Post-transplant Complications Research Articles

Elucidating immune cell dynamics in chronic lung allograft dysfunction: A comprehensive single-cell transcriptomic study

Chronic Lung Allograft Dysfunction (CLAD) is a critical post-transplant complication that predominantly determines the long-term survival rates and quality of life of patients undergoing lung transplantation. The limited efficacy of current immunosuppressive strategies underscores our incomplete understanding of the immunological aspects of CLAD. Hence, there is an urgent need for more comprehensive and targeted research to unravel the complex interplay of immune cells in the development and progression of CLAD. This study conducts an in-depth analysis of the immune environment in CLAD. By examining the gene expression profiles of T cells, natural killer cells, B cells, macrophages, and monocytes, we have elucidated a unique immunological landscape in CLAD compared to healthy controls. We highlight the heterogeneity within the immune populations and provide a comprehensive understanding of the immune mechanisms driving CLAD. Enrichment analysis identified specific pathways that are either overactive or suppressed in CLAD, revealing potential molecular targets for therapeutic intervention. Our findings emphasize the crucial role of T cells in the pathophysiology of CLAD, coordinating the immune response and revealing an amplified immune cell network, potentially leading to maladaptive tissue responses. By integrating a comprehensive cellular and molecular portrait of the immune environment, our research not only deepens our understanding of the pathogenesis of CLAD but also lays a foundational approach for the development of targeted therapies.

The transformative potential of artificial intelligence in solid organ transplantation.

Solid organ transplantation confronts numerous challenges ranging from donor organ shortage to post-transplant complications. Here, we provide an overview of the latest attempts to address some of these challenges using artificial intelligence (AI). We delve into the application of machine learning in pretransplant evaluation, predicting transplant rejection, and post-operative patient outcomes. By providing a comprehensive overview of AI's current impact, this review aims to inform clinicians, researchers, and policy-makers about the transformative power of AI in enhancing solid organ transplantation and facilitating personalized medicine in transplant care.

Oral findings in paediatric patients with severe heart, liver, and kidney failure prior to organ transplantation

PurposeOrgan transplantation is an effective treatment for children with severe heart, liver, and kidney diseases. These patient groups may have more oral and dental diseases than healthy controls. It is important to eliminate oral infection foci before transplantation and to maintain good oral health to avoid potential post-transplant complications. The aim of this study was to describe and compare oral health in Finnish paediatric heart, liver, and kidney transplant recipients prior to organ transplantation.MethodsEighty-six children who received a heart (n = 21), liver (n = 19), or kidney (n = 46) transplant in Finland during the years 2014–2018 were included in this study. The inclusion criterion was a pre-transplantation oral examination. Oral hygiene, enamel anomalies, and the number of decayed, missing, and filled teeth (dmft/DMFT) were analyzed retrospectively from medical and dental records and compared between the three patient groups.ResultsChildren with liver (p = 0.043) or heart (p = 0.047) disease had higher combined primary and permanent dentition dmft/DMFT scores compared to children with kidney disease. A higher combined dmft/DMFT score was associated with poor oral hygiene (p = 0.005). No significant differences in oral hygiene between the patient groups were found. Furthermore, all patient groups had a high prevalence of developmental dental defects.ConclusionChildren with liver or heart disease seem to have a higher combined dmft/DMFT score, indicating a higher prevalence of caries compared to children with kidney disease. Prevention of dental caries, along with promoting a good oral hygiene routine and regular check-ups, is suggested in these patient groups.

Outcomes of Kidneys Transplanted From Hepatitis C Viremic Donors to Naive Recipients From an Appalachian Rural Kidney Transplant Program.

Before the advent of direct-acting antiviral therapy for hepatitis C virus, a large proportion of kidneys from donors with hepatitis C viremia were discarded. Hepatitis C virus is now amenable to effective treatment with excellent seronegativity rates. In this study, we review the outcomes of hepatitis C viremic kidneys transplanted into hepatitis C-naive recipients. In this retrospective observational study, we examined 6 deceased donor kidneys with hepatitis C viremia that were transplanted into hepatitis C-naive recipients between March 2020 and April 2021 at a single center. Because of health insurance constraints, patients were treated for hepatitis C virus with glecaprevir/pibrentasvir for 8 weeks following seroconversion posttransplant. Primary outcome measured was viral seroconversion; secondary outcomes included graft function, posttransplant complications, and all-cause mortality. On average, patients seroconverted 6 days (range, 4-10 d) after transplant and began treatment 26 days (range, 15-37 d) after seroconversion. An 8-week course of antiviral treatment was successful in preventing acute hepatitis C virus infection in all patients. Posttransplant median creatinine was 1.96 mg/dL (range, 1-4.55 mg/dL), whereas median estimated glomerular filtration rate was 41.33 mL/min/1.73 m2 (range, 17-85 mL/min/1.73 m2). Patient survival rate was 66.7%, and death-censored graft survival rate was 100%. Two patients died from unrelated reasons: 1 from acute respiratory failure secondary to SARS-CoV-2 infection and 1 from posttransplant lymphoproliferative disorder. Two patients developed allograft rejection posttransplant (1 developed antibody mediated rejection, 1 developed borderline T-cell-mediated cellular rejection). Other major complications included neutropenia, fungal rash, SARS-CoV-2 infection, cytomegalovirus, BK virus, and Epstein-Barr virus reactivation. Use of hepatitis C-viremic donor kidneys for transplant is a safe option and has great potential to increase the kidney donor pool, as long as high index of suspicion is maintained for allograft rejection and opportunistic infections.

