Clinical Transplantology
The article offers analysis of the problem status as well as World and Russian experience of donor organ recipients participation in sports and physical training. The connection of physical activity with the quality of life of patients after transplantation is reflected. The problems associated with organ donation in Russia and other countries and the importance of sports activities in promoting this problem are described. The analysis of foreign experience in the organization of sports games for people with transplanted organs, which indicates: the importance of research methods in admission to physical education and sports among recipients, the need for dosing and selection of physical activity, the involvement of a transplant doctor for individualization of rehabilitation programs. The personal experience of foreign athletes with transplanted organs, including the experience of the Russian recipient’s participation in the 21st world games 2017 is presented. Experience of carrying out sports activities for people with transplanted organs in Russia is also given.
Aim. To analyze the relationship between the peak panel-reactive antibodies (peak-PRA), the value at the time of transplantation (Tx-PRA) and the results of kidney transplantation.
Materials and methods. The study included 287 patients from the waiting list with anti-HLA antibodies of I and/or II classes. 142 patients underwent transplantation of a cadaveric kidney. All patients received standard immunosuppression: a calcineurin inhibitor, mycophenolate and steroids. Desensitization in the preoperative period was carried out in 11 patients. Screening and identification of antibodies was performed using multiplex technology on Luminex platform.
Results. The median PRA was 47% (interquartile range – 29%; 65%). Depending on the dynamics of PRA, we identified several groups of patients: stable PRA (83 patients), increasing (77 patients) or decreasing value (96 patients), or variable dynamics (31 patients). The change in PRA was accompanied by a change in the mean fluorescence intensity (r = 0.787, r2 = 0.59, p < 0.0001). In the univariate analysis, each 5% of peak-PRA and Tx-PRA increased the relative risk (RR) of humoral graft rejection (1.09 (95%CI 1.06; 1.17), p < 0.001; 1.17 (95%CI 1.09; 1.26), p < 0.001 respectively), and ΔPRA decreased a RR (0.932 (95% CI 0.861; 0.967), p = 0.009). In multivariate analysis (adjusted for sex and age of recipient, duration of dialysis, number of HLA mismatches), we observed a similar scenario: peak-PRA 1.14 (95% CI 1.07; 1.19), p < 0.001; Tx-PRA 1.13 (95% CI 1.09; 1.22), p < 0.001; ΔPRA 0.949 (95% CI 0.871; 0.981), p = 0.017. In the univariate analysis increases in peak- PRA and Tx-PRA increased aRR of graft loss (1.1 (95% CI 1.05; 1.14), p < 0.001; 1.09 (95% CI 1.05; 1.15), p < 0.001 respectively), and increase in ΔPRA decreased RR (0.952 (95% CI 0.891; 0.97), p = 0.011). In the adjusted multivariate model, Tx-PRA did not increasea RR of graft loss (1.04 (95% CI, 0.95; 1.1), p = 0.098), while peak-PRA and ΔPRA remained significant factors (1.1 (95% CI, 1.17; 1.24), p < 0.001; 0.931 (95% CI, 0.855; 0.954), p = 0.007, respectively).
Conclusion. In the selection donor-recipient pair it is necessary to take into account the spectrum of antibodies at the point of peak values of PRA. A decrease in PRA may hide antibodies that have a specificity to donor antigens or on certain epitope.
Aim. To investigate the structure and frequency of occurrence of the infection in the cysts of the kidneys in patients with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease (PKD).
Materials and methods. For the first time the microbiological study of the biological materials obtained from the patients with PKD were performed. That were the polycystic-altered kidneys removed in preparation of potential recipients for kidney transplantation, which were made as a routine step. All patients underwent surgical treatment in order to prepare for kidney transplantation or according to clinical indications. Two groups of patients have been distinguished: the 1st group – 7 (33.3%) patients with asymptomatic course of disease, the 2nd group – 14 (76.7%) patients who had symptoms of infection of kidneys and urinary tract.
Results. As a result of this work, the presence of latent and active infection in 18 (85.7%) patients, including 6 (85.7%) patients with asymptomatic polycystic course, was proved. At microbiological research the causative agent of infection was not revealed only at the 1st patient in the first group and in 2 patients in the second group. Infection of cysts of kidneys of 6 patients with asymptomatic course of PKD was proved only after research of their contents taken intraoperatively. There is no correlation between the presence of infection, symptoms and the size of polycystic kidneys. Multidrug resistant infection only sensitive to modern antibiotics ultrawide spectrum of action was detected in 6 patients, including 2 patients with asymptomatic.
Conclusion. Critically high actual infection of more than 80% of polycystic-altered kidneys has been established, which allows to consider them as a source of chronic infection in the context of future transplantation. The presence of latent, including multiresistant infection in cysts, worsens the prognosis of kidney transplantation in this category of patients without nephrectomy.
