A gene-expression profile has enabled Stanford University researchers to determine the “youthfulness” of kidneys, regardless of a patient’s age.
The research has implications for successful transplants of more kidneys, said researcher Rodwell Graham, a nephrology fellow at Stanford University.
“This study is laying the groundwork — giving us a big picture of something we know almost nothing about,” said Graham. Finding genes to use as biomarkers or potential targets would be a hugely complicated task without this first step of narrowing down the field, he said.
The researchers can look at a profile of 895 genes to see either “good” or “bad” histology, and with further refinement of the profile genes, “it is likely” that the group will be able to predict future kidney function, said Graham.
With that ability, it may be possible to end the exclusion of people over 65 years of age from the kidney donor pool. “Probably a third of these kidneys are in good shape and would do well in transplant, but two-thirds wouldn’t, so we exclude them,” said Graham. Biomarkers able to distinguish viable from feeble kidneys would open up a “huge” number of kidney donors, he said.
Using Affymetrix Human Genome HU133 chips, Graham, lead author Stuart Kim, and colleagues found 985 genes that changed expression levels to correspond with a patient’s age. “We’ve compared these to all the other clinical data we can get on the patients — age, sex, and all of those variables, including where in the kidney it came from — the [renal] cortex or the medulla,” Graham told Pharmacogenomics Reporter. The correlation of profiles to age is significant and real, he said.
The sample of 74 patients — aged from 27 to 92 years — allowed the researchers to study samples as a continuum of ages. The genes that change expression level as a function of age match up well with histologic data, said Graham. “Some patients have an expression profile that stands out as being different from people of the same age group, either older or younger,” he said. Similarly, patients with “young looking” histology have “young-looking” gene-expression patterns and vice versa, Graham added.
These genes are probably reflecting changes downstream of some regulatory process that is age-related. Which genes are directly involved in regulatory processes is not yet known, although they would make for the most promising potential drug targets, said Graham.
“The idea of drugs that affect these [genes or their proteins] is certainly possible, but that’s further away,” said Graham. Drug and diagnostic companies have not yet shown interest in the group’s work, he said.
The next step for Graham and colleagues is to examine other tissues in a search for genes involved in aging in multiple sites, he said. That research, which has already begun and should finish within the year, may give the group an idea of which genes perform a regulatory role, Graham said.
The group’s research will appear in the December issue of the Public Library of Science.