Kidney transplantation is the most common type of organ transplant surgery in the United States with over 17,000 kidney transplantations performed in 2014, according to the National Kidney Foundation. However, long-term survival still remains a challenge. While there is no actual crystal ball to predict whether a transplanted kidney will later develop fibrosis – a chronic injury that is a major cause of allograft loss after the first year – a team of researchers, led by Mount Sinai’s Barbara Murphy, MD, System Chair, Department of Medicine, Murray M. Rosenberg Professor of Medicine, Dean for Clinical Integration and Population Health, has identified a panel of 13 genes that does just that. These recently discovered 13 genes are highly predictive of decline in renal function and eventual loss of transplanted kidneys.
“There is little doubt that kidney transplantation increases the life expectancy of patients with end-stage kidney disease,” said Dr. Murphy. “It is therefore essential that we maximize the life of the transplanted kidney. We were on a mission to find out why and how to improve long-term graft survival, by learning what causes kidney allografts fibrosis and determining how it can be prevented.”
The Genomics of Chronic Allograft Rejection (GoCAR) multicenter study was conducted at five clinical sites in the United States and Australia and examined the use of differential gene expression to predict the development of chronic allograft injury. The results of the GoCAR study – the first of its kind – were recently published in the July 21st edition of The Lancet. By using microarray, the researchers determined which genes correlated with biopsy samples that had an increased Chronic Allograft Damage Index (CADI) score. The CADI score is a measure of the level of fibrosis in the transplanted kidney. By using gene expression profiling of biopsies obtained at three months after transplantation, the researchers found this predictive gene set to identify allografts at risk of injury at one year as well as early allograft loss, and thus were able to identify patients at risk.
The practical implication of this study is to use this gene set to find these specific kidney transplant recipients at risk and then the physicians will be able to change how they monitor, manage and treat renal transplant patients to prevent the irreversible damage of fibrosis from progressing and/or developing before its onset.
“Because of early therapeutic interventions acute rejections have been reduced and short-term outcomes have been substantially improved,” said Dr. Murphy. “But with this new gene panel, we now know if a recipient is going to develop a chronic renal injury a few years down the road. This exciting new information will ultimately be used to extend the recipient’s long-term allograft survival and reduce the need for re-transplants and further surgeries.”