Angiotensin II and polycystic kidney disease

The renin-angiotensin system and the key signaling molecule angiotensin II (Ang II) are central to maintaining physiological homeostasis across multiple systems and tissues. This chapter examines the impact of Ang II on the pathobiology of polycystic kidney disease (PKD). PKD is a monogenic disorder caused by mutations in a repertoire of ciliary genes. Over a hundred genes have been associated with autosomal dominant or recessive forms of cystic kidney disease, and their pathobiology is elusive and heterogenous. The same causative genotype can present with wide phenotypic variation and cross-talk with pathogenic pathways driven by Ang II may be a key factor that can drive PKD progression. In this chapter, we examine the dysregulation of Ang II in PKD and how it may influence cyst growth, mediate abnormal water and salt handling, and contribute significantly to extrarenal presentations of the disease. We overview studies that shed light on potential molecular mechanisms by which Ang II may impact PKD cystogenesis, and we consider the current state of knowledge derived from clinical trials examining the beneficial effect of Ang II inhibition on disease presentation in PKD patients.