Comparing molecular assessment of implantation biopsies with histologic and demographic risk assessment

Abstract

We hypothesized that measurement of previously defined acute kidney injury-induced transcripts at the time of implantation would add a new dimension to existing methods based on donor factors, histology and recipient factors. We analyzed microarray results from implantation biopsies taken after reperfusion from 70 kidneys from 53 deceased donors. We used two definitions of early dysfunction: serum creatinine > 265 umol/L at day 7 posttransplant; and dialysis in the first week. The strongest correlate with early dysfunction was the mean expression of 30 injury transcripts. Older donor and recipient age were associated with early dysfunction, but histologic lesions were not. Prediction was best when the injury transcript expression was combined with donor or recipient age, particularly in standard criteria donors. In contrast, although extended criteria donor kidneys had a high risk of early dysfunction, no variables tested, including injury transcripts, predicted risk significantly, probably because these kidneys were allocated preferentially to old, high risk recipients. The injury transcripts did not predict late function, which was mainly associated with donor age. Thus, measurement of injury-induced transcripts at the time of implantation improves the prediction of early kidney dysfunction, but risk prediction may fail when old kidneys are transplanted into old recipients. The molecular acute kidney injury signal, measured by microarrays, emerges as the best predictor of early function in standard criteria deceased donor kidney transplants, but the application of this test to extended criteria donor kidneys is less predictive because donor age and allocation of such kidneys to high-risk recipients contribute to both short-term and long-term dysfunction. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.