Overview of the Use of RNA Biomarkers to Detect Kidney Acute Rejection

Dany Anglicheau, Service de Transplantation Adulte & Hôpital Necker, Paris, France

Learning Objectives:

1. To describe the rationale for developing noninvasive biomarkers.

2. To define and characterize what would be a good biomarker in renal transplantation.

3. To review the potential application of RNA markers of renal allograft status and their value in predicting acute rejection and fibrosis of the renal allograft.

Organ graft recipients treated with life-long immunosuppressive drugs have a heightened risk of infection and malignancy, whereas insufficient immunosuppressive drug exposure or interruption of drug therapy often increases rejection risk. Development of predictive, diagnostic and prognostic biomarkers of allograft status and outcome is important and challenging, and may be rewarded with individualized therapy of the organ graft recipient.

The current gold standard test for the diagnosis of allograft status remains histological examination of the allograft biopsy. The development and clinical application of mechanistically informative assays for the characterization of alloimmune responses remain formidable challenges in organ transplantation. Ideally, these tools should identify rejection without resorting to invasive procedures, as well as provide reliable indices of the host’s immune status for customizing immunosuppressive drug therapy.

The improved understanding of mechanisms of alloimmune response has led to hypothesis-driven candidate molecular markers for the evaluation of the transplant patient. Recent studies have also focused on noninvasive tests of easily accessible biological fluids such as urine and peripheral blood. We will review recent developments in the field of molecular monitoring of the solid organ transplant recipient.This overview will discuss mainly results obtained with hypothesis-driven candidate mRNA expression patterns ascertained in urine, blood, and allograft tissue; the clinical application of genome-wide analysis will be also briefly addressed since interrogation of the whole transcriptome should yield finer texture to the mechanistic basis for graft dysfunction, rejection, and transplant tolerance. These complementary nucleic acid-based biomarker strategies should ultimately enable the development of personalized management for the organ graft recipient. Ongoing multi-center trials should help further define the clinical utility of noninvasively developed mRNA profiles as biomarkers of allograft status and outcome.