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

Abstract

Objectives: 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 ICU in Japan. Patients: Nonsurgical adult patients who were expected to remain in ICU for greater than 5 days. Interventions: None. Measurements and Main Results: 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 Mobility Scale, and ICU mortality. Fifty-six patients and 232 urinary titin measurements were included. Urinary titin (normal range: 1–3 pmol/mg creatinine) 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 creatinine 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 occurrence of ICU-acquired weakness (p = 0.01) and ICU mortality (p = 0.02) but not with ICU Mobility Scale (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, occurrence of ICU-acquired weakness, and ICU mortality.

Towards Personalized Management of Sarcopenia in COPD

“…75 More recently, elevated levels of urinary titin were demonstrated to correlate with rectus femoris muscle atrophy in intensive care patients. 76 These studies suggest that urinary titin might be a useful, non-invasive potential biomarker for sarcopenia, but more research and validation is still required.…”

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

“…In their study, investigating four critically ill patients, there was a negative correlation between mean urinary titin level during the first seven days of ICU admission and femoral muscle volume measured using computed tomography (r = −0.729). Furthermore, Nakanishi et al reported that in 56 nonsurgical critically ill patients, the cumulative urinary titin concentration on days 3, 5, and 7 was significantly higher in the prominent muscle atrophy group (p ≤ 0.03), suggesting that urinary titin reflects muscle atrophy in nonsurgical critically ill patients [9]. However, in their study, the correlation between muscle atrophy and urinary titin was limited to r = 0.29-0.54 (p ≤ 0.03), suggesting that urinary titin levels are affected by various physiologic conditions.…”

“…Urinary creatinine has also been suggested to be a biomarker of muscle atrophy, but it does not consider kidney function [41]. Thus, urinary titin N-fragment, corrected by urinary creatinine, is a reliable biomarker because it does not depend on kidney function [9,10].…”

“…Two study groups have recently reported the use of urinary titin N-fragment in assessing ICU-AW. Nakanishi et al found that the urinary titin N-fragment reflected muscle atrophy and ICU-AW in critically ill patients [9]. Moreover, the accumulated urinary titin was associated with mortality in these patients.…”

Measuring and Monitoring Skeletal Muscle Mass and Dysfunction After Stroke

“…Two biomarkers are used to assess muscle mass in patients with stroke. Urinary titin N-fragment is an important biomarker in muscle atrophy [85]. Ishihara et al have investigated the use of a urinary titin N-fragment in stroke [53].…”