Delineating a miR Signature in Patients with End Stage Renal Disease to Mitigate Left Ventricular Hypertrophy

Abstract

Identifying the differential expression of microRNAs (miRs) in end-stage renal disease (ESRD)patients may be indispensable for advancing therapeutic targets in this patient population. The dysregulation of Fibroblast Growth Factor 23 (FGF23) and Klotho has been strongly linked to ESRD, particularly by contributing to left ventricular hypertrophy (LVH). Nocturnal hemodialysis (NHD) offers notable physiological benefits over conventional hemodialysis (CHD) modalities, primarily by attenuating LVH. Therefore, it was hypothesized that the differential expression of miRs in patients transitioning from CHD to NHD may regulate LVH through modulating Klotho and FGF23 signaling. We identified six miRs in the serum of patients who transitioned to NHD, with downstream targets involved in the FGF23/Klotho signaling axis. Targeted inhibition of miR-200c-3p and FGF23 resulted in mitigation of LVH and attenuation of fibrosis by downregulating key signaling mediators in this axis. These findings present a novel therapeutic approach for addressing cardiac complications in ESRD patients.