MiRNA in Kidney Transplantation: Association With Kidney Graft Function and Disease Process

ASSOCIATION OF miRNA WITH ALLOGRAFT FUNCTION AND EXPRESSION PROFILES PREDICTIVE OF DISEASES OCCURING AFTER KIDNEY TRANSPLANTATION

MicroRNAs (miRNAs) belong to a class of small non-coding RNAs that modulate physiological and pathological processes by post-transcriptional regulation of gene expression mainly via translational inhibition of target messenger RNAs. Recently, many miRNAs were found to be involved in pathological processes that occur following kidney transplantation, like allograft rejection, de novo disease or disease recurrence after kidney transplantation. As most of the miRNAs involved in kidney diseases are extracted by urine, the diagnostic accuracy of such molecules as biomarkers is questionable.

The aim of this study is to analyze expression of selected miRNAs (miR-29c, miR-126, miR-146a, miR-150, miR-155, miR-223) and evaluate whether their regulation is associated with kidney graft function and disease processes after kidney transplantation (KTx).

MicroRNAs (miRNA) are short, endogenous non-coding RNAs involved in the modulation of gene expression mainly by inhibition of messenger RNAs translation. Recent studies have indicated association of miRNAs with pathological processes following kidney transplantation.

The aim of the study is to determine whether selected miRNAs are related to specific disease process or only reflect kidney graft function.

The study enrolled 100 Caucasian KTRs, who presented with stable renal function (as indicated by stable serum creatinine (Cr) for 3 months and whose kidney graft function was thereafter estimated with various methods, including: cystatin C concentration, three different CKD EPI equations and measured with chromium-51 ethylenediamine tetraacetic acid clearance.

Expression of 6 selected miRNAs (miR-29c, miR-126, miR-146a, miR-150, miR-155, and miR-223) was determined by qPCR using miRNA-103a, miR-191, and miR-423 as reference genes.

Inclusion criteria:

• time of kidney transplantation at least 2 years before the study entry,
• stable function of the transplanted kidney during the previous 3 months (changes in s-creatinine ≤ 20%).

Exclusion criteria:

• age less than 18 years,
• symptomatic heart failure,
• malignancy,
• pregnancy or lactation,
• acute conditions and diseases that can affect the GFR,
• newly-introduced drugs that may affect the function of the graft,
• treatment with trimethoprim-sulfamethoxazole or cimetidine,
• the presence of a pacemaker or any other electronic device in the body.