Tissue and compartment specific based gene expression signatures as new tools to define and predict response to therapeutic renin angiotensin aldosterone system blockage and renal survival in diabetic nephropathy.

• Applicant: Dr. Claudiu-Vivian Komorowsky
• Subject Area: Nephrology
• Term: from 2011 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201530493

Chronic kidney disease (CKD) is now recognized as a growing public health problem of global proportion. The adverse outcome of CKD is not only the progression to persistent renal failure requiring renal replacement therapy, but also the increased risk of cardiovascular complications. Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication and the main cause of end stage renal disease (ESRD) in industrialized countries. A major protagonist is the renin angiotensin aldosterone system (RAAS). RAAS activation has been well established as a multifaceted driver in pathobiology of DN. RAAS activation, leads to impaired intrarenal hemodynamics, activation of inflammatory and fibrogenic pathways, thereby promoting chronic intrarenal hypoxia, which is further causative for progressive deterioration of renal function.Since available therapeutic options only decelerate gradual loss of kidney function, it is of significant importance to define novel disease markers and molecular mechanisms in order to recognize the patients at risk and to prevent complications. We have the unique opportunity to determine the transcriptional response in protocol renal biopsy tissue obtained from patients participating in a double-blind, placebo-controlled interventional trial of RAAS blockade in early DN. To achieve this global goal, we will combine intrarenal gene expression profiles and highly sensitive morphometric analyses to uncover robust molecular markers, which predict renal outcome and change in response to intervention. Moreover, correlation of intrarenal gene expression profiles with morphometric and assessed clinical data enables us to indentify disease promoters and protective factors, which is a crucial step in developing preemptive and therapeutic strategies to overcome current restrictions.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Matthias Kretzler