Understanding Pediatric Kidney Transplant Rejection: Its Pathophysiology, Biomarkers, and Management Strategies.

End-stage kidney disease requires comprehensive management strategies to ensure patient survival and improve quality of life. Kidney transplantation remains the preferred treatment option, offering superior long-term outcomes. However, graft rejection remains a significant concern, and pediatric patients often require tailored immunosuppressive regimens due to differences in immune response compared to adults. Although the past decade has seen significant improvements in graft and patient survival among pediatric kidney transplant recipients, many questions remain unanswered. There is an ongoing search for non-invasive biomarkers capable of timely detecting graft rejection and novel treatment regimens, specifically tailored to pediatric practice. This review aims to discuss the current knowledge on kidney transplant rejection in pediatric patients, including epidemiology, pathophysiology, and risk factors. In addition, it seeks to explore the latest advancements in biomarkers for early detection of rejection and evaluate current and emerging immunosuppressive therapies. The possible outcomes of this review include identifying gaps in current research, providing recommendations for future studies, and suggesting strategies to enhance clinical practice. By synthesizing the latest evidence, this review aims to contribute to improved long-term outcomes and quality of life for pediatric kidney transplant recipients.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): fourth Paediatric EUROMACS (Paedi-EUROMACS) report.

OBJECTIVES: The use of ventricular assist devices (VADs) in children is increasing. However, absolute numbers in individual centres and countries remain small. Collaborative efforts such as the Paedi-European Registry for Patients with Mechanical Circulatory Support (EUROMACS) are therefore essential for combining international experience with paediatric VADs. Our goal was to present the results from the fourth Paedi-EUROMACS report. METHODS: All paediatric (<19 years) patients from the EUROMACS database supported by a VAD were included. Patients were stratified into a congenital heart disease (CHD) group and a group with a non-congenital aetiology. End points included mortality, a transplant and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident and pump thrombosis. RESULTS: A total of 590 primary implants were included. The congenital group was significantly younger (2.5 vs 8.0 years, respectively, P < 0.001) and was more commonly supported by a pulsatile flow device (73.5% vs 59.9%, P < 0.001). Mortality was significantly higher in the congenital group (30.8% vs 20.4%, P = 0.009) than in the non-congenital group. However, in multivariable analyses, CHD was not significantly associated with mortality [hazard ratio (HR) 1.285; confidence interval (CI) 0.8111-2.036, P = 0.740]. Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with body surface area (HR 0.524, CI 0.333-0.823, P = 0.005), CHD (HR 1.641, CI 1.054-2.555, P = 0.028) and pulsatile flow support (HR 2.345, CI 1.406-3.910, P = 0.001) in multivariable analyses. CONCLUSIONS: This fourth Paedi-EUROMACS report highlights the increasing use of paediatric VADs. The patient populations with congenital and non-congenital aetiologies exhibit distinct characteristics and clinical outcomes.

Examining a 12-year experience within Kazakhstan's national heart transplantation program.

Kazakhstan has one of the lowest heart transplantation (HTx) rates globally, but there are no studies evaluating the outcomes of HTx. This study aimed to provide a comprehensive analysis of the national HTx program over a 12-year period (2012-2023). Survival analysis of the national HTx cohort was conducted using life tables, Kaplan‒Meier curves, and Cox regression methods. Time series analysis was applied to analyze historical trends in HTx per million population (pmp) and to make future projections until 2030. The number of patients awaiting HTx in Kazakhstan was evaluated with a regional breakdown. The pmp rates of HTx ranged from 0.06 to 1.08, with no discernible increasing trend. Survival analysis revealed a rapid decrease in the first year after HTx, reaching 77.0% at 379 days, with an overall survival rate of 58.1% at the end of the follow-up period. Among the various factors analyzed, recipient blood levels of creatinine and total bilirubin before surgery, as well as the presence of infection or sepsis and the use of ECMO after surgery, were found to be significant contributors to the survival of HTx patients. There is a need for public health action to improve the HTx programme.

Evaluation of liver transplantation services in Kazakhstan from 2012 to 2023.

There is a scarcity of publications evaluating the performance of the national liver transplantation (LTx) program in Kazakhstan. Spanning from 2012 to 2023, it delves into historical trends in LTx surgeries, liver transplant centers, and the national cohort of patients awaiting LTx. Survival analysis for those awaiting LTx, using life tables and Kaplan-Meier, is complemented by time series analysis projecting developments until 2030. The overall per million population (pmp) LTx rate varied from 0.35 to 3.77, predominantly favoring living donor LTx. Liver transplant center rates ranged from 0.06 to 0.40. Of 474 LTx patients, 364 on the waiting list did not receive transplantation. The 30-day and 1-year survival rates on the waiting list were 87.0% and 68.0%, respectively. Viral hepatitis and cirrhosis prevalence steadily rose from 2015 to 2023, with projections indicating a persistent trend until 2030. Absent targeted interventions, stable pmp rates of LTx and liver transplant centers may exacerbate the backlog of unoperated patients. This study sheds light on critical aspects of the LTx landscape in Kazakhstan, emphasizing the urgency of strategic interventions to alleviate the burden on patients awaiting transplantation.

Preliminary report of extracorporeal blood purification therapy in patients receiving LVAD: Cytosorb or Jafron HA330.

BACKGROUND: Left ventricular assist device (LVAD) candidates are at increased risk of immune dysregulation and infectious complications. To attenuate the elevated proinflammatory cytokine levels and associated adverse clinical outcomes, it has been postulated that extracorporeal blood purification could improve the overall survival rate and morbidity of patients undergoing LVAD implantation. METHODS: We retrospectively reviewed prospectively collected data of 15 patients who underwent LVAD implantation at our center between January 2021 and March 2022. Of these, 15 (100%) who received HeartMate 3™ (St. Jude Medical, Abbott, MN, USA) device were eligible. Intraoperatively, patients were single randomized 1:1:1 to three groups: group 1, patients who received Cytosorb therapy (n = 5; installed in the CPB circuit); group 2, patients who received Jafron HA330 (n = 5; installed in the CPB circuit); and control group 3, patients who did not receive filter (n = 5; usual care, neither Cytosorb nor Jafron during CPB). Baseline patient characteristics and intraoperative data were compared between the groups. Blood sample analyses were performed to assess the levels of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) in both preoperative and postoperative data. RESULTS: Baseline patient characteristics were similar in all three groups. We found that IL1α; IL 6; IL8; Lactatedehydrogenase, PCT, pro-BNP, CRP; Leukocyte, and TNFα levels significantly increased with LVAD implantation and that neither Cytosorb nor Jafron influenced this response. In-hospital mortality and overall survival during follow-up were similar among the groups. CONCLUSION: Our preliminary results showed that hemoadsorption therapy using Cytosorb or Jafron hemoadsorption (HA) 330 may not be clinically beneficial for patients with advanced heart failure undergoing LVAD implantation. Large prospective studies are needed to evaluate the potential role of HA therapy in improving outcomes in patients undergoing LVAD implantation.