Editorial
Clinical Transplantology
Aim. To carry out monitoring of the organization and development of organ donation and transplantation in the Russian Federation according to 2014. 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 2014 in the Russian Federation functioned 36 centers of kidney transplantation, 14 centers of liver transplantation and 9 centers of heart transplantation. The waiting list of kidney transplantation in 2014 included 4636 potential recipients that makes 16% of total number of the patients 29 000 receiving dialysis. The rate of donor activity in 2014 made 3.2 per million population (pmp). Efficiency of donor programs in 2014 continued to increase: the share of effective donors after brain death in 2014 increased to 77.2%, the share of multiorgan explantation made 50.5%, average number of organs received from one effective donor made 2.6. In 2014 the rate of kidney transplantation made 7.0 pmp, the rate of liver transplantation made 2.1 pmp and 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 significant contribution to development of the organ donation and transplantation brings the Moscow region in which 11 centers of transplantation function and nearly a half from all kidney transplantations and more than 65% of all liver and heart transplantations are carried out. Conclusion. In theRussian Federation the potential for further development of the transplantology remains. In particular, at the expense of increase in the efficiency of regional donation programs, introduction of technologies, expansion of the practices of multiorgan donation and transplantations of extrarenal organs, interregional transplant coordination. Preservation of volumes of public funding for transplantological medical care and federal financing of donation programs in regions are of great importance.
Aim: to determine the clinical significance of vascular endothelial growth factors VEGF-A, VEGF-D, PlGF-1 to assess the risk of cardiovascular complications in heart recipients. Materials and methods. 103 patients, aged 16 to 73 years, 85 males and 18 females. 65 recipients (47 men and 18 women) had dilated cardiomyopathy, 38 – coronary heart disease (CHD). The concentration of VEGF-A, VEGF-D, PlGF-1 was measured using xMAP technology with sets of reagents Simplex ProcartaPlex™. Results. After HTx the level of VEGF-A significantly decreased, p = 0.001. There were no correlations between the levels of VEGF-A, VEGF-D and PlGF-1 with age, gender and diagnosis. After HTx VEGF-A level was higher in recipients with ACR than in those without it (p = 0.001). ACR frequency was significantly higher in patients with high VEGF-A level (≥316.5 pg/ml, RR = 5.8 ± 0.5, AUC = 0.779). After HTx PlGF-1 level was higher in recipients with ACR too (p = 0.039). ACR frequency was significantly higher in patients with high PlGF-1 level (≥5.33 pg/ml, RR = 1.8 ± 0.5, AUC = 0.65). There were no correlations between VEGF-D level with ACR and all three biomarkers with AMR. ACR frequency was significantly higher with both high VEGF-A and PlGF-1 levels (RR = 6.4). Conclusion. Serum levels of VEGF-A and PlGF-1 after HTx may be regarded as indicators of increased risk of ACR.
AAim. To identify factors influencing upon decision on pancreas allograft suitability for transplant and their clinical significance. Materials and methods. We reviewed 95 multiorgan donors under the age of 45, who were considered as pancreas donor between January 2010 and December 2013. 28 pancreata were procured (Group I), 67 pancreata were refused (Group II). Demographic, clinical and laboratory data, anatomical hepatopancreatoduodenal varieties were taken into account. Results. We found that only three factors have an effect on pancreas allograft refusal probability. According to our data, non-transplantation of the liver from the same donor increases the pancreas graft refusal in 4 times. Elevated donor’s sodium and urea blood levels also increase the probability of donor pancreas denial for transplantation. For example, the probability of pancreas graft refusal from the donor with sodium level 145 mmol/l and urea level 6.0 mol/l is only 32%. As compared to the donor with sodium level 160 mmol/l and urea 12.0 mol/l where probability reaches 85%. Other factors: demographic, laboratory, clinical indicators, gepatopancreatoduodenal blood supply variations were not predictive for the procurement decision. Conclusion. Main predictors of pancreas allograft refusal to be taken into account, appropriate correction of donor metabolic disturbances and sufficient experience of the surgeon performing the procurement can increase the availability of pancreas transplantation.
Regenerative Medicine and Cell Technologies
Aim. To perform a comparison of three-dimensional nanostructure of porous biocompatible scaffolds made of fibroin Bombix mori and recombinant spidroin rS1/9. Materials and methods. Three-dimensional porous scaffolds were produced by salt leaching technique. The comparison of biological characteristics of the scaffolds shows that adhesion and proliferation of mouse fibroblasts in vitro on these two types of scaffolds do not differ significantly. Comparative experiments in vivo show that regeneration of bone tissue of rats is faster with implantation of recombinant spidroin scaffolds. Three-dimensional nanostructure of scaffolds and interconnectivity of nanopores were studied with scanning probe nanotomography (SPNT) to explain higher regenerative activity of spidroin-based scaffolds. Results. Significant differences were detected in the integral density and volume of pores: the integral density of nanopores detected on 2D AFM images is 46 μm–2 and calculated volume porosity is 24% in rS1/9-based scaffolds; in fibroin-based three-dimensional structures density of nanopores and calculated volume porosity were 2.4 μm–2 and 0.5%, respectively. Three-dimensional reconstruction system of nanopores and clusters of interconnected nanopores in rS1/9-based scaffolds showed that volume fraction of pores interconnected in percolation clusters is 35.3% of the total pore volume or 8.4% of the total scaffold volume. Conclusion. Scanning probe nanotomography method allows obtaining unique information about topology of micro – and nanopore systems of artificial biostructures. High regenerative activity of rS1/9-based scaffolds can be explained by higher nanoporosity of the scaffolds.