The article is devoted to the main aspects of organization of multiorgan donation from donors with brain death in the Republic of Sakha (Yakutia). Transplant services to the population of this region have been in place since 2001, and until 2016 only kidney transplants or liver fragments from a living related donor have been performed. The presence of an effective postmortem donation program will allow to meet the high demand of this region for high-tech assistance by organ transplantation.
Heart Transplantation and Assisted Circulation
A channel centrifugal pump has been developed which have calculated parameters during the nominal operating mode based on 3-dimensional computer simulation (flow rate 5 l/min, pressure drop 100 mm). In addition, pump’s operating conditions in ECMO mode are considered at high pressure drops of 200–300 mm Hg with a speed of rotor up to 3500 rpm. Simulation result was a creation of a new channel- type centrifugal pump with shear stress that do not exceed the allowable threshold of 150 Pa, and also minimizing stagnation and flow recirculation zones. The obtained data were also the result of use design of rotor with constant cross-section channels formed along a logarithmic curve and ensuring minimum turbulence due to the minimum outlet angle of the flow.
We have developed and tested a technique for constructing 3D models of the chest and thoracic cavity organs. Due to the obtained results, the mathematical model was successfully used in the development of classification of variants of placement of implantable auxiliary circulation systems, and also for building 3D models for other purposes. In particular, the patients were graded according to the variants of placing the children’s axial pump DON-3 inside the patient’s chest cavity. Based on the data, the first fitting of the DON-3 pump was performed on a patient aged 7 years.
Aim. To assess the contribution of pannus and calcification to the development of bioprosthetic valve dysfunction after tricuspid valve replacement in a pediatric patient.
Materials and methods. A 3-month-old patient presented with tricuspid valve dysplasia and grade 4 tricuspid insufficiency underwent tricuspid valve replacement with the bioprosthesis «PeriCor» (ZAO «NeoKor», Russian Federation). The patient at the age of 6 years required a redo tricuspid valve replacement 5 years 8 months after initial surgery. Degenerative changes of the dysfunctional bioprosthetic valve explanted from the tricuspid position were assessed using macroscopic description and light microscopy. Cellular composition, the presence of bacteria, colocalization of calcifications with recipient cells were analyzed. The distribution of calcifications and their volume in the biomaterial tissue were estimated using microcomputer tomography imaging (micro-CT).
Results. Bioprosthetic valve dysfunction was mainly caused by the pannus formation which was shown to encapsulate the anterior leaflet, resulting in its total failure and severe stenosis (reduced effective orifice area). There were no signs of ruptures and perforations in the valve tissues found. All leaflets were shown to contain predominantly fibroblastic cells and single blood cells, mainly located in the surface layers of the leaflets in the regions without any signs of calcification. Bacteria staining was negative for all types of the studied biomaterials. Calcifications were present in all xeno-tissue elements of the explanted bioprosthesis (i.e. leaflets, aortic segment, and pericardium). In addition, calcifications were also found in pannus growing during a functioning bioprosthetic valve. Calcifications were predominantly located in the co-optation and commissure zones of the leaflets. Importantly, massive calcifications were observed around the bioprosthetic stent frame. The total volume of calcification accounted for 1/3 of the biological component of the bioprosthesis (729 mm3).
Conclusion. According to the data obtained in this study, we may conclude that the primary cause of the bioprosthesis failure was the growth of connective tissues, resulting in pannus-related dysfunction, rather than severe calcification of all bioprosthetic components. One may assume that bioprosthetic dysfunction is related to the peculiarity of the inflammatory response of the preschool patient. However, this typeof dysfunctions requires further investigation.
Regenerative Medicine and Cell Technologies
Aim. To research the rat bone marrow mesenchymal stem cells (MSC BM) effect to the viability of isolated rat OL during cultivation with microstructured collagen-containing hydrogel (BMCH).
Materials and methods. Rat islets and MSC BM were isolated according to classical technique with some modifications. The experiments on the co- cultivation were carried out under standard conditions. Islet’s viability was determined by immunofluorescence staining.
Results. TheOL cultivation with BMCH and MSCBM resulted in destructive changes of isletson the third day, and complete destruction of OL was observed on the seventh day. At the same time, OL cultured with BMCH remained viable for 14 days of incubation.
Conclusion. Cultivation of OL with BMCH and MSC BM did not contribute to the long-term survival of the islets. Thus, there was no positive effect of MSC BM on the viability of pancreatic islets.
Aim. To establish the ability of the total RNA extracted from the body’s bone marrow cells (BMCs), in which liver tissue was damaged, to serve as a carrier of targeted regenerative signals to this organ.
Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs – 2,5×106; 5,0×106; 3,5×107 cells – group 1 and the total RNA of the same BMCs (30μg/100g of weight) – group 2 from donors in 12 hours after 70–75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA.
