Plasma creatinine and amyotrophic lateral sclerosis prognosis: a systematic review and meta-analysis

<i>Background</i>: Plasma creatinine has been described as a prognostic biomarker for Amyotrophic Lateral Sclerosis (ALS), but with conflicting results in the literature. We performed a systematic review followed by a meta-analysis to address this question. <i>Methods</i>: We performed a systematic review of Pubmed, Embase and Cochrane databases and retrieved 14 distinct cohorts (19 studies) reporting results regarding the relationship between plasma creatinine and a clinical marker for ALS progression, notably ALSFRS (ALS Functional Rating Scale) and survival. <i>Results</i>: For baseline plasma creatinine, mortality risk was 28% lower when creatinine was higher than 88.4 µmol/L (hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.58 to 0.88; <i>p</i> = 0.0003) and was 25% lower if creatinine was above versus below the median (HR: 0.75; 95% CI: 0.63 to 0.89; <i>p</i> = 0.0008). We found a significant positive correlation between plasma creatinine at baseline and functional score, and between creatinine decline and functional score decline (<i>p</i> p = 0.033). The overall quality of the studies was low mainly due to potential attrition bias, and several studies did not report analyzable results raising concern regarding a potential reporting bias. <i>Conclusions</i>: Plasma creatinine seems to be a promising prognostic biomarker for ALS. However, new studies with sound methodology and standardized criteria for the evaluation of ALS progression should be conducted to validate plasma creatinine as a clinical biomarker for ALS prognosis.