Circulating let-7g-5p and miR-191-5p are independent predictors of chronic kidney disease in hypertensive patients

BACKGROUND: Hypertension is associated with target organ damage such as cardiac, vascular and kidney injury. Several studies have investigated circulating microRNAs as biomarkers of cardiovascular disease, but few have examined them as biomarker of target organ damage in hypertension. We aimed to identify circulating microRNAs that could serve as biomarkers of hypertension-induced target organ damage using an unbiased approach. METHODS AND RESULTS: Fifteen normotensive subjects, 16 hypertensive patients, 15 with hypertension associated with other features of the metabolic syndrome (MetS) and 16 with hypertension or chronic kidney disease (CKD) were studied. Circulating RNA extracted from platelet-poor plasma was used for small RNA sequencing. Differentially expressed (DE) genes were identified with a threshold of false discovery rate <0.1. DE microRNAs were identified uniquely associated with hypertension, MetS or CKD. However, only two down-regulated DE microRNAs (let-7g-5p and miR-191-5p) could be validated by reverse transcription-quantitative PCR. Let-7g-5p was associated with large vessel stiffening, miR-191-5p with MetS, and both microRNAs with estimated glomerular filtration rate (eGFR) and neutrophil and lymphocyte fraction or number and neutrophil to lymphocyte ratio. Using the whole population, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191-5p and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.46 (P=8.5e-7). CONCLUSIONS: We identified decreased circulating let-7g-5p and miR-191-5p as independent biomarkers of chronic kidney disease among patients with hypertension, which could have pathophysiological and therapeutic implications.