A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study.

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.

Evaluation of liver function for hepatic resection.

New limits have been established to decrease mortality and morbidity rates after liver resection in cirrhotic and non-cirrhotic patients. Various laboratory data and imaging techniques have been used to complement the Child-Pugh score to predict liver failure after hepatectomy and to assess functional hepatic reserve. The greatest experiences are with the aminopyrine breath test and the galactosyl elimination capacity, which are decreased among hepatic failure patients after liver resection. However, absence of these changes do not totally exclude it. The indocyanine green retention test is the most widely used clearance test. Nevertheless, it remains imperfect because it depends both on hepatic blood flow and on the functional capacity of the liver. Nuclear imaging of the asialoglicoprotein receptors with radiolabelled synthetic asialoglicoproteins provides volumetric information as well a functional assessment of the liver. In summary, while liver function is complex, a successful liver test to assess quantitative functional hepatic reserve still needs to be established. The combination of the Child-Pugh score, the presence of ascites, the serum bilirubin levels, the indocyanine green retention (ICG R15) value, and the remnant liver CT volumetry seems to avoid an index of liver failure after hepatic resection. Cases when ICG R15 is above 15% should be combined with portal vein embolization. If there is no possibility to perform an ICG clearance test, it may be replaced with other available, well known dynamic liver function tests.

Bourneville-Pringle disease for kidney transplantation: a single-center experience.

The Bourneville-Pringle disease is an autosomal-dominant disease affecting the kidneys in about 60%, causing end-stage renal disease in about 10% of the cases. Among more than 2800 renal transplant recipients during the last 33 years, we had two patients with this original disease. A third patient who underwent bilateral nephrectomy is currently awaiting a graft. The first patient was diagnosed at the age of 20 years after a few episodes of retroperitoneal bleeding. At the age of 26 years her left kidney was removed after a rupture; it measured 7500 g, and the histology described angiomyolipomatosis. A year later she underwent a cadaveric kidney transplantation. Subsequently her right kidney was removed due to bleeding. She is currently 5 years posttransplant with stable kidney function and good health. Our second patient was nephrectomized at the age of 35 years and 38 years because of angiomyolipomatosis. She underwent a cadaveric kidney transplantation 7 years later. After 5 years of excellent kidney function and a year after her arteriovenous fistula was ligated her upperarm had to be amputated because of uncontrollable bleeding. After another 6 months, she displayed rapid progression of a jejunal tumor and during operation received 54 U of blood transfusion but died at the age of 49 years with a well-functioning graft. Our third patient consecutively underwent two nephrectomies because of angiomyolipomatosis of her kidneys at the ages of 25 and 28 years. She has two children with the same disease. In addition she carries Leyden mutation, which has caused deep venous thromboses and pulmonary emboli. She is currently on our waiting list for kidney transplantation. The Bourneville-Pringle disease is a rare indication for kidney transplantation; the prognosis of the patient is dependent on the original disease.

Significant differences in the efficacy of kidney transplantation between Hungarian Caucasians and Gypsies.

In a retrospective study we examined the differences between Caucasian (Group A) and Gypsy (Group B) renal allograft recipients transplanted in Hungary. From 1983 to 2001, 1918 transplants were performed in Budapest (1825 Caucasian and 93 Gypsy recipients). Group B patients were younger (34 +/- 12 vs 42 +/- 14 years of age; P < .01) and Group A had more polycystic kidney disease (12% vs 3%; P < .025). Blood group B was more common in Group B (27% vs 19%; P = NS) than in Group A patients, and Group A had seemingly more diabetes (5% vs 1%; P = NS) than did Group B. There were no differences in HLA mismatches or panel reactive antibodies (PRA). No differences were seen in Group A vs Group B patient survivals at 1, 3, 5, or 10 years' posttransplant (98% vs 95%; 90% vs 93%; 85% vs 88%; and 74% vs 82%, respectively). However, Group A graft survivals were significantly better than Group B at 1, 3, 5, and 10 years' posttransplant (89% vs 77%; 82% vs 66%; 76% vs 54%; and 57% vs 34%; each comparison P < .01). Group B recipients experienced a greater number of acute rejection episodes (66% vs 49%; P < .01), irreversible acute rejections (15% vs 6%; P < .001), chronic rejections (34% vs 18%; P < .001), and graft loss due to immunosuppression noncompliance (5% vs 1%; P < .05) than did Group A recipients. As has been previously described for other non-Caucasian ethnic groups (eg, African-Americans), Hungarian Gypsies appear to be at a greater immunological risk for rejection and poorer long-term graft survival.

