Routine blood biochemical biomarkers in amyotrophic lateral sclerosis: Systematic review and cohort analysis

Abstract

Introduction: Blood biochemical biomarkers, including urate, creatinine, albumin, and creatine kinase, have been shown to be useful in ALS. To provide further information about the roles of these four biomarkers roles we performed a systematic review. In addition, we also performed a new study of the role of these biomarkers in predicting survival, using data from our local ALS cohort. Methods: (1) Using established databases and other sources, we searched for papers about the use of urate, creatinine, albumin, and creatine kinase as biomarkers in ALS. Included articles were reviewed for information about biomarker levels in ALS and controls, association with markers of functional decline, and survival. (2) For our local ALS cohort, we performed survival analysis, Cox-proportionate-hazard ratio and ROC curves to investigate the use of these biomarkers in predicting survival. Results: (1) For systematic review, 104 papers were included. There was some variability in the findings. For urate, there was evidence of decreased levels in ALS, with higher levels associated ith longer survival. For creatinine, there was evidence of decreased levels in ALS, and higher levels correlated with longer survival. For albumin, some reports of reduced levels in ALS, but no consistent association with survival. For creatine kinase, some reports of increased levels in ALS, with inconsistent association with survival. (2) For the local ALS cohort there was evidence that urate and creatinine were associated with survival, but no significant association with survival. There was less evidence for albumin and CK. Discussion: This study provides support for further studies of these readily available biochemical measurement as bioamerkers in ALS.

Keywords: Amyotrophic lateral sclerosis; albumin; biochemistry; biomarkers; creatine kinase; creatinine; disease progression; motor neurone disease; survival; urate.