Renoprotection by discriminating favorable from unfavorable genetic backgrounds in polycystic kidney disease

• Applicants: Professor Dr. Jan Halbritter; Ria Anne-Rose Schönauer, Ph.D.
• Subject Area: Nephrology ; Human Genetics
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539950728

Autosomal-dominant polycystic kidney disease (ADPKD) is the commonest genetic disorder causing kidney failure between ages 30-80 years. While current genotype-phenotype correlations poorly explain massive disease variability, we aim to identify genetic traits as early markers of prognostication to warrant optimal renoprotection even before cystic kidney enlargement takes place. To identify protective factors, we will analyze atypically mild cases without diagnostic variants for the presence of genetic aberration in new PKD-disease genes (WP 1). Furthermore, we will explore the genetic background for generic and disease-specific germline modifiers, which correlate with attenuated courses in carriers of similar PKD1-diagnostic variants (WP 2). Lastly, functional candidate gene-validation and modifier-validation will be executed with the help of established Pkd1-knockout and tagged PC1-missense and control cell lines (WP 3). Through successful implementation of these programs, we will be able to define genetic determinants, which contribute to stratified care and targeted treatment of patients with polycystic kidney disease.

• DFG Programme: Research Grants