Pregnancy after kidney transplantation (KT) has become more common, but the risk of complications and adverse obstetric outcomes in this group of women remains high.Objective: to study pregnancy complications and outcomes in kidney recipients and renal graft (RG) survival after childbirth.Material and methods. The study included 22 pregnancies in 20 women with RG (transplants performed in 2006–2020). The comparison group consisted of 20 healthy women who had 20 pregnancies. Frequency and nature of pregnancy complications, neonatal health indicators, and pregnancy outcomes were evaluated. Graft survival was compared in the main group and in a group of 102 women after KT who did not have pregnancies.Results. Compared with healthy women, RG recipients had a higher rate of preeclampsia (25% and 0%, p = 0.047), fetal growth restriction (30% and 0%, p = 0.020), gestational diabetes (40% and 5%, p = 0.020), asymptomatic bacteriuria (35% and 5%, p = 0.044), preterm birth (60% and 0%, p < 0.001), and cesarean section (70% and 10%, p < 0.001). Median gestational age and birth weight were significantly lower in women with RG: 36.0 [33.9; 37.4] vs. 38.9 [38.9; 39.6] weeks, p < 0.001, and 2405 [2023; 2958] vs. 3355 [3200; 3690] g, p < 0.001, respectively. The rate of favorable pregnancy outcomes after KT was 81.8%, or 90% when early pregnancy loss is excluded. Two children were found to have genetic diseases passed from the mother. Graft survival did not differ between RG recipients with and without pregnancy, p = 0.272.Conclusions. Pregnancy outcomes in patients with RG are generally favorable, pregnancy and childbirth do not affect graft survival. When planning pregnancy after KT, it is necessary to consider the risk of complications and the possibility of transmitting genetic disorders to offspring.

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

АКТУАЛЬНОСТЬ АКТУАЛЬНОСТЬ. На сегодняшний день крайне мало исследований, представляющих объективные данные о распространенности минеральных и костных нарушений (МКН) у реципиентов почечного трансплантата (ПТ) в России. ЦЕЛЬ. Провести скрининг, включающий определение основных лабораторных показателей МКН у пациентов, перенесших аллотрансплантацию трупной почки (АТП), а также оценить назначение сопроводительной терапии, направленной на коррекцию МКН при хронической болезни почек (МКН-ХБП). МАТЕРИАЛЫ И МЕТОДЫ МАТЕРИАЛЫ И МЕТОДЫ. В поперечное исследование были включены 236 пациентов, перенесших успешную трансплантацию почки. У всех пациентов определяли уровень интактного паратиреоидного гормона (ПТГ), общего кальция, фосфора, щелочной фосфатазы (ЩФ) сыворотки. РЕЗУЛЬТАТЫ РЕЗУЛЬТАТЫ. Лишь у 6,2% реципиентов ПТ наблюдались целевые уровни всех исследуемых лабораторных показателей МКН, при этом повышенный уровень ПТГ в сочетании с гиперкальциемией был отмечен почти у трети пациентов (31%). Целевой уровень ПТГ наблюдался у 13% реципиентов, 84% пациентов демонстрировали гиперпаратиреоз. Доли пациентов с целевым уровнем ПТГ не различались в группах реципиентов с сохранной и сниженной расчетной скоростью клубочковой фильтрации (рСКФ) (p=0,118). Гиперкальциемия наблюдалась у 29% реципиентов. Уровни неорганического фосфора сыворотки значительно различались в группах пациентов с разной рСКФ (p<0,0001), возрастая по мере снижения функции трансплантата. У 40,7% пациентов было отмечено повышение уровня ЩФ. В качестве сопутствующей терапии 123 пациента получали активный витамин D (альфакальцидол), 33 пациента — препарат неактивной формы витамина D (колекальциферол), 57 пациентов не получали лекарственной терапии МКН-ХБП. Уровень общего кальция сыворотки статистически значимо различался в этих группах (p=0,0006), наиболее высокий его уровень отмечался в группе терапии колекальциферолом. Доля пациентов с нормокальциемией в группе лечения колекальциферолом была наиболее низкой (χ2 р=0,0018). ЗАКЛЮЧЕНИЕ ЗАКЛЮЧЕНИЕ. Распространенность МКН у реципиентов ПТ очень высока. Применение альфакальцидола по сравнению с препаратами неактивной формы витамина D может быть более безопасным в отношении развития гиперкальциемии.

