Kidney

Cardiovascular
Disorders

 

The kidneys are the body’s central filtering apparatus: they cleanse the blood of waste products and ensure that harmful substances are excreted with the urine, while substances that are of use to the body are returned to the blood. The entire blood volume – approximately seven liters – is pumped through the kidneys 200 times per day.

The filtering function is performed by millions of tiny functional entities known as nephrons. They consist of renal corpuscles – tufts made up of tiny blood vessels (glomeruli), surrounded by a capsule – and very fine tubules. Primary urine first forms in the renal corpuscles. Substances that are eliminated with the urine (renally cleared substances) pass from the blood through the capillary walls (blood-urine barrier) together with water molecules, are collected and fed into the tubules. The kidneys produce 180 liters of primary urine per day. 99 percent of the fluid and substances that are important to the body are then returned to the blood from the tubules.

1.5 liters of fluid remain and are excreted as urine, containing only waste products and substances that would be toxic to the body at higher concentrations. As well as cleansing the blood, the kidneys are responsible for regulatory processes that are essential to life: they secrete hormones that maintain the equilibrium of the volume and concentration of the blood, the body’s fluid and salt balance and bone metabolism.

For example, the kidneys produce the hormone renin, which is involved in the regulation of blood pressure, and the hormone erythropoietin (EPO), which stimulates the production of red blood cells. The kidneys additionally produce calcitriol, which is important for absorption of calcium and excretion of phosphate and consequently affects bone metabolism.



The information in this chapter has been compiled from the following sources, among others. Further relevant information can also be found there.

National Kidney Foundation, http://www.kidney.org/kidneydisease/ aboutckd.cfm

Das Nierenportal, Deutsche Gesellschaft für Nephrologie (http://www.dgfn.eu/patienten/ basisinformationen-zur-nephrologie.html)

Deutsche Nierenstiftung (http://www.nierenstiftung.de/ hilfreiche-informationen/)

World Health Organization, The Diabetes Programme, About Diabetes, Complications of Diabetes, including Diabetic retinopathy (eye disease), Nephropathy (kidney disease), Neuropathy (nerve disease), Cardiovascular disease (http://www.who.int/diabetes/action_ online/basics/en/index3.html)





 

 

What is chronic renal failure?
Chronic renal failure is a condition in which kidney function is impaired as a result of disease for a prolonged period. It is often caused by damage to the fine capillaries in the renal corpuscles (glomeruli), for example as a result of high blood pressure (hypertensive nephropathy), diabetes (diabetic nephropathy) or inflammatory kidney diseases (e.g. IgA nephritis).

Chronic renal failure is subdivided into five stages on the basis of the remaining renal function. This is measured in terms of glomerular filtration rate (GFR), which indicates how much blood the kidneys can cleanse of renally cleared substances per minute. In a healthy person, GFR is usually above 100 ml/min, depending on age. In highly advanced renal failure, it falls to below 15 ml/min.

Risks and consequences
In view of the complex tasks performed by the kidneys, declining renal function has a variety of consequences. Harmful substances are not excreted and instead accumulate in the body. Also, the kidneys are no longer adequately able to perform its diverse functions in the regulation of fluid, salt and acid balance, blood pressure, bone metabolism and blood production. A wide range of bodily processes are thrown out of balance as a result.

Typical consequences are anemia and high blood pressure (which, in turn, accelerates damage to the kidneys) and increasing calcification of the blood vessels (medial sclerosis), which raise the risk of life-threatening cardiovascular disorders such as heart attack or stroke. One in two dialysis patients dies of a cardiovascular disorder, with 58 percent dying of sudden cardiac death, 20 percent of a heart attack and 9 percent of a stroke. This risk continues to rise as the disease progresses.

Since early stages of renal failure show no specific symptoms, the disorder is often recognized only late. When renal function declines further, symptoms such as exhaustion, loss of appetite, nausea, nerve pain or bone pain occur. As a result of inadequate excretion of fluid and salts, patients additionally suffer from fluid accumulation (e.g. in the legs).

Data and figures
The American National Kidney Foundation reckons that 26 million adults in the USA suffer from chronic renal failure. The elderly and people with diabetes and high blood pressure are at increased risk.

Treatment
If the declining renal function is recognized promptly, treatments can slow its progression. These include a healthy lifestyle, a low-salt diet with a balanced fluid intake and medicines that help to mitigate risk factors and their consequences, e.g. high blood pressure, anemia and high phosphate levels.

In the most advanced stage (end-stage renal failure), the blood has to be cleansed by alternative means using medical procedures such as dialysis (hemodialysis or peritoneal dialysis) to prevent the body being poisoned. Alternatively, improvement can be achieved by transplantation of a healthy kidney.

