Necroinflammation, kidney regeneration, and long term outcomes of acute tubular necrosis

• Applicant: Professor Dr. Hans-Joachim Anders
• Subject Area: Nephrology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286730110

Acute tubular necrosis is a clincially important entity of acute kidney injury. There are many reasons why there are still no curative therapeutic options for patients with acute tubular necrosis. This project intends to overcome these limitations by five innovative ideas: 1. Minimizing necroinflammation. Cell necrosis and Inflammation dominate the early and late injury phase of acute tubular necrosis. We will at first determine the therapeutic window of inhibitors of regulated cell necrosis, cytokines and chemokies that have proven effective in preemptive study designs. 2. Promoting intrinsic kidney regeneration. Nephron loss is based on an insufficient tubule regeneration. We will at first determine the therapeutic window of pro-regenerative compounds. 3 Clonal tubular cell proliferation? How many of the necrotic tubular cells are really replaced via proliferation of surviving tubular cells is unknown. We will use lineage tracing of clonal proliferation to at first answer this question. 4. Nephron loss determines long term outcomes. Whether acute tubular necrosis is followed by kidney regeneration or atrophy depends on the number of irreversibly lost Nephrons. We will quantify nephron loss and use it as a primary end point for all therapeutic interventions. 5. Sequential combination therapy. We expect the most efficient treatment effect by combining early Inhibition of necrosis and Inflammation followed by stimulating tubule regeneration. This project intends to turn acute tubular necrosis into a treatable disease.

• DFG Programme: Research Grants