THE ROLE OF RENAL NERVES IN VASOPRESSIN CONTROL IN A MODEL OF AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
PublisherThe University of Arizona.
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AbstractAutosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder which frequently leads to kidney failure, often necessitating hemodialysis or kidney transplant. Unlike autosomal dominant polycystic kidney disease (ADPKD), patients with ARPKD develop renal and liver cysts in utero, leading to many developmental abnormalities and high mortality rates for pediatric patients1. There are very few treatments for these patients, as the underlying mechanism for cyst proliferation is unclear. Tolvaptan, a vasopressin-2-receptor (V2R) antagonist, has recently been shown to attenuate the decline in kidney function by reducing cyst growth in patients with PKD. Renal denervation (RDNx), a surgical method of ablating renal nerves, has also been shown to reduce cyst size in PCK rats, a model of ARPKD. We hypothesized that RDNx was mitigating cyst growth through the removal of afferent renal nerves, by causing a decrease in vasopressin secretion. To test this hypothesis, we analyzed the relationship between cyst growth and serum copeptin levels – an indirect measure of arginine vasopressin secretion – in PCK rats after performing either total (T-RDNx) or afferent renal denervation (A-RDNx). Renal denervation had no effect on serum copeptin levels, while cystic index was decreased. These results do not support our hypothesis and suggest that renal nerves are contributing to cyst growth in this model through an alternative mechanism. Future research is required to determine the role and mechanism of renal nerves’ contribution to cystic progression in ARPKD.
Degree ProgramNeuroscience and Cognitive Science