Rare-G

Rare diseases may affect the renal glomerulus, the filter units of the kidney. There are two major forms, rapid-progressive glomerulonephritis (RPGN, or crescentic nephritis) and primary focal and segmental glomerulosclerosis (FSGS). Both diseases often lead to chronic loss of renal function and ultimately to life-long need for renal replacement therapy. Such a condition is associated with a significantly increased risk for cardio-vascular morbidity and mortality. In the recent years members of this consortium have contributed to our understanding of these rare glomerular diseases. We could show that two major cells types, podocytes and parietal epithelial cells (PECs), are crucially involved in the pathogenesis of these diseases. Furthermore, we have observed that the epidermal growth factor (EGF) system is probably involved in mediating signals in both types of diseases.

It was our goal to investigate the functional significance of these cells, their cellular activation and the role of EGF signalling in these rare diseases of the kidney. Our consortium could show that a so far unrecognized cell type (parietal cells, PECs) are indeed involved in all forms of FSGS. Furthermore, we observed that no regeneration of podocytes from these cells (PECs) may occur to replenish essential cells lost in disease. Furthermore, we demonstrated in vivo that podocytes are immobile under physiological conditions and mobile under pathophysiological conditions. We show that these insights may improve diagnostic sensitivity and that the EGF system likely plays only a minor role in FSGS – in contrast to crescentic rapidly progressive glomerulonephritis (RPGN).