Revolutionizing Kidney Transplantation: Connecting Machine Learning and Artificial Intelligence with Next-Generation Healthcare—From Algorithms to Allografts

This review explores the integration of artificial intelligence (AI) and machine learning (ML) into kidney transplantation (KT), set against the backdrop of a significant donor organ shortage and the evolution of ‘Next-Generation Healthcare’. Its purpose is to evaluate how AI and ML can enhance the transplantation process, from donor selection to postoperative patient care. Our methodology involved a comprehensive review of current research, focusing on the application of AI and ML in various stages of KT. This included an analysis of donor–recipient matching, predictive modeling, and the improvement in postoperative care. The results indicated that AI and ML significantly improve the efficiency and success rates of KT. They aid in better donor–recipient matching, reduce organ rejection, and enhance postoperative monitoring and patient care. Predictive modeling, based on extensive data analysis, has been particularly effective in identifying suitable organ matches and anticipating postoperative complications. In conclusion, this review discusses the transformative impact of AI and ML in KT, offering more precise, personalized, and effective healthcare solutions. Their integration into this field addresses critical issues like organ shortages and post-transplant complications. However, the successful application of these technologies requires careful consideration of their ethical, privacy, and training aspects in healthcare settings.

Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam.

Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.

Respiratory problems associated with liver disease in children.

Respiratory manifestations of chronic liver disease have a profound impact on patient clinical outcomes. Certain conditions within paediatric liver disease have an associated respiratory pathology. This overlap between liver and respiratory manifestations can result in complex challenges when managing patients and requires clinicians to be able to recognise when referral to specialists is required. While liver transplantation is at the centre of treatment, it opens up further potential for respiratory complications. It is established that these complications place patients at risk of longer stays in hospital and reduced survival. Additionally, late post-transplant complications can occur, including post-transplant lymphoproliferative disease and immunosuppression-induced interstitial lung disease. Although rare, it is important for clinicians to recognise these conditions to allow for prompt management. Finally, as liver disease progresses in children, respiratory complications can occur. Hepatopulmonary syndrome can occur in the context of portal hypertension, resulting in increased mortality and poorer quality of life for patients. Another consequence is portopulmonary hypertension, which can be associated with poor survival. Failure to recognise these complications in children may result in poorer outcomes and therefore it is vital that clinicians can establish when referral to a paediatric respiratory medicine specialist is required.

Advances in the ocular complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.

Histopathological Features and Role of Allograft Kidney Biopsy Among Recipients With Prolonged Delayed Graft Function: A Review.

Delayed graft function (DGF) is an early posttransplant complication predictive of adverse outcomes. This "acute kidney injury of transplantation" is often defined as allograft dysfunction requiring renal replacement within 7 d posttransplantation. DGF is an important area of study because it is emerging with efforts to expand the donor pool and address the supply-demand gap in kidney transplantation. DGF is often caused by severe kidney injury mechanisms because of multiple donors, recipients, and immunologic factors. The role of kidney biopsy, particularly in prolonged DGF, is an ongoing area of research and inquiry for clinicians and researchers alike to better define, manage, and predict outcomes of this early posttransplant event. This review aims to provide an in-depth, comprehensive summary of the literature to date on the histopathology of DGF and the role of kidney transplant biopsies in prolonged DGF.

