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

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.