• Shinichiro Yamada, Atsushi Hashizume, Yasuhiro Hijikata, Daisuke Ito, Yoshiyuki Kishimoto, Madoka Iida, Haruki Koike, Akihiro Hirakawa, and Masahisa Katsuno.
• Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
• J. Neurol. Neurosurg. Psychiatr. 2021 Oct 1; 92 (10): 1072-1079.

ObjectiveWe aimed to investigate the validity of urinary N-terminal titin fragment as a biomarker for amyotrophic lateral sclerosis (ALS).MethodsWe consecutively enrolled patients with ALS (n=70) and healthy controls (HC) (n=43). We assessed the urinary titin N-terminal fragment, urinary neurotrophin receptor p75 extracellular domain, serum neurofilament light chain (NfL), motor functional measurements and prognosis. We used urinary creatinine (Cr) levels to normalise the urinary levels of titin fragment.ResultsCompared with HC, patients with ALS had significantly increased urinary levels of titin N-terminal fragment normalised with Cr (titin/Cr) (ALS, 27.2 pmol/mg/dL; HC, 5.8 pmol/mg/dL; p<0.001), which were correlated with the scores of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (r=-0.422, p<0.001). A Cox proportional hazards model demonstrated that the high urinary level of titin/Cr was a survival predictor in patients with ALS. Multivariate analysis of prognostic factors showed that the urinary titin/Cr and serum NfL were independent factors for poor prognosis.ConclusionsOur findings indicate that urinary N-terminal titin fragment is a non-invasive measure of muscle damage in ALS, which could be applied in disease monitoring and prediction of disease progression, in combination with serum NfL.© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

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