[Liver transplantation program at the Burnasyan Federal Biophysical Center: experience in 500 procedures]. / Programma transplantatsii pecheni v Federal'nom meditsinskom biofizicheskom tsentre im. A.I. Burnazyana: opyt 500 operatsii.

OBJECTIVE: To analyze the features and outcomes of 500 liver transplantations in adults over a 12-year period. MATERIALS AND METHODS: The study included data on 500 liver transplantations between May 2010 and April 2023. We analyzed 483 adults who underwent transplantation and 438 candidates for this procedure. All data were obtained from local liver transplantation registry. Clinical outcomes were recorded as of June 1, 2023. Statistical analysis was performed using the Statistica 12 (StatSoft Inc., USA) and Jamovi version 2.3.21.0 software (Jamovi project). RESULTS: Among 438 patients in the waiting list between January 2012 and May 2023, liver transplantation was performed in 198 (45%) cases including 27 (6%) transplantations from living-related donors and 37 (8%) procedures in other centers. There were 109 (25%) deaths. The 1- and 3-year survival rates were 81% (95% CI 76-85%) and 50% (95% CI 42-59%), respectively. Organs from deceased donors (n=134, 27%) and living-related donors (n=366, 73%) were used for transplantations. Redo transplantations were necessary in 21 (4%) cases. The median age of recipients was 45 years (range 18-72), median MELD-Na score - 16 (range 6-43). The most common indications for transplantation were viral cirrhosis (37%), cholestatic liver disease (16%), and hepatocellular carcinoma (14%). Monotherapy with calcineurin inhibitors was performed in 39% of cases, combination of calcineurin inhibitors and glucocorticoids, antimetabolites or mTOR inhibitors - 52%, three-component schemes - 8% of cases. Annual, 5- and 7-year survival rates of recipients after primary transplantation were 87% (95% CI: 84-90%), 79% (95% CI: 75-83%) and 75% (95% CI: 70-80%), respectively. In case of liver transplantation from living-related donors, these values were 89% (95% CI: 86-92%), 84% (95% CI: 80-88%) and 80% (95% CI: 75-85%), after transplantation from deceased donors - 81% (95% CI: 74-88%), 66% (95% CI: 57-76%) and 58% (95% CI: 45-72%), respectively. CONCLUSION: Liver transplantation is highly effective for patients with diffuse and focal liver diseases. Living donors not only significantly improve availability of this technology, but also provide substantial advantages in outcomes compared to liver transplantation from deceased donors, reducing the likelihood of recipient mortality by 10% after one post-transplantation year and by more than 20% after five years.

Living Donor Kidney Transplant in Recipients With Glomerulonephritis: Donor Recipient Biologic Relationship and Allograft Outcomes.

Using the Scientific Registry of Transplant Recipients, we examined the association between donor-recipient biologic relationship and long-term recipient and allograft survival among glomerulonephritis (GN) patients. Four GN types were studied: membranous nephropathy, IgA, lupus-associated nephritis, and focal segmental glomerulosclerosis (FSGS). We identified all adult primary living-donor recipients between 2000 and 2018 (n = 19,668): related (n = 10,437); unrelated (n = 9,231). Kaplan-Meier curves were generated for the recipient, death-censored graft survival and death with functioning graft through ten years post-transplant. Multivariable Cox proportional hazard models were used to examine the association between the donor-recipient relationship and outcomes of interest. There was an increased risk for acute rejection by 12 months post-transplant among the unrelated compared to the related group in IgA (10.1% vs. 6.5%, p<0.001), FSGS (12.1% vs. 10%, p-0.016), and lupus nephritis (11.8% vs. 9.2%; p-0.049). The biological donor-recipient relationship was not associated with a worse recipient or graft survival or death with functioning graft in the multivariable models. These findings are consistent with the known benefits of living-related-donor kidney transplants and counter the reports of the potential adverse impact of the donor-recipient biologic relationship on allograft outcomes.

Recipient and kidney graft outcomes of deceased donors with human immunodeficiency virus in the United States.

BACKGROUND: The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab-/NAT- (n = 810), Donor Ab+ /NAT- (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan-Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. RESULTS: In Kaplan-Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab-/NAT- testing compared with Ab+/NAT- or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab-/NAT- testing (p < .001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. CONCLUSIONS: Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT- or Ab+/NAT+ testing shortens dialysis time prior to transplant.

Donor-Recipient Relationship and Risk of ESKD in Live Kidney Donors of Varied Racial Groups.

