Urinary Titin Is a Novel Biomarker for Muscle Atrophy in Nonsurgical Critically Ill Patients: A Two-Center, Prospective Observational Study

Objective: Although skeletal muscle atrophy is common in critically ill patients, biomarkers associated with muscle atrophy have not been identified reliably. Titin is a spring-like protein found in muscles and has become a measurable biomarker for muscle breakdown. We hypothesized that urinary titin is useful for monitoring muscle atrophy in critically ill patients. Therefore, we investigated urinary titin level and its association with muscle atrophy in critically ill patients. Design: Two-center, prospective observational study Setting: Mixed medical/surgical intensive care unit (ICU) in Japan Patients: Nonsurgical adult patients who were expected to remain in ICU for >5 days Interventions: None Methods: Urine samples were collected on days 1, 2, 3, 5, and 7 of ICU admission. To assess muscle atrophy, rectus femoris cross-sectional area and diaphragm thickness were measured with ultrasound on days 1, 3, 5, and 7. Secondary outcomes included its relationship with ICU-acquired weakness (ICU-AW), ICU Mobility Scale (IMS), and ICU mortality. Measurements and Main Results: Fifty-six patients and 232 urinary titin measurements were included. Urinary titin (normal range: 1–3 pmol/mg Cr) was 27.9 (16.8–59.6), 47.6 (23.5–82.4), 46.6 (24.4–97.6), 38.4 (23.6–83.0), and 49.3 (27.4–92.6) pmol/mg Cr on days 1, 2, 3, 5, and 7, respectively. Cumulative urinary titin level was significantly associated with rectus femoris muscle atrophy on days 3–7 (p < 0.03), although urinary titin level was not associated with change in diaphragm thickness (p = 0.31–0.45). Furthermore, cumulative urinary titin level was associated with incidence of ICU-AW (p = 0.01) and ICU mortality (p = 0.02) but not with IMS (p = 0.18). Conclusions: In nonsurgical critically ill patients, urinary titin level increased 10–30 times compared with the normal level. The increased urinary titin level was associated with lower limb muscle atrophy, incidence of ICU-AW, and ICU mortality.