Connection of kidneys and inflammation

Jun 28, 2021

The kidneys are bean-shaped organs that perform important functions in the body. This paired organ that sits just below the ribs on either side of the spine is vital for survival. The main functions of the kidneys are to filter the blood circulating through the body to get rid of excess water and waste products. This article will discuss the connection between these important organs and inflammation.

What is inflammation?

Inflammation is a vital aspect of immune system defense. It is the mechanism by which the body protects itself from harmful and foreign agents such as viruses and bacteria.

When the body tissues are injured by trauma, bacteria, heat, or toxins, the body's immune system gives an inflammatory response. What happens is that chemicals such as histamine, prostaglandins, and bradykinin are released at the injury site.

The chemicals further cause the blood vessels to leak fluid into the tissues and also attract white blood cells to attack the germs and eat up damaged cells. This inflammatory response comes with symptoms of redness, swelling, heat, and fever.

Other signs and symptoms of inflammation include:

  • Fatigue
  • Joint pain
  • Loss of function
  • Chills
  • Mouth sores
  • Rashes
  • A general feeling of malaise

The dangers of inflammation

Inflammation is of two types- acute inflammation and chronic inflammation. Acute inflammation means short-lived inflammation, while chronic inflammation can persist for years and even months.

Chronic inflammation usually occurs when your body's immune system is unable to fix the initial problem that caused the inflammation. Thus, instead of inflammatory symptoms like swelling, pain, redness, and heat-dissipating soon, they remain for long.

While inflammation on its own is not bad (it is one major way the body fights against infections), chronic inflammation can be dangerous. When inflammation lasts for too long, it can trigger the body's immune system to attack healthy organs and tissues of the body. It ends up causing more harm than good to the body system.

If chronic inflammation is not treated, it can increase the risk for some chronic diseases such as heart diseases, cancer, diabetes, rheumatoid arthritis, and even kidney diseases! Unfortunately, chronic inflammation often does not show signs or symptoms and goes unnoticed, but slowly, it attacks your internal organs and your immune system. Persistent inflammation can affect the kidneys.

The connection between your kidneys and inflammation

Sometimes the kidney gets inflamed. Inflammation of the kidney is called nephritis and can be caused by infections, toxins in the body, and autoimmune disorders. Nephritis affects the functional units of the kidneys called the nephrons. In people with nephritis, the tubules and the surrounding tissues get inflamed, which can lead to kidney damage.

Inflammation which has been closely linked to kidney disease involves a complex chain of interactions between the parenchyma cells of the kidney and immune system cells such as the dendritic cells and macrophages. These cells further recruit other circulating body defense cells like the lymphocytes, the monocytes, and the neutrophils.

These cells further activate specialized cells, which trigger the secretion of some inflammatory mediators that can cause irreversible damage to tissues (especially when the inflammation extends for a longer period).

Causes of kidney inflammation

Many things can cause nephritis. There are cases where the causes are unknown (idiopathic). However, most cases of nephritis are caused by infections such as hepatitis B or C and HIV. Also, a physical factor aside from infection can cause inflammation, e.g., exposure to dust, bee sting, or some other physical trauma.

Nephritis, just as other kidney diseases, seem to run in the family. That means there is a possibility of a genetic component at work here.

There are also cases of nephritis induced by the use of certain medications. For instance, the use of antibiotics can cause kidney damage. Also, abuse or excessive use of pain relievers, diuretic pills, or nonsteroidal anti-inflammatory drugs (NSAIDs) can cause nephritis.

Types of nephritis

There are different types of nephritis, such as:

  • Acute glomerulonephritis: This type of nephritis develops suddenly after an infection such as HIV or hepatitis.
  • Chronic nephropathy: This is the type of nephritis that develops gradually, causing only a few detectable symptoms in its early stages. It can be genetic and can cause severe kidney damage and failure.
  • Lupus nephritis: Lupus is used to referring to an autoimmune disease whereby the immune system mistakenly launches attacks on the body's healthy tissues. In the case of lupus nephritis, the immune system attacks the kidneys.
  • Interstitial nephritis: Certain medications or infections usually cause this type of nephritis. The part of the kidney affected here is the interstitium, a fluid-filled space in the kidney. In a case whereby inflammation is caused by medication, taking the patient off the medication can aid full recovery (if much damage hasn't been done).