Researchers at Bayer are working on new approaches to the drug treatment of chronic renal failure.




 

 

What is diabetic nephropathy?
Diabetic nephropathy is a condition in which the renal corpuscles (glomeruli) become damaged as a result of inadequately treated diabetes (diabetes mellitus). The raised blood glucose leads to tissue changes in the glomeruli, which become increasingly scarred and permeable. On the one hand, this reduces the ability of the kidneys to filter the blood effectively, while at the same time the renal tissue is no longer adequately supplied with blood as a result of abnormal narrowing of the blood vessels, key nutrients become scarce and renal cells die off.

High blood pressure, which is common in diabetes patients, further intensifies this process.

Risks and consequences
In advancing disease, albumin, the blood protein that binds water molecules in the blood and serves as a vehicle for transporting various other substances, is excreted in increased amounts with the urine (proteinuria or albuminuria). Detection of excessive albumin excretion is generally one of the first signs of diabetic nephropathy.

If the blood lacks albumin, it is no longer able to remove excess water from the body. Water accumulates in body cavities, such as the abdominal cavity, and in tissues (e.g. in the face and the legs). The progressive damage to the kidneys may ultimately lead to chronic renal failure.

Data and figures
Statistically, 40 percent of all diabetics develop kidney disease, although this often does not occur until ten to fifteen years after the onset of the diabetes. The risk of developing diabetes increases with age (“maturity-onset diabetes”): according to the Centers for Disease Control and Prevention, 25.8 million people with diabetes were living in the USA in 2010, over 10 million of whom were aged 65 or older.

The prevalence of diabetes and, consequently, the risk of diabetic nephropathy are increasing even in younger patients, however, above all as a result of factors such as overweight and lack of exercise.

Treatment
Kidney damage associated with diabetes can be reduced by carefully controlling blood glucose and blood pressure.

Bayer is active in the area of cardiovascular diseases and associated renal diseases and is also working on new approaches to the treatment of diabetic nephropathy.




 

 

What is hypertensive nephropathy?
Hypertensive nephropathy (also known as nephrosclerosis) is a condition in which the kidneys are damaged by high blood pressure. The hypertension triggers biochemical processes that lead to abnormal thickening of the thin arterial walls. The more the blood vessels are narrowed as a result, the greater the impairment also of the blood supply to renal tissue.

Risks and consequences
In hypertensive nephrosclerosis, proliferation of connective tissue (fibrosis), scarring (sclerosis) and deposition of substances in arteries, arterioles (tiny arteries), renal corpuscles, renal tubules and interstitium occurs, typically over a period of many years. Progressive scarring leads to renal fibrosis, where the size of the kidney may be reduced by up to 50 percent (“shrunken kidney”) and the organ may increasingly fail to function (chronic renal failure).

Treatment
The main aim of treatment of hypertensive nephropathy is to maintain blood pressure within normal limits. If chronic renal failure occurs, further treatment steps are initiated.

Bayer is active in the area of cardiovascular diseases and associated renal diseases and is also working on new approaches to the treatment of hypertensive nephropathy.




 

 

What is vascular calcification?
Vascular calcification (also called medial sclerosis) is a condition in which calcification of blood vessels takes place as a result of renal disease. Calcium is deposited in the middle layer of the blood vessel wall tissue. The blood vessels lose their elasticity and “ossify”.

The cause is a disturbance of the calcium/phosphate balance, which may be triggered by chronic renal failure. Phosphate is not adequately excreted and the phosphate molecules bind calcium, which is then no longer available to the body. To make up for the deficiency, calcium is released from the bones. This process eventually spirals out of control, resulting in an excess of calcium that is deposited in tissues and blood vessels.

The hardened and stiff arteries (that even become visible on X-rays) are no longer able to relieve the strain on the heart by cushioning the pumping impulses and relaying them to the body in a milder form. With each heart beat, the blood is therefore conveyed unchecked to the fine capillaries, which do not have the capacity for all the blood.

The blood pressure wave ricochets, so placing a load on the heart. At the same time, the tissue is not continuously supplied with blood flowing from the arteries between heart beats, as in a healthy body. Medial sclerosis develops independently of atherosclerosis.

Risks and consequences
The calcification of the blood vessels means that patients with renal failure are at greatly increased risk of suffering a heart attack or a stroke: roughly half of all deaths in dialysis patients are attributable to cardiovascular disease. One of the main causes is calcification of blood vessels in patients with renal failure.

Since calcium is released from the skeleton, medial sclerosis may be accompanied by a loss of bone stability and osteoporosis.

Data and figures
Medial sclerosis is common in patients with chronic renal failure.

