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.

Is there any connection between the presence of kidney stones in primary hyperparathyroidism and the location of an underlying adenoma?

The majority of the patients with primary hyperparathyroidism (pHPT) recurrently produce kidney stones, while the rest have other clinical manifestations. The aim of this study was to examine the possibility of an association between the presence of kidney stones and the location of an underlying adenoma. This was a retrospective evaluation of the records of 91 patients (10 males, 81 females, mean age: 61.9 years [20 - 70 yrs]) operated for primary hyperparathyroidism between 1995 and 2000. One patient was excluded due to carcinoma. Kidney stones were found in 55 cases and other clinical symptoms in 35 cases. In 50 of the 55 patients (91 %) with kidney stones, the adenoma was located in the left inferior parathyroid gland (chi2 = 67.5, p < 0.00,001), while in 24 of the 35 patients (69 %) without kidney stones, the adenoma was in the right inferior parathyroid gland (chi2 = 43.9, p < 0.0001). These results suggest that the location of the adenoma may influence the presence of kidney stones in pHPT. It is proposed that the biologic effects of parathyroid hormone could differ depending on which of the four parathyroid glands it was secreted in, or the four glands may produce different biologically active fragments.

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.

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.

Changes in Tumor Characteristics in Kidney Transplanted Patients Over the Last 40 Years.

BACKGROUND: Post-transplantation tumors (PTTs) are the greatest limiting factor for patient survival following organ transplantation. AIM: To describe the incidence and main characteristics of malignancies developed in patients who underwent kidney transplantation in Budapest between 1973 and 2014. METHODS: During this period, the essential data for PTTs were repeatedly evaluated. In this study, the results from 1990, 1995, 2000, 2006, and 2013 were evaluated. RESULTS: Incidence of PTTs increased from 2.3% to 11.1%. Male/female ratio was 2:1. Skin, native kidney, and lung cancers were the most common tumors during the entire observation period. Lymphoma was seen rarely at the beginning and became common in 2013. The same was observed in the most frequent general population tumors (colorectal, breast, hepatic, prostate, gastric cancer, and malignant melanoma) where the occurrence increased in the last 10 years. Mean age of patients increased from 35.7 to 56.5 years. During the last 20 years, age of recipients increased: above 50 years from 22.9% to 40.5%, and above 60 years from 8.2% to 23.1%. Patient survival was different according to tumor stage at discovering, i.e. renal cell carcinoma was usually discovered in stage I. resulting in a 66.1% 5-year survival rate, whereas 43.5% of colorectal cancers were diagnosed in stage IV, with a 13.9% 5-year survival rate. CONCLUSION: The frequency of PTTs and proportion of elderly persons undergoing transplants are continuously increasing. Tumor stage is a determining factor for patient survival. Recognition of precancerous conditions, diagnosis of tumors in early stage, and oncological screening can improve survival time.

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%.

Non-cytotoxic blocking antibodies and suppressor cells induced by donor-specific transfusions in healthy volunteers and potential kidney transplant recipients.

Donor-specific transfusion (DST)-induced immunosuppression plays a significant role in clinical and experimental transplantation. To clarify the mechanism of suppression on alloreactivity the suppressor cell induction and the non-cytotoxic blocking antibody production and importance was studied in 15 healthy volunteers and 3 kidney transplant recipients (KTR) after DST on mixed lymphocyte culture (MLC). Significant decrease of anti-donor MLC response was found in all of KTR and in 12 cases of the 15 transfused volunteers. Of 18 cases, 15 had blocking factors in their post-DST serum which strongly (52-91%) inhibited the MLC response. The IgG fractions isolated from the "blocking sera" were responsible for this inhibition. Eighty-one percent of non-cytotoxic blocking antibodies affected the responder cells in MLC and reacted with third party responder cells as well. Both buffy coat and platelet transfusions evoked production of the non-specific blocking antibodies. Our data strongly suggest that DST induces not only the differentiation of suppressor cells and production of anti-idiotypic antibodies, but also the appearance of non-specific, non-cytotoxic antibodies, which may participate in the cell-mediated immune suppression of the alloimmune reactivity.

