Proper Immune System Function Requires Good Kidney Function

By Wayne Persky

RSS Feed

Consider that B cells are like the "memory keepers" and "weapon-makers" of our immune system. They're a type of white blood cell that plays a vital role in defending our body against harmful invaders like bacteria, viruses, and toxins.

When a pathogenic bacteria or virus enters our body, B cells can recognize specific parts of it, called antigens. Think of antigens as the unique "name tags" on the invaders. Once a B cell recognizes an infectious agent, it gets to work making antibodies, which are like custom-designed weapons that specifically target the invader. These antibodies latch onto the invader's antigens and help neutralize it or mark it for destruction by other immune cells.

After the infection is dealt with, some B cells become "memory B cells." These cells stick around and remember the pathogen for a long time. If the same pathogen tries to invade again, these memory B cells can produce antibodies much faster, stopping the infection before it can make us sick. This is why we often don't get the same illness twice and how vaccines work.

B cells don't work alone; they get help from other immune cells, like T cells, to become activated and know which invaders to target.

B Cells are vital for the proper functioning of our immune system because:

• They are essential for creating antibodies that fight infections.
• By forming memory cells, they ensure we're better prepared for future encounters with the same pathogens.
• Vaccines "train" B cells to recognize a disease without making us sick, giving us immunity.

Without properly functioning B cells, our body would struggle to recognize and fight off infections, leaving us vulnerable to illnesses. They're a key part of keeping us healthy and protected over the long term.

Compromised kidney function can interfere with the production of B cells.

Research shows that chronic kidney disease (CKD) reduces the survival and function of B cells (Peroumal, et al., 2024).1 Uremic toxins (molecules that accumulate in the bloodstream due to inadequate kidney functioning), particularly hippuric acid (N-benzoylglycine, an amino acid derivative found in the urine of humans after the consumption of fruits and juices), accumulate due to kidney dysfunction and induce B cell apoptosis (programmed cell death and replacement) by impairing mitochondrial function through the G protein-coupled receptor 109A pathway.​

So what does this actually mean?

Mitochondria are tiny structures inside our cells that act like power plants, producing the energy our cells need to work properly. If something impairs mitochondrial function, it means the energy factories are not working well. When mitochondria are damaged or disrupted, cells can’t produce enough energy to survive or function normally. A "pathway" in this case is like a series of signals inside the cell that help regulate certain processes. The G protein-coupled receptor 109A is a kind of sensor on the cell’s surface. It receives signals (like from molecules in the body) and passes them along, triggering changes inside the cell. In the context of this issue, harmful molecules (like toxins in kidney disease) activate this receptor, leading to disruptions in how the mitochondria work.

This disrupts the normal functioning of the cell.

When the G protein-coupled receptor 109A pathway is activated in a harmful way, it can cause the mitochondria to malfunction. This can lead to the cell not getting enough energy, becoming stressed, or even dying. In simple terms, this means that certain harmful signals in the body can compromise the cell's ability to create the energy it needs to function normally, by interfering with the communication system (the G protein-coupled receptor 109A pathway). This can lead to serious problems, especially in cells like B cells in the immune system, which need energy to fight infections.

This leads to weakened immune system responses.

In mouse models with influenza infections or immunizations, CKD leads to weaker antibody production against pathogens. Patients with CKD exhibit poor responses to both natural infections and vaccines, putting them at heightened risk of severe infections and poor recovery outcomes.​

Infections are the second-leading cause of death in CKD patients, with mortality rates as much as 10 times higher during the COVID-19 pandemic compared to individuals with normal kidney function. The reduced immune response correlates with elevated serum blood urea nitrogen (BUN) levels and the degree of kidney dysfunction.

The uremic toxins that result from CKD cause most of the damage.

Uremic toxins, particularly hippuric acid, cause B cell death, reducing the ability of CKD patients to mount effective immune defenses. Hippuric acid disrupts mitochondrial membrane electric potential, further leading to compromised B cell viability and function.

It behooves us to keep a close eye on our kidney function test results.

If any of our routine kidney function test results are out of range, and our Doctor doesn't follow up with additional tests, or explain why these particular results don't matter, we need to point out and discuss the issue, because by the time our next tests are normally scheduled, the problem might be completely out of hand, with serious consequences. Especially note the eGFR level, and make sure it's in the normal range.

Reference:

1. Peroumal, D., Jawale, C.V., Choi, W., Rahimi, H., Antos, D., Li, D-d., . . . Biswas, P. S. (2024). The survival of B cells is compromised in kidney disease. Nature Communications, 15, 10842, Retrieved from https://www.nature.com/articles/s41467-024-55187-w