Inflammation and Kidney Disease

Neutrophil granulocyte migrates from the blood vessel to the matrix, sensing proteolytic enzymes, in order to determine intercellular connections (to the improvement of its mobility) and envelop bacteria through Phagocytosis. (Photo credit: Wikipedia)

Inflammation is defined by medicine.net as a basic way in which the body reacts to infection, irritation or other injury, the key feature being redness, warmth, swelling and pain. Inflammation is now recognized as a type of nonspecific immune response. This is a definition that everyone who has ever had a cut or bruise can understand easily.

When one speaks of inflammation in kidney disease however the above definition will not adequately describe what is happening in a meaningful way. In fact the definition speaks primarily towards the outward manifestations of inflammation in the skin that have been known for centuries, redness warmth and pain.



However the other manifestations of inflammation within the organs of the body do not quite follow the same pattern as seen on the skin. Inflammation is caused by substances in the blood that are produced by cells of the immune system. It is the function of these cells to detect foreign invaders of the body and destroy them. This is accomplished by cells that detect the foreign invader as foreign and identify it to other groups of cells that are responsible for the actual destruction of the invader. When the invader is destroyed the cells involved form a memory of the event and the next time the invader attempts to gain entry the result is is a faster and stronger response.

The process requires quite a bit of crosstalk between cells of the immune system. These cells talk to each other by way of producing chemicals that act as signals that carry instructions to other cells. These chemicals go by many names but they are best called cytokines. Many of these cytokines are involved in producing the standard inflammatory reaction that is seen in the skin such as after a bee sting.

Various cells that participate in immune functions. Note that even though hematopoietic stemm cell, erythrocyte, maegakaryocyte and platelets are found in the blood, they do not participate in immune functions. (Photo credit: Wikipedia)

Interestingly the cells of the kidney, just like other organs, are capable of reacting to the levels of cytokines within the blood. The function of these cells may be altered by these cytokines. The cells of the kidney also produce cytokines as part of their daily functions as they need to talk to other cells as well in order to keep the whole machine running properly.

Problems arise when an inflammatory reaction takes place such as due to a bee sting, but the inflammation never quite stops. Usually once the inflammation has run its course the cells involved signal an end to the fight and things return to normal with the level of cytokines in the blood falling back to normal.



In circumstances where inflammation continues unchecked, the immune system becomes activated and cytokine levels remain high. This is called a pro-inflammatory state. When the body gets stuck in this state dysfunction of many organ systems can occur due to the high levels of cytokines telling cells that there is a war going on within it. This may actually be necessary if there was a severe chronic infection happening that required such a state. However frequently the pro-inflammatory state is not due to anything correctable by the pro-inflammatory state itself and hence it is not self limited.

The results can be devastating, including muscle loss as if one was malnourished due to effects of high levels of cytokines that produce muscle wasting. Increased risk of cardiovascular disease because the cells of the blood vessels are more likely to produce severe cholesterol plaques which obstruct blood flow to the heart. The blood vessels also have disturbances of function which prevent them from relaxing to allow adequate blood flow to organs that need it, such as the kidney or the exact opposite, too much relaxation, which prevents an adequate pressure head for distribution of blood. The cells of the bone marrow responsible for producing blood do not produce adequate blood cells in response to the signal to do so in the presence of excessive inflammation.

These problems have a striking resemblance to some of the problems being faced by people with kidney disease. There is anemia, muscle wasting and malnutrition and increased heart disease. This may imply that there is a relationship between chronic kidney disease and inflammation. Such a relationship has essentially been shown to exist by ongoing clinical research.

Thus inflammation, not the type that causes swelling pain and redness then goes away, but the chronic continuous activation of the immune system occurs in kidney disease and is responsible for much of the morbidity and death that occurs because of CKD.

Recently the authors of this study have shown that calcium and phosphate levels are important in determining the overall level of inflammation in patients with stage 3 to 4 kidney disease and beyond. What this means is that if calcium and phosphate levels are controllable in some way then the burden of disease produced by chronic inflammation in CKD may be reduced.

Aspirin and Kidney Disease a Love Hate relationship.

Image by Benjah-bmm27

Acetylsalicylic acid otherwise known as aspirin was a major advance in the treatment of inflammation when it was first discovered in 1853. The chemical compound had been used for centuires before that however in the form of bark and herbs which were found by early man to be helpful for the relief of pain.

The chemical structure above served for the development of many novel drugs with potent anti inflammatory effects and became one of the most prescribed classes of medication in history collectively known as the non steroidal antiinflammatory drugs or NSAIDs. The sideffects of the Aspirin are shown below in this mindmap by maderoh88

NEGATIVE EFFECTS ON THE KIDNEY.

Aspirin reduces renal blood flow this is not usually a problem in a healthy person however in a patient who already has decreased blood volume such as patients with dehydration or blood loss this could precipitate acute renal failure. Several types of kidney disease unified by the loss of protein in the urine, may produce a relative low volume state. Despite the obvious retention of fluid in the skin of the feet and around the eyes, the blood vessels are depleted and hence the kidney is also starved for fluid. In such a setting aspirin will further cause reduction of renal blood flow and tip the patient over into acute renal failure.

Aspirin is an anti inflammatory agent yet it has been known to cause inflammation of the tissues of the kidney a state called an allergic interstitial nephritis. Patients with this disorder may have a skin reaction after administration of aspirin followed by high blood pressure abnormal kidney function and decreased urination, thankfully it is usually self limited.

Aspirin has also been associated with an abnormality of the kidney known as membranous nephropathy. This condition results in thickening of the filter of the kidney and loss of protein in the urine.

BENEFICIAL USES.

Aspirins effect on glomerular blood flow can be beneficial. It would be helpful to understand glomerular function to understand why.

Aspirin has the effect of reducing the flow of blood through the kidney in the areas responsible for filtration. While this may not sound like a good thing, this effect is similar to the effect of angiotensin converting inhibitors or ACEI which are prescribed for delaying progression of renal disease. This effect of aspirin is particularly useful in patients with high degrees of protein loss in the urine. Reduction of pressure within the kidney will lead to decreased filtration of protein by the kidney. Hence at one time aspirin was one of the major drugs used in the treatment of membranous nephropathy and other causes of nephrotic syndrome. The drug has fallen out of use for this indication however because of the negative effects on kidney function produced by aspirin. Inflammatory conditions of the kidney were also thought to be treatable by aspirin, conditions such as membranoproliferative glomerulonephritis which is a very rare form of inflammation of the kidney. However all recent trials have discounted any protective effect of aspirin in this and similar conditions.

Although an anti inflammatory agent aspirin has no role in the treatment of inflammatory disorders of the kidney. At this time superior antiinflammatory agents with less negative effects on the kidney are available.