Translational research into early stages of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal dominant polycystic kidney disease (ADPKD) affects up to
13 million individuals and is the 4th common cause of end-stage
kidney disease worldwide, with a major socio-economic burden and
to date without cure. Although ADPKD has been historically
considered as an “adult-onset” disease, nowadays it is recognized
that the adult presentation of the disease is only the tip of the
iceberg. ADPKD is pauci-symptomatic until the 3rd-4th decade, and
deterioration of renal function is not observed until the destruction of
at least 50% of the parenchyma. Current therapies are implemented
at later stages and are less likely to be successful since the patient
may already have reached a point of no return. Awareness is growing
that cysts are already initiated in children and even in utero. Thus,
more early nephron-protective strategies are becoming an attractive
goal for therapy. The overall goal of my research proposal is to
challenge the paradigm of the current management of ADPKD by
demonstrating that this disorder manifests itself already in childhood.
I will spotlight the simple but critical insight that in order to prevent
progression of the disease to end-stage kidney disease, treatment of
ADPKD must start in childhood before a point of no return, using
more safe drugs. For that aim, I will use a holistic translational
approach and focus on the earliest molecular events leading to cyst
initiation in order to identify novel drug targets for interventions in
early ADPKD.