Laurence-Moon-Bardet-Biedl syndrome for kidney transplantation at the age of 57 years.

Laurence-Moon-Bardet-Biedl syndrome represents a very rare indication for kidney transplantation. Previous reports mention only pediatric organ recipients with this diagnosis. We present the case of a Caucasian male patient who underwent a cadaveric renal transplantation at the age of 57 years. Our patient had an uneventful immediate postoperative course; however, 4 months after the operation he suffered pneumonia and cytomegalovirus infection. He recovered fully and had an episode of acute cholecystitis. At the time of the laparoscopic cholecystectomy we also laparoscopically removed his Tenckhoff catheter, a procedure he could not undergo for more than a year because of a chronic scabies infection. Now, 18 months after his transplantation he is fully rehabilitated with a serum creatinine of 90 micromol/L. In selected cases even in older age kidney transplantation could offer a higher quality of life for this mentally retarded, blind population.

Improving results of renal transplantation with the use of elderly donors: the Budapest experience.

The use of elderly donors has become a necessity with the increasing demand for deceased donor organs resulting in transplant centers worldwide expanding their donor criteria. We, therefore, thought it appropriate to review our experience using elderly (>60 years) brain-dead donors for kidney transplantation. We investigated the influence of donor parameters on early graft function and survival. A retrospective comparative analysis of three periods was performed: 1994 to 1998 (P1) n = 40; 1999 to 2000 (P2) n = 28; and 2001 to 2002 (P3) with n = 31 donors. Mean donor age in each period was 63.4 +/- 3.3, 64.5 +/- 3.4, and 63.8 +/- 2.7 years; mean diuresis was 473 +/- 450, 307 +/- 316, and 276 +/- 185 mL/hour; and the need for vasopressors during donor management was 81%, 85%, and 70% respectively. The number of kidney recipients was 59, 30, and 37, mean age was 49 +/- 13, 53 +/- 11 and 54 +/- 8 years, the recipient ratio of patients >60 years was 17%, 33%, and 27% respectively, and no differences among the groups in the HLA mismatch. Primary nonfunction occurred in 8.5%, 0%, and 2.8%; acute rejection ratio at 1 year was 35%, 36%, and 32%, the mean serum creatinine at 12 months was 183.7 +/- 66.0, 157.8 +/- 41.2 and 160.7 +/- 46.5 mumol/L. The 1-year graft survival was 71.2%, 91.0% and 92.0% and the 1-year patient survival 88.2%, 96.6%, and 97.2%, respectively, for periods 1, 2, and 3. There has been a considerable improvement in the 1-year graft and patient survivals. With careful donor and recipient evaluation, individualized immunosuppression, and age matching the results of renal transplantation from elderly deceased donors can be comparable to the results of the "optimal" deceased donor kidney transplantation.

Factors in association with sepsis after liver transplantation: the Hungarian experience.

Sepsis is the major cause of patient death after orthotopic liver transplantation (OLT). To identify risk factors for sepsis, we analyzed all 199 primary OLTs performed between 1995 and 2004. Patients were divided into 2 groups according to whether they experienced sepsis after liver transplantation. Recipient, perioperative factors, and complications were subjected to univariate analyses. Statistically significant factors were exposed to multivariate analyses: Cox regression and Hosmer-Lemeshow test. Sepsis occurred in 45 (23%) patients. Recipient Child-Pugh score, preoperative broad spectrum antibiotic (meropenem) prophylaxis, intraoperative red blood cell transfusion, starch infusion, postoperative bleeding, hepatic artery thrombosis, and biliary leakage/necrosis were independent risk factors for sepsis. Our results agree with the international experience. A high amount of starch infusion and an extended use of broad spectrum antibiotics for prophylaxis adverse experiences in our center and have been removed from the protocol.

Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.

INTRODUCTION: The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies. METHODS: Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis. RESULTS: We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died. CONCLUSION: Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.

Prediction of early renal graft function by the measurement of donor urinary glutathione S-transferases.

BACKGROUND: We have investigated the possibility of urinary alpha- and pi class glutathione S-transferases (GST-a; GST-pi) serving as a valuable parameter to predict early graft function after transplantation. METHOD: Urinary GST concentrations of 61 donors (DON) and recipients (REC) were analyzed at preoperative, intraoperative, and postoperative periods. We grouped recipients according to the early postoperative graft recovery days. RESULTS: The donor graft function, represented by the donor urinary GST concentration (GST-pi:17,1+/-12 microg/l mmol creatinine (crea); GST-a:14,3+/-10 microg/mmol crea), sustained a loss in comparison to the healthy controls (GST-a; pi< or =1 microg/mmol crea). According to statistical analysis, the donor GST-pi level showed a strong correlation with graft recovery days-pi (r = 0.84; P<0.001). The early graft function cannot be predicted by means of cold ischemia time (22.8+/-3.4 hr), nor handling time (42.4+/-11.1 min), nor even the intraoperative enzyme concentrations. The GST-pi cut off level (12.55 microg/mmol crea) might predict the possible posttransplant graft dysfunction. The discriminative analysis showed that using only DON GST-pi alone could discriminate well between the groups among all grafts in 68%. CONCLUSION: Prognosis is poorer if the donor GST-pi concentration is above 12.55 microg/mmol crea. On the basis of the determination of GST-pi concentration in the donor urine, we can predict graft viability before the surgical procedure with a reliability of 68%.

Papillary microcarcinoma of the thyroid gland in renal transplant patients.

Among organ transplant recipients there is a world wide increase in the number of de novo tumors as well as a decrease in the time of the first appearance after the transplantation. Between 1973 and the 31st of August 1999 1709 cadaver renal allograft transplantations were performed in our Department. Four thyroid cancers were detected among the renal transplanted patients. Two of them proved to be papillary microcarcinomas. Although the elevated risk of thyroid cancers is well established in the literature papillary microcarcinomas have never been reported before in an immunosuppressed patient. Authors highlight that the thyroid gland should always be carefully checked in organ transplant recipients, since better survival might be achieved even in the immunosuppressed population. Metastatic tumor is relatively benign which is in correlation with the literature, but there has been little experience in organ transplanted patients so far.

Primary hepatic carcinoid in a renal transplant patient.

There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases were malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression.

A light stabilizer Tinuvin 770-induced toxic injury of adult rat cardiac myocytes.

Tinuvin 770/bis(2,2,6,6-tetramethyl-4-piperidinyl)sebacate is a worldwide used light stabilizer for plastic materials like polyolefins. Tinuvin 770 is a biologically active component of polypropylene tubes. Glossmann and his study group managed to extract this compound by aqueous or organic solvents from laboratory plastic tubes, and propose that Tinuvin 770 is a potent blocker of L-type Ca(2+)-channel through the phenylalkylamine and benzothiazepine-selective drug binding domains of the alpha(1) subunit of the receptor [Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 9523]. We examined the direct morphological effect of Tinuvin 770 in give 25nmol, 0, 30, 60, 120 minute exposure time in isolated cardiomyocytes from adult rats. Incubation of myocytes with Tinuvin resulted in a progressive decline of rod-shaped and viable cells. It was accompanied by an increase in number of hypercontracted myocytes with microbleb formation compared to control and depletion of ATP level. In summary, our results demonstrate that plasma membrane damage and hypercontraction are manifestations of Tinuvin-induced injury of isolated cardiomyocytes.

De novo tumors after kidney transplantation: the Budapest experience.

