ERA-EDTA 2019 | Shedding a new light: The implication of microRNAs in chronic kidney disease

Development of disease is often related to the deregulation of a gene program controlled at the post-transcriptional level by microRNAs (miRNAs). A new review [1], published in Nephrology Dialysis Transplantation during this week’s ERAEDTA Congress in Copenhagen, shows that miRNAs are potential innovative biomarkers, and are promising as groundbreaking drugs. “The review of Laurent Metzinger and colleagues summarizes the current state of art of the research on miRNAs in kidney disease”, explains Professor Denis Fouque, editor-in-chief of Nephrology, Dialysis, Transplantation (NDT).

This review describes how miRNAs were shown in recent years to be implicated not only in cellular and animal models of kidney disease, but also in chronic kidney disease (CKD), hemodialysis and transplant patients, as well as in acute kidney injury patients.

The working group of Metzinger et al. has already shown that miR-126 and miR-223 are implicated in CKD and are associated with vessel damage, such as vascular calcification and atherosclerosis. miR-223 is increased in vitro in vascular smooth muscle cells subjected to uremic toxins and also in vivo in aortas of a murine model of CKD [2] miR-126 and miR-223 levels have been found to be deregulated in murine and human serum in the course of experimental CKD and in human diabetic patients. [2, 3] Previously it was shown that miR223 play a role in monocyte differentiation into osteoclast in the context of chronic kidney disease-mineral and bone disorder [4].

Nowadays miRNAs are considered to be promising biomarkers in nephrology, but larger cohorts, as well as the standardization of methods of measurement, will be needed to confirm their usefulness. It will also be of the utmost importance to select biofluids and specific tissues to make miRNAs appropriate in day-to-day clinical practice. In addition, upor down-regulating miRNAs that were described as deregulated in kidney diseases may represent novel therapeutic ways to cure these disorders. The review outlines the most recent methods that could be used to deliver miRNAs in a specific and suitable way to the kidney and other organs damaged by kidney failure.

“The review of Laurent Metzinger and colleagues summarizes the current state of art of the research on miRNAs in kidney disease”, explains Professor Denis Fouque, editor-in chief of Nephrology, Dialysis, Transplantation (NDT). Taken together, the findings shed new light on the molecular mechanisms involved in CKD.

References:
[1] Metzinger-Le Meuth et al. The expanding roles of microRNAs in kidney pathophysiology. Nephrol Dial Transplant 2018
[2] Taibi F, Metzinger-Le Meuth V, M'Baya-Moutoula E, et al. Possible involvement of microRNAs in vascular damage in experimental chronic kidney disease. Biochim Biophys Acta 2014; 1842: 88- 98
[3] Metzinger-Le Meuth V, Burtey S, Maitrias P, et al. microRNAs in the pathophysiology of CKDMBD: Biomarkers and innovative drugs. Biochim Biophys Acta 2017; 1863: 337-345
[4] M'Baya-Moutoula E, Louvet L, Metzinger-Le Meuth V, et al. High inorganic phosphate concentration inhibits osteoclastogenesis by modulating miR-223. Biochim Biophys Acta 2015;1852(10 Pt A): 2202-2212