The main principle of immunosuppressive therapy, in the opinion of many authors, is gradually becoming the need to take into account all the advantages and disadvantages of the prescribed drugs in each particular patient. Individualization of lifelong immunosuppression acts as the main factor in long-term graft survival and, accordingly, in the life of the recipient. This review analyzes the literature on changes in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly patients, and assesses the prospects for the correction of immunosuppressive therapy in kidney transplantation in elderly patients.

Purpose. To evaluate the potential option of selecting donor–recipient pairs by using the number of epitopemismatches.Materials and methods. An observational cohort study was carried out, which included 824 adult recipients of ABO compatible deceased donor kidneys. The end point was a transplant loss. If a recipient with a functioning graft died, the observation was censored. The number of epitope mismatches (EpMM) was calculated using open source information on the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. After that, the number of donor epitopes absent in the recipient was calculated for each combination with a non-zero probability, whereupon the weighted mean EpMM was calculated, where the weight coefficient was the normalized probability of occurrence of each combination.Results. All of the donor – recipient pairs had HLA-mismatches (HLA MM): 1.9% of recipients had 1 HLA MM, 6.7% had 2 HLA MM, 29.9% had 3 HLA MM, 38.5% had 4 HLA MM, 18.1% had 5 HLA MM, and 4.9% had 6 HLA MM. The HLA MM impacted graft survival was determined: log-rank test p < 0.0001, Breslow test p < 0.0001. The median values and the interquartile ranges of EpMM were 6 [4; 7], 12 [7.74; 17.25], 18 [14; 22], 24 [20; 30], 30.5 [25; 37] and 36 [26.5; 44.5] for the cases of 1, 2, 3, 4, 5 and 6 HLA MMs, respectively. An increase in HLA MM resulted in a higher risk of developing donor-specific anti-HLA antibodies (DSA). Hazard ratio (HR) = 1.21 [95% confidence interval (CI): 0.7; 1.9], 1.71 [95% CI: 1.22; 2.36], 2.04 [95% CI: 1.42; 2.73], 2.25 [95% CI: 1.63; 2.96], 2.59 [95% CI: 2.03; 3.29] for 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also resulted in a higher risk of developing DSA. HR = 1.66 [95% CI: 1.09; 2.47], 2.1 [95% CI: 1.46; 2.91], 2.41 [95% CI: 1.86; 3.03], 2.61 [95% CI: 2.12; 3.12], 2.77 [95% CI: 2.26; 3.33] for 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. An increase in HLA MM was associated with an increased risk of transplant loss. HR = 1.24 [95% CI 0.7; 2.15], 1.48 [95% CI 0.86; 2.33], 1.88 [95% CI 1.32; 2.52], 2.41 [95% CI 2; 2.93], 2, 98 [95% CI 2.59; 3.46] at 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also was associated with an increased risk of transplant loss. HR = 1.71 [95% CI 1.1; 2.49], 2.11 [95% CI 1.59; 2.68], 2.4 [95% CI 1.96; 2.86], 2.59 [95% CI 2.17; 3.04], 2.71 [95% CI 2.31; 3.15] at 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. In order to demonstrate the effectiveness of EpMM accounting, we analyzed graft survival among the patients with 4 HLA MM. With the number of EpMM in the range from 10 to 24 and from 25 to 43 the difference in survival rates was statistically significant, but only at the late stages of the post-transplant period: log-rank test p = 0.0067, Breslow test p = 0.0982. The median survival for EpMM 10–24 was 10.33 [95% CI 9.05; 11.61] years, for EpMM 22–43 – 8.67 [95% CI 7.68; 9.66] years, HR 1537 [95% CI 1.114; 2.12]. At the same time, it was not the median of survival that increased, but the proportion of patients with a functioning graft: at 10-24 EpMM after 15 years, 18.28% [95% CI 8.2; 31.67] grafts functioned, while at 25–43 EpMM only 4.75% [95% CI 0.94; 13.64] functioned.Conclusion. In the routine practice of a transplantation center with a short waiting list of its own, it might be possible to improve the kidney transplant survival as a result of considering epitope mismatches, thus reducing the risk of developing donor-specific anti-HLA antibodies and ensuring a higher graft survival rate. This method can be used for additional ranking of transplantation candidates depending on the number of epitope mismatches within the fixed number of HLA-mismatches and thus select the optimal one. Besides, it is theoretically possible to use this method as an alternative to the traditional donor/recipient histocompatibility evaluation. Additional research is required.

