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Russian Journal of Transplantology and Artificial Organs

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Vol 21, No 2 (2019)
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https://doi.org/10.15825/1995-1191-2019-2

EDITORIAL

ORGAN TRANSPLANTATION

7-15 1155
Abstract

Aim: the aim of the study was a comparative assessment of the quality of life of recipients with donor heart at the stages before and after heart transplantation.

Materials and methods: the study included 150 patients who underwent orthotopic heart transplantation at the «Academician V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs», Ministry of Health of the Russian Federation from January 2009 to March 2018.

Results. Analysis of the research results indicates extremely low rates of both physical activity and overall health assessment at the pre-transplantation stage. During the first month after heart transplantation, the role of functioning due to physical condition (p = 0.02), general health (p = 0.001), mental health (p = 0.01) and vital activity (p = 0.01) significantly increase. Tolerance to physical activity increases by 201.26% during the first month after the heart transplantation (p = 0.02). The most complete indicators of quality of life are restored after one year of operation: physical functioning (p = 0.00007), role-based functioning due to physical condition (p = 0.00006), pain threshold (p = 0.04), general health (p = 0.00007), mental health (p = 0.0001), role functioning due to the emotional state (p = 0.01), social functioning (p = 0.0001), vital activity (p = 0.000032). High rates of quality of life are maintained for periods longer than 5 years after transplantation. The best indicators of quality of life in recipients of transplanted heart are observed a year after surgery and manifest a significant increase in all indicators. A comparative analysis of the results obtained in the preoperative period and a year after the operation of orthotopic heart transplantation indicates a significant improvement in the quality of life of patients.

Conclusion. The results of the study showed that during the year after heart transplantation in patients with terminal heart failure, there was a significant improvement in all indicators characterizing the quality of life. High levels of physical, mental and social activity achieved by the first year are maintained for at least 5 years, which indicates the high efficiency of orthotopic heart transplantation as a radical method of treating severe heart failure.

16-22 1042
Abstract

Aim: to assess the dynamic and prognostic significance of the end-tidal carbon dioxide pressure (PetCO2) during cardiopulmonary exercise testing in recipients before and after heart transplantation (HT).

Materials and methods. The study included 55 patients with severe chronic heart failure (CHF) from the HT waiting list. All patients underwent cardiopulmonary exercise testing before and in the long-term follow-up after TS, including determination of PetCO2 at rest and during exercise.

Results. Physical capacity, the efficiency of pulmonary ventilation and gas exchange in the long-term after the HT significantly improved compared with the preoperative data. Peak oxygen consumption before and after HT was 10.8 (9.4-11.7) ml/min/kg and 18.9 (18.2-21.0) ml/in/kg (p = 0.020), respectively, the value of the VE/VCO2 slope decreased from 38 (34-45) to 32 (30-36), p = 0.017. PetCO2 at rest before the HT was below the norm, amounted to 30 (28-32) mm Hg, increased to the anaerobic threshold by an average of 3.6 (0.2-5.2)%. After the HT, the level of PetCO2 at rest did not change significantly, but the increase during exercise was 7.6 (3.2-9.4)% (p = 0.001). It was shown that a low baseline PetCO2 value and the absence of its increase during cardiopulmonary exercise test significantly increase the risk of adverse outcome in patients with severe CHF before and after HT (OR 0.62 (0.35-0.87), p = 0.035 and, 16 (0.10-0.24), p = 0.002, respectively).

Conclusion. Heart transplantation in patients with severe CHF leads to a significant improvement in the efficiency of pulmonary ventilation and gas exchange in the long-term follow-up. Estimation of the PetCO2 level at rest and during exercise is a promising predictor of adverse outcomes risk stratification in patients with severe CHF before and after HT.

23-30 1165
Abstract

Heart transplantation from сardюpulmonary resuscitated (CPR) donors is one of the way to increase the availability of heart transplantation (HT). The study included 28 recipients: 25 (89,3%) men and 3 (10,7%) women at the age 20-68 (46,2 ± 13,7) who underwent HT from CPR donors in the V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs in the period from 01.01.2011 to 31.12.2017, that was 4.0% of the total number of HT (n = 698). CPR donor group and control group had no significantly differences in early cardiac transplant dysfunction and 1-, 3- and 5-year survival.

