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.

Examination of carbohydrate metabolism parameters after simultaneous pancreas-kidney transplantation.

End-stage renal failure, a frequent complication of type 1 diabetes mellitus, requires renal replacement therapy. Our team examined the laboratory parameters of carbohydrate metabolism in 18 patients with type 1 diabetes at 10 to 89 months after simultaneous pancreas-kidney transplantation. We compared these results with those of 17 patients with type 1 diabetes who had formerly received kidney-alone transplantations, and were undergoing insulin treatment, as well as with those of 16 metabolically healthy controls. The hemoglobin A1c (HbA1c) and blood glucose levels of the pancreas-kidney transplant recipients were within the normal ranges, not differing significantly from those of the healthy controls. In contrast, the HbA1c and glucose levels were significantly elevated among kidney transplanted diabetic subjects. However, fasting and 2-hour insulin levels of pancreas-kidney transplant patients were significantly higher than those of the controls, indicating insulin resistance. According to these results, the insulin secretion by the pancreas graft sufficiently compensated for insulin resistance. Thus 10 to 89 months after successful pancreas-kidney transplantation, carbohydrate metabolism by type 1 diabetic patients was well controlled without antidiabetic therapy.

The significance of the circumaortic left renal vein and other venous variations in laparoscopic living donor nephrectomies.

Among the several vascular variation those concerning the venous system of the kidneys show the most significant variability. They often play an important role when it comes to choosing the kidney to be removed for transplantation. Based on our prior studies, we have surveyed these variations. When performing a laparoscopic living donor nephrectomy owing to the limited field of vision and the restricted possibilities for preparation, preoperative radiologic planning is of utmost importance. We evaluated 55 donors who underwent laparoscopic nephrectomies using the 16-section multidetector-row computed tomography angiography. Among the donors who underwent surgeries we observed circumaortic veins (CAV) in three cases, retroaortic veins in 6 cases, multiple renal veins in 10 cases, and a lumbar vein draining into the left renal vein (RV) in 30 cases. In the 2 cases wherein CAVs were discovered, the team decided to use the other kidney. In 1 case, due to a short right RV, we chose the left kidney. The complex development of the CAV that is sometimes difficult to reconstruct in 3D poses a challenge for both the radiologist and the surgeon.

Cytomegalovirus seroprevalence among solid organ donors in Hungary: correlations with age, gender, and blood group.

BACKGROUND: Cytomegalovirus (CMV) is endemic throughout the world, affecting most of the population, but the seroprevalence of CMV is known to vary among countries. CMV causes a mild infection in persons with intact immunity; however, CMV infection in organ transplantation is associated with significant morbidity and mortality. The present retrospective study was designed to evaluate the age-, gender-, and blood group-adjusted CMV seroprevalence among solid organ donors, representing fairly the overall Hungarian population (according to Hungarian Central Statistic Institute). This information is important for calculating risk-factors for CMV-seronegative recipients. No nationwide estimates of CMV seroprevalence in Hungary (as a representative of Eastern Middle Europe) have been published yet. METHODS: We investigated 2070 organ donors for CMV seroprevalence by measuring the CMV-specific immunoglobulin G. The donors were divided into 3 age groups (2-20, 21-50, and 51-70 years old). A study was also conducted on a fourth group consisting of 200 residents from an old age home. CMV seroprevalence differences were searched according to age-, gender- and blood-group distribution. RESULTS: The CMV seroprevalence of organ donors is 85% and of all investigated persons is 86%. The age-specific prevalence increases, starting from 72% in the first group to 99% in the fourth group. Seroprevalence of females was found to be significantly higher than of males (P=.0001). CONCLUSION: We have shown that the overall CMV seroprevalence in the Hungarian population is moderately high at 86%. The opportunity for CMV-seronegative recipients to get a graft from a seronegative donor is statistically only 2%. The seroprevalence of the youngest age group is 72% and so it can be concluded that the Hungarian population acquires the infection mainly in childhood or in the early adulthood. Female gender is a risk factor for CMV infection. This fact must be taken into consideration during the planning of patients' follow-up, prophylaxis, and therapy.

Renal cell carcinoma of the native kidney: a frequent tumor after kidney transplantation with favorable prognosis in case of early diagnosis.

INTRODUCTION: The frequency of malignant tumors as a cause of death is increasing among kidney transplant patients. The aim of our study was to characterize kidney tumors occurring in the native kidneys of renal transplanted patients, and to determine their impact on recipient survival. METHODS: We retrospectively analyzed the 43/3003 (1.43%) renal cell carcinomas (RCC) in the native kidneys of patients transplanted between 1973 and 2010. RESULTS: During this period we diagnosed 293 posttransplant tumors, 14.6% of which were RCC. The male/female ratio was 2.1:1. The mean age of recipients at the time of tumor detection was 52.4 ± 12.1 years. The mean time from transplantation to diagnosis was 72.4 ± 61.6 months. RCC occurred on both sides in similar numbers. Tumors were multifocal in 8 cases. According to TNM staging, RCC was stage I in 38 cases. The histologic type was clear cell (n=27), papillary (n=13), chromophobe (n=2) or sarcomatoid (n=1). Radical nephrectomy was performed in 41 cases. Immunosuppressive management was converted to proliferation signal inhibitors in 27 patients (sirolimus n=19 or everolimus n=8). Fifteeen patients died at a mean survival time of 38.9 ± 62.4 months with 28 patients still alive at a mean follow-up 43.8 ± 35.6 months. Cumulative survival according to the Kaplan-Meier method was 79.2% at 1 year, 66.1% at 5 years, and 59.0% at 10 years. The patient survival rate was better among papillary than clear cell RCC (P=.038). CONCLUSION: RCC was the second most frequent tumor among kidney transplanted patients at our center. The diagnosis established at an early stage in the majority of cases, leading to favorable patient survivals. A regular yearly abdominal ultrasound screening is suggested for early tumor diagnosis.

