Kidney Biopsy Profiles Predict Delayed Graft Function

By LabMedica International staff writers
Posted on 28 Feb 2018

The probability of renal graft failure can be assessed for donor kidney biopsies through histological analyses; the potential for delayed graft function is not as easily determined by morphology alone, but could potentially be aided by molecular analysis.

A scientific team led by those at Harvard University Office of Technology Development (Cambridge, MA; USA) used donor renal biopsies for both histological assessments and gene expression analysis. RNA was extracted from tissue and reverse transcribed to complementary DNA (cDNA), which was combined with primers designed for genes that were chosen based on literature review related to delayed graft function.

Image: An histology of an early post-transplant allograft biopsy showing a glomerulus with prominent neutrophil infiltration. A few neutrophils are also seen in the interstitium. These findings can be seen in early stages of hyperacute rejection (Photo courtesy of the University of Pittsburgh Medical Center).

The scientists used quantitative real-time polymerase chain reaction (PCR) to perform gene expression analyses, comparing biopsies from 16 kidneys that showed primary function upon transplantation with those 16 exhibiting delayed graft function. Delayed graft function described the condition of a patient requiring dialysis within a week of transplantation. From the set of genes that the team selected for comparison between the two renal biopsy groups, there were four that showed increased expression within the delayed graft function biopsy samples.

One of the four genes expressed more highly in delayed graft function samples was annotated as a gene for matrix metallopeptidase 3 (MMP3; stromelysin 1, progelatinase), which are related to inflammation and immune response. The other three genes showing more expression with delayed graft function were categorized as related to metabolism, and they were annotated as retinol-binding protein 4, plasma (RBP4); cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4 (CYP3A4); and fatty acid binding protein 1, liver (FABP1). For delayed graft function samples, these four genes showed increased expression from about 2.5- to 4.0-fold each. In comparison, for samples with immediate function, expression of these four genes hovered around 1.0-fold, with some signals slightly below 1.0 or between 1.0- and 2.0-fold.

The authors concluded that the results of their study indicated a possible gene fingerprint, with potential to forecast likelihood of delayed graft function for donor renal tissue. They recommended further research to assess the value of this approach in conjunction with existing protocols. The study was presented at the Annual Cutting Edge of Transplantation (CEOT) Meeting held February 8-10, 2018. Phoenix, AZ, USA.

Related Links:
Harvard University Office of Technology Development