Circulating miRNA 122-5p Expression Predicts Mortality and Cardiovascular Events in Chronic Hemodialysis Patients: A Multicentric, Pilot, Prospective Study

Background: Despite patients undergoing chronic hemodialysis (HD) being notoriously prone to adverse cardiovascular (CV) events, risk prediction in this population remains challenging. miRNA 122-5p, a short, non-coding RNA predominantly involved in lipid and carbohydrate metabolism, has recently been related to the onset and progression of CV disease. Methods: We run a pilot, multicenter, longitudinal, observational study to evaluate the clinical significance and prognostic usefulness of circulating miRNA 122-5p in a multicentric cohort of 74 individuals on maintenance HD. Results: Patients displayed lower circulating miRNA 122-5p as compared to healthy controls (p = 0.004). At correlation analyses, ALT (beta = 0.333; p = 0.02), E/e' (beta = 0.265; p = 0.02) and CRP (beta = -0.219; p = 0.041) were independent predictors of miRNA 122-5p levels. During a median follow-up of 22 months (range of 1-24), 30 subjects (40.5%) experienced a composite endpoint of all-cause mortality and fatal/non-fatal CV events. Baseline circulating miRNA 122-5p was higher in these subjects (p = 0.01) and it predicted a significantly higher risk of endpoint occurrence (Kaplan-Meier crude HR 3.192; 95% CI 1.529-6.663; p = 0.002; Cox regression adjusted HR 1.115; 95% CI 1.009-1.232; p = 0.03). Conclusions: Altered miRNA 122-5p levels in HD patients may reflect hepatic and CV damage and may impart important prognostic information for improving CV risk prediction in this particular setting.

Automated summary

Patients undergoing chronic hemodialysis (HD) are at high risk of cardiovascular (CV) events, but risk prediction in this population is challenging. Recent research has shown that circulating miRNA 122-5p is related to the onset and progression of CV disease. This study found that HD patients had lower levels of circulating miRNA 122-5p compared to healthy controls. ALT, E/e', and CRP were identified as independent predictors of miRNA 122-5p levels. Additionally, higher baseline levels of circulating miRNA 122-5p predicted a significantly increased risk of composite endpoint occurrence in HD patients.