[Control and prevention of kidney transplant rejection: the role and possibilities for the clinical use of regulatory T-cells in transplantation]. / Kontrol' i profilaktika ottorzheniya transplantata pochki: rol' i vozmozhnosti klinicheskogo primeneniya T-regulyatornykh kletok v transplantatsii.

This article discusses the need to implement effective methods for monitoring immune status and rehabilitation of patients after kidney transplantation. Induction of immunological tolerance which allows minimizing or even completely canceling supportive immunosuppressive therapy is one of the key tasks in the field of organ transplantation. Regulatory T-cells (TREGs) play an important role in maintaining immunological homeostasis, including limiting kidney transplant rejection, and potentially contribute to the development of immunological tolerance. At the same time, for the introduction of TREG therapy into clinical practice, it is necessary to overcome a number of unsolved problems, such as induction and cultivation of a sufficient number of TREG cells for therapeutic action as well as reducing the risks associated with TREG conversion to effector lymphocytes or an undesirable non-specific immunosuppressive effect. This review examines both the impact of common post-transplant pharmacological immunosuppression approaches on TREGs and the therapeutic potential of TREG cell cultures in prevention of kidney transplant rejection. The questions of ex vivo TREG manufacturing process and possible threats of applying cell technologies in this branch of transplantology were considered.

[Pediatric kidney transplantation: early and long-term outcomes following 1187 procedures]. / Transplantatsiia pochki detiam: neposredstvennye i otdalennye rezul'taty 1187 operatsii.

AIM: To estimate short- and long-term outcomes of pediatric kidney transplants in Russia considering the maximum available number of cases. MATERIAL AND METHODS: Retrospective, observational, multi-center study included data about 1187 kidney transplantation procedures (866 - deceased donor, 281 - living donor and 40 - AB0-incompatible living donor) performed in 1065 patients (age 0-17 years) since 1990 till 2017. Patient and graft survival, causes of recipient deaths and graft losses, as well as, the influence of donor type, blood group incompatibility and recipient age on outcomes were analyzed. Results of redo transplantations (n=131) were also investigated. RESULTS: Annual, 5- , 10- , and 15-year survival of patient was 94, 86, 79 and 69%, respectively; graft survival - 85, 67, 53 and 33%, respectively. Transplantation from related donors including AB0-incompatible cases was associated with 15-30% increase of graft survival (p<0.0001). Up to 23% of children required redo transplantation within 4-5 years after primary procedure and 2/3 of patients - after 10-15 years. There were no significant differences in outcomes after primary and redo procedures: annual, 5-, 10- and 15-year graft survival was 85, 68, 55, 42 and 85, 62, 45, 19%, respectively (p=0.1164). CONCLUSION: It is reasonable to consider the outcomes of transplantations as satisfactory in Russia. However, there is a great potential for improvement. The main problems are high incidence of infectious complications followed by fatal outcomes (41% of all fatal outcomes) and loss of allograft due to primary dysfunction and death of recipients with functioning allografts (19 and 23%, respectively). Primary use of living-related donors for pediatric kidney transplantation seems to be the most effective way to improve both short- and long-term outcomes.

[Disseminated combined small cell carcinoma with graft involvement after kidney transplantation from a deceased donor to two patients]. / Disseminirovannyi kombinirovannyi melkokletochnyi rak s porazheniem transplantatov posle peresadki pochek ot umershego donora dvum bol'nym.

The paper describes cases of disseminated small-cell carcinoma after kidney transplantation from a deceased donor to two patients. Microscopic examination showed that the kidney graft tumor consisted of tightly packed small rounded cells with hyperchromatic nuclei and a narrow cytoplasmic rim with invisible nucleoli. The mitotic index was 25-40/2 mm2. Azzopardi's phenomenon and crush artifact were detected in the tumor. Giant cell and large cell components were 30-40% of the area of sections. Immunohistochemical examination revealed the expression of synaptophysin, chromogranin A, CD56, TTF-1, HMWK, СК7, СК18, and Ki-67 (80% of tumor cells). Histological findings and immunophenotype in both cases led to the conclusion about combined small cell carcinoma with renal graft involvement. Both patients died from tumor dissemination 9 and 11 months after transplantations. In reviewing the literature, the authors found only one such observation.

[Clinical and morphological signs of viral damage to a kidney transplant]. / Kliniko-morfologicheskie priznaki virusnogo porazheniia pochechnogo transplantata.

