Genetics and pathophysiology of proteinuric kidney disease

Genetic background and pathophysiology of proteinuric kidney disease

Our group is primarily interested in the genetic background of proteinuric kidney disease and the associated intracellular communication between podocytes and tubular cells upon proteinuria.

Proteinuria describes the state of plasma protein loss via the urine. Proteinuric kidney diseases is divided into glomerular or non-glomerular forms, depending on whether protein loss occurs across the glomerular filtration barrier or results from impaired reabsorption of filtered protein by the proximal tubule.

Glomerular forms are caused by impairment of the glomerular epithelial cell, the podocytes, either as a primary podocytopathy or secondary to external factors. Primary podocytopathies often have a genetic background with mutations affecting the function of structural proteins of the filtration barrier or proteins involved in regulation of the actin cytoskeleton. Secondary causes (that may have a genetic background as well) include metabolic conditions like diabetes mellitus or adipositas, and dysfunction of the immune system.

In this context, we are focusing primarily on the Wnt/β-catenin pathway, a signaling pathway that is important in development, but which is reactivated in podocytes and tubular cells upon cellular stress (such as proteinuria) as a protective mechanism. However, maintained Wnt/β-catenin activation is detrimental to kidney function, driving cellular dedifferentiation with progression to chronic kidney disease, but also modulating local immune cells that are involved in renal repair or inflammation. Thus, in collaboration with Prof. André Hörning, an expert in immune cell research, we combine our expertise and to further elucidate the role of Wnt/β-catenin pathway related mechanisms in kidney diseases in general.

Altogether, we aim to understand the complexity of cellular interaction in kidney diseases and how we can modify these to alleviate disease progression.