1. NT CVD : Development and Validation of new Diagnostic, Preventive and Therapeutic Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease PRINCIPAL INVESTIGATORS 4 1 2 3 6 5 7 1.Prof. Dr. Jankowski, Dr. Jankowski, Charité, Medizinische Klinik IV, Berlin 2.Dr. Lehmann, PD Dr. Buschmann, Charité, Center for Cardiovascular Research, Berlin 3.PD Dr. Herget-Rosenthal, Universitätsklinikum Essen, Klinik für Nephrologie 4.Prof. Dr. Lehrach, Dr. Herwig, Max-Planck-Institut Berlin, Molecular Genetics 5.Dr. Lemke, EXcorLab GmbH, Obernburg 6.Dr. Krahn, Bayer Schering Pharma, Wuppertal 7.Associated Partner: Membrana GmbH, Wuppertal Figure 1: Organization Chart of the Consortium ■ SME ■ Clinic ■ University ■ Research Institute ■ Industry ■ Molecular Phenotyping ■ Application Development – Work Package Partner – Work Package Leader → Informational Flow SUMMARY The consortium will apply the novel tools “proteomics, peptidomics, metabonomics and genotyping”, which allow assessing the complete transcription and translation of the genomic capital to elucidate the genetic and physiological background of CVD in CKD patients. This approach is focused on human samples i.e. tissues, cells and body fluids as humoral targets are altered in CVD of CKD patients. NT CVD applies "forward genetics" from phenotype to gene to remedy the causes of the enormously accelerated cardiovascular morbidity and death in CKD (stage 3-5) and to develop novel diagnostics and therapeutics, based on molecular genotyping and phenotyping. This will be done (A) by elucidating the role of recently identified mediators relating to CVD in CKD by using bioassay approaches and pattern analysis of CKD patient samples, and (B) by the identification of yet unknown mediators. Figure 2: General approaches of NT CVD Correspondence: Prof. Dr. Joachim Jankowski, Charité, Med Klinik IV, Hindenburgdamm 30, 12200 Berlin, Germany; Joachim.Jankowski@charite.de Specific aims of NT CVD  Identify specific mediators, known and unknown, involved in .accelerated CVD in CKD  Identify among these mediators specific predictive biomarkers of .accelerated CVD in CKD  Identify specifically new therapeutic targets to combat accelerated .CVD in CKD  Integration into a web accessible CKD knowledgebase  Generate the scientific & technical basis for the development of .both pharmaceutical therapies & extracorporeal removal strategies  Translate the results into new diagnostic, preventive and .therapeutic tools and devices Overall aims of NT CVD  Prevention of CVD in CKD patients  Translate diagnostic biomarkers and preventive approaches to .non-CKD population  Remedy the causes of accelerated CVD in CKD  Identify and characterize biomarkers for cardiovascular risk in .CKD patients  Decrease therapy costs for CKD patients  Decrease overall costs, socio-economic challenges and number of .patients  Enhance German competitiveness in producing diagnostic and .therapeutic tools CONCLUSION This project aims to use proven and in some instances proprietary molecular, genomic and proteomic approaches to identify and characterize the unknown mediators potentially involved in the accelerated CVD in CKD (stage 3-5). Furthermore the consortium will have to characterize known mediators in detail with respect to their cardiovascular effects. The findings and results will culminate in the conception and development of innovative tools to diagnose, prevent and treat CVD in CKD patients. COORDINATION: J. Jankowski (Charité) | CO-COORDINATION: T. Krahn (Bayer-Schering-Pharma) PARTNER: V. Jankowski, K. Lehmann (Charite) | H. Bruck (Universitätsklinikum Essen) | R. Herweg (MPI MolGen) | H. Lemke (EXcorLab)