Results and complications after living related kidney transplantation in Hungary: 30 years' experience.

The number of patients suffering from kidney disorders is increasing the need for kidney transplantation. Kidneys originating from living donors (LD) show substantially better results than those originating from cadaveric donors (CD). We performed 3000 kidney transplantations between November 1973 and December 2007, including 154 from LD (5.13%). The early kidney function as measured by the delta creatinine clearance was significantly better among the LD group (P < .001). There was no significant difference in the immunologic data between the LD and the CD groups (P = .047). Four years after transplantation the glomerular filtration rate (GFR) and the serum creatinine level treated to be better among the LD group with tacrolimus versus cyclosporine immunosuppression (P = .089). In the LD group, the acute rejection rate was lower with tacrolimus- versus cyclosporine based immunosuppression (P = .014).

Small difference in international normalized ratio may yield a significant impact on prioritizing patients listed for liver transplantation.

Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.

Significance and imaging of lumbar veins and early-branching arteries in planning living-donor laparoscopic nephrectomy: two case reports from 21 months' experience.

A key aspect in planning laparoscopic living-donor nephrectomy is mapping of vascular variations. Lumbar veins and early-branching renal arteries are of utmost importance. To date, 43 candidates including 18 men and 25 women aged 25 to 67 years have been examined at our clinic using 16-section multidetector-row computed tomography angiography. Each examination was double-checked by an experienced radiologist. Of the 43 patients, 31 underwent surgery. In 29 of 31 patients (93.5%), the anatomy observed during surgery was identical to that demonstrated on the preoperative computed tomography scan. In 1 of 2 patients, 2 separate arteries were found at surgery, rather than the prognosticated early-branching arteries. In this patient, conversion to open surgery was necessary. In the other patient, a lumbar vein running into a retroaortic renal vein was discovered. In this patient, a 6-mm length of the joint stem contained the wall of the aorta and the periaortic tissue; thus, technically they were of separate origins. Careful mapping of the anatomy helps to prevent unexpected operative complications that are difficult to manage. Correct interpretation of the data must always be based on agreement between the radiologist and the surgeon.

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.

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.

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.

Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience.

BACKGROUND: Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R-), who have received an organ from a seropositive donor (D+). OBJECTIVES: We compared the effectiveness of three different prophylactic protocols in CMV D+/R- patients and reviewed data on patients who received no prophylaxis. PATIENTS AND METHODS: We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R-); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only. RESULTS: In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R- patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died. CONCLUSIONS: Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.

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.

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.

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.

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.

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.

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.

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.

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.

[Qualitative and quantitative detection of hepatitis C virus RNA by PCR technique. Monitoring of viral copies after liver transplantation]. / Hepatitis C-vírus (HCV)-RNS kvalitatív és kvantitatív kimutatása PCR technikával. A HCV-RNS-kópiaszám monitorozása májtranszplantációt követóen.

The authors demonstrate the HCV nucleic acid amplification method is not wide-spread in Hungary yet. The HCV-RNA is usually detectable 2-4 weeks after infection independently the immunostate of the patients. The authors help to select the adequate measurement(s) in logical order when HCV infection is suspected. The benefit of the PCR method is emphasized. Monitoring of the HCV-RNA titer of the liver transplanted patients promotes to establish the fluctuation of HCV-RNA copies and the effectivity of therapy following transplantation. The detection of HCV-RNA by PCR method is a proof of an acute or chronic infection and rules out past infection. The quantitative PCR measurement is useful for determination of indication and control of efficacy of antiviral therapy.