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A molecular classifier for predicting future graft loss in late kidney transplant biopsies
Gunilla Einecke, … , Bruce Kaplan, Philip F. Halloran
Gunilla Einecke, … , Bruce Kaplan, Philip F. Halloran
Published May 24, 2010
Citation Information: J Clin Invest. 2010;120(6):1862-1872. https://doi.org/10.1172/JCI41789.
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Research Article Article has an altmetric score of 3

A molecular classifier for predicting future graft loss in late kidney transplant biopsies

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Abstract

Kidney transplant recipients that develop signs of renal dysfunction or proteinuria one or more years after transplantation are at considerable risk for progression to renal failure. To assess the kidney at this time, a “for-cause” biopsy is performed, but this provides little indication as to which recipients will go on to organ failure. In an attempt to identify molecules that could provide this information, we used micorarrays to analyze gene expression in 105 for-cause biopsies taken between 1 and 31 years after transplantation. Using supervised principal components analysis, we derived a molecular classifier to predict graft loss. The genes associated with graft failure were related to tissue injury, epithelial dedifferentiation, matrix remodeling, and TGF-β effects and showed little overlap with rejection-associated genes. We assigned a prognostic molecular risk score to each patient, identifying those at high or low risk for graft loss. The molecular risk score was correlated with interstitial fibrosis, tubular atrophy, tubulitis, interstitial inflammation, proteinuria, and glomerular filtration rate. In multivariate analysis, molecular risk score, peritubular capillary basement membrane multilayering, arteriolar hyalinosis, and proteinuria were independent predictors of graft loss. In an independent validation set, the molecular risk score was the only predictor of graft loss. Thus, the molecular risk score reflects active injury and is superior to either scarring or function in predicting graft failure.

Authors

Gunilla Einecke, Jeff Reeve, Banu Sis, Michael Mengel, Luis Hidalgo, Konrad S. Famulski, Arthur Matas, Bert Kasiske, Bruce Kaplan, Philip F. Halloran

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Figure 4

Relationship between risk score and failure/censoring time.

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Relationship between risk score and failure/censoring time.
Time to even...
Time to event (graft failure, patient death, or end of follow-up) is plotted against the molecular risk score for each biopsy. Each biopsy is represented by one symbol. Biopsies from patients with subsequent graft loss are represented as black triangles; biopsies from patients who died with a functioning graft are represented by asterisks. All other biopsies are represented by white triangles. Regression lines were drawn separately for patients censored for end of study, those censored for patient death with a functioning graft, and those with graft loss.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 5 patents
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