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.

Systematic Review on the Role of IL-6 and IL-1ß in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a leading cause of global morbidity and mortality, significantly driven by chronic inflammation. Interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) are critical inflammatory cytokines implicated in CVD progression. This systematic review evaluates the roles of IL-6 and IL-1ß in CVDs by synthesizing data from relevant studies to understand their impact on cardiovascular outcomes and identify potential therapeutic interventions. A comprehensive literature search was conducted using PubMed and Embase, covering studies from January 2014 to December 2024. Inclusion criteria encompassed studies investigating IL-6 and/or IL-1ß in CVDs, including human and relevant animal models, and reporting clinical outcomes, molecular mechanisms, or therapeutic interventions. Data extraction and quality assessment were performed independently by two reviewers. Our review included 12 studies focusing on the roles of IL-6 and IL-1ß in various CVDs. Elevated IL-6 levels were significantly associated with peripheral artery disease, myocardial infarction, and heart failure, while IL-1ß levels were linked to worse outcomes in coronary artery disease and heart failure. Meta-analyses indicated a significant association between higher IL-6 and IL-1ß levels and increased risk of adverse cardiovascular events. These findings suggest that targeting IL-6 and IL-1ß could offer promising therapeutic strategies for reducing inflammation and improving cardiovascular 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.

Unraveling Acute and Post-COVID Cytokine Patterns to Anticipate Future Challenges.

The aims of this study were to analyze cytokine profiles in patients with COVID-19, gain insights into the immune response during acute infection, identify cytokines associated with disease severity and post-COVID complications, and explore potential biomarkers for prognosis and therapeutic targets. Using a multiplex analysis, we studied the cytokine pattern in 294 acute COVID-19 and post-COVID patients with varying severities of infection. Our findings revealed that disease severity was associated with elevated levels of IL-15, IL-8, and fractalkine. Severe/extremely severe forms in comparison with mild/moderate disease were associated with MCP-1, IFNa2, IL-7, IL-15, EGF, IP-10, IL-8, Eotaxin, FGF-2, GROa, sCD40L, and IL-10. The key cytokines of post-COVID are FGF-2, VEGF-A, EGF, IL-12(p70), IL-13, and IL-6. By the sixth month after recovering from a coronavirus infection, regardless of disease severity, some patients may develop complications such as arterial hypertension, type 2 diabetes mellitus, glucose intolerance, thyrotoxicosis, atherosclerosis, and rapid progression of previously diagnosed conditions. Each complication is characterized by distinct cytokine profiles. Importantly, these complications can also be predicted during the acute phase of the coronavirus infection. Understanding cytokine patterns can aid in predicting disease progression, identifying high-risk patients, and developing targeted interventions to improve the outcomes of COVID-19.

Association of Lung Fibrotic Changes and Cardiological Dysfunction with Comorbidities in Long COVID-19 Cohort.

Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID-19 and its comorbidities have not been established. Methods. In total, 312 patients with long COVID-19 from 21 primary care centers were included in the study. At the six-month follow-up, their lung function was assessed by computerized tomography (CT) and spirometry, whereas cardiac function was assessed by elec-trocardiogram (ECG), Holter ECG, echocardiography, 24 h blood pressure monitoring, and a six-minute walk test (6MWT). Results. Of the 312 persons investigated, significantly higher sys-tolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP were revealed in participants with hypertension or type 2 diabetes. Left ventricular diastolic dysfunc-tion was more frequently present in patients with hypertension. The most common registered CT abnormalities were fibrotic changes (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Among the tested biochemical parameters, three associations were found in long COVID-19 patients with hypertension but not diabetes: increased hemoglobin, fibrinogen, and ferritin. Nine patients had persisting IgM antibodies to SARS-CoV-2. Conclusions. We demon-strated a strong association between signs of cardiac dysfunction and lung fibrotic changes with comorbidities in a cohort of long COVID-19 subjects.

Central and effector memory T cells in peripheral blood of patients with interstitial pneumonia: preliminary clues from a COVID-19 study.

