Published online Dec 24, 2015. doi: 10.5500/wjt.v5.i4.251
Peer-review started: August 13, 2015
First decision: September 17, 2015
Revised: October 31, 2015
Accepted: November 17, 2015
Article in press: November 25, 2015
Published online: December 24, 2015
Processing time: 133 Days and 0.8 Hours
Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B mRNAs, FOXP3 mRNA, CXCL9/CXCL10 and miRNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.
Core tip: Through its urine output, the transplanted kidney can provide a window into the cellular and molecular events occurring within the graft, and potentially offers a noninvasive means of assessing kidney allograft status. An assay consisting of biomarkers of allograft injury using only urine samples from transplant recipients could provide many advantages over the current strategy of relying on changes in the serum creatinine and kidney biopsies. A rising creatinine is a nonspecific marker of graft dysfunction and a relative late marker of intragraft pathology, whereas kidney biopsies are inherently invasive. The role of non-invasive monitoring through plasma or urine biomarkers has been a topic of interest to the transplant community for many years and has been the subject of numerous publications. Our objective is to critically review the current literature to better delineate the role of these urinary biomarkers in predicting the risk of acute allograft rejection in kidney transplant recipients.