RATIONALE & OBJECTIVE: Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 143,750 US kidney donors between 1987 and 2017. EXPOSURE: Biological relationship of donor and recipient. OUTCOME: ESKD. Donors' records were linked to national dialysis and transplantation registries to ascertain development of the outcome. ANALYTIC APPROACH: Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used. RESULTS: Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6). LIMITATIONS: Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients. CONCLUSIONS: Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.

Pelvic radiation therapy with volumetric modulated arc therapy and intensity-modulated radiotherapy after renal transplant: A report of 3 cases.

AIM: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. BACKGROUND: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. MATERIALS AND METHODS: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. CASES DESCRIPTION: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). CONCLUSION: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4 Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.

A paradigm shift in the intention-to-transplant children with biliary atresia: Outcomes of 101 cases and a review of the literature.

For children with BA who do not benefit from Kasai surgery, the only therapeutic option is liver replacement and transplantation. The very decision to proceed for transplantation is a crucial point in time because it is the first step toward the preparation for the transplantation. The former time point is defined in this analysis as "intent-to-transplant" care pathway. In the life of every BA candidate for liver replacement, this point in time varies and mostly depends on the decision of their primary caring teams-about when to switch from supportive care to transplant, and thus to refer to a transplant center. This intent-to-transplant analysis of a series of 101 consecutive infants that were referred to a single transplant team showed that excellent overall outcome (97% survival) has been achieved overall. However, three deaths occurred that were clearly related to a late referral. This analysis and recent observations from other centers strongly support that the timing for referring these children to a transplant center and/or deciding to list them on the waiting list is currently too late and should be anticipated to what it is currently. This paradigm shift in the intention-to-transplant children is likely necessary for giving a better chance to an increased number of children and impacts positively on the general outcome. Networking and defining new tools for a rapid recognition of the infants who need early transplantation are necessary; centralization of these children may be helpful to achieve better outcomes than currently observed.

Effect of terlipressin infusion therapy on recipient's hepatic and renal functions in living donor liver transplantations: Experience from a tertiary hospital.

BACKGROUND: Patients with end-stage liver disease are prone to hemodynamic disturbances which may be aggravated with liver transplantation. Blood pooling in splanchnic area and portal hypertension cause reduction in central blood volume. Terlipressin reduces mesenteric and hepatic blood flow, causing vasoconstriction in the smooth muscles of the arteries in the splanchnic region. OBJECTIVE: We investigated the efficacy of perioperative terlipressin infusion in patients who received living donor liver transplantation (LDLT) on hepatic and renal functions. DESIGN: Retrospective. SETTING: University hospital. METHOD: The study included 86 adult patients who received LDLT, due to end-stage hepatic disease, between April 2014 and July 2016 in our institute. Data were collected by searching the medical archives of patients. A standard anesthesia protocol was administered to all patients. In a selected group of patients, terlipressin infusion was initiated at 3 µg/kg/h, immediately after anesthesia was induced. The dose was halved following arterial anastomosis and was continued at this dose for the subsequent 3 days. Patients who received terlipressin infusion were compared with patients who did not receive it. MAIN OUTCOME MEASURES: There is no evidence in this trial to show evidence of effectiveness as a result of terlipressin infusion. RESULTS: Patients in the terlipressin group were statistically significantly older. Central venous pressure, cardiac index, global end diastolic volume, and extravascular lung volume did not show significant differences between the groups. Urine output was similar in both groups; however, regarding the use of packed red blood cells and fresh frozen plasma, terlipressin group patients needed more packs. Perioperative liver function tests were similar between the groups except for aspartate aminotransferase and alanine aminotransferase values on the first and third postoperative days. CONCLUSION: Terlipressin infusion was not found to be significantly effective among the liver and kidney function tests. LIMITATIONS: This may be a result of randomization defect of our retrospective study design. Many prospective randomized studies should be planned to reach more accurate results.

Living related versus deceased donor liver transplantation for maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9-13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19 ± 12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224 ± 306 µM to 143 ± 44 µM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management.

Long-term outcome of pediatric kidney transplantation: A single-center experience from Greece.

Pediatric kidney Tx has critically altered the outcome in ESRD pediatric patients. The aims of this study were to determine long-term graft and patient survival in a homogeneous ethnic population. We reviewed the medical charts of pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy-five kidney Txs were performed from LRD and 62 from DD. The 10- and 20-yr graft survival was higher in LRD Tx compared with DD Tx. Both patient and graft survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents compared with parents (92.9% vs. 93.4% 20-yr patient survival, 71.4% vs. 78.7% and 57.1% vs. 72.1%, 10- and 20-yr graft survival, respectively). However, there was a decreasing tendency in LRD Tx rates in period 2001-2012 compared with period 1990-2000 (47.1% vs. 62.7%). Risk factors for poor five-yr graft survival were DD Tx, and induction treatment with ALG compared with basiliximab, but their effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer efficient survival outcomes irrespective of donor age, suggesting that even older LRD could be an excellent option for the 1st kidney Tx in children and adolescents.