AIM: Тo compare morphological changes and results of immunohistochemical (IHC) identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in the biopsy specimens with their clinical manifestations in recipients of renal transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted using 71 needle renal transplant biopsy specimens from patients in the study group and 10 renal biopsy specimens from those in the control group. A number of clinical indicators were estimated. RESULTS: IHC examination revealed the expression of adenoviral antigens more commonly in patients with posttransplant nephritis than in recipients without nephritis or in control individuals (p<0.05). The association of patient age and time after kidney transplantation with the severity of viral damage was confirmed: graft loss in children occurred within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in patients with the morphological patterns of polyomavirus nephropathy. Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant associations with morphological changes. CONCLUSION: By taking into account a variety of factors that influence the development of viral nephritis, morphological and IHC examinations should be combined with evaluation of clinical findings.

[The effect of gender on the results of related kidney transplantation].

AIM: To define the effect of donor and recipient gender on the results of kidney transplantation from living related donor. MATERIAL AND METHODS: Group of 271 patients who underwent kidney transplantation from living related donor was analyzed. There were 115 women and 156 men. Age varied from 1 to 63 years (mean 21.30±12.32). There were 127 children aged 1-18 years (mean 11.28±4.63) and 144 adults aged 19-63 years (mean 29.81±11.24). Donors included 162 women and 109 men. Overall survival was calculated using Kaplan-Mayer. Mortality and incidence of transplants failure were determined using Fisher's exact test. RESULTS: All patients were divided into 2 groups depending on recipients' gender and then into 4 subgroups depending on gender of donors and recipients. Comparative statistical analysis showed that transplants survival was higher in women vs. men (T=2.7, p=0.007). Survival of patients was similar in both groups. Moreover it was the best in subgroup of recipients-women with kidneys from donors-men. Difference was statistically significant (T=2.16, p=0.03). There was no significant difference in all other cases. CONCLUSION: The results of kidney transplantation are better in recipients-women than in men.

[Resistant cytomegalovirus infection in related donor kidney allograft recipients].

AIM: To clarify whether cytomegalovirus (CMV) infection can affect the results of living related donor kidney transplantation. SUBJECTS AND METHODS: A study group included 17 (7.27%) patients (10 men and 7 women; 8 children and 9 adults) aged 3 to 51 years who had developed resistant CMV infection. For comparative analysis, a control group was formed from 113 patients (61 men and 52 women; 40 children and 73 adults) aged 1 to 61 years, whose CMV polymerase chain reaction (PCR) had always been negative, i.e. CMV DNA was absent. The duration of CMV infection episodes was 44 to 232 days. RESULTS: The patients were given valganciclovir in a dose of 450 mg/day. CMV PCR was negative in all the patients at the end of therapy. None of the patients died; one graft was lost. In the control (negative CMV PCR) group, 6 grafts were lost in 113 patients lost and 4 patients died. Statistical analysis showed that the results of related donor kidney transplantation were virtually equal. CONCLUSION: Suppression of resistant CMV infection can be achieved with the longer use of valganciclovir or its higher dose. CMV infection fails to affect the results of related donor kidney transplantation.

[Kidney allotransplantation from alive related donor in patients with Alport syndrome].

AIM: To evaluate the results of kidney transplantation from alive related donor in patients with Alport syndrome and to compare with those in patients with kidney hypoplasia. MATERIAL AND METHODS: We have analyzed 8 and 27 medical records of patients with Alport syndrome and kidney hypoplasia respectively. Following parameters were used - Kaplan-Meier survival analysis, Wilcox overall risk, percentage of transplants loss and mortality (Fisher's exact test calculation). RESULTS: It is concluded that percentage of transplants loss and mortality rate as well as overall survival and risk were similar in both groups. CONCLUSION: Despite risk of anti-GBM nephritis development in patients with Alport syndrome results are comparable with those after transplatation for chronic renal failure caused by other reasons.

[Predictors of the results of kidney transplantation from living-related donors].

The aim of investigation is analysis of factors forecasting the results of kidney transplantation from living-related donors. This research is based on the analysis of 272 kidneys' transplantation from living-related donors. It was analyzed such parameters as recipients' age, donors' age, donors' sex, degree of relationship between donor and recipient, degree of HLA-compatibility, type of inductive immunosuppression (monoclonal antibodies, corticosteroids, polyclonal antibodies), recipient's sex, presence or absence of rejection episodes for whole postoperative period. We recognized that far not all above-mentioned parameters could predict the results of kidney transplantation from living-related donors.

[Vaccination in patients with chronic renal failure in the pre- and posttransplantation period].

AIM: To clarify whether vaccination provokes renal graft rejection. SUBJECTS AND METHODS: A total of 131 vaccinations were performed in 92 patients with chronic kidney failure (CKF), including 7 and 85 patients vaccinated before and in different periods after kidney transplantation, respectively. The patients were examined using needle graft biopsy, measurement of proteinuria, and estimation of changes in blood creatinine levels and glomerular filtration rate. RESULTS: Vaccination was not fount to provoke rejection, as suggested by the results of needle biopsy of renal allografts and examination of their function. CONCLUSION: Vaccination is safe for patients with CKF as it causes no rejection episodes.

