Interpretation of LDH Values after Kidney Transplantation.

Kidney transplantation is the gold-standard therapy for end-stage renal disease. However, in the early postoperative period following allograft kidney transplantation, insufficient graft function presents a diagnostic challenge to clinicians. Ischemic damage to the graft and/or an early autoimmune rejection may cause a decrease in function. Ischemic damage is a benign and transient condition, while acute immune rejection requires immediate therapy. A kidney graft ultrasound may produce a false negative result, and graft biopsy is invasive and slow to return results. Serum lactate dehydrogenase (LDH) is under examination as a possible tool for differential diagnosis between ischemic damage and immune rejection. Herein, we analyze the continuous lab results of four patients in the early post-transplantation period, showing patterns correlating with different clinical outcomes and prognoses. In our experience, a persistent elevated LDH accompanies ischemic damage. Immune rejection was, however, associated with a decrease in LDH. Hemodialysis was not a confounding factor, while packed red blood cell transfusion caused severe diagnostic problems.

Novel Noninvasive Paraclinical Study Method for Investigation of Liver Diseases.

Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials.

Optimal Renal Artery-Aorta Angulation Revealed by Flow Simulation.

INTRODUCTION: In the circulatory system, the vessel branching angle may have hemodynamic consequences. We hypothesized that there is a hemodynamically optimal range for the renal artery's branching angle. METHODS: Data on the posttransplant kinetics of estimated glomerular filtration rate (eGFR) were analyzed according to the donor and implant sides (right-to-right and left-to-right position; n = 46). The renal artery branching angle from the aorta of a randomly selected population was measured using an X-ray angiogram (n = 44). Computational fluid dynamics simulation was used to elucidate the hemodynamic effects of angulation. RESULTS AND DISCUSSION: Renal transplant patients receiving a right donor kidney to the right side showed faster adaptation and higher eGFR values than those receiving a left donor kidney to the right side (eGFR: 65 ± 7 vs. 56 ± 6 mL/min/1.73 m2; p < 0.01). The average branching angle on the left side was 78° and that on the right side was 66°. Simulation results showed that the pressure, volume flow, and velocity were relatively constant between 58° and 88°, indicating that this range is optimal for the kidneys. The turbulent kinetic energy does not change significantly between 58° and 78°. CONCLUSION: The results suggest that there is an optimal range for the renal artery's branching angle from the aorta where hemodynamic vulnerability caused by the degree of angulation is the lowest, which should be considered during kidney transplantations.

The First 5 Years of the Newest Eurotransplant Member State: Hungarian Results of International Organ Exchange From 2014 to 2018.

INTRODUCTION: Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible. METHOD: A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges. RESULT: The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96. CONCLUSION: Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors.

[Tacrolimus therapy after renal transplantation. Current questions of concentration/dose ratio]. / Takrolimuszterápia vesetranszplantáció után. A koncentráció/dózis arány aktuális kérdései.

Tacrolimus is an important part of immunosuppressive therapy after solid organ transplantation. The therapeutic range of the drug from the calcineurin inhibitor group is narrow. Adjustment of the blood concentration can be very complicated but to be able to avoid the occurrence of side effects or ineffective immunosuppression it is inevitable. This article summarizes the properties of tacrolimus pharmacokinetics, pharmacogenetics and pharmacodynamics. We will focus on individual variations of cytochrome enzymes. In the following part, a new method for screening high risk patients will be introduced. We will present the publications of the determination of the concentration/dose (C/D) ratio. By determining the C/D ratio, researchers identify fast and slow metabolizing patient groups. Fast metabolizers require higher doses in general and the occurrence of complications is also more frequent in this group. Long-term results are lagging behind the slow metabolizing group. The long-term results of renal transplantation nowadays contribute to the postoperative period and the later years rather than the surgery itself. It includes the proper management of previous illnesses (e.g., hypertension, diabetes, endocrinological problems), detection of complications (e.g., infections, malignancies), and the precise regulation of immunosuppressive therapy. Orv Hetil. 2019; 160(30): 1178-1183.

[Antibody-mediated rejection: challenge of the treatment in kidney transplantated patients]. / Antitestmediált rejekció: kihívás a veseátültetett betegek kezelésében.

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

[Rare bile duct anatomy variant - Right bile duct intraparenchymal junction into the left bile duct]. / Az epeutak ritka anatómiai variánsa − A jobb ductus hepaticus intraparenchymalis csatlakozása a bal oldali ductus hepaticusba.

