Exploring the apelinergic system in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD),
characterized by the development of renal cysts, represents the 4th
common cause of end-stage kidney disease worldwide. The sole
disease-modifying drug is the vasopressin (AVP) receptor 2
antagonist tolvaptan, but its limited therapeutic effect and significant
side effects warrant novel drugs. The antidiuretic effect of AVP is
counteracted by apelin. Together with apela and the apelin receptor
(APLNR), it forms the apelinergic system (AS). Although the AVP
system has been extensively studied in ADPKD, and despite its
potential as a new treatment target in kidney and cardiovascular
diseases, the AS remains to be explored in ADPKD. Our preliminary
research shows that the AS is altered in ADPKD. Although apelin
expression is reduced in the hypothalamus, apelin and APLNR
expression is enhanced locally in kidney cells of ADPKD research
models. Moreover, we found that patients with normal kidney function
have increased circulating apelin. We therefore hypothesize that
altered AS function influences the cellular and molecular ADPKD
phenotype. Therefore, we will investigate in depth the dynamics,
mechanisms and contribution of the AS in cyst formation and its
interaction with the AVP system in patients and in several ADPKD
models (unique patient-derived kidney cell and mouse model). We
aim to gain crucial knowledge on kidney AS physiology, the role of
the AS in ADPKD pathophysiology and its therapeutic potential in
ADPKD