31-38 1429
Abstract

Introduction. In spite of improvements in quality of life and lifetime of kidney transplant recipients the limited time of kidney transplant survival dictate the need for returning back to dialysis or repeat kidney transplantation. In respect that the need of repeat kidney transplantation usually observed in elderly recipients we attach importance in the analysis of outcomes of kidney retransplantation in patients over 60-s.

Aim: to analyse the early outcomes of kidney re-transplantations in middle-aged and elderly recipients.

Material and methods: the retrospective analysis of outcomes of 124 repeat kidney transplantations was made (16 transplantations in elderly recipients -Group I; 108 transplantations in recipients aged 20-59 yrs - Group II). The recovery of kidney transplants, acute rejection rates, the causes and the rate of kidney transplant dysfunction and failure, early patient’s and kidney transplant’ survival rates were analyzed. We used clinical, laboratory, histological and instrumental diagnostics.

Results: in both groups there were no differences in kidney transplant recovery rates (p = 0,546), kidney transplant function (normal function 81,2% vs 86,1%, dysfunction 6,3% vs 4,3%, graft failure 12,5% vs 9,3% (p = 0,876), recipient 100% vs 99,1% (p = 0,34) and graft survival rates 87,5% vs 90,7% (p = 0,30). There were no episodes of acute rejection in patients of group I (0% vs 30,6% (p = 0,006). The reason of graft failure in group I - the graft’s pathology (nephroangiosclerosis (12,5%), group II - intractable acute rejection (4,6%), graft’s pathology (3,7%), patient’s death with functioning graft (0,9%).

Conclusion: there were similar recipient and graft survival rates in both groups. We observed lower acute rejection rate in patients of group I using sufficient immunosuppressive regimens.

39-48 1562
Abstract

Aim. To investigate the renal transplantation results for patients with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease (PKD).

Materials and methods. The study included a prospective and retrospective analysis of the kidney transplantation results in 46 patients with ESRD caused by PKD, performed in the period from 2003 to 2018. Two groups of patients were formed. The comparison group consisted of 23 (50%) cases of kidney transplantation in patients whose polycystic-changed kidneys were preserved at the time of transplantation. The study group included 23 (50%) patients who underwent pretransplantation nephrectomy of native kidneys for clinical indications or to prepare for the waiting list. During the study, an algorithm of examination and surgical preparation for inclusion patients with PKD in the waiting list for kidney transplantation was developed and actively used.

Results. The mean follow up period of patients who underwent pretransplantation nephrectomy was 3.6 ± 2.5 years, patients with preserved native kidneys - 5.3 ± 3.08 years (p > 0.05). Periodic pain in the lumbar region disturbed 12 (52.2%) patients with preserved polycystic-changed kidneys. The frequency of episodes of leukocyturia, bacteriuria and(or) hematuria significantly differed and amounted to 0.27 ± 0.35 cases per year in the study group, 1.49 ± 0.54 (p < 0.05) in the comparison group. Posttransplant nephrectomy of polycystic-changed kidneys at different times after transplantation was required in 5 (21.7%) patients. Five-year graft survival in the study group was 87.5%, in the comparison group - 76.1%. Among the patients of the comparison group, 76.4% of transplants lost their function after 10 years. The 5 and 10-year survival rates of patients with preserved native kidneys were 90.5% and 80%, respectively. In particular, there was one fatal outcome due to sepsis on the background of infection with cysts of preserved polycystic kidney. There were no deaths in the study group.

Conclusion. Among patients whom polycystic-changed kidneys removed, there is a more favorable course of the post-transplant period due to the low frequency of infectious complications. More than 60% of patients with PKD need to perform nephrectomy of native kidneys during life for various reasons, including more than 21,7% need it after kidney transplantation due to complications during immunosuppressive therapy. Reasonable assessment of the polycystic kidneys and timely pretransplantation nephrectomy are an integral part of the preparation and management of the waiting list for transplantation of a patient with PKD.

49-58 987
Abstract

Aim: to analyze features of the causal relationship between the vascular access type at the time of hemodialysis (HD) start and survival rates of patients, taking into account the cause of chronic kidney disease (CKD) and comorbidity.