The authors present a case of a 67-year-old male patient, who previously had been diagnosed with a malignant liver tumor localized in segment II. He underwent bisegmentectomy (II and III) and partial IV segmentectomy. After the primary surgery jaundice developed, the level of bilirubin increased and after several imaging modalities reoperation was indicated. During the surgery a rare bile duct anatomy variant was found. The right hepatic duct joined the left duct in the parenchyma of the left lobe, and was ligated at the resection. As the liver hilum was not explored, the absence of the right duct was not discovered. Reconstruction of the biliary system was accomplished by a Roux-en-Y loop.

PARP inhibition attenuates acute kidney allograft rejection by suppressing cell death pathways and activating PI-3K-Akt cascade.

BACKGROUND: Novel immunosuppressive therapy facilitates long term allograft survival, but acute tubular necrosis and ischemia-reperfusion during transplantation can compromise allograft function. These processes are related to oxidative stress which activates poly- (ADP-ribose) polymerase (PARP) contributing to the activation of cell death pathways. Here we raised the possibility that PARP inhibition curbs cell death pathways and shifts kinase signaling to improved graft survival. METHODS FINDINGS: In an acute rat kidney rejection model, we provided evidence that the PARP inhibitor 4-hydroxy-quinazoline (4OHQ) attenuates rejection processes initiated oxidative/nitrosative stress, nuclear poly-ADP-ribosylation and the disintegration of the tubulo-interstitial structures. The PARP inhibitor attenuated rejection processes induced pro-apoptotic pathways by increasing Bcl-2/Bax ratio and suppressing pro-apoptotic t-Bid levels. In transplanted kidneys, the cell death inducing JNK1/2 is normally activated, but PARP inhibition suppressed this activation with having only modest effects on ERK1/2 and p38 MAP kinases. In untreated transplanted kidneys, no significant alterations were detected in the cytoprotective PI-3K-Akt pathway, but the PARP inhibitor significantly activated Akt (by S473 phosphorylation) and suppressed GSK-3ß, as well as activated acute NF-kappaB activation contributing to graft protection. CONCLUSION: These data show the protective role of PARP inhibition on graft survival by attenuating poly-ADP-ribosylation, oxidative stress, suppressing pro-apoptotic and increasing anti-apoptotic protein level, and by shifting MAP kinases and PI-3-K-Akt pathways to cytoprotective direction. Thus, addition of PARP inhibitors to standard immunosuppressive therapies during kidney transplantation may provide increased protection to prolong graft survival.

[50-year history of kidney transplantation in Hungary]. / A veseátültetés elso 50 éve Magyarországon.

The first Hungarian kidney transplantation was performed by András Németh in Szeged in 1962, approximately 50 years ago. A preliminary agreement with Eurotransplant was signed in 2011, and special patient groups gained benefit from this cooperation in 2012, wnich lead to a full membership to Eurotransplant. This event inspired the authors to review the history of Hungarian kidney transplantation of the past 50 years, from the first operation to recent via the specific cornerstones of the transplant program. The donor of the first Hungarian kidney transplantation was the brother of the recipient. The operation itself was technically successful, but the lack of immunosuppression caused graft rejection, and the patient died after 79 days. His brother, the donor, is still healthy, after 50 years, and he encourages everybody to donate organs. Organized kidney transplant program started more than 10 years later, such as 1973, in Budapest. The program was supported by the Ministry of Health. New centers joined the program later, Szeged in 1979, Debrecen in 1991 and Pécs in 1993. These four transplant centers work currently in Hungary, and 6611 kidney transplantation has been performed up to the end of year 2012.

[Role of simultaneous pancreas-kidney transplantation in the treatment of diabetes mellitus]. / Szimultán hasnyálmirigy-vese transzplantáció helye a diabetes mellitus kezelésében.

The life expectancy of patients with type 1 diabetes mellitus is inferior to that of patients with some malignancies. Simultaneous pancreas-kidney transplantation is the procedure providing the best survival results among all options of renal replacement therapy. The operative techniques and immunosuppresion have been standardized in the last decade. Although the number of transplantable organs falls behind the need, simultaneous pancreas-kidney transplantation is the method of choice for the eligible patients. The results of the two Hungarian simultaneous pancreas-kidney transplantation programs are in accordance with data published in the international literature.

[From the surgical field to the microscope. A new tool to identify the lymph node specimens in oncologic surgery]. / A mutotol a mikroszkópig. A rendszerezett nyirokcsomóminták azonosításának új eszköze a ráksebészetben.

Oncologic surgery and pTNM staging require systemic removal of the locoregional lymphnodes. While the optimal extent and therapeutical and/or prognostic value of the lymphadenectomy/sampling are debated organ by organ and (sub)speciality by (sub)speciality, relevance of the lymphnode sytem-tumor concept itself is beyond doubt. Loss of information and existence of traps on the "surgical field-microscope" pathway is an international phenomenon, calling for solution. An integrated sterile and disposable lymphnode tray system is presented here for applications in the different fields of cancer surgery of the upper GI tract, retroperitoneum (gynecology, urology) and ear-nose-throat surgery.