российская ФедерацияЦель. провести многофакторный анализ влияния количества эпитопных несовпадений на выживаемость почечных трансплантатов.Материал и методы.проведено обсервационное ретроспективное когортное исследование, в которое было включено 824 совершеннолетних реципиента почечного трансплантата.Результаты. все пары донор-реципиент имели HLA-несовместимости (HLA

BACKGROUND:The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology.AIM:To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation.MATERIALS AND METHODS:A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated.RESULTS:Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04).CONCLUSION:ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period.BACKGROUND:The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology.AIM:To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation.MATERIALS AND METHODS:A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated.RESULTS:Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04).CONCLUSION:ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period.

Objective : to analyze the features of the pattern of lymphocyte subpopulations and the functional activity of peripheral blood mononuclear cells in older adult patients with chronic kidney disease. Materials and methods . The study featured 21 patients with chronic kidney disease (CKD), over 55 years of age, who underwent kidney transplantation (KT) from unrelated suboptimal donors. The average age was 61.4 ± 4.5 years (55 to 69). Comorbidity was assessed using the CIRS-G scale; the average number of points was 13.6 ± 5.09. The control group consisted of 21 volunteers, aged 55–70, without acute inflammatory diseases and signs of chronic kidney disease (CKD). The average age was 61.1 ± 4.4 years, the average CIRS-G score was 12.11 ± 6.04. In all patients, the pattern of lymphocyte subpopulations of peripheral blood was evaluated by flow cytometry. Vital computer laser cytomorphometry was used to assess the functional state of peripheral blood mononuclear cells. The Functional Activities Index (FAI) was evaluated to indirectly assess the degree of functional activity of cells. Results . In CKD patients before KT, there was a decrease in the proportion of CD4 cells (p = 0.009), an increase in the proportion of CD8 cells (p = 0.02), a decrease in the CD4/CD8 ratio (p = 0.017), an increase in the proportion of natural killers (p = 0.025) compared with healthy volunteers. Moreover, a decrease in the total proportion of CD3 cells, an increase in HLA-DR expression on CD3 cells, and an increase in the proportion of B cells were statistically insignificant: p = 0.137, p = 0.072 and p = 0.135, respectively. On the fifth day after KT, the proportion of CD3 cells increased (p = 0.017) mainly due to an increase in the proportion of CD4 cells (p = 0.002) compared to the pre- KT index. The proportion of natural killers (p = 0.002) and HLA-DR expression on CD3 cells (p < 0.0001) also increased. An increase in the proportion of CD8 cells and in the CD4/CD8 ratio, and a decrease in the proportion of B cells were statistically insignificant: p = 0.439, p = 0.277, and p = 0.236, respectively. A decrease in FAI was noted in patients with CKD before KT in comparison with healthy volunteers (p = 0.0138). After ATP, this indicator significantly increased compared to the pre-KT value (p < 0.0001) and exceeded the FAI value in healthy volunteers (p < 0.0001). In healthy volunteers, there was no significant correlation between the functional activity of peripheral blood mononuclear cells and age (r = –0.263 [95% CI –0.6236; 0.1907], p = 0.264, r2 = 0.069). At the same time, significant negative correlation between FAI and age was noted in CKD patients: r = –0.52 [95% CI –0.7771; –0.1135], p = 0.0157, r2 = 0.27 before KT; r = –0.418 [95% CI –0.7559; –0.06256], p = 0.0272, r2 = 0.175 after KT. Conclusion . Older adult CKD patients before and after KT were likely to have significant changes in the morphofunctional state of peripheral blood mononuclear cells and pattern of lymphocyte subpopulations. Moreover, the severity of changes in the functional state of these cells had a strong correlation with age, which was not observed in the group of healthy volunteers. This should be considered when choosing immunosuppressive therapy in older kidney transplant recipients.

