotor function in rat cardiac allografts. This is accompanied by reduction of nitrotyrosine and superoxide production. This suggests that the proteolytic enzyme MMP-9 is an effector molecule of oxidant-mediated coronary vasomotor dysfunction.

Amidines↗

PubMed1995

Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts.

Transplantation of kidneys from older donors is being advocated to expand the organ donor pool. However, the prevalence of atherosclerosis and age-induced renal structural alterations account for the variable function of allografts procured from these older donors. Pretransplant biopsies are sometimes used to evaluate kidneys from older donors, but to date there are no defined criteria correlating the extent of structural alterations in these kidneys to subsequent function. We investigated the effect of glomerulosclerosis, a marker for nephrosclerosis, on graft outcome. Sixty-five baseline biopsies of kidney allografts were retrospectively analyzed to identify a referent point of glomerulosclerosis that correlated with inferior graft outcome. Age and death from nontraumatic cerebrovascular injuries were the main correlates for donor glomerulosclerosis (P < 0.001). Allografts with poor function at 6 months defined as serum creatinine > 2.5 mg/dl (n = 13) or nephrectomy (n = 4) had a mean of 20% glomerulosclerosis at the time of implantation compared with only 2% sclerosis in allografts with good function (P < 0.05). Delayed graft function occurred in 22% and 33% of recipients with no glomerulosclerosis and those with less than 20% glomerulosclerosis, respectively. In contrast, patients receiving kidneys with > 20% sclerosis had an 87% incidence of delayed function (P < 0.05). Moreover, graft loss occurred in 7% of recipients of kidneys with less than 20% sclerosis and in 38% of recipients with > 20% sclerosis (P < 0.04). Measurements of serum creatinine in the donors did not distinguish the different degrees of glomerulosclerosis found on biopsy. Our data indicate that donor glomerulosclerosis greater than 20% increases the risk of delayed graft function and poor outcome of transplanted kidneys. Therefore, we advocate the use of routine biopsies of kidneys from older (> 50 yrs) donors and those donors with nontraumatic cerebrovascular accidents, despite seemingly normal preprocurement serum creatinine.

Adolescent↗

PubMed1986

Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate.

The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

Animals↗

PubMed1996

Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft.

Cardiac allograft arteriosclerosis is the most important limiting factor of long-term survival of heart transplant recipients. Several clinical studies have suggested the association between CMV infection and heart allograft arteriosclerosis, chronic rejection. To determine the temporal impact of CMV infection on the development of heart allograft arteriosclerosis we quantitated coronary angiograms obtained from 72 heart transplant recipients followed for 1-6 yr post-transplantation. To examine the graft function, echocardiography was evaluated. CMV infection was associated with early development of allograft arteriosclerosis manifested by intense diffuse pruning of the coronary arteries including their smallest branches already after the second post-transplant year. Even 6 yr post-transplantation the magnitude of arteriosclerotic changes was significantly higher in recipients with CMV infection compared with patients without infection (P < 0.02). No difference in echocardiographic parameters including ejection fraction (EF), left ventricular end diastolic diameter (LVEDD) and left ventricular mass (LVM) between recipients with and without CMV infection was recorded early after transplantation. However, when compared to recipients without CMV, the CMV accelerated chronic rejection seen in coronary angiography associated with impaired late graft function as judged by decreased EF in patients with CMV infection 6 yr post-transplantation (P < 0.02). No differences in LVEDD or LVM between the patient groups occurred. Taken together, these results suggest that CMV infection is associated with intense cardiac allograft arteriosclerosis affecting the whole coronary tree soon after transplantation. The intensity and magnitude of these chronic vascular wall changes increase and persist during subsequent years, indicating that the risk for graft loss and death due to chronic rejection is especially high during the first 5 post-transplant years in CMV-infected patients. Echocardiography may not be a sensitive method to distinguish patients with early CMV-accelerated allograft arteriosclerosis but coronary angiography must be performed.

Acute Disease↗