John M O'Callaghan1, Simon R Knight. 1. Nuffield Department of Surgical Sciences, Centre for Evidence in Transplantation, University of Oxford, Oxford, UK.
Abstract
PURPOSE OF REVIEW: A key aspect of posttransplant management is to identify and treat graft injury before it becomes irreversible. The gold-standard for detection is histology, but biopsy is uncomfortable for the patient and carries a risk of complications. Detection of changes at a molecular level may preempt histological injury, and thereby identify injury earlier. RECENT FINDINGS: Indicators of immune system activation, such as candidate chemokines CXCL9 and CXCL10, and by-products of neutrophil activity, have been related to acute rejection and early allograft function. Transcriptomic studies of multiple-gene panels have identified candidate combinations that have proven very promising in risk-stratification and prediction of acute rejection, as well as diagnosis of both T-cell-mediated and antibody-mediated rejection. Serum and urine cell-free DNA is also a promising area of investigation, particularly in antibody-mediated rejection. SUMMARY: Noninvasive, rapid, and accurate tests for risk-prediction and diagnosis in renal transplant allografts are urgently required. The ideal candidate is one that can be measured in either urine or blood, is cheap, and is both sensitive and specific for the condition of interest. Numerous strategies have been proposed, with varying degrees of clinical and preclinical success. A few that meet the essential criteria have been evaluated; a few have made it as far as clinical testing.
PURPOSE OF REVIEW: A key aspect of posttransplant management is to identify and treat graft injury before it becomes irreversible. The gold-standard for detection is histology, but biopsy is uncomfortable for the patient and carries a risk of complications. Detection of changes at a molecular level may preempt histological injury, and thereby identify injury earlier. RECENT FINDINGS: Indicators of immune system activation, such as candidate chemokines CXCL9 and CXCL10, and by-products of neutrophil activity, have been related to acute rejection and early allograft function. Transcriptomic studies of multiple-gene panels have identified candidate combinations that have proven very promising in risk-stratification and prediction of acute rejection, as well as diagnosis of both T-cell-mediated and antibody-mediated rejection. Serum and urine cell-free DNA is also a promising area of investigation, particularly in antibody-mediated rejection. SUMMARY: Noninvasive, rapid, and accurate tests for risk-prediction and diagnosis in renal transplant allografts are urgently required. The ideal candidate is one that can be measured in either urine or blood, is cheap, and is both sensitive and specific for the condition of interest. Numerous strategies have been proposed, with varying degrees of clinical and preclinical success. A few that meet the essential criteria have been evaluated; a few have made it as far as clinical testing.
Authors: Meera N Harhay; Maya K Rao; Kenneth J Woodside; Kirsten L Johansen; Krista L Lentine; Stefan G Tullius; Ronald F Parsons; Tarek Alhamad; Joseph Berger; XingXing S Cheng; Jaqueline Lappin; Raymond Lynch; Sandesh Parajuli; Jane C Tan; Dorry L Segev; Bruce Kaplan; Jon Kobashigawa; Darshana M Dadhania; Mara A McAdams-DeMarco Journal: Nephrol Dial Transplant Date: 2020-07-01 Impact factor: 5.992