In a retrospective study we analyzed the incidence and characteristics of de novo tumors developing in renal transplant recipients treated in our center. The 5% incidence de novo tumors developing among patients treated with azathioprine and prednisolone (n = 241) was similar to the 5.4% incidence of de novo tumors developing among patients treated with calcineurin-based immunosuppression (n = 1918). The most common malignancies among our patients were basal cell (21.7%) and squamous cell (13.9%) carcinomas of the skin, followed by urogenital (10.4%) and lung malformations (9.6%). A high incidence of Kaposi's sarcoma (9.6%; half cutaneous and half visceral) and a lower than expected incidence of posttransplant lymphoproliferative disorder (PTLD; 3.5%) was found. Among patients developing de novo tumors, the incidence of death with a functioning graft was higher than among recipients without tumors. Moreover, the incidence of tumor-related death was high among the de novo tumor recipients. Among our recipients, the most aggressive tumors were Kaposi's sarcoma, lung tumors, lymphomas, and gastrointestinal tumors, which occurred relatively early after transplantation and were the cause of death in most cases. Compared to tumor registry data, we found an inverse basal-to-squamous cell carcinoma ratio, a lower incidence of PTLD, and a higher incidence of Kaposi's sarcoma.

Successful islet after kidney transplantations in a distance over 1000 kilometres: Preliminary results of the Budapest-Geneva collaboration.

To overcome critical islet processing and to ensure patient safety and quality care, we have established an international collaboration between two geographically distant transplant centers for islet transplantation. Four pancreata were harvested and immediately preserved by the two-layer method (oxygenated perfluorocarbon+University of Wisconsin) and subsequently transported for the automated method isolation to Geneva. After purification, the islets were cultured overnight and transported the next day back to Budapest. Three consecutive kidney transplant patients with type 1 diabetes mellitus underwent islet transplantation via percutaneous transhepatic portal embolization using the bag-method. The immunosuppression consisted of daclizumab, sirolimus, and low-dose tacrolimus. Mean donor age was 43.7 years, mean body mass index: 26.5. The islet isolation process began within 8 hours from the donor aorta cross-clamp in all cases. The isolation success rate was 80% (4 of 5). In Budapest, the islets were assessed for viability. No complications occurred during the transplantation, and the portal pressure remained within the normal range. The first patient received 12,000 IU/BW from two donors and the insulin requirement decreased from 40 U/d to 10 U/d. The second patient received 7200 IU/BW from a single donor and became immediately insulin free. The third patient was given 7100 IU/BW; the insulin requirement decreased from 39 U/d to 14 U/d. Posttransplant follow-up for the three patients are 7 months, 4 months, and 2 weeks, respectively. All patients achieved metabolic stability. These preliminary results demonstrate the feasibility of an international collaborative islet transplantation program at a distance over 1000 km.

Comparative study on reused haemodialysis membranes.

Data have shown that on the internal surface of reused haemodialysis membranes complement elements of plasma proteins, cells and cellular debris from the patient's blood are deposited. The aim of our study was to identify the effect of reuse on the haemodialysis membrane surface. Original and reused haemodialysis membranes were studied by the methods of light, transmission and scanning electron microscopy, immuno-histochemistry and X-ray spectrum element analysis. With reuse the membrane surface becomes uneven, and its continuity may break. Plasma protein and cellular elements are deposited on the damaged surface following continued reuse. Presence of IgM deposists were confirmed by immunohistochemical observation. Moreover, following reuse the X-ray spectrum analysis verified structural changes in the haemodialysis tube compared to the control material; accumulated aluminium, silicon, phosphorus, sulphur and chlorine were detected on the wall of the dialysis membrane.

Economic evaluation of kidney transplantation versus hemodialysis in patients with end-stage renal disease in Hungary.