The main negative consequences of ischemia-reperfusion of the kidneys are the early developing severe chronic dysfunction of the graft, and in the most severe cases the function of the transplanted kidney is not restored (primary non-functioning graft). As a result of loss of transplant function, the patient usually returns to dialysis. These complications are more common in kidney transplants from “donors with extended criteria,” since these organs are most sensitive to damage resulting from ischemia-reperfusion syndrome (IR syndrome). At the same time, the share of such (suboptimal) donors is gradually increasing in Russia. Cold preservation of the organ in special solutions remains the gold standard for kidney transplantation, however, it is not able to fully protect the organ. The article presents the main promising methods that reduce the severity of ischemic and reperfusion injury: donor conditioning, ischemic preconditioning, various variants of kidney preservation, effects on inflammatory mediators, application of biological target drugs. Nevertheless, the pathogenesis of ischemia-reperfusion syndrome has been studied much better than the methods of its correction. Currently, there are only indirect or experimental evidence that the severity of the syndrome of IR can be reduced due to the pharmacoprotection of the ogran before donation, during preservation, as well as in the early postoperative period. Further research is needed to find ways to reduce the severity of ischemic and reperfusion injury of the graft.

Sepsis is a serious condition characterized by a complex dysfunction of internal organs and systems. In the basis of the pathogenesis of sepsis, the leading role is played by the dysregulation of the immune response to the infectious agent, in particular endotoxin of gramnegative bacteria, which is an obligate lipopolysaccharide of the bacterial wall. Aim. To evaluate the prognostic value of cytokine profile, phagocytosis activity indices, endotoxin concentration and activity in blood in gram-negative sepsis. Materials and methods. 78 patients with abdominal sepsis were included in a one-center prospective cohort study, of them 45 died. All the patients were evaluated for the concentration of circulating cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10), cellular molecules (CD3, CD45RO, CD95 and HLA-DR), bactericidal and phagocytic activity of neutrophils and endotoxin (lipopolysaccharide) level in peripheral blood. Results and discussion. The concentrations of all cytokines were slightly lower in the survivors. Significant differences were noted for TNF-α (p=0.001), IL-6 (p=0.001), and IL-8 (p=0.007). The expression of HLA-DR molecules was slightly higher (p=0.055), and CD95 was lower (p=0.146) in survivors than in the dead. However, the differences have not reached the required level of statistical significance. The phagocytic (p

