Scientists have uncovered differences in gene expression of patients with chronic kidney disease compared with healthy individuals, which could explain the development of the condition. This is according to a study published in the journal Genome Biology.

Chronic kidney disease (CKD) is a disorder in which the kidneys are severely damaged, making them unable to sufficiently filter blood. This damage to the kidneys can lead to other health problems, including cardiovascular disease, bone disease and anemia.

According to the American Kidney Fund, kidney disease is the eighth leading cause of death in the US, and approximately 31 million Americans suffer from CKD.

The research team says previous studies have shown that health conditions within the uterus during pregnancy – such as babies who are too small for gestational age due to lack of nutrients, or too large due to pregnancy-related diabetes – may play a role in an infant’s “over-a-lifetime” risk of CKD.

Other research has shown that individuals with diabetes who had “poor control” over the condition 25 years previously may be at increased risk of kidney disease, even if they have had outstanding glucose control 10 years before.

Katalin Susztak, of the Perelman School of Medicine at the University of Pennsylvania and one of the study authors, notes that this is known as the “metabolic memory effect” – the kidney cells are able to remember a previously bad metabolic environment.

Diagram of a human showing internal organs and highlighting the kidneysShare on Pinterest
Researchers have discovered differences in gene expression of patients who have chronic kidney disease, which could help explain the development of the condition.

With this past research in mind, and in order to understand the molecular and genetic mechanisms of CKD, the researchers analyzed human kidney cells of patients who had the condition alongside patients who did not.

From this, the investigators found that although kidney cells from both groups of patients appeared almost identical under a microscope, there were significant differences in the way each group was affected by methyl groups.

They discovered that an increase in the number of methyl groups on a gene switches off gene expression, while a reduction in methyl groups switched on gene expression.

In detail, the investigators found that differences in these methyl groups were mostly on enhancer regions of diseased kidney cells – as opposed to promoter regions – and they were close to genes that are important kidney transcription factors.

Promotor regions are in front of genes and near the gene they influence, the researchers explain, while enhancer regions are further away from the gene of influence.

The findings suggest that both regions are important in gene expression regulation, the researchers note, and that both regions may respond differently to stress.

Explaining what their findings mean, the researchers say:

One possible interpretation of our findings is that the epigenetic differences are established during development. This is the time when the cell type-specific epigenome is established and when these genes and transcription factors play functional roles.

Therefore they can possibly provide the mechanistic link between fetal programming and CKD development – the Brenner-Barker hypothesis put forward many decades ago – proposing that nutrient availability during development has a long lasting programming role in hypertension and CKD development.”

The researchers add that previous research surrounding kidney epigenetics has focused on promotor regions of kidney cancer cells.

But Susztak notes that the differences in dysregulation between promotor and enhancer regions found in this study may indicate that “dysregulation in cancer is different from dysregulation in CKD.”

The investigators say that if genes and proteins that are linked to the dysregulation of epigenetic marks can be identified, this could lead to new biomarkers for CKD, as well as targets for new drugs to treat the condition.

Medical News Today recently reported on a study suggesting that reducing belly fat and consumption of foods containing phosphorous may also reduce the risk of CKD.