Metabolomics: Perspectives on potential biomarkers in organ transplantation and immunosuppressant toxicity

• The basics of metabolomics and analytical strategies used in the field are presented.
• Potential applications of metabolomics in organ transplantation including acute rejection diagnosis, immunosuppressant toxicity, ischemia/reperfusion injuries and delayed graft function are covered.
• Relevant metabolites in organ transplantation are summarized in Table 2.
• The most promising metabolites and limitations of metabolomics are discussed.

Organ transplantation is the treatment of choice for many end stage diseases. The development and appropriate use of new immunosupressants have considerably improved the outcome of patients in the last decades. However, noninvasive, sensitive and specific biomarkers for early detection of complications leading to graft dysfunction are still needed. Current transplantation monitoring mostly relies on non-specific biochemical tests whereas diagnosis of rejection is generally based on invasive procedures such as biopsies. New approaches based on large scale profiling of body fluids and tissues are needed to address the complexity and multifactorial aspect of organ transplantation complications. Metabolomics aim to characterize and quantify the metabolome, which is the collection of the low-molecular weight compounds rising from metabolic pathways. Extracted from tissues or detected in body fluids, the small molecules are measured using nuclear magnetic resonance spectroscopy or mass spectrometry. By profiling the downstream products of cellular activity, metabolomics is most likely to represent the immediate cellular response to stresses. Diagnostic applications have been proposed in cancer, cardiovascular diseases, kidney diseases, neurological diseases and many more. This review will focus on the potential applications of metabolomics in organ transplantation including follow up of graft function recovery, diagnostic of alloimmune rejection as well as monitoring of immunosuppressant toxicity.