Treatment
The aim of treatment is to stop calcification from occurring or to prevent further damage through early and careful monitoring and lowering of the relevant parameters to within the normal range.

Bayer is active in the area of cardiovascular diseases caused by chronic renal diseases and is also working on new approaches to the treatment of medial sclerosis.




 

 

What is IgA nephritis?
IgA nephritis is the most common inflammatory disease of renal corpuscles (glomeruli). It results from an immune reaction, in which antibodies (immunoglobulin A, IgA) are deposited in the glomeruli and cause local inflammatory processes (glomerulonephritis). Unlike bacterial infections, this disease affects both kidneys.

This painless disease often goes unnoticed for years, coming to attention more by chance as a result of a urine test, i.e. if small amounts of red blood cells and/or protein molecules are present in the excreted urine. After infections, for example of the airways or the digestive tract, the urine of patients with IgA nephritis may contain larger amounts of blood (visible with the naked eye).

Risks and consequences
In the majority of cases, the prognosis for affected patients is good. In approximately 25-30 percent of patients, however, the renal corpuscles are so scarred by the inflammation that renal function is ultimately impaired and they develop chronic renal failure.

Data and figures
In a quarter of patients who are reliant on dialysis or kidney transplantation, the renal failure is caused by inflammatory processes in the kidneys. IgA nephritis is the most common form of these inflammatory diseases worldwide. It is common in young adults. Many IgA nephritis patients are between 20 and 30 years of age at the time of diagnosis.

With the disease progressing very slowly, this may therefore mean that many patients still find that their kidney function is impaired during their lifetime. Observation both of clustering within families and of a higher prevalence in certain ethnic groups has led experts to assume that genetic factors play a role in its development.

Treatment
Treatment becomes necessary where there are indications of a severe disease course, such as high blood pressure, increased amounts of blood and protein in the urine or an elevated creatinine concentration in the blood as signs of deteriorating renal function. In such cases, renal tissue is sampled (biopsy) and examined for abnormal changes or deposits of the antibody (IgA).

To prevent further damage to the kidneys, treatment of the high blood pressure is urgently needed. If chronic renal failure occurs, further treatment steps are initiated.

Bayer is active in the area of chronic renal diseases and is also working on new approaches to the treatment of inflammatory renal diseases such as IgA nephritis.




 

 

What is renal anemia?
Renal anemia is anemia resulting from deteriorating renal function. It occurs in particular in the later stages of chronic renal failure. This is because the kidneys play an important role in blood formation. They secrete the hormone erythropoietin (EPO), which stimulates the production of red blood cells.

If renal cells are damaged by progressive renal failure, there is therefore also a decrease in production of EPO. Other disease-related factors, such as accelerated breakdown of red blood cells or overactivity of the parathyroid glands (hyperparathyroidism), which is common in patients with renal disease, also contribute to an increased risk of anemia.

Risks and consequences
If this state persists for some time, there is a risk that oxygen deficiency will damage internal organs. The heart pumps harder to compensate for the deficiency. In the long term, this overload may lead to thickening of the chambers on the left side of the heart. If untreated, renal anemia may prove fatal.

Data and figures
The risk increases as the renal failure progresses: in early stages of chronic renal failure, 28 percent of patients develop anemia, while in late stages this figure rises to up to 87 percent. Existing diabetes further increases the risk.

Treatment
Nowadays, renal anemia can usually be treated by administering EPO.

Bayer is active in the area of cardiovascular diseases and associated chronic renal diseases and is also working on new approaches to the treatment of renal anemia.




 

Chronic renal failure is a condition in which kidney function is impaired as a result of disease for a prolonged period. It is often caused by damage to the fine capillaries in the renal corpuscles (glomeruli, picture).


Diabetic nephropathy is a condition in which the renal corpuscles (glomeruli) in the kidneys become damaged as a result of inadequately treated diabetes. The raised blood glucose leads to tissue changes in the glomeruli, which become increasingly scarred and permeable.


Hypertensive nephropathy is a condition in which the kidneys are damaged by high blood pressure. The hypertension triggers processes that lead to abnormal thickening of the thin arterial walls. Over years progressive scarring leads to renal fibrosis and kidney shrinking.


Vascular calcification is a condition in which calcification of blood vessels takes place as a result of renal disease. Calcium is deposited in the middle layer of the blood vessel wall tissue.


IgA nephritis is the most common inflammatory disease of glomeruli in the kidneys. It results from an immune reaction, in which antibodies are deposited in the glomeruli and cause local inflammatory processes.


Renal anemia is anemia resulting from deteriorating renal function. It occurs in particular in the later stages of chronic renal failure.