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Chronic Kidney Disease

by James I. McMillan, MD

Chronic kidney disease (also called chronic renal failure) is a slowly progressive (months to years) decline in the kidneys’ ability to filter metabolic waste from the blood.

  • Major causes are diabetes and high blood pressure.

  • Blood becomes more acidic, anemia develops, nerves are damaged, bone tissue deteriorates, and risk of atherosclerosis increases.

  • Symptoms can include urinating at night, fatigue, nausea, itching, muscle twitching and cramps, loss of sensation, confusion, difficulty breathing, and yellow-brown skin.

  • Diagnosis is by blood and urine tests.

  • Treatment aims to restrict fluids, sodium, and potassium in the diet, use drugs to correct other conditions (such as diabetes, high blood pressure, anemia, and electrolyte imbalances), and, when necessary, use dialysis.

Many diseases can irreversibly damage or injure the kidneys. Acute kidney injury (see Acute Kidney Injury) can become chronic if kidney function does not recover after treatment. Therefore, anything that can cause acute kidney injury can cause chronic kidney disease. However, in Western countries, the most common cause of chronic kidney disease is diabetes mellitus, followed by high blood pressure (hypertension). Both of these conditions directly damage the kidneys’ small blood vessels.

Other causes of chronic kidney disease include urinary tract blockage (obstruction), certain kidney abnormalities (such as polycystic kidney disease and glomerulonephritis), and autoimmune disorders (such as systemic lupus erythematosus [lupus]) in which antibodies damage the tiny blood vessels (glomeruli) and the tiny tubes (tubules) of the kidneys.

When loss of kidney function is mild or moderately severe, the kidneys cannot absorb water from the urine to reduce the volume of urine and concentrate it. Later, the kidneys have less ability to excrete the acids normally produced by the body and the blood becomes more acidic, a condition called acidosis. Production of red blood cells decreases, leading to anemia. High levels of metabolic wastes in the blood can damage nerve cells in the brain, trunk, arms, and legs. Uric acid levels may increase, sometimes causing gout. Diseased kidneys produce hormones that increase blood pressure. In addition, diseased kidneys cannot excrete excess salt and water. Salt and water retention can lead to high blood pressure and heart failure. The sac that surrounds the heart (pericardium) may become inflamed (pericarditis). The level of triglycerides in the blood is often elevated, which, along with high blood pressure, increases the risk of atherosclerosis.

The formation and maintenance of bone tissue may be impaired (renal osteodystrophy) if certain conditions that accompany chronic kidney disease are present for a long time. These conditions include a high level of parathyroid hormone, a low concentration of calcitriol (the active form of vitamin D ) in the blood, impaired absorption of calcium, and a high concentration of phosphate in the blood. Renal osteodystrophy may lead to bone pain and an increased risk of fractures.


Symptoms usually develop very slowly. People with mild to moderately severe loss of kidney function may have only mild symptoms, such as the need to urinate several times during the night (nocturia). Nocturia occurs because the kidneys cannot absorb water from the urine to reduce the volume and concentrate it as normally occurs during the night.

As kidney failure progresses and metabolic wastes build up in the blood, people may feel fatigued and generally weak and may become less mentally alert. Some have a loss of appetite and shortness of breath. Anemia also contributes to fatigue and generalized weakness. The buildup of metabolic waste also causes nausea, vomiting, and an unpleasant taste in the mouth, which may lead to undernutrition and weight loss. People with chronic kidney disease tend to bruise easily or bleed for an unusually long time after cuts or other injuries. Chronic kidney disease also diminishes the body’s ability to fight infections. Gout may cause acute arthritis with joint pain and swelling.

As metabolic wastes build up to higher levels in the blood, damage to muscles and nerves can cause muscle twitches, muscle weakness, cramps, and pain. People may also feel a pins-and-needles sensation in the arms and legs and may lose sensation in certain areas of the body. They may develop restless legs syndrome. Encephalopathy, a condition in which the brain malfunctions, may ensue and lead to confusion, lethargy, and seizures.

Heart failure may cause shortness of breath. Pericarditis may cause chest pain and low blood pressure. People who have advanced chronic kidney disease commonly develop gastrointestinal ulcers and bleeding. The skin may turn yellow-brown, and occasionally, the concentration of urea is so high that it crystallizes from sweat, forming a white powder on the skin. Some people with chronic kidney disease itch all over their body. Their breath may also be foul.


Blood and urine tests are essential. They confirm the decline in kidney function.

When loss of kidney function reaches a certain level in chronic kidney disease, blood levels of urea and creatinine, metabolic waste products that are normally filtered out by the kidneys, are increased. Typically, the blood becomes moderately acidic. The level of potassium in the blood is often normal or only slightly increased but can become dangerously high when kidney failure reaches an advanced stage or if people ingest large amounts of potassium or take a drug that prevents the kidneys from excreting the potassium. Usually, people have some degree of anemia. The levels of calcium and calcitriol in the blood decrease, and the phosphate and parathyroid hormone levels increase. Analysis of the urine may detect many abnormalities, including protein and abnormal cells.