Aim. To compare the effectiveness of different methods for bone marrow (BM) harvesting from non-heart beating donors taking into account the number and the quality of collected hematopoietic stem cells (HSC). Materials and methods. The study was performed on 43 non-heart beating donors. For BM harvesting two bone marrow aspiration needles were installed in each iliac bone. The needles were installed in one bone connected to closed system, combined with surgical suction and volumetric pump. BM aspiration was performed using different values for vacuum and combining with perfusion solution into the bone. The volume, the number of nucleated cells (NC), HSC and cell viability were evaluated in the obtained samples. Results. Compared with the standard mode the usage of vacuum 0.6–0.7 atm increased the collection of NC by 65.6%, HSC 87%, and did not reduce their viability. Using a vacuum of 0.9 atm reduced the amount of collected HSC and damaged cells. While using combined aspiration and perfusion of BM HSC were prepared at more than 86.2%, but the viability of the cells was lower than under the standard aspiration. Having coherently performed a standard aspiration and aspiration with perfusion from one iliac bone 407.2 ± 46.7 ml BM, 8.0 ± 0.8 × 109 NC and 194.2 ± 20.8 × 106 HSC were harvested. The proportion of viable cells was not less than 75.2 ± 3.2%. Conclusion. Method of BM harvesting implying coherently performing aspiration and aspiration-perfusion with the usage of vacuum 0.6–0.7 atm allows to prepare more progenitor cells without losing their quality. As a result, from one non-heart beating donor different types of progenitor cells can be collected in the amount sufficient for systemic infusion in adult patient.
Heart Transplantation and Assisted Circulation
Aim. To improve the efficiency of treatment of the patients with pancreatic necrosis through correcting the platelet-coagulation potential by methods of combined plasma filtration, selective sorption of cytokines with hemofiltration and plasmapheresis. Methods. The effects of selective sorption of cytokines with hemofiltration and plasmapheresis upon coagulation potential were studied in 70 patients with acute pancreatitis. Plasmapheresis was performed on PCS 2 (Haemonetics, USA); selective sorption of cytokines with hemofiltration – on Lynda ® machine (Bellco, Italy). The method of computer laser phasemeter was used for vital assessing of platelet morphofunctional status. Results. In patients with pancreatic necrosis in the fermentation phase the percentage of resting platelets was 51.3%, which is 12% below the control numbers. The number of activated platelets increased: 25.1% of the cells were represented by platelets with low activation; 15.5% – highly activated cells. The number of degenerative-modified platelets increased by two times – up to 8.1%. In the phase of sequestration and suppurative complications the percentage of resting platelets was only 42.3%, which is 1.5 times lower than the control numbers. 34.2% of the cells were presented by platelets with low activation; 11.0% – highly activated cells. The number of degenerative-modified platelets exceeded 12.5%. The analysis of the morphological structure of the platelets population revealed that due to plasmapheresis inclusion into therapeutic complex in the phase of intoxication of pancreatic necrosis the normalization of platelet activation status of hemostasis was observed. In 5 (20%) patients the normalization of average platelets morphometric parameters was shown after selective sorption of cytokines with hemofiltration and plasmapheresis. These patients demonstrated positive clinical dynamics. In 15 patients morphometric values of platelets either remained at the same value or continued to increase progressively. In this subgroup of the patients purulent complications progressed in 9 patients, mortality was 35%. Conclusion. Thus, the level of thrombocyte hemostasis in different phases of pancreatic necrosis can be quantified using indicators of morphofunctional status of circulating platelets. When dealing with coagulation version of disseminated intravascular coagulation syndrome the number of activated cells is on the rise up to 40% or more. The development of consumption coagulopathy is characterized with progressive increase of degenerative platelets up to 10% or more. Combined plasma filtration, selective adsorption of cytokines with hemofiltration and exchange plasmapheresis are effective methods for adjusting of platelet and coagulation hemostasis in patients with necrotizing pancreatitis.
Clinical Cases
Materials. The forty five y.o. man with ESRD had underwent kidney transplantation from cadaveric 31 y.o. non biting heart donor 02.04.2013. He has received standard immunosupression: MP+Tc+MMF and for 4 weeks was discharged from hospital with serum creatinine 0.25 mmol/1. On the fifth post transplant month the patient discovered on the face skin multiple tumors. The tumors had moderate growth during next month. Kaposi's sarcoma had been proven by biopsy, so we stopped tacrolimus therapy in the recipient and started everolimus treatment. During next month there was no new skin lesions and the previously registered tumors had no futher growth. From that time we have seen gradual regression of skin lesions. We support everolimus blood level 4–8 ng/ml. month of the everolimus therapy proteinuria was appeared in the patient approximately 0.5– 0.7 g per day. The next month proteinuria increased till 1.8–2.4 g per day. The daily metilprednizolon dose was increased since 4 till 10 mg. The proteinuria decreased till 0.5–0.6 g per day. The kidney function during all period was stable with serum creatinine 0.22–0.26 mmol/1. Conclusion. Everolimus treatment with simultaneous calcinevrine inhibitors withdrawn offers a promising approach to the management of Kaposi's sarcoma in kidney transplant recipients without an increased risk of acute rejection.