The epidermal growth factor receptor pathway in polycystic kidney disease
|PhD ceremony:||Ms L.R. (Laura) Harskamp|
|When:||April 05, 2023|
|Supervisors:||prof. dr. R.T. (Ron) Gansevoort, prof. dr. H. (Harry) van Goor|
|Co-supervisor:||dr. E. Meijer|
|Where:||Academy building RUG|
|Faculty:||Medical Sciences / UMCG|
In polycystic kidney disease cysts (fluid-filled sacs) develop in both kidneys eventually leading to kidney failure. For several years there has been a drug, Tolvaptan, used in clinical practice that can slow down this disease process atlhough leading to considerable side effects. Hence, there is a need for potentially effective treatments without these side effects. The Epidermal Growth Factor Receptor pathway might fill this gap. Activation of EGFR by its growth factors (ligands) plays an important role in repair after kidney injury, while overstimulation of the EGFR has shown to result in cyst formation in the kidneys.
Harskamp discovered in her thesis that EGFR ligand EGF is reduced in patients with polycystic kidney disease and associated with disease severity. In a larger cohort of polycystic kidney disease patients, she confirmed these results and moreover, found that a lower EGF was associated with kidney function decline. In support of these findings, Harskamp found that EGFR was also present in cysts derived from kidney tissue of patients with polycystic kidney disease.
Furthermore, this thesis investigated whether a more suitable model can be used to study the development of cystic kidneys, namely very thin slices of kidney tissue. Harskamp found that kidney slices derived from patients with cystic kidneys remained viable for up to 48 hours and showed cell proliferation (characteristic of polycystic kidneys).
Finally, this thesis investigated whether EGF can also be used to predict kidney function decline in the general population. A lower EGF was associated with an increased risk of rapid kidney function loss and developing chronic kidney disease in two general population cohorts.