[THE INFLUENCE OF CYTOMEGALOVIRUS ON THE RESULTS OF KIDNEY TRANSPLANTATION].

To understand whether the presence of cytomegalovirus in blood influences the results of kidney transplantation from live relative donors, we analysed materials from 258 recipients divided into 2 groups. Group 1 included 113 patients with negative results of PCR for cytomegalovirus, group 2 contained 139 patients with positive PCR. We evaluated lethality, the loss of transplanted kidneys, frequency of rejection and infectious complications. Statistical treatment of the data obtained included Kaplan-Meier survival analysis, the Wilcoxon test showing the cumulative hazard risk, and comparative analysis by Fisher's and Student's tests. It was shown that cytomegalovirus present in blood increases lethality and the frequency of infectious complications in recipients of transplanted kidneys but does not influence their rejection. The cumulative survival rate was significantly higher and cumulative risk lower in group 1 than in group 2.

[Effect of tacrolimus on the results of living related kidney donor transplantation].

AIM: To elucidate whether and how tacrolimus affects the cumulative survival of patients after living related kidney donor transplantation. SUBJECTS AND METHODS: The clinical materials of 246 related kidney transplant recipients, including 108 patients in whom tacrolimus (Prograf and Advagraf) Astellas Pharma US, Inc) was included in the immunodepression protocol (Group 1) and 138 patients who did not receive the agent (Group 2), were analyzed. Comparative analysis used the following tests: the Kaplan Meier test estimating the cumulative survival of recipients and transplants; the Cox test assessing the cumulative risk; and the log-rank test. Allorenal graft losses and mortality rates were also calculated. RESULTS: Mathematical analysis of the above indicators demonstrated that the allograft and survival rates were far higher (p < 0.05) and the cumulative risk was much less in Group 1 (p < 0.02). Graft losses and the recipients' deaths were higher in Group 2. CONCLUSION: The analysis suggests that the incorporation of tacrolimus into the immunodepression therapy protocol positively impacts the results of lung related kidney donor transplantation.

[Neutrophil gelatinase-associated lipocalin (u-NGAL) in the assessment of renal function in patients after kidney allotransplantation].

BACKGROUND: Early dysfunction of transplanted kidney is a serious complication that can lead to the premature loss of transplant. Ischemic and reperfusion injury of donor kidney leads to the disturbance of the function of the graft, which is a form of post-transplantation acute kidney injury that causes the relevance of search of early markers for diagnosis. OBJECTIVE: Evaluation of the diagnostic value of determination in the urine neutrophilgelatinase-associated lipocalin (u-NGAL) in patients in the early period after kidney transplantation. METHODS: An open, randomized, retrospective comparative study of 80 patients, who underwent kidney transplantation from a living human-related donor (group 1, 50 patients) and from donor with brain death documentation (group 2, 30 patients) was carried out. In 20 patients of the second group (group 2a) rapid recovery of graft function was observed, and in 10 patients (group 2b)--delayed graft recovery as a result of postischemic acute kidney injury. During the first five post-transplantation days investigated biochemical analysis of blood and urine, as well as the marker u-NGAL. RESULTS: Because of kidney transplantation was performed to the patients with end-stage chronic renal failure, high values of urea and creatinine in the blood samples during the first postoperative days were noted, that reflected the severity of the preoperative state of the patients. In the patients, who underwent human-related kidney transplantation, a more favorable picture of the investigated laboratory parameters was seen. Values of u-NGAL in this group in the early post-transplant period were normal, which attested to the absence of significant ischemic injury of transplanted kidney. In 30 patients with cadaver kidney transplantation average u-NGAL value during the first post-transplant day was 14-times fold exceeded normal range (160 ng/ml), while in 50 patients of the group with human-related transplantation--only 2 times. In the first day in group 2a average u-NGAL value decreased to normal, while in group 2b, where renal replacement therapy was carried out from the first day, remained extremely high (more than 2000 ng/ml, p<0.001 to compare with other two groups) during all 5 days of investigation. Conducting of hemodialysis sessions during the first week was required in 10 patients of group 2b, on the 2nd week--9 patients, on the 3 and 4 week in 5 patients 5, and on the fifth week--in 3 patients. CONCLUSIONS: Due to prolonged period of ischemia in kidney transplantation from a donor with established brain death the level of u-NGAL in these patients was significantly higher than in the kidneys transplantation from living human-related donor. In patients after transplantation dynamics of u-NGAL allows to identify patients with delayed graft function recovery and the need for renal replacement therapy already in the early postoperative period.

[Kidney allotransplantation from the AB0-incompatible donors].

