The Role of the Inflammasome in Hyperoxaluric Kidney Disease

• Applicant: Professor Dr. Felix Knauf
• Subject Area: Nephrology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258451658

• Final Report Year: 2019

Final Report Abstract

Our work in this DFG project has brought new insights into the role of oxalate in chronic kidney disease. Specifically, we have developed a murine model of oxalate-induced chronic kidney disease. Using this model we have defined the inflammatory and signaling pathways responsible for mediating oxalate-induced inflammation and subsequent organ fibrosis. Our murine model has been shown useful to other groups of investigators, allowing to examine the mechanisms of crystal adhesion and progression of CKD in general. Moreover, as part of our work we have established a protocol to measure plasma oxalate concentrations, validated our assay accuracy in samples of patients with end stage kidney disease. This has led to new translational projects beyond the original aims of this project. The major findings obtained as part of this research proposal have now been integrated in a larger research collaboration as part of the newly funded SFB 1365: Nephroprotektion.

Publications

• “An update on the role of the inflammasomes in the pathogenesis kidney diseases.” Pediatr Nephrol. (2015)
  Darisipudi M, Knauf F
  
• Core curriculum in Nephrology – Update on Nephrolithiasis. American Journal of Kidney Diseases (2016)
  Pfau A, Knauf F
  
• Oxalate, inflammasome, and progression of kidney disease. Current Opinion in Nephrology and Hypertension (2016)
  Ermer T, Eckardt KU, Aronson PS, Knauf F
  
• “Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications.” Am J Physiol Renal Physiol. (2016)
  Mulay S, Eberhard J, Pfann V, Marschner J, Darisipudi M, Daniel C, Romoli S, Desai J, Grigorescu M, Kumar S, Rathkolb, Eckhard Wolf, Martin Hrabě de Angelis, Tobias Bäuerle, Barbara Dietel, Kerstin Amann, Carsten A. Wagner, Kai-Uwe Eckardt, Peter S. Aronson, Hans Joachim Anders, Knauf F
  
• Impact of Regular or Extended Hemodialysis and Hemodialfiltration on Plasma Oxalate Concentrations in Patients With End-Stage Renal Disease. Kidney Int Rep. (2017)
  Ermer T, Kopp C, Asplin JR, Granja I, Perazella MA, Reichel M, Nolin TD, Eckardt KU, Aronson PS, Finkelstein FO, Knauf F
  
• Characterization of renal NaCl and oxalate transport in Slc26a6-/- mice. Am J Physiol Renal Physiol. (2019)
  Knauf F, Velazquez H, Pfann V, Jiang Z, Aronson PS