Analysis of routine blood parameters in patients with amyotrophic lateral sclerosis and evaluation of a possible correlation with disease progression—a multicenter study

Abstract

ObjectiveAmyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, progression rate, and survival. Additionally, we analyzed disease and patients' characteristics relating to baseline blood parameter levels.MethodsWe analyzed creatine kinase (CK), albumin (ALB), creatinine (CREA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) levels around time of diagnosis in 1,084 ALS patients. We carried out linear regression analyses including disease and patients' characteristics with each blood parameter to detect correlations with them. Linear regression models were performed for ALSFRS-R at study entry, its retrospectively defined rate of decay and prospectively collected progression rate. Different survival analysis methods were used to examine associations between blood parameters and survival.ResultsWe found higher CK (p-value 0.001), ALB (p-value <0.001), CREA (p-value <0.001), and HDL levels (p-value 0.044) at time of diagnosis being associated with better functional status according to ALSFRS-R scores at study entry. Additionally, higher CREA levels were associated with lower risk of death (p-value 0.003).ConclusionsOur results indicate potential of CK, ALB, CREA, and HDL as disease severity or progression markers, and may also provide clues to ALS pathogenesis. However, these values are highly dependent on other variables, and further careful, longitudinal analyses will be necessary to prove the relevance of our findings.

The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis

“…Total protein levels and albumin were initially used as separate variables, possibly accounting for the association observed only for total protein but not albumin. Indeed, after exclusion of total protein levels from the survival analysis, albumin was retained as an independent prognostic factor, consistent with the literature [ 4 , 6 , 22 ], suggesting that it may be a reasonable outcome measure in ALS clinical trials, as recently suggested in the Co-ALS trial [ 24 – 27 ]. Instead, despite some evidence for the presence of a systemic low-grade inflammation in ALS [ 7 , 28 , 29 ], we did not find an association between CRP and survival, similar to other large cohort studies [ 22 , 30 , 31 ].…”

“…Besides its use as a surrogate index of renal function, serum creatinine is also known to reflect muscle mass. In ALS, serum creatinine appears to decrease up to 2 years before diagnosis [ 18 ], with baseline values being consistently positively associated with progression and survival [ 4 , 6 , 19 ]. We confirmed that serum creatinine is a reliable marker of disease severity and mortality in ALS, with a 14% reduction in risk of death observed for each 0.1 mg/dL increase at diagnosis.…”

“…Other studies looked for potential repurposing of common blood parameters, attracted by their easy availability and inexpensiveness. Among all, serum creatinine levels showed the strongest association with ALS, correlating with disease disability, severity and survival [ 4 – 6 ]. Markers of muscle loss, such as creatine kinase [ 4 ], and of inflammation, including serum albumin [ 6 ] and C-reactive protein [ 7 ], also showed significant correlations with disease survival, but more studies are needed to validate these findings.…”

Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients’ Specific Immunological and Biochemical Biomarkers

“…Additionally, changes in muscle mass are one of the signs of ALS, and they are one of the biochemical parameters that can be assessed in this case is CK. According to the study by Hertel et al, an increased CK level can increase survival time and provide a good interpretation of the ALSFRS-R score [61]; however, a decreased level was indicated in the case of muscle atrophy [34].…”

Unraveling the Heterogeneity of ALS—A Call to Redefine Patient Stratification for Better Outcomes in Clinical Trials

“…The same applies to other well-known ALS markers, such as markers of muscle metabolism (creatine kinase, creatinine, uric acid), and nutritional status (protein, albumin etc.) measured in routine blood workup, even if they correlate with motor neuron loss, disability, and survival [ 119 , 120 , 121 , 122 , 123 ]. Concentrations of the extracellular domain of the common neurotrophin receptor (p75 ECD ) in urine have been reported to reflect motor neuron loss and disease progression as they increase over the course of disease.…”