SFB 1365:  Renoprotection

• Subject Area: Medicine ; Biology
• Term: from 2019 to 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 394046635

Damage to the kidney, even in spite of apparent recovery, markedly reduces life expectancy. Our interdisciplinary research consortium aims to identify and target common pathways to kidney failure. Chronic kidney disease (CKD) poses a rapidly increasing public health threat, with the incidence of CKD doubling each decade. Currently, more than 10% of the general population and over 30% of all elderly are affected. Acute kidney injury (AKI) is likewise very common. One in five hospitalized adults, and one out of three in-patient children, develop AKI. Our interdisciplinary research consortium involves internists, surgeons, physiologists, pharmacologists, molecular biologists, geneticists, physicists, anatomists, and radiologists, all focusing on renoprotection. Together, we will perform basic research on isolated cells, tissue preparations, and animal models including yeast, zebrafish, rodents, and genetically engineered swine, and translate the outcomes to patient care. These research efforts will be accompanied by strategies for standardized identification and assessment of patients with AKI and CKD in the clinical setting, thus providing the basis for sustained implementation. We have at our disposal the Germany-wide largest patient cohort with CKD and various other renal diseases. By creating this interdisciplinary critical mass, CRC 1365 will unravel and target specific pathways of renal damage. For instance, we will illuminate receptor and channel structures using high-resolution crystallography, and state-of-the-art techniques will allow us to characterize these structures. We will advance model organisms much closer to the human setting, i.e., from zebrafish to rodents and swine. Human renal microvessels are world-wide exclusively investigated by the proposed CRC. Ultimate translation of our broad model spectrum will rely on the latest MRI technology to track distinct hypoxic regions and inflammatory processes.Our vision is to reduce the burden of kidney disease by establishing CRC 1365 Renoprotection as a comprehensive, interdisciplinary network to foster tailored therapeutic strategies aiming at the shared routes to CKD. Within the next 12 years, we will Identify and characterize pathways underlying CKD development and progression, establish new therapeutic targets, and initiate clinical trials.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Gut microbiome in renoprotection (Project Heads Forslund-Startceva, Sofia ;  Müller, Dominik N. ;  Wilck, Nicola )
• A02 - Dilating renal medullary microvessels by the NO-sGC-cGMP pathway for renoprotection (Project Heads Patzak, Ph.D., Andreas ;  Persson, Pontus Börje )
• A03 - Renoprotection by understanding functional and structural G-protein-coupled receptor activation (Project Heads Dragun, Duska ;  Scheerer, Patrick )
• A04 - Renoprotection in primary aldosteronism – development and testing of mutant KCNJ5 inhibitors in genetically engineered pigs (Project Head Scholl, Ute )
• A05 - Targeting renoprotection downstream of the angiotensin II type 1 receptor (Project Heads Gollasch, Maik ;  Schleifenbaum, Johanna )
• A06 - Molecular mechanisms of PDE3A-mediated renoprotection (Project Heads Alenina, Ph.D., Natalia ;  Bader, Michael ;  Klußmann, Enno )
• A07 - Cldn10a in kidney injury susceptibility (Project Heads Günzel, Dorothee ;  Schmidt-Ott, Kai )
• A08 - Acid-activated Cl- channels in kidney function and protection (Project Head Jentsch, Thomas J. )
• A09 - Renoprotection by discriminating favorable from unfavorable genetic backgrounds in polycystic kidney disease (Project Heads Halbritter, Jan ;  Schönauer, Ph.D., Ria Anne-Rose )
• B01 - A renal function of 2,3-bisphosphoglycerate mutase (BPGM) (Project Heads Fähling, Michael ;  Rosenberger, Christian )
• B02 - Role of volume-regulated anion channels (VRACs) in kidney integrity (Project Head Jentsch, Thomas J. )
• B03 - Targeting PDE3A for protecting from hypertension-induced chronic kidney disease (Project Heads Bähring, Sylvia ;  Klußmann, Enno )
• B04 - Promoting renoprotection by unravelling the roles of renal oxygenation, energy metabolism and inflammation by physiometabolic magnetic resonance (Project Heads Niendorf, Ph.D., Thoralf ;  Seeliger, Erdmann )
• B05 - The polyamine system in gender-related renoprotection (Project Heads Kirschner, Karin ;  Scholz, Holger )
• B06 - Renoprotective role of Angiotensin-(1–7) (Project Heads Alenina, Ph.D., Natalia ;  Bader, Michael )
• B07 - Targeting oxalate metabolism for renoprotection (Project Heads Eckardt, Kai-Uwe ;  Knauf, Felix )
• C01 - Renoprotection in crescentic glomerulonephritis by ANCA (Project Heads Kettritz, Ralph ;  Schreiber, Adrian )
• C02 - Renoprotective role of Lipocalin-2 in allograft rejection following kidney transplantation (Project Heads Aigner, Felix ;  Ashraf, Muhammad Imtiaz ;  Sauer, Igor Maximilian )
• C03 - Renoprotective prostaglandin reductase 2 (PTGR2) (Project Heads Kreutz, Reinhold ;  Panakova, Daniela )
• C04 - Managing calcineurin inhibitor-induced nephrotoxicity for renoprotection (Project Heads Bachmann, Sebastian ;  Mutig, Kerim )
• C05 - Targeting interleukin-1α for renoprotection in crystal-induced kidney disease (Project Heads Eckardt, Kai-Uwe ;  Knauf, Felix )
• C06 - Targeting collecting duct barrier function for renoprotection (Project Head Schmidt-Ott, Kai )
• C07 - Structure-based identification of optimized mutant Kir3.4 inhibitors for renoprotection (Project Heads Scheerer, Patrick ;  Scholl, Ute )
• S01 - Imaging techniques – Advanced histopathology – superresolution microscopy – live imaging – electron microscopy (Project Head Bachmann, Sebastian )
• S02 - Advanced magnetic resonance imaging for in vivo phenotyping of renal pathophysiology and renoprotection (Project Head Niendorf, Ph.D., Thoralf )
• Z01 - Central Tasks of the Collaborative Research Centre (Project Head Persson, Pontus Börje )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating Institution: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP); im Forschungsverbund Berlin e.V.; Max-Delbrück-Centrum für Molekulare Medizin (MDC)
• Spokesperson: Professor Dr. Pontus Börje Persson