Altered Expression of MicroRNAs Following Chronic Allograft Dysfunction with Interstitial Fibrosis and Tubular

Ehsan Soltaninejad1, Mohammad Hossein Nicknam2, Mohsen Nafar3

  • 1Department of Immunology, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Insights

Specific microRNAs (miRNAs) show altered expression in kidney transplant biopsies and blood samples from patients with chronic allograft dysfunction (CAD) and interstitial fibrosis and tubular atrophy (IFTA). These miRNAs could serve as biomarkers for diagnosing CAD and predicting graft function.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Immunology

Background:

  • Chronic allograft dysfunction (CAD) is the primary cause of renal transplant failure, characterized by interstitial fibrosis and tubular atrophy (IFTA).
  • MicroRNAs (miRNAs) play crucial roles in biological processes, including immune responses, and are potential regulators of transplant outcomes.

Purpose of the Study:

  • To investigate differential expression of miR-142-5p, miR-142-3p, and miR-211 in renal allograft biopsies and peripheral blood mononuclear cells (PBMCs) from patients with CAD and IFTA.
  • To determine if these miRNA expressions can serve as diagnostic biomarkers for CAD with IFTA and predict renal allograft function.

Main Methods:

  • Samples from 16 CAD with IFTA patients and 17 normal allograft recipients were analyzed.
  • Taqman MicroRNA Assays were used to quantify the expression levels of miR-142-5p, miR-142-3p, and miR-211 in both biopsy and PBMC samples.
  • Receiver Operating Characteristic (ROC) curve analysis was performed to assess diagnostic and predictive capabilities.

Main Results:

  • miR-142-5p and miR-142-3p were significantly upregulated in renal allograft tissues of CAD with IFTA patients compared to normal allografts (p<0.0001).
  • miR-211 was significantly downregulated in renal allograft tissues (p<0.0001).
  • In PBMCs, miR-142-3p was significantly upregulated and miR-211 was significantly downregulated (p<0.0001).
  • ROC analysis indicated miR-142-5p (biopsy), and miR-142-3p and miR-211 (both biopsy and PBMC) are potential diagnostic biomarkers for CAD with IFTA and predictors of allograft function.

Conclusions:

  • Differential expression of miR-142-5p, miR-142-3p, and miR-211 occurs in both kidney allograft biopsies and PBMCs of patients with CAD and IFTA.
  • PBMC-derived miRNAs show promise as non-invasive biomarkers for monitoring post-transplant status and predicting kidney graft function and CAD.
  • These findings suggest potential for using circulating miRNAs as accessible biomarkers for kidney transplant management.

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