Effects of joining peptide (1-18) and histamine on dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) production of human adrenocortical cells in vitro.

Joining peptide 1-18 (JP 1-18), added alone in concentrations of 10(-13)-10(-7) M to collagenase-dispersed human adrenocortical cells, did not affect the basal production of corticosterone, cortisol, aldosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS). JP 1-18 potentiated the ACTH-stimulated production of steroids. When administered in combination with histamine (10(-8)-10(-3) M), JP 1-18 (10(-8) or 10(-10) M), enhanced the synthesis of DHEA and DHEAS. JP 1-18, together with histamine, may play a role in the regulation of DHEA and DHEAS production.

DNA content of parathyroid tumors.

BACKGROUND: The significance of DNA ploidy in indicating the benign or malignant character of parathyroid and other endocrin tumors is controversial. MATERIALS AND METHODS: DNA content of paraffin embedded parathyroid samples from 25 patients was measured with flow cytometry. RESULTS: The DNA index (DI) was 1.0 in all nonneoplastic samples as well as in 50% of adenomas (10/20) and in one carcinoma (1/2). The remaining 45% of the adenoma cases (9/20) and the other carcinoma showed doubled DNA content (DI = 1.9-2.0). The increased DI did not correlate with either clinical data (sex, age, tumor size, preoperative serum Ca++ or parathormone, primary or secondary hyperparathyroidism) or morphology. CONCLUSIONS: These results indicate that the DI has no value in deciding the benign or malignant character of a given sample. However, the prognostic value of tetraploidization (the potentially increased risk for malignancy) could not be ruled out.

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.

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.

Prevention of apoptosis reperfusion renal injury by calcium channel blockers.

Apoptosis has been shown in the literature to be the form of cell death occurring in renal tubular epithelial cells during the reperfusion phase after brief periods of renal ischaemia. In the present study apoptosis was examined in the rat kidney in the first 24 hours after 30 min ischaemia and apoptosis was influenced by administration of the Ca channel blockers Verapamil, Bepridil, Nifedipin and Sensit. Apoptosis was observed in the renal tubular cells two hours after the start of reperfusion and reached in maximum at hour 6. All above mentioned Ca channel blockers decreased the occurrence and degree of apoptosis.

Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.

OBJECTIVES: This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. METHODS: In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months. RESULTS: Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S). CONCLUSION: Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.

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 autologous substitute vascular graft for transplantation surgery.

Vascular complications in liver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs. The patency was followed by palpation and Doppler ultrasound. The grafts were removed after one month. Five grafts remained patent. The Doppler showed good, relatively increased flow (median flow rate: 383 cm/sec) after one month in all of the cases. Slight increase in diameter was present in all cases. By microscopy the five patent grafts showed viable morphology, fibroblasts, smooth muscle cells and thin fibrin layer in the wall. The grafts were lined partially with a neoendothelial monolayer and a thin fibrin layer. In conclusion, this graft presents an acceptable patency rate and low thrombogenicity, and could be useful in transplantation. Further investigations are needed to study the effect of immunosuppression and rejection on long-term morphology and patency of the grafts.

[Liver transplantation in Hungary]. / Májtranszplantáció Magyarországon.

Necessities and possibilities being in Hungary are discussed. All the requirements involving personal, organization and material (room, equipment, diagnostics) necessities are particularly listed. Possibilities of donors are satisfactory. Problem is the viral diagnostics of donors. The quality of liver transplantation to be waited in Hungary is calculated with activity number in the world. At least 70 liver transplantation are to be yearly waited in Hungary, against this only some patients are on the waiting list. The most important gate is the insufficient quantity of blood according into the selection of program of liver transplantation. The author particularly analyses the covering expenses; the Transplantation and Surgical Department is a good background for liver transplantation, this way the National Health Insurance Institute ought to assure the activity expenses.

[Screening of patients waiting for kidney transplantation]. / A veseátültetésre váró betegek kivizsgálása.

The authors summarise the indications and contraindications of kidney transplantation according to their our experiences. They report the changes of the number of kidney transplantation in Hungary, the distribution of the kidney diseases and they also report the risk factors, which can influence the results of the kidney transplantation.

[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.