[Clinical study of non-melanoma skin cancer following human organ transplantation]. / A szervtranszplantációt követo non-melanoma bortumorok klinikai vizsgálata.

INTRODUCTION: Increasing evidence suggests that non-melanoma skin cancers (NMSC) are the most frequent tumours in transplanted patients. In this study, we present the first Hungarian dermatological screening program to establish the incidence of NMSC after organ transplantations. PATIENTS AND METHODS: 116 adult, "Caucasian" (white skin) transplanted (kidney, simultaneous-pancreas-kidney) patients (70 male and 46 female) of the Surgical Department of Pécs University were enrolled from September 2008. All patients underwent a a full skin examination by a dermatologist for NMSC as well as a standardized questionnaire was filled in to assess risk factors. RESULTS: Screening resulted in 16 NMSC (13.8%, median age: 49.3 years, male : female = 1 : 1) diagnoses with a median duration from transplantation of 4.1 years. Histology showed 13 basal cell carcinoma (BBC), 3 squamous cell carcinoma (SCC), with a 4 : 1 ratio of BCC : SCC. Incidence of NMSC was significantly higher on patients who were treated with cyclosporine as immunosuppressant, who had more than 2 sunburns prior to transplantation, or had outdoor workplace ( p < 0.05). CONCLUSIONS: These data confirm the importance of skin cancer surveillance in transplant recipients via a close cooperation between Transplantation and Dermatological Centres. Our results reflect the international data, except for the BCC : SCC ratio. Further studies needed to elucidate this difference.

[Surgical treatment of primary leiomyosarcoma of the inferior vena cava]. / Primer vena cava inferior leiomyosarcoma (VCI-LMS) sebészi kezelése.

CASE REPORT: pLMS in the wall of the inferior vena cava is an extremely rare form of retroperitoneal malignancies. A case in a young female patient is presented; clinical symptoms, pre- and postoperative diagnosis and surgical treatment are discussed. A retroperitoneal mass detected by imaging was found to be a large tumor mass located at the middle segment of the IVC on exploration. The tumour was successfully excised and the IVC was reconstructed with a synthetic graft. Eight years later, this patient needed a repeat surgery due to local recurrence. This time tumour was attached to the left renal vein. A re-resection of the IVC was performed with subsequent synthetic graft reconstruction and the distal end of the left renal vein was reimplanted into a lower segment of IVC. DISCUSSION: Primary leiomyosarcoma of the inferior vena cava (pLMS-IVC) is an extremely rare form of retroperitoneal malignancies. The tumour arises from the medial layer of the venous wall and can grow either intraluminally, or extraluminally or in both directions, as well. It can be localized in the first segment of IVC (above the hepatic veins), in the second segment between hepatic and renal veins and finally in the third segment between the right common iliac vein and renal veins. Therefore, the tumour can infiltrate both hepatic and/or renal vessels. Upper segment tumours can cause Budd-Chiari syndrome (hepatomegaly, abdominal pain, jaundice and ascites) with a bad prognosis. Middle segment tumours usually present with right upper quadrant pain, or may mimic biliary tract disease with a much better prognosis. Accumulating experience suggests that radio-chemotherapy alone seems to be less effective than "en bloc" resection with clear margins including loco-regional lymph nodes. Therefore, our choice of treatment was the latter. Although radical resection can be carried out in most of cases, 50% of patients develop a late recurrence yet.

Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation.

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.

[The first case of single pancreas transplantation in Hungary]. / Szoliter hasnyálmirigy-átültetés elsô esete Magyarországon.

UNLABELLED: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement for type I diabetes mellitus patients with end stage renal disease. Several patients have some complications of diabetes without renal failure. For these patients pancreas transplantation alone is a therapeutic option. The first pancreas transplantation alone was performed 6 years after the launch of our pancreas transplant program. The patient was a 40-years-old man. Enteric drainage was used with portal venous drainage. Anti IL-2. R antibody, daclizumab was given as prolonged induction therapy. In spite of the technical and immunological difficulties there were neither technical failures nor acute rejection. 3 years after the transplantation the patient has a good quality of life without insulin therapy with excellent renal function. CONCLUSION: PTA transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients without end stage renal disease.

[Surgical treatment of pulmonary metastases of colorectal cancers]. / A colorectalis tumorok tüdô metastasisainak sebészi kezelése.

