How Inflammation Threatens Your Kidneys and Heart

How Inflammation Threatens Your Kidneys and Heart

Spiders are helpful. Having a spider or two in the house, hidden behind a cabinet or in an attic corner, will eat the odd crawly insect or mosquito and keep you safe. But if you have too many, well, then you have a house full of spiders. Inflammation is like having spiders in your blood. When you get a bug, such as the flu, some inflammation is helpful to get rid of it.  However, too much inflammation, or inflammation for extended periods of time, can result in serious problems with key organs like the heart and kidneys.

 

Inflammation is part of the innate immune system. Inflammation consists of a web of immune cells, complex signaling systems, molecules, and particles that quickly respond to threats inside our bodies. When an invader or rogue cell (such as from precancer) is detected, an inflammation cascade is activated, kicking brutish cells into action.[1] Inflammation can affect nearly every organ and tissue in the body and its effects vary greatly depending on the location and duration of the inflammatory process. Acute inflammation is typically a helpful, short-term response to an injury or infection.  However, some organ systems, like the kidneys, heart, and blood vessels, can be dangerously damaged by chronic or excessive inflammation.[1]

 

Kidneys have many roles in the body, primarily blood filtration and regulation. Kidney function is measured by estimating the glomerular filtration rate (eGFR), with higher numbers indicating more efficient filtration.[2,3] An eGFR rate below 60mL/min/1.73m2 indicates kidney disease, as does the presence of excessive protein or blood in the urine.[1,3] Problems that last more than three months may indicate chronic kidney disease (CKD).[1,3]

 

Chronic kidney disease is extremely prevalent, affecting 1 in every 7 Americans and over 800 million people worldwide.[2,4] The risk of developing CKD is higher among women, minorities, older people, and those with high blood pressure and diabetes.[2,3] Our kidneys are uniquely vulnerable to inflammation because kidney cells come in contact with a large amount of blood, which may be full of dangerous inflammatory molecules.[1] Inflammation can damage kidney filters and tubes, slow filtration, and expose cells to inflammatory damage.[1]

 

Like spiders, inflammation is useful in low amounts. When there is an acute event, such as an injury or a bacterial infection, the innate immune system responds to kill, clean, and repair the area. This is called an inciting incident. This incident starts an inflammatory cascade, where cells recruit other cells, which amplify and continue this process. Inflammatory cascades can be triggered by excessive or dysfunctional cholesterol lipoproteins (like LDL and HDL), crystallized minerals, or the compounds released by dying cells.[5] These particles are detected by specialized protein complexes called inflammasomes.

 

Inflammasomes are key to the inflammatory cascade.[1,5] These machines sense their environment and activate when they encounter inflammatory triggers.[5] Inflammasomes (including one potent one called NLRP3) start the inflammatory cascade machinery in immune cells and amplify small signals into big effects.[1,5,6] Inflammatory cells in the cascade release signaling molecules called interleukins, a type of cytokine. Important interleukins in this cascade include IL-1β and IL-18.[1]

 

A normal, healthy inflammation cycle then winds down as inflammatory signals are expelled from the kidney and as anti-inflammatory molecules calm everything down.[1] Unfortunately, while inflammation is a frequent cause of CKD, the kidneys also act as a critical moderator of inflammation, meaning that when they are damaged inflammation can spin out of control as fast as a banana spider spins a web.[1] The kidneys remove signals like cytokines, interleukins, and bacterial antigens from blood, along with dead cells, debris, and old immune cells.[1] When these systems break down under chronic inflammation, inflammatory molecules linger in the blood for longer amounts of time and anti-inflammatory agents may be compromised.[1]

 

Chronic inflammation doesn’t just affect the kidneys. Inflammation can cause changes to the gut, cholesterol, brain, blood, cells, and cardiovascular system.[6] The cardiovascular system, consisting of the heart, blood, and blood vessels, can suffer heavily from inflammation and lead to dire consequences.[7] Cardiovascular disease is responsible for a large portion of CKD deaths, and decreasing GFR can increase the chances of cardiovascular disease.[5] In addition, interleukins can affect cholesterol and possibly the lymphatic system, which are both critical to heart health.[1]

 

There is no cure for chronic kidney disease. The main goal of most treatments is the preservation of kidney function to improve outcomes and stave off the sting of dialysis and kidney transplant.[3] Lifestyle changes can slow disease progression and include increased exercise, a healthy low-sodium, low-protein, plant-based diet, weight loss, and quitting smoking.[3] Medications can’t reverse kidney disease, but may help limit damage. Many classes of medications, such as angiotensin inhibitors, RAAS blockers, SGLT2 inhibitors, and mineralocorticoid receptor (MR) antagonists, modulate the contents of blood and the production of urine, which may help lower pressure within the kidneys.[3] Blood pressure, diabetes, cholesterol, and diuretic medications can limit the danger of cardiovascular disease. Finally, newer medications are being investigated in clinical trials to bite at the root of the problem, inflammation itself. Limiting chronic and excessive inflammation without compromising the useful effects of acute inflammatory response is a tricky balancing act. Clinical trials are enrolling now to help get that balance right and sweep those spiders out of your blood!

 

Creative Director Benton Lowey-Ball, BS, BFA

 

Click Below for ENCORE Research Group's Enrolling Studies

Click Below for Flourish Research's Enrolling Studies

  

 

References:

 

[1] Kadatane, S. P., Satariano, M., Massey, M., Mongan, K., & Raina, R. (2023). The role of inflammation in CKD. Cells, 12(12), 1581. https://doi.org/10.3390/cells12121581

 

[2] Kovesdy, C. P. (2022). Epidemiology of chronic kidney disease: an update 2022. Kidney international supplements, 12(1), 7-11. https://doi.org/10.1016/j.kisu.2021.11.003

 

[3] Kalantar-Zadeh, K., Jafar, T. H., Nitsch, D., Neuen, B. L., & Perkovic, V. (2021). Chronic kidney disease. The lancet, 398(10302), 786-802. https://www.thelancet.com/article/S0140-6736(21)00519-5/abstract

 

[4] Bajaj, A., Xie, D., Cedillo-Couvert, E., Charleston, J., Chen, J., Deo, R., ... & Townsend, R. R. (2019). Lipids, apolipoproteins, and risk of atherosclerotic cardiovascular disease in persons with CKD. American journal of kidney diseases, 73(6), 827-836. https://doi.org/10.1053/j.ajkd.2018.11.010

 

[5] Speer, T., Dimmeler, S., Schunk, S. J., Fliser, D., & Ridker, P. M. (2022). Targeting innate immunity-driven inflammation in CKD and cardiovascular disease. Nature Reviews Nephrology, 18(12), 762-778. https://www.nature.com/articles/s41581-022-00621-9

 

[6] Zoccalli C and Mallamaci F. Innate Immunity System in Patients With Cardiovascular and

Kidney Disease. Circ Res. 2023, 132(8):915-932. https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.122.321749


[7] Mazhar, F., Fu, E. L., Faucon, A. L., Hjemdahl, P., Mathisen, J., Muhammad, I. F., ... & Carrero, J. J. (2025). Systemic inflammation and the risks of adverse kidney outcomes in adults with atherosclerotic cardiovascular disease. American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2025.04.011