Circulating microRNAs as biomarkers of chronic kidney disease and its association with renal and cardiovascular outcomes in non-dialysis patients

Abstract

Chronic kidney disease (CKD) affects over 10% of the population worldwide and entails a significant risk for cardiovascular disease (CVD), leading to a 500-fold increase in cardiovascular mortality in advanced stages. Still, the pathophysiological mechanisms underlying kidney-heart intercommunication remain largely unknown. In recent years, microRNAs (miRNAs) emerged as important key regulators of gene expression that may serve as biomarkers for several diseases, however, their role in kidney-heart crosstalk in CKD remains underexplored. In this study, we evaluated the expression of a miRNA panel in plasma samples from non-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow-up. Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients presenting a significant power to discriminate the disease state. Importantly, only miR-30c-5p was downregulated in early glomerular filtration rate (GFR) categories, being able to discriminate these CKD patients from non-diseased individuals. Concerning cardiovascular outcomes, miR-199a-5p was found to be associated with an increased frequency of CVD. When analyzing the major disease outcomes in a 5-year time, miR-199a-5p upregulation at baseline was associated with increased mortality, while miR-324-3p was downregulated in patients who progressed to more advanced stages of the disease. These findings highlight the involvement of novel circulating miRNAs in CKD onset and progression, and identify, for the first time, the enrollment of miR-199a-5p in kidney-heart pathophysiological crosstalk, paving the way for the establishment of new biomarkers and therapeutic targets for CKD and its outcomes.