Materials and methods. The retrospective analysis included 604 HD patients divided into three groups: «AVF» (n = 336) patients started and continued HD with AVF; «CVC-AVF» (n = 152) patients started HD with CVC and later successfully converted to AVF; «CVC» (n = 116) patients who started and continued HD with CVC only. Patients with other types of conversions were not included in the analysis. The mean follow-up period since the beginning of HD was 38 [interquartile range 19; 48] months.

Results. Unadjusted survival rate after 5 years in the AVF group was 61% [95%CI 51.8; 71.9], that in the CVC-AVF group - 53.9% [95%CI 42.5; 67], and that in the CVC group - 31.6% [95% CI 21.4; 41.4]. Survival rate in the CVC group varied from that in the AVF (p < 0.0001) and CVC-AVF (p < 0.0001) groups. CVC-AVF and CVC groups patients had significantly worse comorbidity than that of AVF group patients. After adjustment for comorbidity, age, sex, and cause of CKD, the survival rate in the groups after 5 years came to the following: 56.7% [95%CI 51.1; 62.8] in the AVF group, 51.7% [95%CI 42.5; 61.7] in the CVC-AVF group, 33.3% [95%CI 24; 42.8] in the CVC group. The results in the AVF group differed significantly from that in the CVC group (p < 0.001), but not from that in the CVC-AVF group (p = 0.425). The results in the CVC-AVF group are also statistically significantly varied from that in the CVC group (p = 0.009). Diabetes mellitus and systemic diseases were important risk factors. In the 5 years’ time period the survival rate of the group of patients with diabetes mellitus within in the AVF group adjusted (for sex, age, cause of CKD and comorbidity) was 38.1% [95% CI 29; 47.1], that in the CVC-AVF group - 29.7% [95% CI 18.9; 41.2] and that in the CVC group - 20.3% [95% CI 11.6; 31.8]. The results in the AVF group statistically significantly differed from that in the CVC group (p = 0.001), and from that in the CVC-AVF group (p = 0.011). The results in the CVC-AVF group are also statistically significantly varied from that in the CVC group (p = 0.021). In the 5 years’ time period the adjusted survival rate within the patients in the AVF group with systemic processes, was 34.2% [95% CI 18.8; 50.3], that in the CVC-AVF group - 23.9% [95% CI 10.5; 40.3], and that in the CVC group - 20.5 % [95% CI 7.3; 38.5]. We did not note statistically significant differences between the groups (p > 0.05 in all cases).

Conclusion. The HD beginning with the use of CVC does not increase the risk of death in case of successful conversion to AVF. The use of CVC as the only vascular access is associated with a significant increase in the adjusted risk of death. Within the patients with diabetes mellitus, the use of CVC is associated with a deterioration of the adjusted survival rate even with subsequent successful conversion to functional AVF. Patients with systemic processes (vasculitis, myeloma, HIV-associated nephropathy, renal neoplasms, etc.) have low predicted survival rate disregarding the type of vascular access (there are no significant differences between the types of vascular access). The differences in survival rates are determined not only by the types of vascular access, but also by the comorbid background.

