Determining the mechanisms behind onset and progression of chronic kidney disease

The research projects in this proposal are focused on the mechanisms behind chronic kidney disease (CKD), specifically glomerular disease with mesangial cell involvement. CKD affects over 10% of the population worldwide and is increasing with an ageing population. There are currently no specific, curative therapies available.

Our unique, large-scale kidney biopsy material with attached detailed clinical data, in combination with state-of-the-art models, allow us to isolate specific molecular events and correlate them to actual clinical outcomes.

In line with this, we aim to: (1) Perform a comprehensive analysis of disease drivers in IgA nephropathy (IgAN) and establish the role of galactose deficient IgA1 (gd-IgA1) immune complexes in the onset and progression of IgAN. (2) Determine the significance of receptor-mediated interaction of gd-IgA1 in mesangial cells in IgAN (3) Specify how mesangial cell proliferation and glycosylation in IgAN lead to dysregulation of glomerular crosstalk and (4) Identify the key events behind diabetic kidney disease (DKD) by investigating the role of mesangial expansion and impaired glomerular crosstalk.

The data obtained from the studies will be important for the understanding of the underlying mechanisms of CKD leading to loss of kidney function.

We believe that the results will contribute towards identifying new targets suitable for diagnostics and treatment in CKD with specific implications for IgAN and DKD.