Purpose: To conduct a systematic review of preclinical and clinical peer-reviewed evidence linking alterations in oxidative stress biomarkers or outcome measures that were also prevalent in specific age-related lower urinary tract (LUT) disorders. Methods: PubMed, Scopus, CINAHL, and Embase were searched for peer-reviewed studies published between January 2000 and March 2021. Animal and human studies that reported on the impact of oxidative stress in age-related LUT disorders through structural or functional changes in the LUT and changes in biomarkers were included. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol was followed. Results: Of 882 articles identified, 21 studies (13 animal; 8 human) met inclusion criteria. Across LUT disorders, common structural changes were increased bladder and prostate weights, ischemic damage, nerve damage and detrusor muscle hypertrophy; common functional changes included decreased bladder contraction, increased bladder sensation and excitability, decreased perfusion, and increased inflammation. The disorders were associated with increased levels of biomarkers of oxidative stress that provided evidence of either molecular damage, protective mechanisms against oxidative stress, neural changes, or inflammation. In all cases, the effect on biomarkers and enzymes was greater in aged groups compared to younger groups. Conclusions Increased oxidative stress, often associated with mitochondrial dysfunction, plays a significant role in the pathogenesis of age-related LUT disorders and may explain their increasing prevalence. This systematic review identifies potential markers of disease progression and treatment opportunities; further research is warranted to evaluate these markers and the mechanisms by which these changes may lead to age-related LUT disorders.

Purpose: The pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP. Methods: Patients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and <65 years old. Urine samples were collected and analyzed for natriuretic peptide (NT-proANP, NT-proBNP, and NT-proCNP) levels. Peptide levels were compared between patients with and without nocturia/NP and within age subgroups; correlation to the NP index (NPi) was determined. Results: Compared to patients without nocturia (N=15), patients with nocturia (N=36) had higher median levels of urinary NT-proANP (15.8 pmol/mmol Cr vs. 10.9 pmol/mmol Cr, P=0.016) and NT-proBNP (6.3 pmol/mmol Cr vs. 4.5 pmol/mmol Cr, P=0.021), but showed no differences in NT-proCNP (2.4 pmol/mmol Cr vs. 2.5 pmol/mmol Cr, P=0.967). Patients ≥65 years old with nocturia had higher NT-proANP (29.8 pmol/mmol Cr vs. 11.0 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 5.0 pmol/mmol Cr, P<0.001) than patients <65 years old. Additionally, patients with NP (N=30) showed higher urinary NT-proANP (19.6 pmol/mmol Cr vs. 10.5 pmol/mmol Cr, P<0.001) and NT-proBNP (6.7 pmol/mmol Cr vs. 4.7 pmol/mmol Cr, P=0.020) compared to patients without NP (N=21). NP patients ≥65 years had higher NT-proANP (29.8 pmol/mmol Cr vs. 12.5 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 4.4 pmol/mmol Cr, P=0.004) than patients <65 years old. NPi positively correlated with urinary NT-proANP (RS=0.417, P=0.002) and NT-proBNP (RS=0.303, P=0.031), but not with NT-proCNP (RS=-0.094, P=0.510). Conclusions Since urinary NT-proANP and NT-proBNP were greater in aged patients with nocturia and NP, natriuretic peptides may contribute to the pathophysiology of these conditions and further research should aim to explore them as targets for management.

Purpose: Nocturia significantly impacts patients’ quality of life but remains insufficiently evaluated and treated. The “Sleep C.A.L.M.” system categorizes the factors thought to collectively reflect most underlying causes of nocturia (Sleep disorders, Comorbidities, Actions [i.e., modifiable patient behaviors such as excess fluid intake], Lower urinary tract dysfunction, and Medications). The purpose of this study was to assess the association of nocturia with the Sleep C.A.L.M. categories using a nationally representative dataset. Methods: Retrospective analysis of the National Health and Nutrition Examination Survey from 2013/14–2017/18 cycles was conducted. Pertinent questionnaire, laboratory, dietary, and physical examination data were used to ascertain the presence of Sleep C.A.L.M. categories in adults ≥20 years of age. Nocturia was defined as ≥2 nighttime voids. Results: A total of 12,274 included subjects were included (51.6% female; median age, 49.0 years [interquartile range, 34.0–62.0 years]; 27.6% nocturia). Among subjects with nocturia, the prevalence of 0, ≥1, and ≥2 Sleep C.A.L.M. categories was 3.5% (95% confidence interval [CI], 2.8%–4.4%), 96.5% (95% CI, 95.6%–97.2%), and 81.2% (95% CI, 78.9%–83.3%), respectively. Compared to those with 0–1 Sleep C.A.L.M. categories, the adjusted odds of nocturia in subjects with 2, 3, and 4–5 Sleep C. A.L.M. categories were 1.77 (95% CI, 1.43–2.21), 2.33 (1.89–2.87), and 3.49 (2.81–4.35), respectively (P<0.001). Similar trends were observed for most age and sex subgroups. When assessed individually, each of the 5 Sleep C.A.L.M. categories were independently associated with greater odds of nocturia, which likewise persisted across multiple age and sex subgroups. Conclusions Sleep C.A.L.M. burden is associated with increased odds of nocturia in a dose-dependent fashion, and potentially a relevant means by which to organize the underlying etiologies for nocturia among community-dwelling adults.