INCIDENCE OF KIDNEY STONES IN KIDNEY TRANSPLANT RECIPIENTS

The incidence of kidney stones in kidney transplant recipients is a significant concern within the realm of post-transplant complications. The study's main objective is to find the incidence of kidney stones in kidney transplant recipients. This retrospective study was conducted at the Institute of Kidney Diseases Peshawar from 2017 to 2023. Data was collected from 420 kidney transplant patients. All patients above 18 years with available medical records who underwent renal transplants in IKD and outside IKD and who presented to IKD for follow-up were included in the study—patients with a history of kidney stones before the transplant process were excluded. Demographic information, including age, gender, and pre-transplant comorbidities, was recorded for each patient. Data were collected from 420 patients with kidney transplants. Out of 420 patients, 35 patients developed kidney stones after transplantation. The mean age of the patients who developed stones was 48.7 ± 10.2 years. There were 45.7% male and 54.3% female patients in the kidney stone group. 25.7% of patients had pre-transplant DM. Most kidney stones analyzed in the study comprised calcium oxalate, representing 18 cases, followed by calcium phosphate with eight instances. The correlation analysis revealed that age and gender did not significantly correlate with kidney stone formation in transplant patients, with p-values of 0.32 and 0.17, respectively. It is concluded that kidney transplant recipients exhibit a notable incidence of kidney stone formation, with tacrolimus-based immunosuppressive regimens potentially contributing to this risk. While age and pre-transplant diabetes show trends toward association with kidney stone development.

Simultaneous total internal biliary diversion during liver transplantation for progressive familial intrahepatic cholestasis type 1: Standard of care?

Patients post liver transplant (LT) with progressive familial intrahepatic cholestasis type 1 (PFIC-1) often develop progressive graft steatohepatitis, intractable diarrhea, and growth failure. A total internal biliary diversion (TIBD) during an LT may prevent or reverse these adverse events. Children with PFIC-1 who underwent an LT at our institute were divided into 2 groups, A and B based on the timeline where we started offering a TIBD in association with LT. Pre-LT parameters, intraoperative details, and posttransplant complications like graft steatosis and diarrhea were also analyzed between the 2 groups, and their growth velocity was measured in the follow-up period. Of 550 pediatric LT performed between 2011 and 2022, 13 children underwent LT for PFIC-1. Group A had 7 patients (A1-A7) and group B had 6 (B1-B6). Patients A1, A4, B4, and B5 had a failed partial internal biliary diversion before offering them an LT. Patients A1, A2, and A6 in group A died in the post-LT period (2 early allograft dysfunction and 1 posttransplant lymphoproliferative disorder) whereas A3, A4, and A5 had graft steatosis in the follow-up period. A4 was offered a TIBD 4 years after LT following which the graft steatosis fully resolved. In group B, B1, B2, B5, and B6 underwent TIBD during LT, and B3 and B4 had it 24 and 5 months subsequently for intractable diarrhea and graft steatosis. None of the patients in group B demonstrated graft steatosis or diarrhea and had good growth catch-up during follow-up. We demonstrate that simultaneous TIBD in patients undergoing LT should be a standard practice as it helps dramatically improve outcomes in PFIC-1 as it prevents graft steatosis and/or fibrosis, diarrhea, and improves growth catch-up.

Impact of Early Tracheostomy After Lung Transplantation: A National Analysis

BackgroundProlonged mechanical ventilation is common among lung transplant recipients, affecting nearly one-third of patients. Tracheostomy has been shown as a beneficial alternative to endotracheal intubation, but delays in tracheostomy tube placement persist. To date, no large-scale study has investigated the effect of tracheostomy timing on posttransplant outcomes. MethodsAll adults receiving tracheostomy after primary, isolated lung transplantation were identified in the 2016 to 2020 Nationwide Readmissions Database. Early tracheostomy was defined as placement before postoperative day 8 based on exploratory cohort analysis. Multivariable regression was used to evaluate the association of early tracheostomy with in-hospital mortality, select posttransplant complications, and resource utilization. ResultsOf an estimated 11,048 patients undergoing first-time lung transplantation, 1509 required a tracheostomy in the postoperative period, with 783 (51.9%) comprising the early cohort. After entropy balancing and risk adjustment, early tracheostomy placement was associated with reduced odds of death (adjusted odds ratio, 0.59; 95% CI, 0.36-0.97) and posttransplant infection (adjusted odds ratio, 0.54; 95% CI, 0.35-0.82). Further, tracheostomy within 1 week of transplantation was associated with decreased length of stay (β-coefficient, −16.5 days; 95% CI, −25.3 to −7.6 days) and index hospitalization costs (β-coefficient, −$97,600; 95% CI, −$153,000 to −$42,100). ConclusionsThe present study supports the safety of early tracheostomy among lung transplant recipients and highlights several potential benefits. Among appropriately selected patients, tracheostomy placement before postoperative day 8 may facilitate early discharge, lower costs, and reduced odds of posttransplant infection.

