Muscle mass biomarker is associated with risk of developing ALS: Study
Lower creatinine-to-cystatin C ratio linked with greater chance of disease
A muscle mass biomarker called the creatinine-to-cystatin C ratio (CCR) may indicate the risk of developing amyotrophic lateral sclerosis (ALS), a study that relied on a large-scale database shows.
A lower ratio was associated with higher ALS risk, particularly in the participants between the ages of 40 and 65.
“To our knowledge, this is the first study to demonstrate a prospective relationship between low CCR and the risk of developing ALS decades before a clinical diagnosis,” the researchers wrote. The study, “Lower creatinine-to-cystatin c ratio associated with increased risk of incident amyotrophic lateral sclerosis in the prospective UK biobank cohort,” was published in Scientific Reports.
ALS damages motor neurons, the nerve cells that control voluntary movement, leading to progressive muscle weakness. While the cause of ALS remains unclear, genetic, environmental, and lifestyle factors are thought to contribute. Loss of muscle mass may indicate disease progression and help predict the disease’s prognosis. Early diagnosis is essential for managing ALS better.
Creatinine is a waste product from muscle and protein breakdown, but cystatin C is a marker of kidney function whose levels typically remain stable if muscle mass is unchanged. The two proteins can be used to evaluate muscle mass loss in ALS patients.
“Given the characteristics of serum [blood] creatinine and cystatin C, the CCR was developed to assess muscle mass,” the researchers wrote. “It has been validated as a more reliable measure of muscle mass changes in ALS compared to serum creatinine [alone].”
Link between ALS, CCR values
The study investigated data from more than 446,000 people, ages 40-69, from the UK Biobank, a large-scale biomedical database, who were tracked for a median of 13.8 years, during which 589 were diagnosed with ALS.
The ALS patients showed significantly lower median CCR than those without the disease (78.26 vs. 79.81) and lower CCR values showed a significant association with a higher incidence (new cases) of ALS in the study population.
Age, sex, body weight, and kidney function can influence CCR, so the analyses were adjusted for demographics, lifestyle factors, and medical history. The association between low CCR and ALS risk remained consistent after those adjustments, which also included education level, smoking status, and sleep duration.
The participants were divided into three groups based on their CCR values. The highest third was used as a reference group. Those in the lowest third had a 1.39 times higher risk of ALS and the middle third a 1.35 times greater ALS risk than the highest third.
Among those younger than 65, the lowest CCR group had nearly twice the risk of ALS than those with higher CCR levels. Those in the second third also showed a high risk of ALS relative to the reference group.
The study suggests loss of muscle mass may be implicated in ALS disease processes, said the researchers, who wrote that more “investigation into the molecular basis of these changes could lead to the development of presymptomatic biomarkers and novel therapeutic targets.”
“Both creatinine and cystatin C can be quickly measured by blood sampling, making CCR a significant advantage for risk monitoring in large populations,” wrote the researchers, who noted that, despite the study’s strengths, including its large sample size, most of its participants were of European descent, meaning the results may be different in other populations. The researchers said they hope to validate their findings with other populations in the future.
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