PhD defence C.J. (Charles) Blijdorp

Dissertation in short:

What if we could study processes that occur in the kidney without performing a kidney biopsy? Are there any ways to screen for early kidney injury when current tests still give normal results? How can we personalize our treatments for kidney disease and hypertension in each individual patient?

These are questions that have occupied internist in training and author of this thesis – Charles Blijdorp – for over six years. He concluded that the most promising approach to achieve these goals, is by studying urine extracellular vesicles (uEVs). Why? Because everybody who can urinate excretes billions of uEVs every day. And while they are extremely small and hard to detect, they contain proteins and nucleic acids that can be used to study (disease) processes in the kidney. On top of things, uEVs contain information that we can use to trace back which part of the kidney they were excreted from. 

Though the significance of uEVs was established as early as in 2004, it has been a long and difficult journey to find ways to reliably isolate and charecterize them. When the author started his search, the most pressing hurdle that needed to be taken was how to get uEVs clinic-ready. How should results of uEV analysis be interpreted in case of differences in urinary concentration, sex and kidney mass? Are there reliable ways to speed up the analysis of uEVs, and circumvent the existing cumbersome isolation approaches along the way? And do they have a role in the discovery of active disease progression in patients with polycystic kidney disease, even before the kidney function is affected?