Incontinence-associated dermatitis by infected urine: biological mechanisms and prevention strategies

Research Project

Project/Area Number	19K24194
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Multi-year Fund
Review Section	0908:Society medicine, nursing, and related fields
Research Institution	The University of Tokyo
Principal Investigator	KOUDOUNAS SOFOKLIS 東京大学, 大学院医学系研究科(医学部), 特任研究員 (70849968)
Project Period (FY)	2019-08-30 – 2021-03-31
Project Status	Granted (Fiscal Year 2019)
Budget Amount *help	¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	IAD / infected urine / urinary-incontinence / older patients / dermatitis / bacteria / rat
Outline of Research at the Start	IAD is a painful complication among elderly patients, leading to a reduced quality of life. Physiological urine does not lead to the development of IAD; however, infected urine is severely irritating and increases the risk of skin damage. How infected urine leads to the development of IAD has never been investigated. Therefore, this study aims to elucidate the histopathological/molecular mechanisms of IAD caused by infected urine in order to develop new nursing interventions for complete prevention of IAD and ultimately improve the patients’ quality of life.
Outline of Annual Research Achievements	Last year, my research focused on revealing the effects of urine on bacteria responsible for urinary-tract infections (UTIs). I examined the hypothesis that urine has an inhibitory effect on bacteria. To address this hypothesis, I conducted an in vitro study with synthetic-urine (s-urine) to simulate physiological urine, and common bacteria responsible for UTIs. I examined the effects of s-urine on bacterial growth and motility over time. Remarkably, my results demonstrated that s-urine enhances bacterial growth. It was revealed that during the early phase of growth (0-6 hrs) the growth inhibitory effect of urine is evident, but with increasing time of incubation (over 8 hrs) the inhibitory activity of urine decreases and promotes bacterial growth. On the contrary, there was no effect of s-urine on bacterial motility. These findings elucidated the role of urine on bacteria and contradicts with what we believed up to now. This further supports the hypothesis that infected urine contributes to the development of incontinence-associated dermatitis (IAD) and suggests that urine promotes bacterial skin colonization and invasion, leading to enhanced tissue breakdown and IAD. This needs to be elucidated in vivo and highlights the motivation for the proposed study.
Current Status of Research Progress	Current Status of Research Progress 3: Progress in research has been slightly delayed. Reason Due to the unfortunate events of Covid-19, the animal study of this research project has been delayed and will commence the sooner the current situation is over.
Strategy for Future Research Activity	An in vivo animal study will be conducted to investigate the skin physiology following exposure to an established model of UTIs. Sprague Dawley (SD) rats will be used, as they share common biological and behavior characteristics closely resembling those of humans. SD rats will have their dorsal skin exposed to s-urine and common bacteria responsible for UTIs, as in my previous in vitro study. Exposure time will be decided through preliminary experiments, which will be conducted to induce IAD and establish this animal model of UTI. To assess the integrity of the skin, measurements of transepidermal water loss, an indicator of skin barrier, and skin pH will be obtained before and after exposure. Skin appearance and morphology will be assessed macroscopically and by microscopic anatomical methods, respectively. Histology and immunohistological analysis will be performed to reveal the changes in skin tissue structure in response to urine and bacteria. Considering the recent advancements in genomics, multiomics will also be used to reveal the key bacterial virulence mechanisms involved in IAD pathophysiology and identify the molecular pathway alterations in IAD. Together, these methods will decipher the mechanisms following exposure to bacteria and urine. Based on these findings, preventive interventions will be developed targeting specific virulence mechanisms, such as urease enzyme and motility.