Clinical Transplantology
Aim. To carry out monitoring of the state and prospects of the development of organ donation and transplantation in the Russian Federation according to 2013. Materials and methods. Questioning of heads of all the centers of transplantation is carried out. The comparative analysis of the obtained data in dynamics of years, between certain regions of the Russian Federation, the transplantation centers, and also with data of the international registers is made. Results. According to the register in 2013 in the Russian Federation functioned 35 centers of kidney transplantation, 15 centers of liver transplantation and 10 centers of heart transplantation. The waiting list of kidney transplantation included more than 4000 potential recipients that makes 15–16% of total number of the patients receiving dialysis. The rate of donor activity made 2,9 per million population (pmp). Effi ciency of donor programs continues to increase: the share of effective donors after brain death in 2013 increased to 72,4%, the share of multiorgan explantation increased to 52,9%, average number of organs received from one effective donor made 2,6. The rate of kidney transplantation made 6,5 pmp, the rate of liver transplantation made 1,9 pmp; the rate of heart transplantation made 1,1 pmp. In the Russian Federation the number of transplantations of liver and heart continues to increase. The signifi cant contribution to development of the organ donation and transplantation brings the Moscow region in which 11 centers of transplantation function and nearly a half of all kidney transplantations and 70% of all liver and heart transplantations are carried out. In 2013 Ministry of Health of Russia continued development of the new federal law «On donation of human organs and their transplantation». Under the auspices of the Russian Transplant Society 11 clinical guidelines about organ donation and transplantation were developed and approved. Together with earlier approved orders and standards of medical care clinical guidelines make methodical base for clinical work in transplantology. Conclusion. The main source of further increase in the number of organ transplantation in the Russian Federation (according to real requirement) is, in our opinion, opening of new programs in regions and development of interregional coordination.
Aim: evaluation of the incidence of early postoperative complications after simultaneous pancreas-kidney transplantation.
Materials and methods. The analysis of early postoperative complications after simultaneous pancreas-kidney transplantation is presented in the paper, the most rational diagnostic algorithms, non-surgical and surgical complications’ treatment; the outcomes of the SPKT are reported.
Results. 15,6% of patients experienced surgical complications, 12,5% – immunological complications, 12,5% – infectious complications, 6,25% – complications of the immunosuppressive therapy. 1-year patient survival after SPKT was 91,4%; pancreas graft survival – 85,7%; kidney graft survival – 88,6%.
Conclusion. The incidence of early postoperative complications after simultaneous pancreas-kidney transplantation remains signifi cant in spite of progressive improvement of simultaneous pancreas-kidney transplantation due to surgical technique improvement, introduction of new antibacterial and immunosuppressive agents. Data, we recovered, fully correspond to the data obtained from the global medical community.
Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation) allograft dysfunction caused by late acute rejection (LAR, n = 193) or chronic rejection (CR, n = 78) or both (n = 23). C4d staining was performed by immunofl uorescence (IF) on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy). 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01) better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%). Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection.
Aim of our clinical study was evaluation of the possibility of diagnosing of renal posttransplant complications in recipients using dynamic renal scintigraphy.
Materials and methods. In this study were included 118 patients (age 21–60 (38,4 ± 9,8 yrs)), who underwent dynamic renal scintigraphy and renal transplantat biopsy. We determined time to peak uptake and excretion half-life time of radiopharmaceutical in renal transplantat and graft parenchyma. Recipients were subdivided into three groups according to histopathological findings: first – normal (n = 32), second – acute rejection (n = 43), third – chronic nephropathy (n = 43).
Results. Time to peak uptake of radiopharmaceutical in graft parenchyma in patients in the fi rst group – 3,24 ± 0,54 min, second – 6,61 ± 3,28 min, third – 6,21 ± 3,17 min (p < 0,001). Time to peak uptake of radiopharmaceutical in renal graft in patients in the fi rst group – 3,87 ± 0,62 min, second – 7,4 ± 3,8 min, third – 8,03 ± 3,28 min (p < 0,001). The half-life time of radiopharmaceutical in graft parenchyma – 10,4 ± 2,95 min, second – 37,09 ± 19,44 min, third – 29,6 ± 15,52 min (p < 0,01). The half-life time of radiopharmaceutical in renal graft in the fi rst group – 12,31 ± 3,09 min, second – 43,29 ± 27,39 min, third – 52,71 ± 26,2 min (p < 0,001). Anderson–Bahadur distance: Tmax of graft parenchyma is the most signifi cant between the fi rst and the second group of patients (1,23); Tmax of renal graft gives maximum index value in chronic nephropathy (0,89), T1/2 of graft parenchyma is more once differentiated between acute rejection and chronic nephropathy (0,95). The sensitivity and the specifi city of renal scintigraphy parameters in the diagnosis of renal posttransplant complications amounted to 71,43–95,24% and 67,7–96,43%, respectively.
