New kidney clue to high blood pressure

Scientists have discovered a “cure for killer blood pressure”, the Daily Express claimed today. In its dramatic front-page story, the newspaper reported that a breakthrough which identified the cause of high blood pressure “could save millions of lives every year”.

These bold claims are premature, as they come from a very small laboratory study that looked at kidney tissue samples from just 22 men. Comparing the genetics within the kidneys of 15 men with high blood pressure and 7 with normal blood pressure, the researchers found variations in the activity levels of certain genes containing the instructions for making proteins. In particular, men with high blood pressure had lower activity in the gene containing the code for making the kidney hormone renin, which regulates blood pressure.

While this highly complex study provides an insight into the activity of genes in the kidney, the researchers themselves do not suggest that it could lead to a new treatment or cure for high blood pressure. This worthwhile research has identified areas for further exploration by scientists and doctors, but this single study has certainly not uncovered a revolutionary cure for high blood pressure, as some newspapers have suggested.

Where did the story come from?

This research was carried out by the Universities of Sydney and Ballarat in Australia, and the University of Leicester. The study received funding from various sources, including a University of Sydney Research Infrastructure grant, grants from the National Health and Medical Research Council of Australia and an Australian Research Council grant. The study was published in the peer-reviewed medical journal Hypertension.

This scientific research was well conducted, but its implications have been over-inflated by the Express and the Daily Mail . While this relatively small study does present some important findings, they are of an exploratory nature and do not directly point the way towards a cure for high blood pressure, as the media have implied.

What kind of research was this?

This laboratory study investigated the genetics that may underlie high blood pressure. It looked specifically at the way genetic material produces proteins in the kidneys, the organs that filter waste substances and excess water from the blood and have a strong influence on regulating blood pressure.

Numerous key functions in the body rely on specific proteins, many of which our body makes for itself. Sections of DNA called genes contain the genetic code for producing specific proteins, including hormones, enzymes and the proteins that form structures within our cells.

The DNA molecule is made up of two long strands bound to each other in a special type of spiral, called a “double helix”. To produce proteins from genes within the DNA, the genetic code from the double-stranded DNA is first transferred into a single-stranded molecule called messenger RNA (mRNA). This provides a template sequence for the production of a protein. This process also involves another type of RNA called microRNA (miRNA). This very small molecule regulates the translation of mRNA into a protein. In short, DNA contained within a gene cannot directly produce proteins, and so uses mRNA as the protein’s blueprint and miRNA to regulate the production process.

However, knowledge of the effects of miRNA on blood pressure is reported to be limited. This study tested the theory that the expression of different genes (i.e. how readily they are used to make proteins) and the presence of miRNAs can affect a person’s blood pressure. To test the theory, researchers looked at the genetic material in the kidneys of people with high blood pressure and in people with normal blood pressure. In doing so, they hoped to gain important insights into what drives the disease process.

What did the research involve?

Kidney tissue samples were retrieved from the Silesian Renal Tissue Bank (SRTB), which holds samples from Polish individuals of white European ancestry who had a single kidney removed because of non-invasive kidney cancer. Samples were stored in the bank with the aim of studying candidate genes that may be involved in cardiovascular disease.

Diagnoses of high and normal blood pressure in these tissue donors had been previously established through medical assessments. For the purposes of this study, they included only male patients: 7 men with normal blood pressure and 15 with untreated “essential” hypertension. The term essential is used in the medical profession to define cases of high blood pressure for which the cause is unknown, which is most cases. The men had an average BMI of 26.8kg/m2 and an average age of 57 years. The researchers did not consider there to be any differences between the two groups. The 1cm3 tissue samples used in this study were reportedly taken from a region of the kidney that was not affected by cancer.

Gene analysis methods were used to compare the activity of genes and the amounts of mRNA and miRNA in the participants’ kidneys. The researchers looked separately at two regions of the kidney called the medulla and the cortex, respectively the inner and outer regions of the kidney. The cortex of the kidney is a region of the kidney that is rich in blood vessels, allowing it to transfer blood to and from the kidney. Within the cortex is a highly complex network of blood-filtering structures, some of which span into the medulla. The medulla primarily contains the structures that control salt and water balance in the body, and regulate the amount of these substances that are filtered out into urine.

What were the basic results?

The researchers found that there were differences in the activity of 14 protein-coding genes and 11 miRNAs in the kidneys of those with hypertension compared to those without. After the researchers made adjustments for age, they found differences in the activity of 12 genes, and only 3 genes after they adjusted for BMI.

When they looked at the cortex region of the kidney, the researchers found there were differences in the activity of 46 different genes, and differences in the production of 13 different miRNAs. Using further genetic techniques, they validated that the levels of seven miRNAs were different between the two groups.

The researchers next examined kidney cells grown in a laboratory to look at the role of two miRNAs that were differently expressed in the kidney cortex of people with high blood pressure. They found that the miRNAs were involved in regulating the production of the protein renin from the gene REN. The hormone renin is involved in blood pressure regulation. The miRNAs were additionally involved in regulating the mRNAs produced from two further genes (called APOE3 and AIFMI).

How did the researchers interpret the results?

The researchers observed that their results provide “novel insights” into the potential causes of hypertension, shedding light on the involvement of certain chemical pathways in the kidneys that involve renin, other protein-coding genes and miRNAs.

Conclusion

The researchers conclude that their study provides novel insights into the causes of high blood pressure, but do not extend their conclusions any further than that. They certainly do not say that they have found a definite or single cause of high blood pressure, or make any suggestion that their findings could have implications for new or existing treatments.

As the researchers acknowledge, the limited availability of kidney tissue meant that their study sample size was small. Results are also limited to only white males. The researchers said they included only men to limit further genetic variability that would come through comparing men and women.

It is worth noting that all tissue samples came from people who had kidney cancer. Though participants with high blood pressure were classed as having essential hypertension (without a known cause) and tissue samples were taken from a region of the kidney unaffected by cancer, it is possible that genetic expression in the kidneys of these people may differ from those of the general population with high blood pressure. However, as both the men with and without high blood pressure had cancer, the cancer could be expected to have an equivalent effect between the two groups (i.e. any genetic differences between them should be due to something other than cancer).

This study can only suggest, and not prove, that the expression of these genes and microRNAs might be associated with high blood pressure. As the researchers did not look at samples from before and after the patients developed high blood pressure, it is not possible to tell whether the activity of these genes caused high blood pressure or whether other disease processes led to the activity of the genes being altered.

This worthwhile research provides insights and areas for further examination among the scientific and medical communities. However, as a single study, it does not give a revolutionary answer to high blood pressure, and its implications have been over-inflated by the press.