Biologically Unrelated Living Donor for Kidney Transplantation Associated With Higher Acute Rejection Rate but With Similar Graft Survival of a Related Living Donor.

INTRODUCTION: Kidney transplantation (KT) from living donors has been shown to have multiple benefits compared to those from deceased donors. We sought to compare significant graft outcomes, namely acute rejection (AR), graft function, and survival between transplant recipients who received a kidney from living related donor (LRD) and living unrelated donor (LURD). METHODS: Our cohort comprised 198 donor and recipient pairs undergoing living-donor KT at our center over 10 years. The LRD recipients were compared with LURD recipients according to demographic and clinical characteristics, transplant variables (including immunosuppression), graft function, survival, and AR rate. RESULTS: The estimated glomerular filtration rate (eGFR) was similar in both groups over the follow-up time i.e., 60-65 mL/min (p>0.05 over 10 years). Censored graft survival was similar between LRD and LURD recipients (96.9% vs. 98.0% at five years and 87.8% vs. 79.4% at 10 years, respectively; p=0.837). The LURD recipients had a higher incidence of AR, although LURD recipient status was not an independent risk factor for AR. Multivariate analysis showed that human leukocyte antigen (HLA)-DR mismatch (MM) was an independent predictor of AR (hazard ratio (HR) 2.256, p<0.05). Both HLA-A and HLA-B MM did not affect the AR HR between the groups. CONCLUSION:  Graft function and censored graft survival rates were similar between LURD and LRD KT recipients in our study. The AR was higher in LURD recipients, although the LURD recipient status was not an independent risk factor for AR. The HLA-DR MM was an independent predictor of AR, while HLA-A and HLA-B MM did not affect AR HR between groups of patients.

Case Report: Allogenic Simple Limbal Epithelial Transplantation From a Human Leukocyte Antigen-Matched Living Related Donor to Treat Bilateral Corneal Chemical Burns Post Laser-Assisted in situ Keratomileusis.

A 35-year-old woman who had undergone laser-assisted in situ keratomileusis in both eyes experienced bilateral total limbal stem cell deficiency (LSCD) due to chemical burns. Due to bilateral severe LSCD, allogenic simple limbal epithelial transplantation (SLET) from a human leukocyte antigen (HLA)-matched living related donor was the first choice of treatment for her left eye. We report the first case of HLA or ABO matching living related allogenic SLET for permanent restoration of the cornea for bilateral LSCD treatment. Our ABO-HLA-matched living related allogenic SLET alleviation of the systemic immunosuppressant to topical corticosteroids alone. It also came the limitations of prolonged systemic immunosuppressant usage in conjunctival-limbal allografts and keratolimbal allograft.

Surgical complications of open nephrectomy in living related donors in Yemen: a prospective study.

OBJECTIVE: Renal transplantation from living related donor is the best treatment option for chronic renal failure with experience for more than 50 years. However, this procedure may expose the health and even the life of otherwise normal individuals to risk. In this prospective study we described the surgical complications of open donor nephrectomies by Clavien grading system. MATERIAL AND METHODS: Between May 2002 and December 2014, one hundred and seventy-two potentially healthy kidney donors were admitted to Althawrah General Hospital, Ibn-Sina Hospital and Military Hospital. The median age was 34 years (19-60 years) with male predominance in 64.5% of the cases. This prospective descriptive study reviews intra-, and post-operative surgical complications using Clavien grading system for surgical complications. RESULTS: The procedure was done via supracostal lumbotomy incision (above 12th rib) in 112 cases (65.1%) and transcostal incision with resection of 11th rib in 60 cases (34.9%). Left kidney was taken in most of the cases (68%) while right kidney in the remaining 42% with an average warm ischemia time of 31 seconds (range, 22-34 seconds). Surgical complications by Clavien grading system were observed in 18.6% of the cases (32 cases). Grade 1 in 28 (16.4%); Grade 2 in 2 (1.2%) and Grade 3 in 2 cases (1.2%) were detected. There was no grade 4 or 5 cases in our series. Median postoperative hospital stay was 3 days (range: 2-4 days). CONCLUSION: We found that most of the complications of open living donor nephrectomy are of grade I and higher grade complications are negligible compared to the advantages for the recipients.

Beyond the Pediatric end-stage liver disease system: solutions for infants with biliary atresia requiring liver transplant.