Aim: to analyze the survival of patients on the waiting list for kidney transplantation and the results of transplantation depending on the duration of waiting.Materials and methods. We performed a retrospective observational analysis that included 1,197 patients on the waiting list. The end point was exclusion from the waiting list (WL). The causes for exclusion (death, exclusion due to deterioration of the comorbid background or transplantation) were considered in terms of competing risks.Results. In total, 72.5% of patients reached the end point: 21.1% of them died, 11% were excluded, and 40.4% underwent transplantation. Kaplan–Meier estimate showed that cumulative risk of death was 80.4% [95% CI 77.9; 88.6], of exclusion was 77.9% [95% CI 65.4; 88.2], of transplantation was 63.6% [95% CI 58.3; 69] after 10 years on the waiting list. However, such an assessment cannot be directly interpreted as a prediction of the relevant event risk of occurrence for the patient in the WL, because it does not take into account competing events. According to a balanced assessment of the competing risks (Fine and Gray estimate), cumulative incidence was 30.9% (95% CI 27.7; 34.2) for death, 18.2% [95% CI 15.5; 21.1] for exclusion and 49.4% [95% CI 46; 52.6%] for transplantation after 10 years on WL. The probability of transplantation was significantly higher than the risk of death up to and including 5 years of waiting (incidence rate ratio – IRR 1.769 [95% CI 1.098; 2.897]). When waiting 7 to 8 years, the probability of transplantation was less than the risk of death: IRR 0.25 (95% CI 0.093; 0.588; p = 0.0009). Of the 483 recipients, 61 died and 119 returned to dialysis. The risk of graft loss after 10 years was 68.5% [95% CI 57.5; 79.1] and the risk of death of a recipient with a functioning graft was 48.3% [95% CI 34.7; 63] according to Kaplan–Meier estimate. The cumulative incidence of the method was 30.8% [95% CI 23.3; 38.5%] and 55.7% [95% CI 46.6; 63.5%] according to Fine and Gray estimate, respectively. The risk of death after transplantation increases significantly when waiting for more than 6 years – IRR 4.325 [95% CI 1.649; 10.47], p = 0.0045 relative to a shorter waiting period. With an increase in the waiting period, the comorbid background (CIRS scale) deteriorates significantly, even adjusted for the initial patient condition: the partial correlation r = 0.735; p < 0.0001.Conclusion. 1. In the context of competing risks, the Fine and Gray estimate gives a more balanced risk assessment compared to the Kaplan–Meier method. 2. Increasing the waiting time for transplantation significantly increases the risk of death of the candidate on the waiting list and reduces the probability of transplantation, as well as increases the risk of death of the recipient after transplantation. Apparently, this is mainly due to the deterioration of the comorbid background.

Introduction. Tuberculosis is one of the most common infections in the general population, as well as among the recipients of solid organs. In kidney transplant recipients, the diagnosis of tuberculosis is often extremely difficult to make because of unclear clinical and radiological symptoms, and a highly frequent atypical (extrapulmonary) localization. The tuberculosis treatment in patients on drug immunosuppression is a significant problem.Clinical case. At five years after renal transplantation, the patient noted the onset of fever up to 38 degrees C. It was suspicious of respiratory infection. Chest X-ray, computed tomography, and ultrasound examination of the graft revealed no pathology. Antibacterial and antiviral therapy brought stable improvement. A repeated computer tomography demonstrated an enhanced pulmonary pattern in S6 of the left lung with visualization of small grouped lesions located peribronchially, the terminal ileitis in the abdominal cavity: (an intensive contrast accumulation in the mucosa of the affected part of the small intestine, the mesentery hypervascularity at this level). A colonoenteroscopy with a ileum intestine biopsy was performed; the findings were highly consistent with a tuberculous process. A targeted treatment of tuberculosis was carried out, which had a marked positive trend.Conclusion. Thus, the diagnosis of tuberculosis in kidney transplant recipients is complex; the clinical signs and instrumental test results are often ambiguous, which greatly complicates the timely diagnosis. An integrated approach with the use of modern diagnostic methods is required.

