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The effect of renal dysfunction and haemodialysis on circulating liver specific miR-122.

Abstract：

AIMS:microRNA-122 (miR-122) is a hepatotoxicity biomarker with utility in the management of paracetamol overdose and in drug development. Renal dysfunction and haemodialysis have been associated with a reduction in circulating microRNA. The objective of this study was to determine their effect on miR-122. METHODS:Blood samples were collected from 17 patients with end-stage renal disease (ESRD) on haemodialysis, 22 healthy controls, 30 patients with chronic kidney disease (CKD) and 15 patients post-kidney transplantation. All had normal standard liver function tests. Samples from ESRD patients were collected immediately pre- and post-haemodialysis. Serum alanine transaminase activity (ALT), miR-122 and miR-885 (liver enriched) were compared. RESULTS:Circulating miR-122 was substantially reduced in ESRD patients pre-haemodialysis compared with the other groups (19.0-fold lower than healthy controls; 21.7-fold lower than CKD). Haemodialysis increased miR-122 from a median value of 6.7 × 103 (2.3 × 103 -1.4 × 104 ) to 1.6 × 104 (5.4 × 103 -3.2 × 104 ) copies ml-1 . The increase in miR-122 did not correlate with dialysis adequacy. miR-122 was reduced in the argonaute 2 bound fraction pre-haemodialysis; this fraction was increased post-dialysis. There was no change in miR-122 associated with extracellular vesicles. miR-885 was also reduced in ESRD patients (4-fold compared to healthy subjects) and increased by haemodialysis. CONCLUSION:miR-122 is substantially lower in ESRD compared to healthy controls, patients with CKD and transplanted patients. Haemodialysis increases the concentration of miR-122. These data need to be considered when interpreting liver injury using miR-122 in patients with ESRD on dialysis, and specific reference ranges that define normal in this setting may need to be developed.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Rivoli L,Vliegenthart AD,de Potter CM,van Bragt JJ,Tzoumas N,Gallacher P,Farrah TE,Dhaun N,Dear JW

doi

10.1111/bcp.13136

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

584-592

issue

eissn

0306-5251

issn

1365-2125

journal_volume

pub_type

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The effect of renal dysfunction and haemodialysis on circulating liver specific miR-122.