Efficacy of sotrastaurin plus tacrolimus after de novo kidney transplantation: randomized, phase II trial results.

Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging non-inferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n = 77; discontinued in December 2011) or 200 mg (n = 73) b.i.d. plus standard tacrolimus (sTAC; 5-12 ng/mL), sotrastaurin 300 mg (n = 75) b.i.d. plus reduced tacrolimus (rTAC; 2-5 ng/mL) or enteric-coated mycophenolic acid (MPA) plus sTAC (n = 73); all patients received basiliximab and corticosteroids. Composite efficacy failure (treated biopsy-proven acute rejection ≥ grade IA, graft loss, death or loss to follow up) rates at Month 12 were 18.8%, 12.4%, 10.9% and 14.0% for the sotrastaurin 100, 200 and 300 mg, and MPA groups, respectively. The median estimated glomerular filtration rates were 55.7, 53.3, 64.9 and 59.2 mL/min, respectively. Mean heart rates were faster with higher sotrastaurin doses and discontinuations due to adverse events and gastrointestinal adverse events were more common. Fewer patients in the sotrastaurin groups experienced leukopenia than in the MPA group (1.3-5.5% vs. 16.5%). Sotrastaurin 200 and 300 mg had comparable efficacy to MPA in prevention of rejection with no significant difference in renal function between the groups.

Biochemical energetics of simulated platelet plug formation. Effect of thrombin, adenosine diphosphate, and epinephrine on intra- and extracellular adenine nucleotide kinetics.

Washed human platelets were incubated in a modified Ringer's solution, pH 7.1, at 37 degrees C for 1 hr. Intracellular basal levels for glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and orthophosphate were 31.1, 2.52, 1.39, 0.36, and 1.2 mumoles/ml of platelets, respectively. Extracellular ATP, ADP, and AMP remained fairly constant and represented 4, 2, and 4% of total adenine nucleotide content. Total adenine nucleotide content remained unchanged during the period of control incubation. Glycogen depletion was 17.8 mumoles/ml at the end of 1 hr; lactate production was 20.7 mumoles/ml per hr. In the presence of glucose, lactate production increased 100%, and glycogen depletion was spared 13%. Approximately 55% of glucose or glycogen fuel was converted to lactate. The agglutinating agents, thrombin, ADP, and epinephrine, resulted in increased glycogen depletion and lactate production both in the presence and absence of glucose. The effect of thrombin was greater than epinephrine. The effect of epinephrine was greater than ADP. All three agglutinating agents resulted in loss of high energy phosphates (net decline in adenine nucleotides) with release of adenine nucleotides into the extracellular environment. The effect of thrombin was greater than ADP. The effect of ADP was greater than epinephrine. In experiments with ADP addition, significant quantities of ADP were converted to AMP extracellularly. In experiments with thrombin and epinephrine appreciable quantities of extracellular orthophosphate were taken up by plateletes and could not be accounted for by changes in intracellular orthophosphate or adenine nucleotide. Sufficient ADP was released during exposure to thrombin and epinephrine to account for platelet agglutination. Changes in intracellular adenine nucleotides and orthophosphate could be correlated with the activation of regulator glycogenolytic and glycolytic enzymes.

Glycogenesis and glyconeogenesis in human platelets. Incorporation of glucose, pyruvate, and citrate into platelet glycogen; glycogen synthetase and fructose-1,6-diphosphatase activity.

Washed human platelets are capable of depositing 1-4 as well as probable 1-6 glucosyl linkages onto preexistent glycogen primer. They are also capable of degrading (glycogenolysis) newly synthesized 1-4 as well as probable 1-6 glucosyl linkages. A higher rate of glycogen synthesis was found in platelet suspensions containing lower concentrations of platelets. This was shown to result from decreased glycogen degradation and consequent increased residual glycogen primer in low platelet suspensions. The increased glycogen content of low platelet suspensions was not a result of platelet washing, removal of platelets from plasma, or release of platelet metabolites into the media. The enzyme glycogen synthetase was found to be present at a rate of 5.2 mumoles of uridine diphosphate (UDP) glucose incorporated into glycogen per gram platelets per hour at 37 degrees C. The K(m) for UDP glucose was 6.6 mmoles/liter. At optimum concentration of glucose 6-phosphate, the K(m) was reduced 4.6 fold and V(max) was increased 4.3-fold. Human platelets contain the glyconeogenic pathway. They incorporate pyruvate-(14)C and citrate-(14)C into platelet glycogen and contain an apparent fructose-1,6-diphosphatase. The apparent fructose-1,6-diphosphatase was activated by adenosine monophosphate (AMP) and adenosine diphosphate (ADP), inhibited by adenosine triphosphate (ATP), and shown to be rate limiting for glyconeogenesis at physiologic concentration of adenine nucleotide.

