Measurement of oxidative stress to allow the development and use of new therapies in lower urinary tract dysfunction: ICI-RS 2025

Abstract

Aims Evaluate current knowledge of the physiological and clinical consequences of oxidative stress on the development of lower urinary tract dysfunction (LUTD), identify clinically relevant biomarkers and potential therapeutics.Methods This review summarizes topics discussed during Proposal #7 at the International Consultation on Incontinence Research Society 2025 meeting and derives a consensus of future research directions.Results Pelvic ischemia/hypoxia can result in LUTD including detrusor over-/underactivity, bladder pain syndrome and nocturia. Major causes of bladder ischemia include aging, atherosclerosis and bladder outlet obstruction. The bladder wall undergoes physiological cycles of ischemia and reperfusion with normal filling and emptying: thus, infrequent voiding habits, co-morbidities and some medications can exacerbate LUTD. Ischemia can lead to oxidative stress which is an increase in reactive oxygen species (ROS), superoxide and the hydroxyl radical, over enzymatic antioxidants, superoxide dismutase and glutathione peroxidase. ROS can be generated by monoamine, xanthine and nicotinamide adenine dinucleotide phosphate oxidases, but the main source is dysfunctional mitochondria. Biomarkers of oxidative stress such as 8-hydroxydeoxyguanosine, indicative of DNA damage, can be measured in plasma and urine. Soluble guanylate cyclase activators have been recently demonstrated to have beneficial actions in several LUTD by ameliorating prostatic hyperplasia, bladder overactivity, cellular senescence and fibrosis.Conclusion Many LUTD were identified as having links to oxidative stress. There are still questions regarding correlation of the severity of oxidative stress to LUTD symptomology, the selectivity of biomarkers and the most efficacious druggable target. These were considered key research directions for future studies.