Identification of new molecular mechanisms for diagnosis and treatment of polycystic kidney disease

Resumo

The major objectives that were set up in this thesis project were related to the development of new molecular tools for early diagnosis of renal diseases, which complement the genetic tests for all inherited renal diseases previously developed by our group; to look for new biomarkers for diagnosis and prognosis, simpler, faster, more efficient and cheaper than the existing ones; to study the developmental biology of PKD, the most common inherited renal disease, and development of nanocarriers for specific drug delivery to the cystic kidney. We developed a new analytical method for diagnosis and prognosis of diseases in liquid biopsy (KITGAG). This new tool allowed us to discover a pattern of proteins associated to glycosaminglycans (GAGs) in urine and a new distance mechanism for renal communication, UGE complex. Moreover, we significatively puzzled out some pieces in cystogenesis, defining, not only some parts of the developmental biology of this process, the role of TWEAK and the immunitary system in PKD, but also indicating that timing is vital for effectiveness of PKD treatment. Finally, we developed 2 sets of nanoparticles functionalized for specific kidney delivery, allowing us to control the time of residence of any active principle carried in the target tissue. All these results along with a complete early diagnosis of the disease and specific drugs, would change the way of PKD patients are managed.