The Role of Renal Nerves in the Development and Maintenance of a Model of Autosomal Recessive Polycystic Kidney Disease

Abstract

Polycystic kidney disease (PKD) is characterized by the development of renal cysts, which replace healthy kidney tissue, leading to kidney failure. Afferent (sensory) renal nerves convey information to the central nervous system in response to intrarenal stimuli, while sympathetic nerves travel from the CNS to the kidneys and modulate renal function. Renal nerves have a central role in the pathogenesis of hypertension (HTN) and other cardiorenal conditions, but little work has been done to investigate whether they play a role in the pathogenesis of PKD. Furthermore, arginine vasopressin (AVP) is elevated in PKD and increases cyst growth. There is evidence that activation of the afferent renal nerves can contribute to secretion of AVP. Given this evidence, we propose an overarching hypothesis that elevated afferent renal nerve activity (ARNA) increases AVP secretion, thereby increasing cyst growth. The studies outlined in this thesis aim to begin to address this hypothesis. They investigate the role of afferent and efferent renal nerves in the pathogenesis of PKD at various points throughout the progression of the disease in the PCK rat, a model of autosomal recessive PKD (ARPKD). Overall, we demonstrate that renal nerves contribute to the development and maintenance of PKD at a very early point in the progression of the disease, as well as in more advanced disease, though the role of AVP in this effect is unclear. We also directly assess levels of afferent and sympathetic renal nerve activity (ARNA) and demonstrate an elevation in afferent renal nerve activity in young PCK rats compared to healthy, non-cystic control animals. These results demonstrate a role for renal nerves in PKD. However, the underlying mechanisms and relationship between renal nerves and cyst growth is complex, and merits further study.