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

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

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

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

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

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

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

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

De novo tumors after kidney transplantation: the Budapest experience.

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

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

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

De novo Prograf versus de novo Advagraf: are trough level profile curves similar?

BACKGROUND: According to the clinical trials, Advagraf (ADV) has efficacy and safety profile similar to Prograf (PROG). The aim of this study was to compare the graft functions, dosages, and tacrolimus (TAC) trough level profile curves of patients on de novo PROG and ADV therapy. METHODS: The ADV group included 39 de novo renal cases who had received initial immunosuppression (IS) with once-daily TAC (1 × 0.2 mg/kg from day1 after transplantation). We compared them with a PROG group of 38 transplant patients who received equivalent IS with twice-daily TAC (2 × 0.1 mg/kg from day1). In both groups, the IS was combined with antimetabolites and steroids. The mean follow-up time was similar (13.5 ± 7 days) in both groups after renal transplantation until the emission of the patients from our clinic. RESULTS: TAC mean total daily dose was reduced and whole-blood trough levels decreased over the time in early postoperative days. Only on day 3 and day 4 after transplant, a significant higher adjustment in the ADV dosage was necessary to achieve sufficient TAC trough levels. The average TAC trough level profile curves were similar in PROG and ADV groups, but the individual curves were very different. Mainly in patients on ADV therapy, the initial concentrations were often >30 ng/mL, and in some cases on the 9th posttransplant day decreased to <5 ng/mL, then slowly increased into the required therapeutic range. CONCLUSIONS: The results demonstrate that patients after renal transplantation can be safely treated de novo with ADV. Setting the required therapeutic TAC blood levels may require more attention to avoid the "fluctuations" of trough level profile curve during the early postoperative period. Our data suggest that dose adjustment of ADV can be carried out more carefully compared with PROG on the basis of clinical symptoms and the value of TAC blood levels to avoid acute rejection and toxicity.

Endogenous thrombin potential and examination of a further 31 analytes in liver transplant candidates.

BACKGROUND: To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. METHODS: Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. RESULTS: International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (ATIII) values. In the factor analysis, 3 factors were found, which explained 81.6% of the total variance. Combination of aspartate aminotransferase and ATIII mostly separated the basic disease groups from each other in the discriminant analysis. From 35 variables, the lactate dehydrogenase (LDH) and ATIII have been suited for predicting the change in patient status. Eighty percent of patients with low ATIII and high LDH levels had deterioration of their clinical status. CONCLUSIONS: Our study demonstrated that the ETP parameters did not provide additional information compared with "conventional" coagulation tests in cirrhosis. On the basis of our study, LDH and ATIII appear to be promising analytes to assess the clinical status of patients with cirrhosis. In our opinion, the classification system of liver transplant-listed patients can be improved with their use.

Exchange of best practices within the European Union: surgery standardization of abdominal organ retrieval.

Considering the growing organ demand worldwide, it is crucial to optimize organ retrieval and training of surgeons to reduce the risk of injury during the procedure and increase the quality of organs to be transplanted. In the Netherlands, a national complete trajectory from training of surgeons in procurement surgery to the quality assessment of the procured organs was implemented in 2010. This mandatory trajectory comprises training and certification modules: E-learning, training on the job, and a practical session. Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation) Joint Action coordinated by Spain and co-funded under the European Commission Health Programme, 3 twinning activities (led by France) were set to exchange best practices between countries. The Dutch trajectory is being adapted and implemented in Hungary as one of these twinning activities. The E-learning platform was modified, tested by a panel of Hungarian and UK surgeons, and was awarded in July 2013 by the European Accreditation Council for Continuing Medical Education of the European Union of Medical Specialists. As a pilot phase for future national training, 6 Hungarian surgeons from Semmelweis University are being trained; E-learning platform was fulfilled, and practical sessions, training-on-the-job activities, and evaluations of technical skills are ongoing. The first national practical session was recently organized in Budapest, and the new series of nationwide selected candidates completed the E-learning platform before the practical. There is great potential for sharing best practices and for direct transfer of expertise at the European level, and especially to export this standardized training in organ retrieval to other European countries and even broader. The final goal was to not only provide a national training to all countries lacking such a program but also to improve the quality and safety criteria of organs to be transplanted.

Increasing living donor kidney transplantation numbers in Budapest.

