The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

Roedder, Silke; Sigdel, Tara K.; Salomonis, Nathan; Hsieh, Szu‐Chuan; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Adriana; Gritsch, Albin; Cheeseman, Jennifer A.; Macedo, Camila; Peddy, Ram; Medeiros-Domingo, Mara; Vincenti, Flavio; Asher, Nancy; Salvatierra, Oscar; Shapiro, Ron; Kirk, Allan D.; Reed, Elaine F.; Sarwal, Minnie M.

doi:10.1371/journal.pmed.1001759

Cited by 151 publications

(129 citation statements)

References 41 publications

(73 reference statements)

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“…32) and multigene assays to diagnose rejection 33,34 . Other tests have used urine and identi fied mRNAs encoding CD3ε and IP10 as well as 18S ribosomal RNA to diagnose T cellmediated rejection (TCMR) 35 ; and mRNA encoding vimentin, the sodiumpotassium-chloride cotransporter NKCC2, Ecadherin, and 18S ribosomal RNA to predict fibrosis 36 .…”

Section: Key Pointsmentioning

confidence: 99%

Molecular assessment of disease states in kidney transplant biopsy samples

2016

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Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis. TCMR and ABMR share IFNγ-mediated effects and TCMR has emerged as a cognate T cell-antigen presenting cell process in the interstitium, whereas ABMR is a natural-killer-cell-mediated process that occurs in the microcirculation. The specific features of these different processes have led to the creation of classifiers to test for TCMR and ABMR, and revealed that ABMR is the principal cause of kidney transplant deterioration. The molecular changes associated with renal injury are often more extensive than suggested by histology and indicate that the progression to graft failure is caused by continuing nephron injury, rather than fibrogenesis. In summary, advances in the molecular assessment of disease states in biopsy samples has improved understanding of specific processes involved in kidney graft outcomes.

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Section: Key Pointsmentioning

confidence: 99%

Molecular assessment of disease states in kidney transplant biopsy samples

2016

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“…Obviously, before the implementation in clinical practice, larger clinical studies of a ddcfDNA-based algorithm are needed alongside other molecular diagnostic methods of graft rejection (18,19).…”

Section: Liver Allograftsmentioning

confidence: 99%

“…This gene expression profiling assay has been investigated and validated in cardiac transplant recipients and has been included in the current heart transplantation guidelines to rule out the presence of a moderate to severe acute rejection in low-risk patients between 6 months and 5 years after transplantation (12). In the field of kidney transplantation, the use of the kSORT (kidney solid organ response test)-a peripheral blood gene set assay-has been investigated to identify patients at high risk of acute rejection (19). However, as discussed recently (20), more studies are needed to validate its predictive ability.…”

Section: Introductionmentioning

confidence: 99%

Cell-Free DNA: An Upcoming Biomarker in Transplantation

Gielis

Ledeganck

Winter

et al. 2015

American Journal of Transplantation

149

104

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“…Based upon this and other publications, 51,52 the same group of researchers has subsequently developed a 17-gene qPCR based assay (kidney solid organ response test (kSORT) assay) from peripheral blood of both adult and pediatric recipients that diagnosed AR with an AUC of 0.94 in the development cohort (n=143), and was validated with an AUC of 0.95 in a separate validation cohort (n=124). 53 Prospective studies using this panel are ongoing. Reeve et al studied 403 allograft biopsies (divided into development and validation cohorts) and compared transcriptional profiles of histologically confirmed ACR (with/without ABMR lesions) to biopsies with other diagnosis in a supervised manner.…”

Section: Genomics Of Acute Rejectionmentioning

confidence: 99%

The Use of Genomics and Pathway Analysis in Our Understanding and Prediction of Clinical Renal Transplant Injury

et al. 2016

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The development and application of high-throughput molecular profiling have transformed the study of human diseases. The problem of handling large, complex datasets has been facilitated by advances in complex computational analysis. In this review the recent literature regarding the application of transcriptional genomic information to renal transplantation, with specific reference to acute rejection, acute kidney injury in allografts, chronic allograft injury and tolerance is discussed, as is the current published data regarding other “omics” strategies- proteomics, metabolomics and the micro-RNA transcriptome. These data have shed new light on our understanding of the pathogenesis of specific disease conditions following renal transplantation but their utility as a biomarker of disease has been hampered by study design and sample size. This review aims to highlight the opportunities and obstacles that exist with genomics and other related technologies in order to better understand and predict renal allograft outcome.

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The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

Abstract: Minnie Sarwal and colleagues developed a gene expression assay using peripheral blood samples to detect patients with renal transplant at high risk for acute rejection. Please see later in the article for the Editors' Summary

Cited by 151 publications

References 41 publications

Molecular assessment of disease states in kidney transplant biopsy samples

Molecular assessment of disease states in kidney transplant biopsy samples

Cell-Free DNA: An Upcoming Biomarker in Transplantation

The Use of Genomics and Pathway Analysis in Our Understanding and Prediction of Clinical Renal Transplant Injury

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