Advances in biomarkers of acute allograft rejection and interstitial fibrosis/tubular atrophy in kidney transplantation; future perspective and challenges in clinical implementation

Abstract

Acute rejection (AR) and interstitial fibrosis/tubular atrophy (IFTA) are significant complications of kidney transplantation that have a negative impact on renal graft lifespan. Kidney transplant monitoring is currently performed with the use of on nonspecific biomarkers (serum creatinine and proteinuria) which have significant limitations and detect AR and IFTA only after significant damage to the kidney has been done. Moreover, many transplant patients are found to have histological evidence of rejection despite a stable creatinine (subclinical rejection - SCR). The "gold standard" diagnostic test for AR and IFTA is the transplant biopsy that also comes with limitations and can have major complications; therefore, it is not an ideal test for routine graft monitoring. The use of novel non-invasive (blood and urine) and invasive (graft biopsy) biomarkers, partly driven by advances in omics technologies, can lead to earlier and more accurate detection of AR/SCR and IFTA and to improved graft monitoring. The identification of the immunological pathways of AR/IFTA may also enable the design of tailormade treatments. This minireview provides a state-of-the-art update on current evidence and limitations from key studies on non-invasive and invasive biomarkers of AR/SCR and IFTA and gives a perspective on their potential future implementation and the underlying challenges.

Keywords: Acute rejection; Biomarkers; Cell-free DNA; Interstitial fibrosis; Kidney transplantation; Multi-omics; Subclinical rejection; Tubular atrophy.