Conclusion. Renal scintigraphy is an additional test for early detection of renal posttransplant complications and correction of recipient surveillance. The kinetic parameters of renotrophic radiopharmaceuticals provide diagnosis of acute rejection and chronic nephropathy of renal graft. The introduction of radionuclide imaging to monitor the state of renal transplantat optimizes approaches to graft biopsy.
It is shown that liver transplantation (LT) from donor with incompatible blood type (AB0i) may be effective and safe, but the impact of such operation upon the various systems of the body has not been investigated yet. Insulinlike growth factor-1 (IGF-1) is synthesized in the liver and mediates the action of growth hormone. The level of IGF-1 is a marker of the processes of cell proliferation and tissue regeneration. Aim. To evaluate levels of IGF-1 in children-recipients with liver transplant from AB0i (incompatible) and AB0c (compatible) donors.
Materials and methods. 140 children aged 3 to 36 (19,5 ± 16,5 months) with congenital diseases of the hepatobiliar system, 58 of them boys, were surveyed. All patients underwent transplantation of left lateral liver sector from living related donors: 111 children were transplanted with fragment of the liver from AB0c donors, 29 – from AB0i donors; in 10 children with AB0i liver before and/or after LT operation anti-group antibodies (anti-A/B) were revealed. The concentration of IGF-1 was determined by ELISA using specifi c kits (Immunodiagnostic System, USA) in samples of blood plasma, which were received up to a month and a year after a liver transplant.
Results. Average level of IGF-1 21,0 ± 29,5 μg/l in patients before LT was signifi cantly lower than in healthy children (52,2 ± 26,3 μg/l, p < 0,001) and did not vary in children, having received later a piece of liver from a compatible (AB0c) donor and from donor AB0i (23,5 ± 30,9 and 21,2 ± 23,2 μg/l respectively, p = 0,70). In patients with anti-A/B prior to surgery average level of IGF-1 was not different from that of the patients without antibodies (32,6 ± 27,6 and 22,3 ± 29,6 μg/l respectively, p = 0,4). One month after LT level of IGF-1 has increased both in the general group, and in patients with AB0c and AV0i liver (92,1 ± 77,8 and 131,2 ± 106,7 μg/l respectively, p = 0,09). The level of IGF-1 was not varied in the group with antibodies (152,5 + 150,4 μg/l) and without them (95,9 ± 77,0 μg/l). A year after LT the average level of IGF-1 in recipients of AV0c and AV0i liver was not varied and was signifi cantly higher than before LT (82,0 + 60,7 and 91,2 ± 77,8 μg/l, p < 0,005 and p = 0,03 respectively). The content of IGF-1 in patients with anti-A/B and without them (104,7 ± 67,5 and 84,7 ± 63,7 μg/l respectively) also did not differ.
Conclusion: the results of our studies have shown that restoration of the level of IGF-1 is not dependent on transplantation of compatible or incompatible blood type liver, as well as on the availability of anti-group antibodies.
Aim evaluated function and perfusion of myocardium in 12 cirrhotic patients before and after liver transplantation (LT).
Materials and methods. ECG-gated single photon emission computed tomography (SPECT) was used.
Results. It was found that hyperdynamics diminished liver transplantation: left ventricle (LV) end-systolic volume (ESV) rose from 23 to 33 ml (p = 0,026), LV ejection fraction decreased staying normal from 76 до 60% (p = 0,08), calculated cardiac output declined from 4941 to 3066 ml/min (p = 0,009), peak ejection rate (PER) from 314 to 218 ml/sec, (p = 0,003), peak fi lling rate decreased from 248 to 182 ml/sec (p = 0,037), eccentricity coeffi cient also decreased from 0,81 to 0,77 (p = 0,028). Local alteration of perfusion was found only in 2 cases.