BACKGROUND: Kidney transplantation is generally acknowledged as the more clinically effective and more cost-effective option in managing patients with end-stage renal disease, compared with dialysis. This study looked for confirmatory evidence in a Hungarian population. METHODS: Patients (n = 242) with end-stage renal disease who received cadaveric kidney transplantation during 1994 were followed up for 3 years. They were compared with patients (n = 840) receiving hemodialysis who were on a waiting list for transplantation. Data were collected retrospectively. Treatments were compared for clinical efficacy and for cost-effectiveness. RESULTS: At month 36, the standard mortality hazard function was 3.5 times higher in the group receiving hemodialysis (P < .0001) than in the transplant recipients. Average treatment costs per patient over the 3 years were also significantly higher (P < .0001) in the hemodialysis group than in the group than received transplants. The cost of 1 year gained by transplantation was significantly less (P < .0001) than the cost associated with hemodialysis. CONCLUSIONS: Compared with hemodialysis, kidney transplantation provides greater survival benefits to patients with end-stage renal disease, at less cost.

Mixed lymphocyte cultures (MLC) and acute pancreatitis after renal transplantation.

MLC was performed preoperatively in 35 out of 57 candidates for renal transplantation. Three patients developed acute pancreatitis in the early postoperative stage, 2 of them died. In these three cases MLC revealed complete non-reactivity of the recipient lymphocytes, compared with the donor as well as with the positive control lymphocytes. None of the other patients showed this phenomenon and none of them developed acute pancreatitis. It is suggested that the recipient's immune responsiveness may be involved in the aetiology of the production of acute pancreatitis after renal transplantation.

Herpes zoster and acute rejection crisis of renal homograft.

The case of a patient developing acute rejection crisis 8 months after transplantation in the prodromal stage of a herpes zoster infection is reported. The joint therapeutic measures resulted in suppression of rejection and control of the infection. Complications did not occur. The case suggests a definite association between the viral infection and acute homograft rejection. The case report is followed by a critical review of the pertinent literature.

Experimental vascular graft for liver transplantation.

Hepatic artery thrombosis is a major cause of graft failure in liver transplantation. Use of donor interponates are common, but results are controversial because of necrosis or thrombosis after rejection. Reperfusion injury, hypoxia and free radical production determinate the survival. The aim of the study was to create an 'ideal' arterial interponate. Autologous, tubular graft lined with mesothelial cells, prepared from the posterior rectus fascia sheath, was used for iliac artery replacement in eight mongrel dogs for six months under immunosuppression. Patency rate was followed by Doppler ultrasound. Eight grafts remained patent and another two are patent after one year. The patency rate was good (median Doppler flow: 370 cm/sec) and there was no necrosis, thrombosis or aneurysmatic formation. The grafts showed viable morphology with neoangiogenesis, appearance of elastin, smooth muscle and endothelial cells. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. Tissue oxygenation was good in all cases with normal (< 30 ng/ml) myeloperoxidase production. In conclusion, this autologous graft presents good long-term patency rate. Viability, arterialisation and low thrombogenicity are prognostic factors indicating usability of the graft in the clinical practice without the risk of rejection. Further investigations such as cell cultures and standardisation are necessary.

[Anesthesiologic and intensive care requirements in liver transplantation]. / A májátültetés anesztéziájának és intenzív terápiájának feltételei.

The complex anaesthesia and intensive care of liver transplantation require special instruments beside expert's knowledge. We monitorize the haemodynamics invasively during the operation and immediately afterward. In the later period of intensive care we prefer the noninvasive haemodynamic monitoring techniques. The transoesophageal echocardiography has special role in the anaesthesia of liver transplantation. One of the most important equipment during the operation is the biopump that assures the shunt between the lower and the upper body. Controlling it also belongs to the tasks of anaesthesiologist. During the anaesthesia and early period of intensive care the most serious problem can be the disfunction of blood coagulation system of the recipient. To investigate it the thrombelastography is the most suitable technique which can show the in vivo processes. To analyze the curve of the thrombelastography requires special knowledge. Similarly, the analysis of the electroencephalogram during the anaesthesia is not the everyday task of an anaesthesiologist. To reduce the blood requirements during the operation we use the autotransfusion techniques. During the anaesthesia of the liver transplantation we use other equipment that belong to the everyday work of an anaesthesiologist i.e.: rapid blood infusion and patient warming and cooling systems, rapid laboratory and blood-gas analyzing methods. The anaesthesia and intensive care of liver transplantation claim wideranging knowledge of anaesthesiologist not only theoretically but also practically.