Alterations to arginine vasopressin (AVP) secretion, the urinary bladder urothelium (UT) and other components of the bladder, and the water homeostasis biosystem may be relevant to the pathophysiology of nocturia and nocturnal polyuria (NP). AVP is the primary hormone involved in water homeostasis. Disruption to the physiological release of AVP or its target effects may relate to several urinary disturbances. Circadian dysregulation and the effects of aging, e.g., the development of oxidative stress and mitochondrial dysfunction, may play a role in nocturia voiding symptoms. The urinary bladder urothelium not only acts as a highly efficient barrier that is maintained during the filling and voiding of the urinary bladder, but is also capable of sensory and transducer function through a network of functional receptors and ion channels that enable reciprocal communication between urothelium cells and neighboring elements of the bladder mucosa and wall. Functional components of the urothelium (e.g., claudins and receptors or ion channels) play important roles in AVP-mediated water homeostasis. These components and functions involved in water homeostasis, as well as kidney function, may be affected by the aging process, including age-related mitochondrial dysfunction. The characteristics of NP are discussed and the association between NP and circadian rhythm is examined in light of reports that suggest that nocturia should be considered as a type of circadian dysfunction. Many possible pathological mechanisms that underlie nocturia and NP have been identified. Future studies may provide further insight into pathophysiology with the hope of identifying new treatment modalities.

Urology. 2019 Jul 29 [Epub ahead of print]

Lori A Birder, Philip E V Van Kerrebroeck

Departments of Medicine and Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: ., Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: .