Magic and mysteries in the kidneys

With great magic tricks, we can pay special attention to every part of a magician’s performance and try to recreate it at home, but fail. In the same way we can study the kidney in a laboratory and try to recreate the flow of substances inside it with a computer model. But to date, we have not been able to replicate the things we see in the body in models. The way the kidney makes urine seems like a great magic trick: what we see happening does not fit our understanding of reality.

A group of researchers in Johannesburg is now working on a new approach to answer the remaining questions around how the kidney makes urine.

It is an important question that relates back to the fundamental theories of biology: the interaction between water molecules, proteins and salt ions. Two-thirds of your body’s volume is water, but because water molecules are so small compared to protein molecules, about 99% of the molecules in your body are water molecules.

According to Gilbert Ling, a prominent American biochemist, and Professor Gerald Pollack, editor-in-chief of the scientific journal WATER, there is still a lot more to discover about water’s possible behaviours. They argue that getting a better understanding of how water and salt interact with proteins may have critical implications for our understanding of biology.

Is a deeper understanding of the way molecules interact the key to unraveling the kidney’s secrets to making urine? This is one of the questions being investigated by a South African research team, including members from the Materials and Process Synthesis (MaPS) research unit at Unisa and the Biomedical Engineering Research Group at Wits University. Our team is approaching the problem from two angles: what pushes water and salts through the membranes in the kidney, and where the energy could come from to do this work.

The kidney does its work in two steps. First, it separates blood into two liquids with a filter. The one liquid contains the remaining blood, which is now a concentrated soup of proteins and red blood cells. The other liquid, called the filtrate, contains almost everything else that is normally found in blood except the larger components, like proteins. Eventually the kidney will turn this filtrate into urine.

To do this, it has to recover valuable substances, like sugar, from the filtrate. It also has to take back just the right amount of salt and water, without taking back too much urea and other waste. Most of the kidney’s structures are dedicated to forcing water, salts, urea and other solutes to flow between the filtrate and the concentrated blood. Almost all of the filtered substances flow back into the blood, which returns to the body. What remains of the filtrate flows to the bladder and is excreted as urine.

Other researchers have determined where substances flow freely from the filtrate to the blood and where the flow needs to be forced. It is possible to determine this by combining measurements in the laboratory and textbook theories. The problem these researchers have shown is that the current theories do not describe the inner part of the kidney accurately.

The textbook answer to how the kidney forces the movement of substances is that the kidney’s cells get energy from food, which they use to provide energy to small “pumps”. (These are complex proteins, the most well-known of which is the sodium-potassium pump.) Confusingly, from the latest research it appears that something more is needed to drive the flow of substances back into the blood. But then, most of the latest research on the kidney’s urine production process does not consider the possible effects of blood proteins’ interaction with water and salts.

Our research team has recently published a new hypothesis: the process of creating a filtrate and concentrate of blood can be a way to store energy. We think it is similar to when you squeeze a sponge dry: it stores energy that can later be used to suck up water. In a similar way, there is a quantifiable amount of energy associated with separating a filtrate from blood, which can be applied to suck the filtrate back into the concentrated blood. At this stage it is still unclear how the blood proteins behave during this process and how it affects the energy that is stored in the filtration process.

But it should be possible to estimate the maximum amount of energy that can be stored. 

On a scientific level, it comes down to believing there is no such thing as magic. According to the first law of thermodynamics, energy cannot magically appear; energy can only change from one form to another. This means that the energy that is applied in the form of pressure to squeeze the filtrate out of the blood is the amount of energy that can be used later to do the work of recovering the filtrate.

The next step is for the team to focus on the energy calculations, using established thermodynamic equations. We can determine how much of the filtrate can be sucked back by looking at what energy is applied to separate the filtrate from the blood and by looking at the energy cost of the work that is being done.

This calculation will outline the possibilities for future discoveries concerning the urine production in the kidney. Although the team is not working on any medical applications for their research, we are optimistic that the research will help us to better understand medical conditions such as hepato-renal syndrome.

Robert Louw attends the University of South Africa.

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