Identification of novel diagnostic, predictive and therapeutic strategies in chronic kidney disease

Projektbeschreibung

Einblicke in die Pathophysiologie der Nierenerkrankung: Weg zur Prognose

Chronische Nierenerkrankungen sind mit Nierenschäden verbunden, die zu einem fortschreitenden Verlust der Nierenfunktion führen. Das klinische Erscheinungsbild ist heterogen, und es gibt nur wenige Therapien und Instrumente zur Patientenklassifikation. Insgesamt erfordern diese Einschränkungen ein besseres Verständnis von Nierenerkrankungen. Das vom Europäischen Forschungsrat finanzierte Projekt TargetCKD hat die Aufgabe, die zellulären und molekularen Mechanismen zu untersuchen, die chronische Nierenerkrankungen auslösen. Anhand von Patientenproben wollen die Forschenden krankheitsassoziierte Biomarker und Schlüsselereignisse ermitteln, die den Krankheitsausbruch und das Fortschreiten zum Nierenversagen fördern. Die Projektaktivitäten sollen die Entwicklung neuer diagnostischer und prädiktiver Instrumente sowie therapeutischer Strategien erleichtern.

Ziel

Chronic Kidney Disease (CKD) represents an important medical, social and economic burden with high morbidity and mortality. The prevalence of CKD has reached >10% in the developed world, and CKD globally accounts for more years lived with disability than all neoplasms combined. Therapeutic strategies to treat CKD or tools for risk stratification of patients are limited and the field has produced the fewest translational randomized clinical trials in medicine while diagnosis is still based on invasive tissue biopsies. TargetCKD aims to establish a holistic understanding of cellular and molecular mechanisms that drive disease to develop novel diagnostic, predictive and therapeutic options. Concrete objectives are: (1) the development of a platform for identification of novel predictive markers and therapeutic targets in kidney biopsies; (2) the identification of conserved spatio-temporal mechanisms and cellular cross-talk events driving CKD; (3) the validation of mechanisms and therapeutic targets in human 3D organoid systems and development of therapeutics and (4) the development of a noninvasive diagnostic platform from urine. TargetCKD will utilize a broad interdisciplinary expertise with various novel single cell and spatial genomic and computational technologies combined with transgenic mouse models and cutting-edge in vitro platforms. The integration of all these technologies in clinical relevant specimen with follow up data and large independent validation cohorts will allow TargetCKD to radically transform nephrology towards a better understanding of kidney diseases, development of novel diagnostics and risk stratification tools for patient allocation and clinical testing as well as urgently needed therapeutics for patients suffering from CKD. The passion that drives this project results from a simple emerging hypothesis: It is possible to predict CKD and develop therapeutics by an in-depth systems approach utilizing emerging genomic technologies.