The experience of 28 kidney allotransplantations from the AB0-incompatible donors was analyzed. The comparative group consisted of 38 patients, who received the AB0-compatible organ. The results were assessed using the following parameters: renal function, morphology of the biopsy samples of the transplanted kidney and actuary survival of the recipients with functioning transplants in both groups. The comparative analysis showed no significant difference between the two groups, giving the right to consider the kidney allotransplantation from the AB0-incompatible donors safe and effective.

[Time course of morphological changes in humoral renal allograft rejection in ABO incompatibility between donor and recipient].

One hundred and five biopsy specimens taken in different periods after 34 ABO-incompatible mismatched related kidney transplantations were examined to establish the patterns of humoral activity from the morphological changes and expression of C4d deposits in the peritubular capillaries. Severe reversible forms of acute humoral rejection (AHR) (2 patients) and minimal morphological manifestations (13 patients) were observed in the biopsy specimens taken as long as 2 months later in Group 1 (C4d+). In the early period, the minimal manifestations of AHR did not cause organ dysfunction; but in the late period, 5 of them developed chronic humoral rejection in persistent humoral activity; 4 grafts were removed 531,720, 1019, and 1252 days later. Group 2 (C4d-) (n = 19) showed no graft losses or significant chronic changes; the late minimal manifestations of AHR had no impact on the duration of organ function in 3 recipients. The timely detection of early humoral activity and minimal manifestations of AHR is needed for the measures taken to reduce a risk for late function loss of the grafted organ.

[The combined transplantation of the pancreatoduodenal complex and kidney].

Patients with diabetic nephropathy comprise up to 30% of dialisis population. The treatment optimum for these patients remains the transplantation of pancreas and kidney. There were no successful attempts in Russia so long ago as the end of the previous century. The issue analyses the experience of the SCS (where the first successful transplantation of kidney-pancreas complex was conducted) and other Russian institutes, where the problem is elaborated. Flaws and advantages of the used operative methods of pancreas and Β-cells transplantation; early and long-term results are thoroughly discussed.

[The kidney transplantation from the ABO-incompatible donors].

The experience of 28 allotransplantations of ABO-incompatible kidneys was compared with the treatment results of 38 ABO-compatible renal transplantations. The transplanted kidney function, morphological changes of the transplanted kidney and the comparative analysis of actuary survival in both groups showed no significant difference. The results of the study prove the validity of the kidney transplantation from the ABO-incompatible donors.

Prevalence and subtypes of BK virus in pediatric renal transplant recipients in Russia.

BKV reactivation is associated with impaired graft function in kidney transplant patients. The objective of our study was to determine the prevalence of BKV infection in consecutive pediatric kidney transplant recipients at our center. Fifty-eight pediatric kidney transplant recipients were studied. The mean age at screening was 9.4 ± 2.8 yr, and samples were obtained at a median of 2.4 ± 1.4 yr after transplantation. BKV-DNA was analyzed in urine and plasma by quantitative PCR. Occurrences of BK-DNAuria and BK-DNAemia did not change in the first two yr after transplantation in children and amounted to 21-23% and 7-8%, respectively (p > 0.05). In the third year, the occurrences of BK-DNAuria and BK-DNAemia increased insignificantly to 27% and 9% in the pediatric patients. We also determined the subtypes and subgroups of BK virus isolated from Russian renal transplant recipients and found that BKV isolates were composed of subtypes Ib-2 and IV/c2. The data we obtained indicate that although only 5% of BKVAN cases occurred between years two and five post-transplantation, it seems necessary to regularly monitor pediatric patients for BKV infection through the third year after transplantation.

[Anemia after renal transplantation].

The study aimed the estimation of posttransplantant anemia (PTA) frequency between the recepients of allogenic kidneys and testing the influence of different factors on the anemia development. The study was ased on the analysis of 129 patients with ERSD, to whom 129 donor kidneys were grafted. An actuarial survival of patients and allografts were calculated. The analysis demonstrated that a duration of the pretranplant hemodialysis influences the dynamics of hemoglobin level and the red blood cells count. The shorter were the dialysis terms, the easier was the anemia to correct. Shorter terms of the pretransplant dialysis also correlated with the higher rates of the overall survival after the transplantation.

[Efficacy and safety of cyclosporin A withdrawal in children long after kidney transplantation].

AIM: Evaluation of cyclosporine (CSA) withdrawal safety and efficacy in children late after kidney transplantation. MATERIAL AND METHODS: Graft and patient survival was analysed in 30 kidney recipients operated in the central children's hospital in 1991-1999. Fifteen of 30 patients came for follow-up to the Russian Research Center for Surgery where CsA was withdrawn 6.8 +/- 2.7 after transplantation. The other 15 children continued immunosuppression with CsA. RESULTS: Higher graft survival was observed in children in whom CsA was discontinued. CONCLUSION: Discontinuation of cyclosporine late after kidney transplantation results in improvement of graft survival in most of the patients.