Serum creatinine as a biomarker for dystrophinopathy: a cross-sectional and longitudinal study

Abstract

Background Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy. Methods We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients’ demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes. Results Our results showed SCRN levels correlated with motor function (FDR < 0.001) and timed test results (FDR between < 0.001–0.012), as well as with muscle fatty infiltration (FDR < 0.001) and dystrophin levels (FDR = 0.015 and 0.001). SCRN levels increased with maturation in control individuals; it slowly increased with maturation in patients with BMD but decreased generally with maturation in patients with DMD. The longitudinal study further demonstrated that SCRN levels were associated with motor function. Conclusions These findings indicated that the SCRN level is a promising biomarker for assessing disease progression in dystrophinopathy and could be used as a potential outcome measure in clinical trials.

Diaphragmatic and Rectus Femoris Muscles Ultrasonography in Relation to Motor and Respiratory Functions in Ambulatory Boys with Duchenne Muscular Dystrophy

“…A significant higher difference in the median and IQR of the total score of GSGC of patients with grade IV modified Heckmatt scale was found in comparison to grade II and III (15 [12][13][14][15][16][17] vs. 8 [7][8][9][10], 11 [11][12][13], p < 0.001).…”

“…Furthermore, serial tests are of value in detecting disease progression over time. 9 16 Hence, we aimed to study correlation between GSGC scale and RF muscle US findings.…”

Longitudinal Assessment of Creatine Kinase, Creatine/Creatinineratio, and Myostatin as Monitoring Biomarkers in Becker Muscular Dystrophy

“…With loss of muscle mass that is typical for muscular dystrophies, less creatine is converted into creatinine leading to an increased ratio of creatine to creatinine. Serum creatinine has been shown to be reduced in several neuromuscular diseases including DMD, BMD and spinal muscular atrophy 14,15,[32][33][34] . Two studies in a large cohort of mainly pediatric dystrophinopathy patients demonstrated that creatinine levels distinguished DMD from BMD, and that it was inversely correlated to function; creatinine was also associated with disease progression in a smaller longitudinal subset with deteriorating DMD (n=32) and BMD (n=4) patients with two time points spanning multiple years 32,33 .…”

“… 14 , 15 , 32 - 34 Two studies in a large cohort of mainly pediatric patients with dystrophinopathy demonstrated that creatinine levels distinguished DMD from BMD, and that it was inversely correlated with function; creatinine was also associated with disease progression in a smaller longitudinal subset with deteriorating DMD (n = 32) and BMD (n = 4) patients, with 2 time points spanning multiple years. 32 , 33 Myostatin (or growth differentiation factor 8) is a member of the transforming growth factor β superfamily and acts as a muscle growth inhibitor. 35 It is produced and released by myocytes and fibroblast residing in skeletal muscle tissue.…”