Conclusion. Hyperdynamic systolic dysfunction and diastolic dysfunction improve after liver transplantation. Further studies are required to estimate the applicability of SPECT in liver transplantation candidates’ evaluation.
Aim of our clinical study was to analyze the waiting list and evaluate the results of heart transplantation in the center of transplantology in Sverdlovsk Regional Hospital № 1 in Ekaterinburg.
Materials and methods. The article presents the results of selection of patients in the waiting list and the 7-year results of prospective study, which included 27 heart transplantations for end-stage heart failure, performed in Sverdlovsk Regional Hospital № 1 in Ekaterinburg.
Results. Survival rate was 78% (21 patients). Causes of death in the early postoperative period were: graft dysfunction, heart graft rejection, acute heart failure and cardiac arrhythmias. In the late postoperative period the most frequent complications were: graft rejection, septic complications and sick sinus syndrome. In a year after heart transplantation chronic heart failure (CHF), I functional class (NYHA), was diagnosed in 15 patients, 3 patients had CHF II functional class (NYHA) and 3 patients had no heart failure.
Conclusion. Heart transplantation is an effective treatment for end-stage heart failure.
Implants and Artificial Organs
The most reliable intraoperative mechanical extracorporeal support is conventional сardiopulmonary bypass (CPB). However, CPB increases a risk of intraoperative bleeding and primary graft dysfunction. ECMO is more benefi cial method of intraoperative cardiopulmonary support than CPB in LTx.
Aim. 10 LTx were retrospectively analyzed in the period from 01.2012 till 01.2014.
Methods. Indications for ECMO were acute grafts edema after reperfusion (n = 4, group I). In group II (n = 6) indications for ECMO were severe hypoxia (РаО2 and FiO2 ratio < 1,0) and/or acidosis (pH < 7,2) during one lung ventilation. We used central type of veno-arterial ECMO: right atrium to ascending aorta.
Results. Intraoperative ECMO lasted 4,1 ± 1,0 hours in group I and 8,5 ± 0,7 hours in group II. ECMO was prolonged into postoperative period in all patients from group I due to primary graft dysfunction. Application of ECMO in group II enabled to stabilize gas exchange and circulation as well as to decrease pulmonary arterial pressure in the time of reperfusion. ECMO was fi nished just after transplantation in group II. The 1-year survival in group I and II was 75,0 and 83,3%, respectively.
Conclusion. Central veno-arterial ECMO is an adequate method of intraoperative cardiopulmonary support in LTx. It prevents postreperfusion edema of the lung grafts.
Aim. To study the effect of hemofi ltration and coupled plasma fi ltration adsorption on tacrolimus blood concentration in renal transplant recipients.
Methods and results. The study included 8 renal transplant recipients. In these patients immediately after the operation was performed the coupled plasma fi ltration adsorption with hemofiltration using a cartridge Mediasorb to reduce the severity of reperfusion injury. We have found that during this extracorporeal blood correction procedure there was statistically not signifi cant decrease of tacrolimus blood concentration. However, concentration of tacrolimus remained in the therapeutic range even after the procedure and it was not signifi cantly different from the control point С0.
Conclusion. Coupled plasma fi ltration adsorption is safe in renal transplant recipients and has no signifi cant impact on tacrolimus blood concentration. However, the downward trend in the concentration of tacrolimus in the course of these procedures, especially in continuous or semicontinuous mode, as well as in patients with low hematocrit and hypoalbuminemia, requires individual monitoring.
Introduction. One of the current tasks of transplantology is to overcome «graft-host» immune confl ict. Partially this confl ict is caused by the presence of circulating pre-existing antibodies. Highly sensitized patients have a greater risk of rejection and subsequent graft loss. There are several methods to remove the antibodies, one of which is a double fi ltration plasmapheresis (DFPF). This report presents our experience of DFPF in recipients of high immunologic risk.
Aim: to compare the effectiveness of traditional and double filtration plasmapheresis in desensitization of patients with high risk of immunological complications.
Methods. The study included 30 patients after kidney transplantation. All patients were classifi ed as high-immunologic risk group. In 15 patients of study group we performed DFPF, in 15 patients of comparison group – traditional plasmapheresis. We monitored the immune status: markers of humoral immunity activation – IgG, IgM, IgA before and after the procedures. DFPF procedure was performed on OctoNova (MeSys, Germany) with a plasmafi lter and plasma components separator. Protocol biopsies were performed on days 30 and 90.