59-68 3779
Abstract

There is no doubt that the optimal vascular access is arteriovenous fistula (AVF). However, the proportion of patients receiving hemodialysis using central venous catheters is very high. Largely due to this, the incidence of central venous stenosis (CVS) in this category of patients is one of the highest: the prevalence ranges from 2 to 40%. Against the background of functioning AVF from the ipsilateral side, CVS proceeds with much more pronounced symptoms than in the general population of patients with this pathology. There is no doubt that stenosis of the central veins is a precursor of AVF thrombosis, recurrent infections, reduction of blood flow in the limb in general and AVF in particular, and consequently - increase in recirculation and decrease in the effectiveness of HD. Endovascular surgery is the «gold standard» treatment for CVS. Technical success is at least 80-90% of the cases. As a rule, endovascular operations not only lead to the immediate reduction of symptoms of venous hypertension, but also allow the use of fistulas for hemodialysis in the near future after the intervention. At the same time, clinical success is achieved much less frequently. Primary patency in six months is about 50%, secondary patency in two years - 60-80%. The use of cutting balloon catheters may be associated with greater secondary patency than using standard balloon catheters, but slightly increases the risk of complications. An effective way to improve the results of CVS plastic is the use of stents, which allow to increase the patency after surgery. Indications for the primary use of stents is a debatable issue. However, stenting is undoubtedly effective in the case of rapid occurrence of recurrent stenosis or rigid stenosis and recoil immediately after surgery. In addition, one of the problems associated with the use of stents is the risk of their migration. This risk increases in patients with functioning AVF. Skepticism about the use of stents in patients on hemodialysis is also added by the fact that in randomized controlled studies, when comparing isolated balloon angioplasty and angioplasty using uncovered stents, there was no significant difference in the recurrence of stenosis. At the same time, the use of covered stents provides a significant increase in access survival. In addition, the use of drug-coated balloon catheters may provide some advantage over standard uncoated balloon catheters. Open surgical interventions have slightly better results in the treatment of CVS (annual primary patency of 80-90%) compared to endovascular methods. Nevertheless, open reconstructions are associated with a much greater risk of intra- and postoperative complications, in most cases require clavicle section or sternotomy, general anesthesia, and are associated with greater postoperative mortality. In this regard, percutaneous transluminal angioplasty is deservedly considered to be a common method of treatment of CVS. Open surgery can be used in case of unsuccessful attempts to resolve stenosis endovascular while maintaining a pronounced clinical symptoms. On the face of the fact that the available methods of treatment of this pathology in patients on hemodialysis with functioning vascular access do not fully meet the clinical needs. Currently, there is no consensus on many aspects of the use of endovascular interventions for the correction of vascular access dysfunction, which requires additional research.

69-74 845
Abstract

The first case of heart transplantation in the Far Eastern Federal District described. Transplantation of heart is executed in Republican hospital No. 1 - the National center of medicine (Yakutsk) on July 6, 2018. In our opinion, transplantation of heart is necessary and feasible in such regions as the Republic of Sakha (Yakutia) which have difficult and extreme climate and geography, remote settlements with population less than 1 million people.

ARTIFICIAL ORGANS

75-83 948
Abstract

Aim: to assess the contribution of primary tissue failure, calcification, bacterial contamination and pannus to bioprosthetic valve dysfunction.

Materials and methods. To evaluate degenerative changes of the «UniLine» bioprosthesis explanted from the mitral position with macroscopic examination, light and scanning electron microscopy, and micro-computed tomography (micro-CT). Light microscopy was used to analyze cell composition, the presence of bacteria, the localization of calcific deposits and recipient cells. Scanning electron microscopy allowed confirming the presence of bacteria. Micro-CT was used to evaluate the deformation of the bioprosthetic elements, the distribution of calcific deposits and their volume in the valve tissue.

Results. The presence of pannus, calcification, primary tissue failure and bacterial contamination were found among the causes leading to bioprosthetic dysfunction. Prosthetic leaflets showed pannus growth from the inflow tract. Excessive circumferential pannus extended into outflow tract. Calcific deposits were mostly localized in the commissural zone and the central portion of the leaflets. The total volume of calcification accounted for 1/3 of the bioprosthetic tissue component. The relationship between calcification and stress-strain properties of the bioprosthetic elements has been indicated. The asymmetric deformation of the bioprosthetic stent frame and leaflets with 1.5-fold thickening of the last has been found. The areas with loose and fragmented collagen and elastic fibers contained red blood cells and neutrophils. Endothelial cells and fibroblastic cells were present in the outer surface layers. There were no signs of calcification in the areas accumulating cells and bacteria.

Conclusion. We can assume that primary tissue failure, calcification, bacterial contamination and pannus independently contribute to the onset of bioprosthetic heart valve dysfunction.

REGENERATIVE MEDICINE AND CELL TECHNOLOGIES

84-91 1018
Abstract

Aim. This research is aimed to devise the technique for transplantation of 3D spheroids retinal pigment epithelium (RPE) in the experimental animal’s eyes (rabbits).