Evaluating the Effects of Kidney Preservation at 10 °C with Hemopure and Sodium Thiosulfate in a Rat Model of Syngeneic Orthotopic Kidney Transplantation.

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia-reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia-reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.

Predictive Factors of Renal Graft Failure in Tunisian Children and young adults: A Retrospective Study.

Pediatric end-stage renal disease is a rare but severe condition that causes numerous complications and impairs the quality of life of children. Kidney transplantation is the therapy of choice in pediatric end-stage renal disease. Our study aimed to identify the predictive factors of renal graft failure after kidney transplantation in Tunisian children and young adults. We conducted a retrospective bicentric study of children and young adults (age≤20 years) who had undergone renal transplantation between 1989 and 2019 in Tunisia. We analyzed long-term survival rates and complications after pediatric kidney transplantation and searched for predictive parameters for graft dysfunction. We used a univariate and a multivariate analysis to identify predictive factors of graft survival. A total of 112 patients underwent 115 kidney transplantations. Graft failure occurred in 30% of the cases. The overall 1-, 3-, 5- and 10-year graft survival rates were 92%, 89.1%, 85.9% and 74.5% respectively. The following parameters strongly influenced graft survival: immunosuppressive regimen including an association other than Mycophenolate mofetil- tacrolimus and corticosteroids (p=0.002), year of transplant (p<0.0001 for 1987-2000), deceased donor (p = 0.039), underlying etiology of end-stage renal disease (p=0.045), occurrence of acute or chronic rejection (p<0.001), a urine protein greater than 0.3 g/l per day (p=0.002), post-transplant urologic complications (p=0.002), five-year creatinine level>1.28 mg/dl (p<0.001). The overall 1-, 3-, 5- and 10-year patients survival rates were 97%, 95%, 90.2% and 84.4% respectively. Our study identified several predictive factors of graft failure in Tunisian children and young adults undergoing renal transplantation.

Monitoring of the right ventricular responses to pressure overload: prognostic value and usefulness of echocardiography for clinical decision-making.

Regardless of whether pulmonary hypertension (PH) results from increased pulmonary venous pressure in left-sided heart diseases or from vascular remodeling and/or obstructions in pre-capillary pulmonary vessels, overload-induced right ventricular (RV) dysfunction and its final transition into right-sided heart failure is a major cause of death in PH patients. Being particularly suited for non-invasive monitoring of the right-sided heart, echocardiography has become a useful tool for optimizing the therapeutic decision-making and evaluation of therapy results in PH. The review provides an updated overview on the pathophysiological insights of heart-lung interactions in PH of different etiology, as well as on the diagnostic and prognostic value of echocardiography for monitoring RV responses to pressure overload. The article focuses particularly on the usefulness of echocardiography for predicting life-threatening aggravation of RV dysfunction in transplant candidates with precapillary PH, as well as for preoperative prediction of post-operative RV failure in patients with primary end-stage left ventricular (LV) failure necessitating heart transplantation or a LV assist device implantation. In transplant candidates with refractory pulmonary arterial hypertension, a timely prediction of impending RV decompensation can contribute to reduce both the mortality risk on the transplant list and the early post-transplant complications caused by severe RV dysfunction, and also to avoid combined heart-lung transplantation. The review also focuses on the usefulness of echocardiography for monitoring the right-sided heart in patients with acute respiratory distress syndrome, particularly in those with refractory respiratory failure requiring extracorporeal membrane oxygenation support. Given the pathophysiologic particularity of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection to be associated with a high incidence of thrombotic microangiopathy-induced increase in the pulmonary resistance, echocardiography can improve the selection of temporary mechanical cardio-respiratory support strategies and can therefore contribute to the reduction of mortality rates. On the whole, the review aims to provide a theoretical and practical basis for those who are or intend in the future to be engaged in this highly demanding field.