INTRODUCTION: Results of a retrospective study of patients who underwent pulmonary metastasectomies after colorectal surgery in the last five years are reported here. Prognostic factors are evaluated and analyzed in the context of current literature. MATERIAL AND METHODS: 37 lung resections were performed in 33 patients between 2001 and 2006, the male:female ratio was 19:14. The average age was 61.3 years (49-76). We analyzed the extent of lung resections, disease free intervals (DFI), laterality of the tumours, number and locations of metastases, lymph node involvements and the incidence of resection of hepatic metastases. Altogether, 20 solitary lung metastases were removed and 17 multiple resections were performed. 25 sublobar resections, 11 lobectomies and one pneumonectomy were carried out. 18 patients had right sided, eight patients had left sided and six patients had bilateral disease. 6 of the 33 patients underwent either synchronous or metachronous liver resection for hepatic metastases. RESULTS: Survivals were calculated by the Kaplan-Meier method. The average DFI was 27.6 months. When all patients were considered, the average survival was 28 months. 52% of the patients had a 3-year postoperative survival, if lung metastases were present only. CONCLUSIONS: Patients benefit from surgical removal of lung metastases of colorectal cancer. There were no differences in survival rates between patients who underwent resection of solitary or multiple lung metastases up to seven deposits. However, the average survival was 12 months shorter if hilar/mediastinal lymph nodes were involved. Furthermore, the average survival of six patients with hepatic metastases was 10 months shorter than the rest of the group. There was no benefit of DFI over 24 months. None of the other prognostic factors showed significant difference.

Association between carcinosarcoma and the transplanted kidney.

BACKGROUND: Renal carcinosarcoma is a rare tumor with 12 reported cases in the world literature. To our knowledge, carcinosarcoma of a renal allograft has not been reported to date. CASE REPORT: A multifocal urothelial carcinosarcoma of a transplanted kidney in a 49-year-old woman is described. Genomic analysis of the extracted nuclei of all the neoplastic cells showed uniformly XY genotype proving the transplant origin of the tumor. RESULTS: The carcinogenic role of immunosuppressive medications in kidney-transplanted patients is reported in the literature. In this case, immunosuppression may have promoted the carcinosarcoma. CONCLUSION: Renal transplant patients should be monitored for the development of malignancy in the allograft and elsewhere.

Pulmonary embolization as primary manifestation of hepatocellular carcinoma with intracardiac penetration: a case report.

Intracardiac manifestation of hepatocellular carcinoma (HCC) is a rare condition and an uncommon finding even at autopsy. Pulmonary tumor embolism as a presenting feature of HCC has been published only twice previously. In our case report, a 63-year-old man presented with high fever and six episodes of recurrent pneumonias during the last half year. Echocardiography was performed, a solid mass was found in the right atrium. Transesophageal echocardiography proved a tumor mass in the inferior vena cava (IVC) extending into the right atrium, abdominal ultrasound revealed tumor mass in the IVC and a solid tumor in the liver. Combined liver and heart surgery was attempted in order to remove the tumor mass from both the liver and the right atrium. Acute cor pulmonale occurred during tumor removal from the right atrium and the patient expired. In addition to local factors the possibility of embolization should arise in the background of recurrent pneumonia. Occult carcinoma must be included in possible causes of recurrent pulmonary embolism. Searching for primary malignancy should include HCC as frequent cause of hypercoagulability. In case of HCC, echocardiography is suggested because of the possibility of expansion in IVC or right atrium and tumor-embolization.

[Simultaneous pancreas-kidney transplantation--an alternative option for the treatment of type 1 diabetes mellitus with renal failure]. / Kombinált hasnyálmirigy-veseátültetés--veseelégtelenséggel szövodött 1. típusú diabetes mellitus kezelésének alternatív módja.

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement. AIMS: Analysis of the five years' experience of the first Hungarian SPK transplants. MATERIAL: From 29 October 1998. through 31 December 2003. 32 SPK transplants were performed from 53 type 1 diabetes mellitus patients with ESRD on the waiting list. Enteric drainage was performed in all transplanted patients in 20 combined with systemic venous drainage, whereas in 12 patients portal venous drainage was used. In 18 patients only maintenance immunosuppression was administered without ATG induction therapy. Anti IL-2R antibody, daclizumab was given as induction therapy in 14 patients. RESULTS: 24 patients out of 32 transplanted are insulin independent with excellent renal function. 2 patients were lost in the perioperative period due to septic complication. 2 patients died 5 months after transplantation. 1 patient became insulin dependent in 7 month following the SPK transplant, while preserving a marginal renal function. One patient became insulin dependent 2 years after the SPK transplant and was returned to chronic hemodialysis treatment one more year later. 2 patients are insulin independent but lost his renal graft due to therapy resistant rejection. CONCLUSION: SPK transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients with ESRD.