Understanding the Ureter: Challenges and Opportunities

Abstract

The ureter is possibly the least studied and most poorly understood organ of the urinary tract. The pathophysiologic basis underlying the use of a-blockers to improve ureteral stone passage or to treat ureteral stent symptoms is poorly understood. This, in part, may explain why clinical studies of medical expulsive therapy for ureteral stone passage are fraught with conflicting data. Methods to study human ureter in vivo are few and challenging. The findings of many of the ureteral studies are from observational in vitro studies and were evaluated in other animal species that may not be applicable in human beings. There are few mechanistic studies evaluating the underlying molecular pathophysiologic mechanisms of human ureter. This is critical to our understanding and treatment of stent symptoms, including the development of a patient friendly ureteral stent and for the pharmacologic modulation of ureteral activity. The following is an overview of some of the observational and mechanistic ureteral studies evaluating the pharmacologic and stent effects, including potential areas for further research.

Activation of Piezo1 or TRPV2 channels inhibits human ureteral contractions via NO release from the mucosa

“…For instance, stent insertion initially increased peristaltic activity, which was later reduced or terminated ( Venkatesh et al, 2005 ). In a swine model, normal peristalsis was absent 24 h following ureteral stenting and restored on day 5 ( Park and Venkatesh, 2016 ). In another study, peristaltic activity of porcine ureter increased immediately in response to stent placement, but was decreased after 4–5 h, and was markedly reduced or completely abolished after 1 week ( Venkatesh et al, 2005 ).…”

Indwelling stents cause severe inflammation and fibrosis of the ureter via urothelial–mesenchymal transition

“…NF-κB is the most relevant transcription factor in inflammation, enhancing the transcription of inflammatory cytokines such as IL-6 and IL-8, as well as cellular mediators of inflammation 22 . Moreover, NF-kB and STAT3 are major drivers of chronic inflammation 7 . We observed STAT3 activation by immunodetection in the lamina propria of stented ureters.…”

“…However, as stents are often inevitable, an effort has been made to improve stent technology to prevent adverse effects 4 , 5 . Little progress, however, has been made to understand the mechanisms of stent-associated morbidities, long-term functional impairment and its impact on renal function 6 , 7 .…”