BACKGROUND: SARS-CoV-2 pre-existing T-cell immune reactivity can be present in some people. A general perturbation of the main peripheral lymphocyte subsets has been described in severe COVID-19 patients, but very few studies assessed the general memory T-cell homeostasis in the acute phase of COVID-19. Here, we performed a general analysis of the main memory T cell populations in the peripheral blood of patients admitted to the hospital for a confirmed or probable COVID-19 diagnosis. METHODS: In this cross-sectional study, adult patients (aged ≥ 18 years) needing hospital admission for respiratory disease due to confirmed or probable COVID-19, were recruited before starting the therapeutic protocol for this disease. In addition to the assessment of the general lymphocyte subpopulations in the early phase of COVID-19, central memory T cells (Tmcentr cells: CD45RO+CCR7+) and effector memory T cells (Tmeff cells: CD45RO+CCR7-) were assessed by multi-color flow cytometry, in comparison to a control group. RESULTS: During the study period, 148 study participants were recruited. Among them, 58 patients turned out positive for SARS-CoV-2 PCR (including both patients with interstitial pneumonia [PCR+Pn+] and without this complication [PCR+Pn-]), whereas the remaining 90 patients resulted to be SARS-CoV-2 PCR negative, even though all were affected with interstitial pneumonia [PCR-Pn+]. Additionally, 28 control patients without any ongoing respiratory disease were recruited. A clear unbalance in the T memory compartment emerged from this analysis on the whole pool of T cells (CD3+ cells), showing a significant increase in Tmcentr cells and, conversely, a significant decrease in Tmeff cells in both pneumonia groups (PCR+Pn+ and PCR-Pn+) compared to the controls; PCR+Pn- group showed trends comprised between patients with pneumonia (from one side) and the control group (from the other side). This perturbation inside the memory T cell compartment was also observed in the individual analysis of the four main T cell subpopulations, based upon the differential expression of CD4 and/or CD8 markers. CONCLUSION: Overall, we observed both absolute and relative increases of Tmcentr cells and decrease of Tmeff cells in patients affected with interstitial pneumonia (regardless of the positive or negative results of SARS-CoV-2 PCR), compared to controls. These results need confirmation from additional research, in order to consider this finding as a potential biological marker of interstitial lung involvement in patients affected with viral respiratory infections.

Mortality predictors of hospitalized patients with COVID-19: Retrospective cohort study from Nur-Sultan, Kazakhstan.

BACKGROUND: First reported case of Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in Kazakhstan was identified in March 2020. Many specialized tertiary hospitals in Kazakhstan including National Research Cardiac Surgery Center (NRCSC) were re-organized to accept coronavirus disease 2019 (COVID-19) infected patients during summer months of 2020. Although many studies from worldwide reported their experience in treating patients with COVID-19, there are limited data available from the Central Asia countries. The aim of this study is to identify predictors of mortality associated with COVID-19 in NRCSC tertiary hospital in Nur-Sultan, Kazakhstan. METHODS: This is a retrospective cohort study of patients admitted to the NRCSC between June 1st-August 31st 2020 with COVID-19. Demographic, clinical and laboratory data were collected from electronic records. In-hospital mortality was assessed as an outcome. Patients were followed-up until in-hospital death or discharge from the hospital. Descriptive statistics and factors associated with mortality were assessed using univariate and multivariate logistic regression models. RESULTS: Two hundred thirty-nine admissions were recorded during the follow-up period. Mean age was 57 years and 61% were males. Median duration of stay at the hospital was 8 days and 34 (14%) patients died during the hospitalization. Non-survivors were more likely to be admitted later from the disease onset, with higher fever, lower oxygen saturation and increased respiratory rate compared to survivors. Leukocytosis, lymphopenia, anemia, elevated liver and kidney function tests, hypoproteinemia, elevated inflammatory markers (C-reactive protein (CRP), ferritin, and lactate dehydrogenase (LDH)) and coagulation tests (fibrinogen, D-dimer, international normalized ratio (INR), and activated partial thromboplastin time (aPTT)) at admission were associated with mortality. Age (OR 1.2, CI:1.01-1.43), respiratory rate (OR 1.38, CI: 1.07-1.77), and CRP (OR 1.39, CI: 1.04-1.87) were determined to be independent predictors of mortality. CONCLUSION: This study describes 14% mortality rate from COVID-19 in the tertiary hospital. Many abnormal clinical and laboratory variables at admission were associated with poor outcome. Age, respiratory rate and CRP were found to be independent predictors of mortality. Our finding would help healthcare providers to predict the risk factors associated with high risk of mortality. Further investigations involving large cohorts should be provided to support our findings.