Pediatric Nephrology Research Team
The Pediatric Nephrology Research Team focuses on the optimization of therapy for kidney transplantations and dialysis with emphasis on the field of translational research in renal failure and replacement. We recently detected a new pathomechanism, the “inadequate cellular stress response”, in experimental in-vitro and in-vivo models of renal ischemia and peritoneal dialysis.
Our interest in cellular stress response in nephrology began with a cooperation with the pediatric nephrology laboratory at Yale (Norm Siegel, Scot Van Why and Michael Kashgarian). For the first time we showed in a model of ischemic kidney failure a functional role for cytoprotective heat shock proteins (HSP) in maintaining the integrity of epithelial architecture. Despite promising results, we were unable at first to confirm the experimental results of post-ischemic up-regulation of HSP in clinical kidney transplantation.
This situation led to increasing focus of our laboratory on cytotoxic damage in the model of peritoneal dialysis (PD). Our working group was the first to describe the cellular stress response in experimental PD, over-expression of HSP induced cytoprotection allowing improved cellular survival. In an inter-university cooperation (Andreas Rizzi, Bernd Mayer), we introduced system-biology approaches and showed that stress responses in PD were not adequate for sufficient cytoprotection. Currently, novel therapeutic interventions are developed that counteract sterile inflammation and cytotoxity in order to re-establish adequate cellular repair mechanisms.
Parallel to basic research we carried out clinical studies on the optimization of therapy for kidney transplantations and dialysis. In particular, a new fashion of initial immunosuppression in pediatric kidney transplantation (sequential immunosuppression with ATG, later IL-2 antibody) was introduced and evaluated. Furthermore, lipid profile following transplantation and urinary tract infections were investigated. After the introduction of mTOR inhibitors into the field of transplantation, we investigated the role of a calzineurin free protocol by conversion to sirolimus. Currently a retrospective analysis on the impact of donor age on outcome in pediatric kidney transplantation is carried out.
The resulting publications led to the establishment of a clinical-scientific working group that brought improvements in the quality of care through our own research results.