Aim: to analyze the results of the regional center for the creation and maintenance of vascular access for hemodialysis.Materials and methods. We performed a retrospective analysis. In five years (2012–2016) we performed 3,837 different operations on vascular access (VA) in 1,862 patients.Results. There is a strong dependence of type VA and the cause of CKD 5D. At the time of the HD start, the proportion of arteriovenous fistula (AVF), synthetic vascular graft (SVG) and central venous catheter (CVC) was 73.7, 0.3 and 26% for glomerulonephritis; 58.4, 0.4 and 41% for pyelonephritis; 53, 1 and 26% for diabetes mellitus; 32, 8 and 60% for polycystic disease and 33, 2 and 65% for systemic processes, respectively. After one year on HD the shares of AVF, SVG and CVC were 89, 2 and 9% for glomerulonephritis; 76, 6 and 18% of pyelonephritis; 70, 5 and 25% for diabetes mellitus; 68, 10 and 22% for polycystic disease and 53, 5 and 42% for systemic processes, respectively. In a case of start of HD via AVF, five years survival was 61% [95% CI 51.8; 71.9]; in a case of start HD via CVC with followed by conversion to AVF – 53.9% [95% CI 42.5; 67]; in a case of CVC remained the only access – 31.6% [21.4; 41.4]. Non-maturation of AVF was observed in 5.9% of new AVF (the risk increased in a case of diabetes mellitus), early thrombosis (before the first use of AVF) was observed in 12.7% of new AVF (the risk increased with diabetes, polycystic and systemic diseases). Creation of AVF a week before the start of HD or 1–2 weeks later significantly increased the risk of thrombosis. Primary patency in a year, three and five years was 77.2% (95% CI 71.7; 81.7); 48% (95% CI 41.6, 54.1); 34.1% (95% CI 27.8, 40.5) respectively; secondary patency – 87% [95% CI 83.7; 89.7]; 74.4% [95% CI 70.3; 78,12]; 60.9% [95% CI 56.4; 65.1] respectively. The use of temporary CVC is associated with a three-fold increase of the risk of infection compared with permanent CVC: IRR 3,31 (2,46; 4,43), p < 0,0001.Conclusion. A more detailed analysis is required to identify risk factors for complications of vascular access and to optimize approaches to its creation and maintenance.

The article presents the developed and approved test-systems for evaluation of the level of expression of immune system responsible activation and inhibition of T-cell response in recipients of renal transplant under application of extra-corporal photochemotherapy.

Aim – to perform a comparative study of the long-term results of the combined use of extracorporeal photochemotherapy (photopheresis) and drug immunosuppression and standard immunosuppressive therapy in patients after kidney transplantation.Materials and methods. An open cohort randomized study was conducted, including 60 patients with chronic kidney disease stage 5D. All patients underwent single-group cadaveric kidney transplantation. Patients were randomly divided into two groups. All transplants were paired, the fi rst kidney transplant was received by the patient of the main group, the second – by comparison group. 30 patients of the main group received standard protocol of immunosuppression and 10–15 sessions of photopheresis during the fi rst six months after transplantation. All patients of the comparison group received standard immunosuppressive therapy only. End points: primary – graft loss, surrogate – the number of acute rejection episodes and infectious complications, the dynamics of creatinine blood concentration, the glomerular fi ltration rate and daily proteinuria, the dynamics of tacrolimus C0 blood concentration. To study the mechanism of photopheresis action in the late postoperative period, we evaluated the immunological parameters: subpopulation of naive T-cells (CD3+CD4+CD45RO–CD28+), the level of CD28 molecule expression (MFI) on these cells and also – subpopulation of T-regulatory cells (CD3+CD4+CD25 (Hi)CD127–).Results. The use of photopheresis leads to the graft function improvement in the late postoperative period: the creatinine concentration (p = 0.017) in the blood and daily proteinuria (p = 0.011) were lower in patients of the main group, the glomerular fi ltration rate was higher (p = 0.027). The incidence rate ratio (IRR) of rejection in the main group was signifi cantly lower than in the comparison group: 0.2509 (95% CI 0.05386, 0.9167), p = 0.0358. The risk of graft loss was also lower in the main group: IRR 0.2782 (95% CI 0.07562, 0.8657), p = 0.026, as well as the risk of infectious complications: IRR 0.3888 (95% CI 0.2754; 0, 5445), p < 0.0001. Survival rate of transplants was higher in the main group (Log Rank p = 0.009; Breslow p = 0.005). The use of photopheresis made it possible to reduce the concentration of tacrolimus in the late postoperative period (p = 0.0017) without increasing the risk of graft rejection. The photopheresis tolerogenic effect in the late postoperative period may be due to an increase in the population of T-regulatory cells with the CD3+CD4+CD25(Hi)+CD127– phenotype compared to the patients which received only standard immunosuppressive therapy (p = 0.024).Conclusion. The preventive use of photopheresis contributes to improvement of the kidney transplantation long-term outcomes. Further studies are needed to study the mechanisms of photopheresis action and markers of partial immunological tolerance to the allograft.

