We previously reported that human kidney transplants with early acute kidney injury (AKI) biopsied in the first six weeks express transcripts indicating injury-repair (IRRATs). Expression of the IRRATs correlated with both delayed graft function (DGF) and worse eGFR. The present study investigated the expression of IRRATs (the AKI signal) in kidney biopsies taken late (> 1 year post-transplant) for indications other than AKI. Our hypothesis was that the molecular AKI signal is detectable in patients presenting late and may be related to the future graft outcome. We analyzed microarray data for 186 patients, defining the AKI signal as the summarized expression of the top 30 IRRATs. The collagen (COL) signal was the summarized expression of fibrillar collagen transcripts (GO category) and served as a molecular surrogate of fibrosis. AKI and COL signals were determined for all biopsies. We studied the ability of the AKI signal in biopsies from patients presenting late (population at risk, with progressive diseases) to predict future graft loss, compared to variables such as scarring (ci), inflammation, eGFR at the biopsy, proteinuria and COL signal. For the prediction models we used only last biopsy per patient.

In univariate analysis, all variables were associated with future graft loss, but the best p value was for the AKI signal. In multivariate analysis, the AKI signal was the strongest predictor, followed by proteinuria and eGFR.

Fibrosis (ci), inflammation, diagnosis of a potentially progressive disease and COL signal were no longer significant. Thus the AKI signal, not fibrosis or inflammation, is the predictor of future graft loss in late kidney transplants undergoing indication biopsies.

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