How inflammation can cause acute kidney injury and chronic kidney disease

Chronic kidney disease (CKD) and acute kidney injury (AKI) are two renal conditions linked with high mortality and morbidity levels. A study showed that about 30 million Americans suffered from chronic kidney disease in 2017 (a prevalence of about 15%). Another study showed that about 60% of people in the intensive care unit suffer from acute kidney injury.

Some studies suggest that CKD and AKI are inextricably interlinked. Also, inflammation is the main pathogenic mechanism for both renal conditions. How this happens is that immune cells interact with the renal parenchymal cells to cause an inflammatory response in the presence of a stressor.

This, in turn, causes irreversible damage to cells and tissue of the kidney, finally resulting in organ failure. Therefore, clinicians have suggested targeting inflammation as a strategy in the management of AKI and CKD.

The role of inflammatory markers and oxidative stress on CKD

One of the episodes that characterize inflammation is the increase in inflammatory markers, which involves the cells of the innate immune response system. In the case of CKD, the inflammatory markers involved include interleukin-6 (IL-6), C-reactive protein (CRP), adhesion molecules, tumor necrosis factor-ɑ, and adipokines.

These inflammatory markers have been linked with different complications during chronic kidney disease such as atherosclerosis, malnutrition, heart failure, and atrial fibrillation.

Factors that contribute to the chronic inflammatory state in CKD include oxidative stress, increased production of proinflammatory cytokines, chronic or recurrent infections, and acidosis.

Proinflammatory cytokines such as IL-1, IL-6, and TNF-ɑ are produced by adipose tissue and lymphocytes and have been associated with the deterioration of CKD. IL increases the risk of developing atherosclerosis and has been associated with depression in patients with CKD and reduction in nutrient consumption. Research has suggested that IL-1 and IL-6 suppress the secretion of the parathyroid hormone. Low parathyroid hormones can, in turn, cause malnutrition. TNF-ɑ has been linked with markers of inflammation and malnutrition as well.

Oxidative stress is a risk factor for everything that causes mortality and has been commonly observed in CKD or end-stage renal disease. A condition of oxidative stress is often induced when there is an imbalance between oxidizing agents and the scavenger defense system.

Studies have revealed that high levels of oxidative stress have been noticed, especially in the early stages of CKD. It increases as the condition progresses to end-stage renal disease.

Even after renal transplantation, oxidative stress may still persist. It has been associated with the release of highly reactive intermediates during the process of inflammation. Increased levels of oxidative stress have been observed in patients with CKD due to their impaired physiological defense system. Oxidative stress at this level can cause a progression to renal damage, which can, in turn, lead to renal ischemia, cell death, and apoptosis.

Conclusion

Studies have established that inflammation is an essential part of chronic kidney disease and is a risk factor for its development as well as the development of other renal pathologies. Low-grade chronic inflammation predisposes to CKD, which in turn increases mortality and morbidity.

Several interventions have been suggested as strategies to deal with kidney problems like AKI and CKD. Such interventions include the use of pharmacological agents, lifestyle modifications, and the optimization of dialysis.

References/Links

https://www.frontiersin.org/articles/10.3389/fphar.2019.01192/full

https://www.medicalnewstoday.com/articles/312579

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981831/

https://www.davita.com/education/kidney-disease/risk-factors/inflammation-diseases-of-the-kidneys

https://www.elcaminohealth.org/stay-healthy/blog/causes-effects-of-inflammation#

https://www.intechopen.com/books/chronic-kidney-disease-from-pathophysiology-to-clinical-improvements/inflammation-and-chronic-kidney-disease-current-approaches-and-recent-advances

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