témavezető: Cseprekál Orsolya
helyszín (magyar oldal): Semmelweis Egyetem helyszín rövidítés: SE
A kutatási téma leírása:
Renal transplantation (RT) is the treatment of choice in end-stage renal disease (ESRD) patients. Complex predictive score systems composing of recipient-, donor- and transplantation-specific risk factors have been investigated and appear to be an integrative part of precision medicine in transplant settings. Big-data analysis became standard for identifying modifiable risk factors and for improving graft and patient survival. Several risk prediction scores have been established in the last ten years worldwide (iBox, Kasiske score, TransplantScore, Dynamic score), however, none of them is directly generalizable due to population differences. By implementing prospective prevalent and incident registry of the Budapest Kidney Transplant center, an evolutional mapping of in-center experiences could serve the basis for developing new protocols in the future to achieve the longest possible graft survival and the best quality of life for our patients. Structured database could provide the background to survey Patient Reported Outcome Measure (PROM) as well.
While there was significant progress of diagnostic tools, and new, effective immunosuppressive medications appeared, improvement in the long-term graft survival and overall mortality still remains stable in the last fifteen years; almost 40% of graft loss is due to antibody-associated rejection (ABMR). Diagnostic approaches of ABMR have exploded to grow in the recent years.Banff criteria, which summarizes the cornerstones of diagnostics, already contains genetically based biomarkers, which promote the classification and early detection of active and/or chronic ABMR. Clinical and histology based diagnostic criteria have yet to be completed by molecular diagnostics, to describe T and B cell, and complement system activity, which could already become new therapeutic targets of ABMR. Consecutive case biopsies are planned to be analyzed by Nanostring. The complete analysis of mRNA expression and its associations with histological and clinical outcomes are planned to be studied.
Potential novel therapeutic approaches have been used on the basis of our in-center protocol to treat chronic active ABMR between 2017-2021. The 1-year and long term graft survival as primary and the level of proteinuria, creatinine change, donor specific antibody titer change as secondary end points as compared to patients on standard treatment protocol are planned to be assessed. Therefore, validating novel approaches of outcome prediction and examining new options of ABMR diagnostic and treatment could serve additional elements of tailored diagnostic and therapy in kidney transplantation.
Cardiovascular (CV) diseases are the leading cause of death in chronic kidney disease patients. Although transplantation improves the outcome significantly compared to the waiting list, the overall mortality still does not reach the risk of the general population. Nonetheless the acquired CV risk factors are considered to be well-studied, information on the prevalence of inherited diseases is still to be completed. Fabry disease is an X-linked genetic disorder, causing renal and cardiac morbidities. Its prevalence is approximately 0.31-0.95% in CKD and KTx patients. Although KTx does not treat the underlying cause (enzyme deficiency), graft survival is comparable, and disease recurrence is not common. Patients transplanted due to Fabry disease are known to have higher risk of CV morbidity, which may be improved by enzyme replacement therapy; therefore its proper screening would be essential. The prevalence and the association of Fabry disease with short and long-term outcome in the Budapest Kidney Transplant cohort has yet to be revealed.
Main perspectives:
1. Implementation of a prevalent and incident patient cohort to a registry based decision supporting software and follow the patients with time series data capturing. External validation of existing transplant prediction scores on the Budapest Kidney transplant cohort.
2. To analyze case biopsies by Nanostring and assessing the specific associations of mRNA expression patterns with histopathological and clinical outcomes.
3. To observe retrospectively and analyze the effectiveness and safety of tocilizumab in ABMR treatment between 2017-2021.
4. The prevalence and the association of Fabry disease with short and long-term outcome in the Budapest Kidney Transplant cohort
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