Renal tubular cell necrosis and apoptosis in transplanted kidneys.

Renal wedge biopsies were taken from donors' kidneys immediately at the end of cold ischaemia and 30 min after transplantation in 11 cases. Five renal grafts showed immediate and six showed delayed renal function clinically. The ratio of apoptotic and necrotic renal tubular cells and Ki67 activity was determined in both biopsies. Necrotic and apoptotic as well as proliferating renal tubular cells were seen in all samples. Both apoptotic and proliferative activity was decreased in samples taken 30 min after transplantation in cases of immediate renal function compared to the samples taken before transplantation. This phenomenon was not observed in cases of delayed renal function.

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.

Comparative analysis of kidneys retrieved from the same donor and transplanted into different recipients.

We have reviewed the outcome of kidney transplantations where both kidneys retrieved from the same donor were transplanted at our Department and the factors which might be decisive in the outcome. Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. In 360 cases, both kidneys retrieved from the same donor were transplanted at our Department. We evaluated only first transplant cases who were treated with a combination of cyclosporin and prednisolon. After this selection, 248 pairs of kidneys were left for analysis. We divided them into three groups. The first comprised immediately functioning kidneys (135 pairs), the second, no immediate graft function in any of the recipients (29 pairs). The third group was mixed: the kidneys retrieved from the same donor were functioning in one recipient and not in the other, so this group was omitted from the analysis. We therefore analysed the donor factors of age, sex and cause of death. We found no significant difference between the groups relating to the cause of donor death. There was, however a significant difference in the age of donors: those kidneys functioning well in both recipients derived from a younger donor group (16-40 years), 18/58 versus 136/270, P < 0.01, chi 2 = 7.17. There were significantly fewer older donors (41-65 years) in the immediately functioning group than in the other, 38/58 versus 110/ 270, P < 0.001, chi 2 = 11.84. We investigated the number of HLA mismatches, ischaemic time, cytotoxicity index and the type and duration of pretransplantation dialysis. It appears from this analysis that the age of the donor is a significant factor in the short-term outcome of transplanted kidneys. Recipient factors as HLA match, ischaemic time and cytotoxicity index seems to be less important.

Evaluation of the state of health of living related kidney transplantation donors.

Renal transplantation is the optimal mode of therapy for patients with end-stage renal disease; the results are even better with living related donors. This procedure, therefore, favours the recipients, but what are the consequences for the donor? At our Department, between 1973 and 1996, 1325 kidney transplantations were performed, 78 from living, related donors (5.89%). We decided to follow up these patients and investigate the function of the remaining kidney and also their current general health status. Thirty donors (38.4%) were investigated. Of these, 25 of had normal blood pressure and 5 were hypertensive, needing antihypertensive treatment. The average age was higher in the hypertensive group (60.2/53.25 years). The time interval since transplantation was longer in the hypertensive group than in the normal one. We carried out a scintigraphy of the kidney with Tc-99mMAG-3. The mean value of the glomerular filtration rate calculated from the MAG clearance was 98.1 ml/min and this value is higher than half of the normal isotope clearance value, i.e. higher then the expected value for a single kidney. We conclude that no impairment of renal function is observed in the living, related kidney donors. In 16.66% a mild hypertension developed. With isotope investigation we found hypertrophy of the remaining kidney. Thus, after a correct preoperative assessment, unilateral nephrectomy has no long-term consequences in healthy donors.

Attitudes of donors towards organ transplantation in living related kidney transplantations.

The demand for transplantation exceeds the availability of cadaveric organs, which is why the importance of living, related kidney transplantation is increasing. In our study we wanted to evaluate the experiences of living related donors (LRD). Between 1973 and 1996, 1325 kidney transplantations were performed at our Department. Of these 1247 were from cadaver donors while 78 were from LRD. We contacted each living donor by post. We carried out a physical examination, laboratory tests, ultrasound and isotope investigations and they were interviewed and completed a questionnaire. Thirty previous kidney donors came to our Department who were all blood relatives of the recipients. In the recipient group, 16 still have a functioning kidney, the average time since transplantation being 8.92 years. The longest kidney survival time is 18 years. All the donors willingly donated their kidney, none was worried about their own health and their only concern was whether the kidney would function or not. Regarding general attitudes towards living related organ transplantation, all were in favour of blood relative donor transplantation and also husband/wife transplantation. Opinions regarding non-related transplantation were more mixed; 63.3% would have given their kidneys to a friend, only 46.6% to a stranger. Almost two-thirds (63.3%) of donors were not in favour of selling and buying organs but, controversially, they would have bought an organ had one been available. All agreed that the donation did not change their general health. In conclusion, the donors of living, related kidney transplantation all agreed that it was a good thing to donate; All confirmed they would go through the same procedure again in order to help. Apart from one person, who emphasised that he is agnostic, all belonged to a Christian religion.

The results of 1009 kidney transplantations performed in Hungary.

Kidney transplantation is a widely used method throughout the world for the treatment of end-stage renal disease. Following the pioneering work of Szeged Medical University Hospital and Miskolc District General Hospital, the first successful kidney transplantation in Hungary was performed at the Department of Transplantation and Surgery at Semmelweis Medical University on November 16, 1973. This patient is still alive with a functioning kidney graft after 21 years. We report herein our review of the global results of Hungarian kidney transplantation. Hungary is a medium-developed country with a population of over 10 million where the gross national product is about 4000 U.S. dollars per person per year. In Hungary there are 49 dialysis centers, 4 immunological laboratories, and 4 transplantation centers.