Gene Panel Predicts Damage in Donated Kidneys

Clinical and histological events associated with interstitial fibrosis and tubular atrophy are poorly predictive of allograft loss, making it difficult to identify allografts that could benefit from early interventions to prevent progression of fibrosis.

A multicenter team of scientists led by those at the Icahn School of Medicine at Mount Sinai (New York, NY, USA) prospectively collected biopsies from 204 renal allograft recipients with stable renal function three months after transplantation. They used microarray analysis to investigate gene expression in 159 of these tissue samples. Their aim was to genes that correlated with the Chronic Allograft Damage Index (CADI) score at 12 months, but not fibrosis at the time of the biopsy. The CADI score is a measure of the level of fibrosis in the transplanted kidney.

Two tissue cores were taken from each of the three-month and one year protocol renal biopsies of the Genomics of Chronic Allograft Rejection (GoCAR) cohort. One core was processed for histology and the other core was processed for messenger ribonucleic acid (mRNA). Immunohistochemistry was done on an automated stainer on paraffin sections stained with a rabbit polyclonal antibody (American Research Products, Inc, Waltham, MA, USA). All slides were scanned with an Aperio CS whole slide scanner (Leica, Wetzlar, Germany) and high-resolution digital images and archived in an image database. Total RNA was extracted from percutaneous graft biopsy samples, processed onto gene chips and scanned using GeneChip Scanner 7G (Affymetrix Inc, Santa Clara, CA, USA).

The investigators identified a set of 13 genes that was independently predictive for the development of fibrosis at one year. The 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 rate of correlation of the identified gene set with damage was greater than the clinico-pathological variables currently used in practice to identify kidney transplant recipients at risk of allograft damage and loss.

Barbara Murphy, MD, the study leader, said, “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 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.” The study was published on July 22, 2016, in the journal The Lancet.

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