A multicenter study led by investigators from the Icahn School of Medicine at Mount Sinai recently identified an array of biomarkers that could help predict whether a transplanted kidney will later develop fibrosis—a panel of disorders which can cause the organ to fail. The findings from the new study—“Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study”—published recently in The Lancet, suggest that the identified gene panel could be used to detect kidney transplant recipients at risk of allograft loss before the development of irreversible damage.
“This is the first finding of its kind,” explained senior study author Barbara Murphy, M.D., professor and system chair and dean for clinical integration and population health at Mount Sinai. “By helping us better understand the causes of damage to transplanted kidneys, this study has the potential to change how we monitor and manage all renal transplant patients.”
The researchers in the current study—dubbed Genomics of Chronic Allograft Rejection (GoCAR)—obtained biopsy samples from transplanted kidneys three months and twelve months after transplantation. Using microarray analysis, the researchers determined which genes were correlated with biopsy samples which had an increased Chronic Allograft Damage Index (CADI) score—a measure of the level of fibrosi in the transplanted kidney—at the 12-month biopsy.
“We identified a set of 13 genes that was independently predictive for the development of fibrosis at one year (i.e., CADI-12 ≥2). The gene set had a high predictive capacity, which was superior to that of baseline clinical variables and clinical and pathological variables,” the authors wrote. “Furthermore routine pathological variables were unable to identify which histologically normal allografts would progress to fibrosis, whereas the predictive gene set accurately discriminated between transplants at high and low risk of progression.”
The researchers also narrowed the genes down to a predictive set that identified patients at risk for decline in renal function and loss of the transplanted kidney beyond one year. The rate of correlation of the identified gene set with damage was greater than the clinicopathological variables currently used in practice to identify kidney transplant recipients at risk of allograft damage and loss.
“The 13 genes also accurately predicted early allograft loss,” the authors noted. “We validated the predictive value of this gene set in an independent cohort from the GoCAR study and two independent, publically available expression datasets,” Dr. Murphy stated. “The study offers the potential to identify renal transplant recipients at risk for a loss of the new organ prior to the development of irreversible damage. This would mean that doctors might eventually have the opportunity to change the therapeutic treatment approach in order to prevent fibrosis from progressing at all.”
