MicroRNAs as biomarkers of acute antibody-mediated rejection in renal transplant patients.

Background: Rejection remains the main cause of renal graft loss, currently the gold standard for diagnosis is by allograft biopsy, being an invasive procedure and not free of complications. It has been suggested that variation in the expression of miRNAs could be a promising biomarker for the diagnosis of renal pathologies. The aim of this study was to analyze miRNAs involved in microvascular damage in plasma of patients with suspected acute antibody-mediated rejection (ABMR).

Material and methods: We carried out a cross-sectional investigation involving adult kidney transplant recipients. Our inclusion criteria encompassed patients with an estimated glomerular filtration rate (eGFR) equal to or exceeding 20 ml/min/1.73 m2 and a post-transplant period beyond 12 weeks. This study took place at the Instituto Nacional de Cardiología Ignacio Chávez. The study cohort comprised 27 renal transplantation (RT) patients, with 15 having ABMR and 12 without ABMR. We conducted plasma miRNA quantification using RT-qPCR to assess a total of 5 miRNAs. Additionally, we examined the clinical relevance of these miRNAs and their correlation with the histological characteristics of patients with ABMR.

Results: Of the 5 miRNAs in the ABMR group (miR-1, miR-21, miR-126, miR-150-5p, and miR-155-5p), miR-150-5p was significantly increased in plasma with respect to patients without rejection (p=0.0012) Figure 1. In addition, significant changes were found in miR-150-5p expression and histopathological findings of microvascular inflammation, glomerulitis (p=0.046), and peritubular capillaritis (p=0.011), showing a moderate correlation with the degree of inflammation in both glomerular and peritubular capillaries, and not so with other histological lesions both acute and chronic, Figure 2. Its clinical utility was determined by ROC analysis with an area under the curve of 0.873. 

Conclusion: Our findings indicate that patients with RT and RAMA show a significant increase in miR-150-5p expression levels compared to those without rejection. This increase could have clinical implications, in addition to suggesting a possible utility of miR-150-5p as a biomarker in the early diagnosis of ABMR in RT.