A model of the kidney

Olga Sosnovtseva dreams of creating a model of the kidney that will increase the understanding of the causes of high blood pressure and also facilitate the development of new and better medicines.

By Eline Mørch Jensen

Olga Sosnovtseva

Olga Sosnovtseva

Olga Sosnovtseva holds a PhD in physics and mathematics from Russia and PhD in human biology from Germany. Her dream is to create a model of the kidney which among other things will make it possible to get a better understanding of the causes of high blood pressure and also facilitate the development of new and better medicines.

- In physics we have a tradition of using mathematical models to understand complex biological systems, particularly to try to predict how these systems, such as the kidney, will evolve over time. The use of models goes hand in hand with the use of experimental techniques. The models and experimental techniques have been improved gradually over the years, says Olga Sosnovtseva, adding:

- It is a field which I have worked in for the past 10 years - and probably will continue to work in and be absorbed by for the rest of my life - but there are still times when we find ourselves lacking the correct models. Hence, moving forward requires resources - and talented postdocs and PhD's of course, particularly physicists with a good understanding of mathematics as a tool.

And this is exactly what KU's strategic research project "Dynamical systems: mathematical modelling and statistical methods in social science, health and science" is all about, and why Olga Sosnovtseva has high expectations for the results:

- The hope is to create a model of the entire kidney, similar to how researchers in Oxford have made a model of the heart and how research groups elsewhere in the world are modeling the brain and the entire body. Of course I can´t guarantee that we will succeed, only say that I hope so. It would be a dream come true!

- Unfortunately we are extremely limited in what we can actually examine in our experiments with rat kidneys. In fact, we can only just enter into the surface of the kidney, as we measure with the laser and can only go about one millimetre into the kidney. In addition the human kidney holds a million nephrons compared to just 30,000 in a rat kidney, says Olga Sosnovtseva.

Will it be a model of a human kidney or rat kidney then?

- A rat kidney, because the model has to be based on experimental data; the blood flow of the kidney for example. Mathematical models can enable us to discern patterns that we might not otherwise discover.

- With such models we could, for instance, block various mechanisms to take a closer look at what happens in the system. They also allow us to combine techniques so that we can gain a better understanding of the relationship between the anatomical structure of the kidney and its functions, explains Olga Sosnovtseva .

She describes it as reminiscent of moving in a circle where new experimental results can lead to adjustments in the models. Or vice versa: that the use of a model leads to ideas and new predictions that can shortly be tested experimentally and perhaps verified. In other words, an ideal symbiosis between experiments and models.

The next phase in this process is the simulation of an entire kidney so that in future it will be increasingly possible to investigate the root network of nephrons which is extremely difficult to measure experimentally.

How would such a model of the kidney enrich research?

- We know that the kidneys are connected with the blood pressure and have the ability to control it. By developing models that give us a better understanding of how the vessels are situated and how the blood flow is regulated, we become better at analysing and predicting renal behaviour.

- For example it is well known that blood pressure is higher in the deeper nephrons, but unknown what impact this has on the blood flow or whether they behave the same way as the nephrons in the surface. We hope that a model could make us significantly wiser concerning this problem. This is one part of the research, what we might call basic research.

- The second part is about the development of new drugs and the improvement of the drugs which have already been developed so they can be personalized, meaning that the drugs can be dosed as needed. Here models help us understand how drugs work on the individual according to weight, age, etc., and so are used to calculate the most accurate dosages.

- Which in turn could lead to making sure the effect of various medications, such as those targeting hypertension, will be as good as possible and - equally important - that the side effects will be as few as possible, says Olga Sosnovtseva.

- So along with basic research what we scientists can offer and which we hope to contribute to this research project is the development of new, better and safer medicines. Although I do know of private pharmaceutical companies that are also working at both modelling, development and improvement of drugs, including attempts to reduce the negative side effects associated with the intake of certain medications.

Finally, Olga Sosnovtseva emphasizes the ethical dimension that lies in a considerable reduction in the amount of experiments on rats with an expanded use of models, even though animal experiments will probably always be needed for research to some degree.

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