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.

• Authors: Nobuto Nakanishi, Rie Tsutsumi, Kanako Hara, Takuya Takashima, Emiko Nakataki, Taiga Itagaki, Masafumi Matsuo, Jun Oto, Hiroshi Sakaue
• Journal: Critical care medicine (Crit Care Med) Vol. 48 Issue 9 Pg. 1327-1333 (09 2020) ISSN: 1530-0293 [Electronic] United States
• PMID: 32706557 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Connectin
• Creatinine

Topics

• Aged
• Aged, 80 and over
• Biomarkers
• Connectin (urine)
• Creatinine (urine)
• Critical Illness
• Diaphragm (diagnostic imaging, pathology)
• Female
• Hospital Mortality
• Humans
• Intensive Care Units
• Japan
• Length of Stay
• Male
• Middle Aged
• Muscle Weakness (pathology)
• Muscular Atrophy (diagnostic imaging, pathology)
• Physical Functional Performance
• Prospective Studies
• Quadriceps Muscle (diagnostic imaging, pathology)
• Ultrasonography