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).

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Failure and Rejection
• Intervention / Treatment: Diagnostic test: miRNA expression

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study included 100 kidney transplant recipients (KTRs) with at least 3 months of stable kidney graft function established with estimated GFR (eGFR) according to CKD Epidemiology Collaboration equations, serum creatinine concentration (CKD-EPI Cr), serum cystatin C concentration (CKD-EPI CysC) and measured GFR with 51Cr-EDTA clearance.

Evaluation of kidney graft function was subject to previous, already completed, and published study (Borštnar Š, et al. Clin Nephrol. 2019;92(6):287-292. doi:10.5414/CN109882). Serum samples from patients participating in this study (taken at the moment of 51Cr-EDTA clearance measurement) were further analyzed in the contemporary study.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of miRNA and kidney graft function	correlation of selected miRNAs expression with parameters of kidney graft function	sample collection within one month of enrollement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of miRNAs expression and kidney graft rejection or disease recurrence	Correlation of selected miRNAs expression and kidney graft rejection or disease recurrence	2 years

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: miRNA; kidney transplant function; kidney transplant rejection; disease recurrence; cystatin; micro RNA
• Other Study ID Numbers: P20190104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No