Living related kidney donations (LRD) have had a significant impact on therapy of kidney diseases. Due to their ease of scheduling in the general surgery program and better half-life of about 21.6 versus 13.8 years for deceased donor kidneys, this approach has revolutionized nephrology and transplantation medicine. Since the first Hungarian LRD which was performed in 1974 in Budapest, Hungary, donations have expanded especially in the last 3 years. This has been followed in 2000 by living unrelated kidney donations (LURD). Since 2000 LURD can be also performed in Hungary. From the 251 LRD in our country in the last 3 years, 79 living donations have accounted for nearly one-third of the cases. In comparison of 2008, and 2011 the absolute numbers of LRD as well as LURD have more than doubled from 9 to 20 and 6 to 14 respectively. Based on international ranking data from the global observatory on donation and transplantation Budapest has improved from 1.20 in 2000 to 6.20 LRD per million persons (p.m.p.) in 2010. The increase in LURD has also led to some side effects: an increase in recipient age from 26 years in 2000 to 46 in 2011 and greater HLA mismatches. In 2010, Budapest ranked higher than Croatia or Portugal but still behind Germany (8.13 LRD p.m.p.) and the leading countries: the Netherlands (28.49 LRD p.m.p.) and Norway (16.94 LRD p.m.p.). Because of the tremendous progress in LRD, the gap between today's leading countries and Budapest is closing.

Kidney transplantation in hereditary coproporphyria using tacrolimus and mycophenolate mofetil: a case report.

BACKGROUND: The porphyrias are a group of disorders of the heme biosynthesis pathway that may present with acute life-threatening attacks, commonly exacerbated by a wide variety of medications. Many newer immunosuppressive medications, which are in use following kidney transplantation, have not been fully explored in acute porphyrias. CASE REPORT: A 53-year-old woman received a kidney from a deceased donor, after being on hemodialysis for 4 years. Hereditary coproporphyria was diagnosed at age 19 years. We administered tacrolimus, mycophenolate mofetil and steroid immunosuppression. In the immediate post-transplant periods she displayed abdominal pain and transient uroporphyrin elevation in parallel with slightly elevated (15 ng/mL) tacrolimus concentrations. As the target tacrolimus level was achieved, these findings disappeared. CONCLUSIONS: Tacrolimus, mycophenolate- mofetil, and steroid therapy for hereditery coproporphyri was safe, in the long term.

Successful treatment of renal failure caused by multiple myeloma with HLA-identical living kidney and bone marrow transplantation: a case report.

Here we have described a successful HLA-identical living allogeneic kidney transplantation after bone marrow transplantation in a patient with end-stag liver disease caused by multiple myeloma (MM). Our case is unique, because this combined transplantation is rarely possible and because of our unique immunosuppressive and management strategies. A 45-year-old man with ESRD MM and κ light-chain nephropathy was diagnosed. Cytostatic treatment resulted in partial remission, so autologous peripheral stem cell transplantation (SCT) was performed leading to a complete remission; however the patient remained anuric. The patient's HLA-identical brother offered to be a donor of peripheral stem cells for collection and cryopreservation. Kidney transplantation was performed with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well-functioning kidney graft, allogeneic SCT was performed in the incipient relapse phase of MM, after total body irradiation. Severe oropharyngeal infections, diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we administered steroid bolus. He experienced therapy with gradual restoration of kidney function. Then, steroid-responsive acute graft-versus-host disease (grade II, predominantly bowel) was diagnosed on the background of diarrhea, which returned once. Later he experienced a left subclavian vein thrombosis at the site of a central venous catheter and sepsis. Having recovered from these events, the patient enjoys good health, with stable kidney function and normal protein excretion. After the steroid was stopped, a bone marrow biopsy revealed full-donor type normocellular hemopoiesis. Because of the chimerism, we gradually discontinued the immunosuppression including, sirolimus and finally tacrolimus, since with minimal trough levels there were no complications. Bone marrow biopsy showed a complete remission. In MM with ESRD HLA-identical combined kidney and bone marrow transplantation from a living donor may offer not only complete remission and good renal function, but also good health without immunosuppression.

Superiority of AbCross enzyme-linked immunosorbent assay cross-match over the B-cell complement-dependent lymphocytotoxicity cross-match.

BACKGROUND: The AbCross enzyme-linked immunosorbent assay (ELISA) cross-match is a recently introduced solid phase cross-match technique with several technical advantages over the currently available Antibody Monitoring System ELISA cross-match. METHODS: In the present study, we investigated the potential superiority of AbCross over the traditional complement-dependent lymphocytotoxicity (CDC) B-cell cross-match (BXM). Pretransplant sera of 271 kidney transplant recipients who were transplanted at our center between 1998 and 2010 were tested in ELISA screening for the presence of human leukocyte antigen (HLA) antibodies and in AbCross and CDC for antibody reactivity against solubilized donor HLA class I and II antigens and donor B cells, respectively. RESULTS: Patients positive for HLA class I or II antibodies on ELISA screening had a significantly poorer graft outcome 2 years after transplantation than recipients who were negative for HLA antibodies (21% vs 6% graft loss; P = .002). Corresponding with this finding, 37 recipients positive for HLA antibodies in AbCross against donor HLA class I or II antigens had a 2-year post-transplant graft loss rate of 19%, which is significantly higher than the 8% rate in 186 recipients who were negative for both antibody classes in AbCross (P = .043). The 2-year graft loss rate in 34 AbCross positive but BXM negative patients was 21%, compared with 7% in 172 AbCross and BXM negative patients (P = .012) and 9% in 11 AbCross negative but BXM positive patients (P = .39). CONCLUSIONS: Our data indicate that the AbCross ELISA cross-match is superior to the CDC BXM, most likely because it detects antibodies against donor HLA antigens at a higher sensitivity.