Biliary atresia (BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches: (1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and (2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Nefrectomía robótica del donante vivo para trasplante: primer caso en latinoamérica / Living robotic donor nephrectomy: the first case in latin america

Introduction: Living donor nephrectomy is the best alternative of treatment for patients with chronic renal disease. Even though open surgery remains the gold standard for donor nephrectomy, laparoscopic surgery has become a feasible alternative in referral centers. To minimize the long learning curve associated with this procedure, some centers have introduced robotic donor nephrectomy as a surgical option. Aim: To present the first robotic-assisted laparoscopic donor nephrectomy in Latin America. Clinical case: The donor is a 50 years old male, living-related to the recipient by affinity (husband/wife). The recipient is a 54 years old female with history of end-stage renal disease waiting to initiate dialysis program. A left transperitoneal robotic-assisted laparoscopic nephrectomy employing the da Vinci Si® (Intuitive Surgical, Sunnyvale CA.) is performed. Mean operative time was 188 minutes with an estimated blood loss of 300 ml. Mean ischemia time was 6 minutes. The graft presented immediate function. Both patients were discharged at 72 h. Conclusion: Living donor robotic-assisted laparoscopic nephrectomy is a safe and viable procedure. Larger series are needed to establish its role.

Introducción: La donación renal en pacientes vivos relacionados es la mejor alternativa de tratamiento para pacientes con insuficiencia renal crónica. La cirugía abierta es el procedimiento de elección; sin embargo, la nefrectomía laparoscópica se ha convertido en una opción viable en centros con experiencia. Con el propósito de disminuír los tiempos de la curva de aprendizaje, algunos centros han introducido la nefrectomía robótica del donante vivo como una opción quirúrgica. Objetivo: Presentar la primera nefrectomía robótica del donante vivo realizada en Latinoamérica. Caso clínico: Paciente de 50 años, esposo, donante vivo relacionado, por afinidad (esposo-esposa). La receptora tiene 54 años con antecedente de insuficiencia renal crónica terminal en espera de ingreso a programa de hemodiálisis. Se realizó nefrectomía robótica izquierda del donante utilizando el sistema robótico da Vinci Si® (Intuitive Surgical, Sunnyvale CA.) mediante abordaje transperitoneal. El tiempo quirúrgico total fue de 188 min, con un sangrado estimado de 300 ml., y un tiempo de isquemia de 6 min. El injerto presentó inicio inmediato de la función. Ambos pacientes fueron dados de alta a las 72 h. Conclusión: La nefrectomía robótica del donante vivo para trasplante es una alternativa segura y factible. Comunicaciones con series con mayor número de pacientes, son necesarias para establecer su definitivo rol.

Trasplante renal: dilemas y bioética / Kidney transplantation: bioethics and dilemmas

El progreso de la ciencia y en especial el de los trasplantes de riñón amerita muchas reflexiones éticas, pues no todos los dilemas que se presentan se han solucionado y algunos no han sido tomados como tales. Los donantes vivos pueden ser sujetos a coacción, pues adquieren un compromiso con la familia, la sociedad y el equipo de salud para donar su riñón. Muchos en realidad no lo quieren hacer, aunque en los libros aparezca la donación como el mayor acto de amor y solidaridad. No todos los hijos quieren a sus padres y viceversa, ni todos los hermanos se quieren entre sí. Son muy importantes los conceptos de solidaridad y amor, que no suelen aparecer de manera espontánea en la vida de los individuos. Amor es un arte que implica dar pero de una forma madura. ¿Tendrán todos los donantes esta capacidad de dar? Si no la tienen es probable que estén siendo víctima de una coacción. Como existen tantos dilemas éticos con el trasplante de riñón, la bioética ayuda a dar respuesta a tantas inquietudes para poder colaborar con más efectividad a los involucrados en él.

Scientific breakthroughs, especially kidney transplantation, deserve serious ethical reflections for not all dilemmas that arise have been addressed and some have not been contemplated as such. Live donors could be subject to coercion in favor of donating their kidney for they have acquired a commitment with their relatives, society and health teams. Although donation appears in literature as the greatest act of love and solidarity not all live donors are actually willing to give up their kidney. Not all sons and daughters love their parents or parents love their children, nor all siblings love each other. Such important concepts as solidarity and love are not commonly manifest spontaneously in the life of individuals. Love is considered an art which implies giving in a mature manner. Will all donors have this ability? If they lack this ability they are more likely being victims of coercion. As various ethical dilemmas on kidney transplantation exist, bioethics has helped answer many questions in order to furnish an effective support to all who are involved.