Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

Abstract

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interconnects the contraction of actin-containing thin filaments and myosin-containing thick filaments. Titin breaks down to form urinary titin N-fragments, which are measurable in urine. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies have reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

A sandwich ELISA kit reveals marked elevation of titin N‐terminal fragment levels in the urine of mdx mice

“…As a result, high urinary titin levels have been identified in association with not only diseases 23 but also physical activities 23 . Clinically, urinary titin has been nominated as a biomarker for catabolism of neonates 24 and muscle atrophy of patients in intensive care unit 20,25 . Similar examinations could be performed in mice using the developed kit in the future.…”

„Intensive Care Unit-Acquired Weakness“

“…Aktuelle Evidenz weist darauf hin, dass bereits ein MRC-SS < 55 mit einem schlechterem Behandlungsergebnis assoziiert ist [27]. Darüber hinaus wurden unterschiedliche diagnostische, therapeutische und präventive Ansätze zu Detektion, Behandlung und Prognoseabschätzung der ICU-AW publiziert [6,10,12,13,16,21,28].…”

Successful establishment of crowdfunding to develop new diagnostic tools for chronic prostatitis

“…As a result, crowdfunding has recently emerged as a novel method for academic researchers to fund their research in and outside Japan. Some notable examples include the Muscle Atrophy Zero Project of a Japanese emergency doctor, 2 and the neuroscience project HORAD, whose aim was to develop a method to visualize neuronal fiber tracts during brain surgery from Europe and the United States 3 . Crowdfunding platforms were originally designed to enable people to fund certain projects and ventures.…”

“…The present study by Tohi et al launched crowdfunding campaigns to develop new diagnostic tools for chronic prostatitis and successfully collected funds through crowdfunding named Otsucle established by the University of Tokushima, where they are engaged in research, and the University Support Organization to raise external research funds. 2 JSPS KAKENHI, academic support from pharmaceutical companies or research grants from each organization are conventional ways; however, it is getting more competitive and harder to obtain these funds. Therefore, this new method to raise funds should be widely known among researchers, especially who have financial difficulty.…”