Materials and methods. 3D spheroids of RPE for subsequent transplantation were created using agarose tablets (3D Petri Dishes, Microtissue, USA). The phenotype of the obtained cell cultures was studied by immunocytochemical tests (laser scanning confocal microscope “Fluo View FV10i”, Olympus, Japan). Vitrectomy - 2500 cuts per minute, vacuum 600 mm Hg (Alcon, Accurus, USA) was performed on all rabbits (n = 10). Then, we made retinotomy and injected spheroids in subretinal space (MicroDose injection kit 1 ml, Med One, USA). The following methods of control: ultrasound B-scan (Ultrasonic UD-6000, Tomey, Japan) and optical coherence tomography (OCT), (Askin Spectralis, Heidelberg engineering, Germany). Eyes were enucleated for histological examination on 7, 10, 14 and 20 days.

Results. Immunocytochemical tests revealed preservation of the RPE epithelial phenotype in 3D spheroids. Clinical map was similar in all experimental animals - during the first 7 days after surgery we saw cystic edema and flat retinal detachment in the surgery area. As we observed, the retina was adjoining and retinal edema was decreasing. Also, on day 3, 7 and 10 on OCT we saw subretinal round conglomerates with a diameter of 60 to 80 µm - presumably RPE 3D spheroids. According to histological findings, there was observed adhesion of the RPE spheroids to the choroid with subsequent spreading and formation of new cell layer with the increase of observation periods.

Conclusion. The proposed technology of cultivation of rabbit RPE with subsequent construction of 3D spheroids allows to preserve the epithelial phenotype of cells. The developed surgical technique of RPE transplantation is acceptable and can be used for further experimental studies to be implemented in clinical practice.

92-103 1454
Abstract

For the treatment of patients with organs damaged or removed by medical indications, transplantation from donors is currently used. High risks of death, lifelong immunosuppression and an acute shortage of donor organs worsen the prospect of their use. Recent advances in the field of biofabrication indicate the imminent possibility of the emergence of real alternatives to the methods currently used. The biomaterials used create a three-dimensional space in which cells can attach, grow and form new tissues with an appropriate structure and function. Modern research pays special attention to the choice of materials and technologies to ensure the mechanical and physiological properties of the newly created tissue. The review examines modem technologies of regenerative medicine, as well as the results of experimental studies in the field of biofabrication for creating scaffolds, tissue-engineering structures, as well as hollow and fragments of complex organs that already have practical implementation.

104-111 1045
Abstract

Aim: to study the effect of implantation of tissue-engineering pancreatic construct (TEPC) on the course of experimental diabetes mellitus.

Materials and methods. The TEPC samples received as a result of joint incubation in vitro floating islet-like cultures (FILC), obtained from the pancreas of newborn rabbits, and the biopolymer microheterogeneous collagen hydrogel (BMCH). Stable diabetes mellitus was caused in Wistar rats by the method of fractional streptozotocin administration.

Results. The formation of TEPC occurred at 7-10 days of incubation FILC with BMCH. At the same time, the presence of β-cells with insulin-producing activity was revealed in the TEPC. After intraperitoneal implantation of TEPC samples in rats with streptozotocin diabetes mellitus, there was a significant and persistent decrease in glycemia until the end of the 8-week period of the experiment. Morphological study of pancreas of recipient rats revealed signs of regeneration of own β-cells.

Conclusion. The data obtained suggest the combined antidiabetic effect of intraperitoneal injection of TEPC, due to both the direct functioning of the implant and its stimulating effect on the regeneration of β-cells in their own islets of rats with streptozotocin diabetes mellitus.

112-120 2456
Abstract

Aim: to assess the safety of transplantation of autologous bone marrow mononuclear cells when performing coronary artery bypass grafting in the combined treatment of ischemic heart disease in patients with coronary and heart failure.

