When waste products accumulate in the body, problems occur. In chronic kidney disease, the filter organ’s function becomes progressively less efficient until it is completely lost. In collaboration with American kidney specialists, Bayer researchers are looking to find new medications and improve the quality of life for those affected by chronic kidney disease.
Kidney damage can cause severe, chronic diseases. By the time symptoms appear, it may be too late and a cure may no longer be possible.
Bayer researchers are working together with kidney specialists from the United States to investigate how kidney diseases develop and how they can lead to long-term kidney damage. The collaboration is aimed at developing new active ingredients that can protect against chronic damage.
At present, very few drug products are available for the treatment of patients with kidney disease. New active ingredients could help patients who are still at an early stage of the disease, before they develop the dramatic complications that can range right up to organ failure.
Without functioning kidneys, the human body can only live for a few days. This is because many substances, such as urea, accumulate in the body rather than being eliminated through urination. As a breakdown product, urea ensures that no toxic ammonia is produced. However, helper molecules like urea also have to be expelled from body. In individuals suffering from advanced chronic kidney disease, substances found in urine build up in the blood (uremia), causing a life-threatening condition.
“We want to ensure that it doesn’t get to that stage. That is why we are searching for new substances that can help people with kidney diseases,” says Professor Frank Eitner, responsible for research on kidney diseases at Bayer. Since 2017, Bayer kidney specialists have been collaborating with their U.S. counterparts at the Vanderbilt University in Nashville, Tennessee, where scientists have been researching the basis of many kidney diseases for decades. “We are a university hospital, and are therefore always thinking about the applications for patients in everything we do,” says Professor of Medicine Raymond Harris. Bayer’s team and the Vanderbilt researchers are collaborating on a number of very promising projects. “Each group is working on different signaling pathways, aiming to intervene in cellular metabolism and improve kidney function,” adds Eitner. The experiments are at different stages, but all are still in the preclinical phase, which means they have not yet been tested on humans.
Heart and kidneys: inseparable partners
The blood circulation delivers nutrients to every cell in the body and makes sure that metabolic waste products are transported away. This process is vital for the human body’s survival. The organs that play a crucial role in this process are the heart and the kidneys. The heart is responsible for maintaining the flow of blood, while the two kidneys ensure that superfluous fluids and waste products are excreted.
The blood is filtered in small filter units in the kidneys, called glomeruli. Large constituents such as cells and proteins remain in the bloodstream. The result is some 180 liters of primary urine in the kidneys, which is then heavily concentrated in the organ’s interior. This explains why humans ultimately excrete a considerably smaller amount of fluid, around 1.5 liters per day.
Damage to the filter organs can cause the blood pressure to increase, weakening both the kidneys themselves and the heart. It is therefore important to keep an eye on both and choose any medicines accordingly. Only in this way can the delicate balance between the heart and the kidneys be maintained.
In 2015, approximately 1.2 million people worldwide died as a result of kidney failure.
The starting point for the researchers was the causes of the disease: kidney injuries, such as those due to diabetes, poor blood circulation, or high blood pressure. These reasons are why the kidneys in people suffering from heart diseases are particularly vulnerable. Chronic kidney disease develops over a long period of time and signs or symptoms often do not appear until the late stages, after a great deal of damage has already occurred. “If the kidneys are damaged, this often leads to a paradoxical situation. Damaged cells are not replaced by cells of the same type, but by connective tissue cells, or fibroblasts. “This leads to fibrosis whereby functional kidney tissue is replaced by excessive fibrous connective tissue, continuously diminishing kidney functionality,” explains Harris. Although a certain amount of connective tissue is essential for the organ’s structure, fibrosis ultimately leads to organ failure. In endstage kidney failure, those suffering from the disease will require dialysis or a kidney transplant. According to the World Health Organization, around 1.2 million people died of kidney failure in 2015. Harris experiences the fundamental issue in his daily work at the clinic. “There are still only a few drugs available for the treatment of patients suffering from kidney diseases.”
For this reason, the collaboration research groups are exploring several distinct molecular targets in order to advance new preclinical drug candidates. The collaboration project run jointly by a team under Dr. Michael Becker, a lab head at Bayer, and Harris is the most advanced. “At Bayer, we had already internally identified a molecule that interferes with a signaling pathway leading to organ fibrosis,” explains Becker. Some of the Vanderbilt researchers had intensively studied exactly this signaling pathway. “Thanks to the base knowledge acquired by the Vanderbilt researchers, we have been able to refine our uncut diamond more quickly,” adds Eitner. Becker’s and Harris’s team is currently optimizing the active substance candidate so that it can be even more effective. “We aim to have developed the molecule to such an extent that it can be tested in humans by 2020,” says Becker.
Diabetes can also lead to chronic kidney disease resulting in fibrosis. “In other projects, we are pursuing different strategies to provide people suffering from this disease with new medications,” says Eitner. As his colleague Becker adds, “We are learning from each other every day so that the lives of patients suffering from chronic kidney disease can be improved.”
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