2023-05-11 13:36:37
Once membranous nephropathy has been diagnosed, it is difficult to predict how the disease will progress. Some patients eventually need dialysis or a transplant to survive. About seventy percent of patients with MN have antibodies against PLA2R, which damage certain cells in the kidney filters, the podocytes.
The research group in Nijmegen, to which Bart Smeets belongs, has been researching podocytes for years because these cells are often the weak link in many disorders. However, podocytes are complex cells and once they are brought into culture they are simplified and no longer resemble the cells in our body. “A kind of flat pancake”, Smeets describes. A relatively new technique called ‘renal organoids’ or ‘mini kidneys’, in which kidney tissue is grown from stem cells, has been shown to the solution to offer. The researchers were surprised to finally be able to mimic the cells.
Problems in membranous nephropathy
The researchers will expose the podocytes in the renal organoids to the PLA2R antibodies of MN patients to understand how these cells become damaged. “You can only start developing medicines if you understand what is happening,” explains Smeets.
Understanding how cells behave in their microenvironment or how diseases develop and spread throughout the body is what matters most. This is also the case when studying scar tissue or cancer metastases in the bloodstream. Research groups consisting of universities, companies, foundations and knowledge institutions have developed a standardized modular platform for organ-on-a-chip technology for this purpose. .
Many kidney diseases are not currently treated specifically and patients are given drugs such as prednisone in the hope that they will help, without knowing exactly why or how they work. These drugs also often have unpleasant side effects. “Only when the molecular processes that lead to damage to podocytes are known, can we intervene and develop a targeted treatment that really tackles the problem,” says Smeets, who sees this as a good follow-up process.
Antibodies
There is another group of patients with MN in which about thirty percent no antibodies against PLA2R are found. To better understand these patients, Smeets will investigate whether other autoantibodies are present in their blood that bind to the podocytes. If this is the case, the researchers can try to find out which substances these antibodies are directed against. In addition, they will look at the molecular changes to see if they are comparable to the group with PLA2R antibodies. This can lead to a treatment that applies to everyone.
Smeets explains that this part of the research is a bit more uncertain, but he hopes that many other autoantibodies can be detected. At present, it is difficult to diagnose these patients. Although the clinical picture may indicate membranous nephropathy, a biopsy is necessary to confirm this, which can be stressful for the patient. A possible next step is to develop a diagnostic test for this group of patients without the need for a biopsy.
Innovation
Smeets strives to develop a new innovation using the mini kidneys. He is hopeful that this model will enable researchers to look more closely at the molecular processes, finally solving these questions.
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