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 evaluate the influence of prophylactic use of photopheresis on the risk of long-term infective complications after kidney transplantation. MATERIALS AND METHODS The open cohort randomized study was conducted. A total of 60 recipients after cadaveric kidney allotransplantation from 30 donors were assessed. The patients were randomized into two groups (n=30). All transplants were paired, and one kidney was transplanted to patient in intervention group and the another one was transplanted to patient in control group. In the intervention group all patients received standard immunosuppression therapy (tacrolimus, mycophenolate, prednisone) and 10-15 sessions of photopheresis during first 6 months after the transplantation. In the control group only the immunosuppression therapy was given. The follow-up period ranged from 2 to 7 years, an average 4.5+/-2.0 years. RESULTS The rate infective complications in the both groups gradually decreased as the postoperative period increased exponentially, but it was lower in the intervention group than in the control group. The rate of respiratory infection, asymptomatic bacteriuria and viremia, verified by the genetic amplification was 4, 2 and 1.5 times lower in the intervention group. The risk of clinically meaningful infection was significantly lower in the intervention group than in the control group: IRR 0.3888 (95% CI 0.2754; 0.5445; <0.0001). 6-year survival in the intervention group was 100% in comparison to 82.8% in the control group (95% CI 51.6; 93.16). CONCLUSION The prophylactic use of the photopheresis allows to decrease the risk of infective complications after the kidney transplantation.

Background: Sepsis is a severe life-threatening condition characterized by combined dysfunction of the inner organs and systems and by dysregulation of the platelet and coagulation compartments of hemostasis, in particular.Aim: To assess the character of abnormalities in morphofunctional state of platelets in the pathophysiology of sepsis and the multiple organ failure syndrome by means of coherent interference microscopy.Materials and methods: This single center, prospective, observational study included 78 hospitalized patients with abdominal sepsis; in 40 of them, the syndrome of multiple organ failure was diagnosed. The causes of sepsis were peritonitis of various etiologies in 55 patients, acute necrotic pancreatitis with suppurative and septic complications in 23. The control group included 25 physically healthy subjects. Coherent interference microscopy was used for vital assessment of the platelet morphofunctional state, with simultaneous analysis of routine coagulogram and platelet aggregation parameters.Results: The group of patients with sepsis (n = 38) had higher fbrinogen levels, compared to that in the control (4.5 ± 1 g/L, p = 0.0001), with mild thrombocytopenia (238 ± 12 × 109/L, p = 0.0001). Platelet aggregation was also increased (48 ± 3%, p = 0.0001). Assessment of circulating platelets by coherent interference microscopy showed a progressive increase of the mean populational morphodensitometrical parameters, such as the diameter (p = 0.0002), perimeter (p < 0.0001), and area (p = 0.0002), as well as a decrease in mean values of the phase height (p = 0.0002) and volume (p = 0.0002). There was an increase in the proportion of activated cells to 41% (vs. 33% in healthy control) and the proportion of degenerative cells up to 8%. The patients with severe sepsis complicated by multiple organ failure (n = 40), compared to the control ones, demonstrated exhausted of compensatory mechanisms with the development of consumption coagulopathy: prolonged activated partial thromboplastin time (57 ± 2 s, p = 0.0001), increased prothrombin index (117 ± 4, p = 0.0025), decreased fbrinogen level (1.6 ± 2 g/L, p = 0.0001) and platelet counts (110 ± 9 × 109/L, p = 0.0001), and their lower aggregation (24 ± 3%, p = 0.0001). According to the results of the coherent phase microscopy, the types of the morphodensitometrical abnormalities were similar to that in the main group, albeit they were more signifcant. The proportion of the activated cells was 43%, while that of the degenerated and functionally incompetent platelets, 15%. There were signifcant correlations between the morphodensitometrical parameters of the platelets and basic parameters of their aggregation induced by adenosine diphosphate and collagen.Conclusion: Sepsis is associated with advanced abnormalities in the morphofunctional state of peripheral blood platelets progressing concomitantly to the deterioration of the patient's state. Coherent interference microscopy allows for a real-time assessment of the morphological particulars and functioning of circulating thrombocytes. Further studies are required to validate the results of this method.