Materials and methods. During the period from 2013 to 2016 years 117 patients, who meet the established criteria, were included in the work. Randomization was performed in observation groups: group 0 -control group (coronary artery bypass grafting (CABG) and intramyocardial administration of a 0.9% NaCl solution), group 1 - CABG surgery and intramyocardial administration of autologous bone marrow mononuclear cells (ABMMS), group 2 - CABG surgery and intramyocardial and intragraft administration of ABMMS. Clinical, laboratory - CPK MB, myoglobin, troponin I, HCT, Hb, K +, ABC; instrumental (stress tests, echocardiography, speckle tracking, coronary angiography) data were evaluated in these groups. The analysis of the frequency of postoperative complications (hydrothorax, hydropericardium, rhythm disturbances) was performed; the length of stay in the intensive care unit, the length of stay in the hospital and other indicators. After 6 and 12 months, the overall mortality was assessed, major cardiac events - the development of acute myocardial infarction, ventricular arrhythmias, oncological alertness. Number in international register clinical trials Clinical Trial. gov Identifier: NCT02059512.

Results. Statistical analysis showed no statistically significant differences in the observation groups for the compared criteria.

Conclusion. Transplantation of autologous bone marrow mononuclear cells during aorto-coronary bypass surgery in the combined treatment of coronary heart disease is a safe method.

CLINICAL REPORTS

121-124 906
Abstract

A case of observation of a patient who developed Kaposi’s sarcoma after kidney transplantation is presented. For the purpose of its treatment, conversion from tacrolimus to everolimus, courses of administration of prospidin were applied, in General, the intensity of immunosuppressive therapy was reduced. Stable remission was achieved only after removal of the renal transplant and complete withdrawal of immunosuppressive therapy.

LITERATURE REVIEWS

125-137 1921
Abstract

Lung transplantation is the final treatment option for end-stage lung disease when all possible conservative treatment is exhausted. According to the International Society for Heart and Lung transplantation Registry, more than 60000 lung transplantations have been performed worldwide. The early post-transplant period following lung transplantation remains critical because of numerous complications. These complications can be divided into several groups. These are surgical complications, primary graft dysfunction and acute rejection, infection, cardiovascular, abdominal and renal disorder. This complications may result in significant morbidity, mortality and limit short and long-term survival. The aim of this review is to describe the main postoperative complications in first month after lung transplantation in the world practice.

138-144 777
Abstract

This review summarizes the current literature devoted to the analysis of diagnostic role of biomarkers in rejection of the transplanted lung. Numerous researches have focused on small non-coding RNAs (micro-RNA) that regulate gene expression and affect various cell functions. Variations in the concentration of different micro-RNA have been shown in some pathological processes, including rejection of solid organs. Probably, measuring the level of micro-RNA in lung transplant may have value in the assessment of risk of rejection and possibility of minimizing immunosuppressive therapy. The accumulation of clinical data on the correlation of profiles of various biomarkers with clinical and laboratory parameters in lung recipients will help in finding non-invasive methods for the diagnosis rejection and improving long-term results of transplantation.

145-149 936
Abstract

This review summarizes the current literature devoted to the analysis of the diagnostic and prognostic role of biomarker galectin-3 in patients with heart failure and heart recipients. Measuring the level of galectin-3 in heart recipients may presumably be important for assessing the risk of developing rejection and fibrosis of the transplanted heart, but data on the effectiveness of galectin-3 as a biomarker for the development of post-transplant complications are not enough, further studies are needed.

150-160 968
Abstract

Primary tumors of the heart are presented by different morphological types. One of the rarest forms is a schwannoma of the heart. It consists of the Schwann cells or neurolemmocytes, which produces the myelin constituent of peripheral nerves. Frequency is from 0.02 to 0,056% of all primary tumors. First time it was described in 1972 and it is currently the subject of intense study by clinicians and morphologists, which is associated with the extreme rare diagnostic and peculiarities of the histological structure. Thus far 23 cases of this disease have been reported in the literature, 8 of them located primarily in the right atrium. During the study of this type of tumor in 1920, the Swedish scientist N. Antoni identified two types of tumors depending on the type of cellular architecture (type A and type B). Type A consists of spindle-shaped cells in the form of bundles, and type B consists of polygonal cells with abundant cytoplasm and they are not tightly arranged. Also, in addition to identifying specific cells, the diagnosis of schwannoma can be confirmed due to the strong diffuse staining of the S100 protein. The only method of treatment is surgical correction with the replacement of the tissue deficit with various biological and synthetic materials after tumour resection. If it is impossible to perform a complete excision of the tumor, heart transplant is the only kind of treatment.

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ISSN 1995-1191 (Print)