Results. In group 2 in 48 and 72 h. there was the increasing of mitotic and proliferative cell activity in the liver, but not in the kidneys (control of the specificity of regenerative signals); in group 1 there was no transfer of regenerative signals to these organs.
Conclusion. The authors believe that the total RNA from BMCs, activated by hepatectomy, accumulates targeted (hepatospecific) regeneration signals, but they are perceived only when RNA has been obtained by the damaged tissue.
Editorial
Clinical Cases
Heart transplantation is the «gold standard» of treatment severe heart failure. Patient survival after heart transplantation has improved dramatically since the availability of calcineurin inhibitor (CNIs). However, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction and reduces long-term patient survival. Use mTOR inhibitor in immunosuppressive therapy may improve renal function when everolimus is administered associated with a progressive reduction of CNIs. The purpose of our report is to demonstrate the successful case of conversion of the recipient after heart transplantation to everolimus and to evaluate the effectiveness of this drug during the observation year after heart transplantation.
Presented the case of a combined approach preparation of 47 years old patient with primary biliary cirrhosis for orthotopic liver transplantation (OLT) and arterial flow insufficiency correction after surgery. The patient was under waiting list for OLT due liver cirrhosis progression. The patient underwent Intraportal infusion of autologous bone marrow mononuclear cells (MNC) which is allowed temporary stabilized the cirrhotic transformation. The transjugular intrahepatic portosystemic shunt (TIPS) procedure performed due to portal hypertension progression with episodes of bleeding from the esophageal and gastric varices, that allowed to receive organ donor and OLT. At 6 months after OLT the patient had clinical signs of a jaundice caused by splenic artery steal syndrome which was corrected by endovascular intervention: splenic artery trunk embolization.
Aim. The evaluation of donor’s duodenum histological examination in diagnosis of pancreaticoduodenal graft rejection.
Materials and methods. The 35-yo patient with terminal diabetic nephropathy undergone simultaneous retroperitoneal kidney and pancreas transplantation with enteric exocrine drainage of the graft via inter-duodenal anastomosis. When performing the esophagogastroduodenoscopy 2 years posttransplant we implemented histologic examination of the duodenum of the graft.
Results. We diagnosed and verified severe cellular rejection of pancreaticoduodenal graft. Successful etiopathogenetic treatment of acute rejection of the graft (pulse therapy with glucocorticoids) was performed.
Discussion. The diagnostic value of donor’s duodenum morphological examination in the diagnosis of pancreaticoduodenal graft rejection, the efficacy of anti-rejection treatment were performed in this case.
Literature Reviews
Allogeneic kidney transplantation is the optimal approach for the treatment of patients with terminal stage of chronic kidney disease. Moreover, post-transplant monitoring and optimization of immunosuppressive therapy with early non-invasive molecular-biological markers can significantly improve the long-term outcome of transplantation. As markers of damage to the kidney transplant, it is proposed to use micro-RNAs that play a fundamental role in the regulation of the activity of various genes. The level of expression of micro-RNA in different tissues can correlate with certain pathological conditions. In this review, the literature data on the study of the perspectives for the use of micro-RNA as biomarkers of the post-transplantation period in kidney transplant recipients are considered.
Autotransplantation of immune cells to induce immunological rejection of tumors can be a useful approach in tumor treatment. Despite the low efficiency of this approach demonstrated in the past, the active development of cell technologies and genetic engineering has led to the significant improvement in clinical outcomes. A great success was achieved in adoptive immunotherapy with the T-lymphocytes specific to tumor antigens. This review describes the clinical experience in application of various antigen-specific adoptive immunotherapy methods including tumor-infiltrating T-lymphocytes, T-lymphocytes with redirected transgenic T-cell and chimeric antigenrecognizing receptors. The possibilities and limitations of these biomedical technologies are also analyzed in the article.
Chronic HCV infection is the leading cause of liver transplantation in adults in developed countries. Unfortunately, the reinfection of the graft inevitably occurs in all patients with persistent replication of the virus. Against the background of the necessary immunosuppressive therapy, the progression of the disease accelerates, leading to rapid decompensation of the liver. Antiviral therapy significantly improves the results of transplantation, but the use of standard interferon-based regimens is associated with low efficacy (no more than 30% for the most common 1 genotype of the virus) and poor tolerance. The article describes new interferon- free oral regimens used to treat the recurrence of HCV infection of 1 genotype.
Ethical issues
There is renewal of interests to the organs that could be obtained from asystolic donors. Our goal was to identify ethical issues raised by attempts of classification and terms such kind of organ donors depended on time and place of cardiac arrest. Based only on the reasoning of medical experts group these principles going to be routine State policy. That followed by erased roles of physicians and misleading the meaning or organ transplant program. From our point of view there should be clear opposite position between death and life in order to initiate organ procurement activity. That is possible only in case of artificial blood supply for preserving transplant-to-be-organs after relevant time between cardiac arrest and start of such kind of perfusion procedure.