Results. The concentration of antibodies may be effectively reduced with DFPF. Total IgM and IgG antibodies were reduced by 30–55% of the original level. There was a less albumin loss in case of DFPF application. There is 1 patient with antibody-mediated rejection with graft dysfunction in study group. There are no signs of rejection in 30- and 90-day biopsy in study group. But there were three patients with subclinical antibody-mediated rejection in the comparison group.
Conclusion. DFPF can safely and effectively reduce the high titers of antibodies that are responsible for humoral rejection of renal allograft. Reduction of antibodies in sensitized patients immediately after transplantation may improve graft function.
Clinical Cases
Aim: to present an exceptional case of the combined pathology – an abnormal drainage of portal system to the coronary sinus, hypoplasia of the right branch of the portal vein and high pulmonary hypertension. Materials and methods. The patient P. of 22 years old arrived at congenital heart diseases surgical unit of V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs. After the examination he was diagnosed with congenital disease – abnormal confl uence of the portal vein in the right atrium. Insuffi ciency of the tricuspid valve 3–4. High pulmonary hypertension. Insuffi ciency of blood circulation of IIa, III functional class. After computer tomography there is no division of the portal vein. Vein is drained in the right atrium bypass with a diameter of 2,3 cm following from the portal vein to the coronary sinus. Results. Considering hopelessness of conservative therapy the only method of the radical help to the patient is two-stage surgical intervention – transplantation of a heart-pulmonary complex and liver transplantation. Conclusion. Presented rare clinical case demonstrates the combination of congenital anomalies of the portal system and the heart with high pulmonary hypertension, and is based on a functioning fetal venous duct (ductus venosus), bypassing the liver in the right atrium (coronary sinus) in combination with hypoplasia of the right portal vein.
Aim. To present rare clinical observation of successful surgical treatment of the patient with double-chamber right ventricle in combination with ventricular septal defect, subaortic fi brosis and muscular stenosis, insufficiency of the aortic valve and extrahepatic portal hypertension.
Description. Patient F., 15 years old, was diagnosed with Congenital Heart Disease – double-chambered right ventricle, ventricular septal defect. Fibromuscular subaortic stenosis. Aortic valve insuffi ciency II. Circulatory failure II A., functional class III. Extrahepatic portal hypertension. Splenomegaly. Thrombocytopenia. The state after the imposition of splenorenal anastomosis in September 1998 and the imposition of mesocaval H-shaped anastomosis in 1998. Non-functioning anastomoses. Patient indicated for surgical correction of CHD, however, given the low level of platelets, expressed splenomegaly, leucopenia, the patient was referred for a preliminary treatment to Rogachev’s Pediatric Hematology, Oncology and Immunology Center. The treatment (stimulating thrombopoiesis using romiplostim) gave no signifi cant effect. Platelet count reached 70–90 Å~ 109. Seeing of frequent bleeding from esophageal varices, the patient underwent varix sclerosis. At the time of hospitalization – no esophageal varices. The patient appealed to V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs where he was recommended for surgical treatment.
Result. The patient performed surgery: radical correction of CHD: resection of the stenosis of the outfl ow tract of the right ventricle, subaortic stenosis resection, closure of ventricular septal defect, AV plasty under cardiopulmonary bypass. The early postoperative period was uneventful. Leukopenia was observed to 1,2 Å~ 109, thrombocytopenia 70–90 Å~ 109. Despite the low level of platelets bleeding in pre-and postoperative period was not registered. Antibiotic therapy with tienam. Good postoperative results were obtained. Liver function was not affected.
Conclusion. Presented clinical case demonstrates the possibility of surgical intervention of combined heart disease with cardiopulmonary bypass in patient with extrahepatic portal hypertension.
Literature Reviews
In this article it was discussed the problem of creation implanted hepatic tissue engineering designs as a modern stage of complex investigation for working out bioartifi cial liver support systems. It was determined that for the positive decision of numerous biological and technological problems it is necessary: to use matrices with determined properties, which mimic properties of hepatic extracellular matrix; to use technology for stereotype sowing of these matrices by both parenchymal and non-parenchymal hepatic cells and to improve the technologies for making and assembling of hepatic tissue-engineering designs.