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.

History of eurotransplant.

In 1967, the Dutch immunologist Jon van Rood called Eurotransplant into life. From the beginning it was a non-profit private foundation. Initially it was a loose cooperation, where tissue typing laboratories and transplantation centers joined to achieve a better result for their kidney patients, a longer survival based on better immunological matching from a bigger donor pool. Other centers from the Benelux states, Germany and Austria soon joined the first few cooperating centers. Switzerland was also a member of Eurotransplant, but left the organization in 1978. Based on the pioneering work of the Leiden histocompatibility lab, the allocation system became more and more sophisticated and was extended to other solid organs. Since the 1980s Eurotransplant has allocated donor livers, hearts, and pancreas. Thereafter, the allocation also included lungs and small bowel. From 1996 a new kidney allocation system, the ETKAS, was introduced, and after the Acceptable Mismatch program and the Eurotransplant Senior Program (known unofficially as "old-for-old" program) were introduced. The main principle remains to adapt the allocation rules continuously according to the newest scientific data serving all organs. In 1991 the German reunification centers in the former Eastern Germany became part of Eurotransplant. In 1999, Slovenia, and in 2007 Croatia joined Eurotransplant. For the transplant centers in these two countries, membership meant positive changes and is regarded as a success story. Both donor numbers and transplant possibilities increased and equal chances are assured for their patients on the common Eurotransplant waiting list. Hungary, joining Eurotransplant next year, hopes to experience the same.

Role of early systemic inflammatory response in simultaneous pancreas-kidney transplantation.

Pancreas grafts are susceptible to surgical complications mostly related to exocrine secretions and the low microcirculatory blood flow through the gland. During simultaneous kidney-pancreas transplantation, the systemic response depends on reperfusion of two organs acute graft pancreatitis, immunotherapy, coagulopathy, bleeding, and other factors. We performed a retrospective review of 10 adult simultaneous pancreas-kidney transplant patients to evaluate progression of early postoperative inflammation in the absence of infection. All patients were treated with four-drug therapy. We performed analyses of procalcitonin (PCT), C-reactive protein, serum creatinine, amylase, and lipase levels over the first 5 postoperative days. Relatively high peak PCT levels (maximum 130 ng/mL) were reached within 24 to 48 hours postoperatively followed by a moderate decrease. Consistent with this observation, the serum creatinine, amylase, and lipase levels decreased continuously to normal concentrations within the first week. The increased PCT levels seemed depend upon the surgical procedure and intraoperative events. PCT was superior to C-reactive protein to discriminate infection from inflammation in this setting. The dynamics of PCT levels, rather than absolute values, seemed to be important. Lack of a decrease in PCT levels after the peak, suggested an infectious complication or the development of sepsis. Monitoring and assessment of PCT levels may help in early recognition of infection and institution of therapy.

The safe introduction of angiotensin-converting enzyme inhibitor in renal allograft recipients.

Antihypertensive and renoprotective treatment with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker is indicated in almost all chronic renal failure patients. However, this treatment is not widely used for renal allograft recipients mainly because of the potential side effects, including a decrease in renal function as well as onset of hyperkalemia or anemia. Herein we investigated the effects of ACEI introduction to hypertensive renal transplantation patients who did not display renal artery stenosis. At least 2 months after transplantation, we exchanged amlodipine (5 mg) for either ramipril or perindopril (5 mg) in 25 patients who were free of renal artery stenosis as determined indirectly by measuring the renal arterial resistance index with the noninvasive, inexpensive Doppler ultrasound method. The resistance index was evaluated again at 2 weeks. Systolic and diastolic blood pressure, serum creatinine, calculated creatinine clearance, serum potassium, hemoglobin and hematocrit were also measured before as well as at 2, 4, and 12 weeks after conversion to ACEI. The conversion did not change the mean renal arterial resistance index, nor did it influence renal function or blood count, and it was equally effective for controlling blood pressure. The serum potassium level increased at 2 and 4 weeks; however, it was within the normal range in all patients. Our data suggested that measurement of the renal arterial resistance index is a noninvasive, inexpensive, and reliable preselection method before introduction of ACEI in renal allograft recipients.