Ultrasonography is often done to rule out obstruction and check the size of the kidneys. Small, scarred kidneys often indicate that loss of kidney function is chronic. Determining a precise cause becomes increasingly difficult as chronic kidney disease reaches an advanced stage. Removing a sample of tissue from a kidney for examination (kidney biopsy) may be the most accurate test, but it is not recommended if results of an ultrasound examination show that the kidneys are small and scarred.


In most people, ultimately, chronic kidney disease progresses regardless of treatment. The rate of decline in kidney function depends somewhat on the underlying disorder causing chronic kidney disease and on how well the disorder is controlled. For example, diabetes and high blood pressure, particularly if poorly controlled, cause kidney function to decline more rapidly. Chronic kidney disease is fatal if not treated. When the decline in kidney function is severe (sometimes called end-stage kidney failure), survival is usually limited to several months in people who are not treated, but people who are treated with dialysis can live much longer. However, even with dialysis, most people with end-stage kidney failure die within 5 to 10 years. Most die from heart or blood vessel disorders or infections.


Conditions that can cause or worsen chronic kidney disease and its consequences that might adversely affect overall health should be treated promptly. For example, bacterial infections are treated with antibiotics, and any obstructions in the urinary tract are removed or relieved.

Measures are also taken to prevent worsening of kidney function or complications of chronic kidney disease. These measures often include

  • Controlling diabetes, blood pressure, and cholesterol and triglyceride levels

  • Restricting dietary protein, salt, potassium, phosphorus, and fluids

  • Sometimes, increasing fruit and vegetable intake or using sodium bicarbonate

  • Using drugs to control potassium, phosphorus, and parathyroid hormone levels and to treat heart failure or anemia

  • Eventually, giving dialysis

Controlling the level of sugar (glucose) in the blood as well as high blood pressure in people with diabetes substantially slows deterioration in kidney function. Drugs called angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may decrease the rate of decline in kidney function in some people with chronic kidney disease. However, people with end-stage kidney failure should not take these drugs.

Meticulous attention to diet helps control several potential problems. Sometimes, mild acidosis can be controlled by increasing the intake of fruits and vegetables and reducing the intake of protein. However, moderate or severe acidosis may require treatment with sodium bicarbonate. The decline in kidney function can be slowed slightly by restricting the amount of protein consumed daily. People need to consume sufficient carbohydrates to offset the reduction in protein. The triglyceride and cholesterol levels may be controlled somewhat by limiting fat in the diet. Drugs such as statins, ezetimibe, or both may be required to correct the levels of triglycerides and cholesterol.

The restriction of salt (sodium) is usually beneficial, especially if heart failure occurs. Diuretics may also relieve symptoms of heart failure, even when kidney function is poor, but dialysis may be needed to remove the excess body water in severe chronic kidney disease.

During chronic kidney disease, fluid intake may need to be restricted to prevent the sodium concentration in the blood from becoming too low. Foods that are extremely high in potassium, such as salt substitutes, must be avoided, and foods that are somewhat high in potassium, such as dates, figs, and many other fruits, should not be consumed in excess. (See the National Kidney Foundation’s publication Potassium and Your CKD Diet for more information.) A high potassium level in the blood increases the risk of abnormal heart rhythms and cardiac arrest. If the potassium level becomes too high, drugs such as sodium polystyrene sulfonate may help, but emergency dialysis may be required.

The elevated phosphorus level in the blood can cause deposits of calcium and phosphorus to form in tissues, including the blood vessels. Restricting the intake of foods that are high in phosphorus, such as dairy products, liver, legumes, nuts, and most soft drinks, lowers the phosphate concentration in the blood. Drugs that bind phosphate, such as calcium carbonate, calcium acetate, and sevelamer, taken by mouth, may also lower the phosphorus level in the blood. Calcium citrate should be avoided. Calcium citrate is found in many calcium supplements and is in many products as a food additive (sometimes called E333). Vitamin D and similar drugs are often taken by mouth to reduce high levels of parathyroid hormone.

The anemia caused by chronic kidney disease responds to the drugs erythropoietin and darbepoietin. Blood transfusions are given only if the anemia is severe, is causing symptoms, and does not respond to erythropoietin or darbepoietin. Doctors also look for and treat other causes of anemia, particularly dietary deficiencies of iron, folate (folic acid), and vitamin B12. Most people who take erythropoietin or darbepoietin regularly need to be given iron intravenously to prevent iron deficiency, which impairs the body’s response to these drugs. Erythropoietin and darbepoietin should be used only when necessary because they can increase the risk of stroke. The tendency to bleed can be temporarily suppressed by transfusions of blood products or by such drugs as desmopressin or estrogens . Such treatment may be needed after an injury or before a surgical procedure or a tooth extraction.

Doctors avoid prescribing drugs that are excreted by the kidneys, or they prescribe lower doses of such drugs. Many other drugs may need to be avoided. For example, ACE inhibitors, angiotensin II receptor blockers, and the diuretics spironolactone, amiloride, and triamterene may need to be stopped in people with severe chronic kidney disease and high potassium levels because these drugs can increase potassium levels. High blood pressure is treated with antihypertensive drugs to prevent further impairment of heart and kidney function.

When the treatments for chronic kidney disease are no longer effective, the only options are long-term dialysis (see Dialysis) and kidney transplantation (see Kidney Transplantation). End-of-life care is important (see Introduction to Death and Dying).

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