Standardized risk-stratified cardiac assessment and early posttransplant cardiovascular complications in kidney transplant recipients.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in kidney transplant recipient (KTR). There is a dearth of standardized guidelines on optimal cardiovascular evaluation of transplant candidates. This single-center cohort study aims to determine the effectiveness of our standardized risk-stratified pretransplant cardiovascular screening protocol, which includes coronary angiography (CAG), in identifying advanced CVD, the proper pretransplant management of which could lead to a reduction in the incidence of major cardiac events (MACE) in the early posttransplant period. Out of the total 776 KTR transplanted between 2017 and 2019, CAG was performed on 541 patients (69.7%), of whom 22.4% were found to have obstructive coronary artery disease (CAD). Asymptomatic obstructive CAD was observed in 70.2% of cases. In 73.6% of cases, CAG findings resulted in myocardial revascularization. MACE occurred in 5.6% (N = 44) of the 23 KTR with pretransplant CVD and 21 without pretransplant CVD. KTR with posttransplant MACE occurrence had significantly worse kidney graft function at the first year posttransplant (p = 0.00048) and worse patient survival rates (p = 0.0063) during the 3-year follow-up period compared with KTR without MACE. After adjustment, the independent significant factors for MACE were arrhythmia (HR 2.511, p = 0.02, 95% CI 1.158-5.444), pretransplant history of acute myocardial infarction (HR 0.201, p = 0.046, 95% CI 0.042-0.970), and pretransplant myocardial revascularization (HR 0.225, p = 0.045, 95% CI 0.052-0.939). Asymptomatic CVD is largely prevalent in KTR. Posttransplant MACE has a negative effect on grafts and patient outcomes. Further research is needed to assess the benefits of pretransplant myocardial revascularization in asymptomatic kidney transplant candidates.

Impact of post-transplant stroke and subsequent functional independence on outcomes following heart transplantation under the 2018 United States heart allocation system

This study evaluates the clinical trends, risk factors, and effects of post-transplant stroke and subsequent functional independence on outcomes following orthotopic heart transplantation under the 2018 heart allocation system. The United Network for Organ Sharing registry was queried to identify adult recipients from October 18, 2018 to December 31, 2021. The cohort was stratified into 2 groups with and without post-transplant stroke. The incidence of post-transplant stroke was compared before and after the allocation policy change. Outcomes included post-transplant survival and complications. Multivariable logistic regression was performed to identify risk factors for post-transplant stroke. Sub-analysis was performed to evaluate the impact of functional independence among recipients with post-transplant stroke. A total of 9,039 recipients were analyzed in this study. The incidence of post-transplant stroke was higher following the policy change (3.8% vs 3.1%, p=0.017). Thirty-day (81.4% vs 97.7%) and 1-year (66.4% vs 92.5%) survival rates were substantially lower in the stroke cohort (p<0.001). The stroke cohort had a higher rate of post-transplant renal failure, longer hospital length of stay, and worse functional status. Multivariable analysis identified extracorporeal membrane oxygenation, durable left ventricular assist device, blood type O, and redo heart transplantation as strong predictors of post-transplant stroke. Preserved functional independence considerably improved 30-day (99.2% vs 61.2%) and 1-year (97.7% vs 47.4%) survival rates among the recipients with post-transplant stroke (p<0.001). There is a higher incidence of post-transplant stroke under the 2018 allocation system, and it is associated with significantly worse post-transplant outcomes. However, post-transplant stroke recipients with preserved functional independence have improved survival, similar to those without post-transplant stroke.

First Russian experience of treating dyslipidemia with siRNA drugs in patients after heart transplantation

Patients after heart transplantation (HT) are at very high risk for cardiovascular disease. Protocols for the management of heart recipients include the initiation of lipid-lowering therapy (LLT), regardless of sex, age and origin of heart failure. Given drug interactions and the risk of post-transplant complications, the LLT possibilities are limited in the transplanted population. The paper presents first Russian experience of using siRNA LLT for the treatment of dyslipidemia in solid organ transplant recipients.

The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge

Despite limited organ availability and post-transplant complications, kidney transplantation remains the optimal treatment for End-Stage Kidney Disease (ESKD). However, innovative dialysis technologies such as portable, wearable, and implantable bioartificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An ideal implantable device could combine bioreactors and blood ultrafiltration to replicate key native cell functions for solute reabsorption, secretion, and endocrinologic activities. Today, the feasibility of an implantable bioreactor for renal cell therapy opens the challenge of developing a fully implantable bioartificial kidney based on silicon nanopore membranes to ensure immunological isolation, cell viability, and the possibility of maintaining a blood substrate for metabolic activities. Current technology is not sufficient to obtain an efficient artificial bioreactor to reach physiological blood purification, which requires a more complex system to produce an ultrafiltrate from the blood that can be processed by cells and eliminated as urine. The number of cells in the bioreactor, endocrine activity, immunological cell isolation, solute and fluid secretion/reabsorption, cell viability, blood and ultrafiltration flow control, and thrombogenicity are fundamental issues that require a new technology that today appears to be a challenge for the design of an implantable artificial kidney. This review aims to analyze the state of the art in this particular field of kidney replacement therapy to highlight the current limitations and possible future technology developments to create implanted and wearable organs capable of treating ESKD with artificial organs that can replicate all native kidneys functions.

Identification of predictive models including polymorphisms in cytokines genes and clinical variables associated with post-transplant complications after identical HLA-allogeneic stem cell transplantation.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001. Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.