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

Laura Rivoli, Bastiaan Vliegenthart, Carmelita de Potter, Job van Bragt, Nikolaos Tzoumas, Peter Gallacher, Tariq Farrah, Neeraj Dhaun, James Dear

Research output: Contribution to journalArticlepeer-review

Abstract

Aim
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 6.7x103 (2.3x103–1.4x104) to 1.6x104 (5.4x103–3.2x104) copies/mL. 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 extra-cellular vesicles. miR-885 was also reduced in ESRD patients (4-fold compared to health) and increased by haemodialysis.


Conclusion
miR-122 is substantially lower in ESRD compared to health, 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.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Early online date21 Sep 2016
DOIs
Publication statusE-pub ahead of print - 21 Sep 2016

Fingerprint

Dive into the research topics of 'The effect of renal dysfunction and haemodialysis on circulating liver specific miR-122'. Together they form a unique fingerprint.

Cite this