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Chronic Kidney Disease Overview

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Normal kidneys and kidney function

The kidneys are a pair of bean-shaped organs that lie on either side of the spine in the
lower middle of the back. Each kidney weighs about 5 ounces and contains
approximately one million filtering units called nephrons. Each nephron is made of a
glomerulus and a tubule. The glomerulus is a miniature filtering or sieving device while
the tubule is a tiny tube like structure attached to the glomerulus.
The kidneys are connected to the urinary bladder by tubes called ureters. Urine is
stored in the urinary bladder until the bladder is emptied by urinating. The bladder is
connected to the outside of the body by another tube like structure called the urethra.

Illustration of the kidneys, urinary tract, and bladder.

The main function of the kidneys is to remove waste products and excess water from
the blood. The kidneys process about 200 liters of blood every day and produce about 2
liters of urine. The waste products are generated from normal metabolic processes
including the breakdown of active tissues, ingested foods, and other substances. The

kidneys allow consumption of a variety of foods, drugs, vitamins and supplements,

additives, and excess fluids without worry that toxic by-products will build up to harmful
levels. The kidney also plays a major role in regulating levels of various minerals such
as calcium, sodium, and potassium in the blood.

As the first step in filtration, blood is delivered into the glomeruli by microscopic leaky blood
vessels called capillaries. Here, blood is filtered of waste products and fluid while red blood cells,
proteins, and large molecules are retained in the capillaries. In addition to wastes, some useful
substances are also filtered out. The filtrate collects in a sac called Bowman's capsule.

The tubules are the next step in the filtration process. The tubules are lined with highly functional
cells which process the filtrate, reabsorbing water and chemicals useful to the body while secreting
some additional waste products into the tubule.

The kidneys also produce certain hormones that have important functions in the body,
including the following:

Active form of vitamin D (calcitriol or 1,25 dihydroxy-vitamin D), which regulates absorption of
calcium and phosphorus from foods, promoting formation of strong bone.

Erythropoietin (EPO), which stimulates the bone marrow to produce red blood cells.

Renin, which regulates blood volume and blood pressure. Continue Reading

Illustration of kidney and surrounding anatomy.

Medically Reviewed by a Doctor on 11/11/2014
Medical Author:
Pranay Kathuria, MD, FACP, FASN, FNKF
Medical Editor:
Melissa Conrad Stppler, MD, Chief Medical Editor

Chronic Kidney Disease Causes

Although chronic kidney disease sometimes results from primary diseases of the
kidneys themselves, the major causes are diabetes and high blood pressure.

Type 1 and type 2 diabetes mellitus cause a condition called diabetic nephropathy, which is the
leading cause of kidney disease in the United States.

High blood pressure (hypertension), if not controlled, can damage the kidneys over time.

Glomerulonephritis is the inflammation and damage of the filtration system of the kidneys, which
can cause kidney failure. Postinfectious conditions andlupus are among the many causes of

Polycystic kidney disease is a hereditary cause of chronic kidney disease wherein both kidneys
have multiple cysts.

Use of analgesics such asacetaminophen (Tylenol) and ibuprofen(Motrin, Advil) regularly over
long durations of time can cause analgesic nephropathy, another cause of kidney disease. Certain
other medications can also damage the kidneys.

Clogging and hardening of the arteries (atherosclerosis) leading to the kidneys causes a
condition called ischemic nephropathy, which is another cause of progressive kidney damage.

Obstruction of the flow of urine by stones, an enlarged prostate, strictures (narrowings), or

cancers may also cause kidney disease.

Other causes of chronic kidney disease include HIV infection, sickle cell disease, heroin abuse,
amyloidosis, kidney stones, chronic kidney infections, and certain cancers.

If one has any of the following conditions, they are at higher-than-normal risk of
developing chronic kidney disease. One's kidney function may need to be monitored

Diabetes mellitus type 1 or type 2

High blood pressure

High cholesterol

Heart disease

Liver disease


Sickle cell disease

Systemic lupus erythematosus

Vascular diseases such as arteritis, vasculitis, or fibromuscular dysplasia

Vesicoureteral reflux (a urinary tract problem in which urine travels from the bladder the wrong
way back toward the kidney)
Require regular use of anti-inflammatory medications

How Common Is Chronic Kidney Disease (CKD)?

Chronic kidney disease is a growing health problem in the United States. Approximately 26
million Americans have chronic kidney disease. The United States Renal Data Systems 2011 Annual
Data Report determined that 15.1% of all adults above the age of 20 years have chronic kidney

It is estimated that more than 10% of adults in the United States - more than 20 million people may have CKD at varying levels of seriousness.

The number of transplants per year is from 15,000 to 18,000.

Kidney disease is more common among Hispanic, African American, Asian or Pacific Islander,
and Native American people.

Older age, female gender, diabetes, hypertension, and cardiovascular disease are associated
with a higher incidence of chronic kidney disease. Continue Rea

Chronic Kidney Disease Symptoms and When to Seek Medical Care

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The kidneys are remarkable in their ability to compensate for problems in their function.
That is why chronic kidney disease may progress without symptoms for a long time until
only very minimal kidney function is left.
Because the kidneys perform so many functions for the body, kidney disease can affect
the body in a large number of different ways. Symptoms vary greatly. Several different
body systems may be affected. Notably, most patients have no decrease in urine output
even with very advanced chronic kidney disease.
Effects and symptoms of chronic kidney disease include:

need to urinate frequently, especially at night (nocturia);

swelling of the legs and puffiness around the eyes (fluid retention);

high blood pressure;

fatigue and weakness (from anemia or accumulation of waste products in the body);

loss of appetite, nausea and vomiting;

itching, easy bruising, and pale skin (from anemia);

shortness of breath from fluid accumulation in the lungs;

headaches, numbness in the feet or hands (peripheral neuropathy), disturbed sleep, altered
mental status (encephalopathy from the accumulation of waste products or uremic poisons),
and restless legs syndrome;

chest pain due to pericarditis (inflammation around the heart);

bleeding (due to poor blood clotting);

bone pain and fractures; and

decreased sexual interest and erectile dysfunction.

When to Seek Medical Care

Several signs and symptoms may suggest complications of chronic kidney disease.
One should call a health care professional if they notice any of the following symptoms:

change in energy level or strength;

increased water retention (puffiness or swelling) in the legs, around the eyes, or in other parts of
the body;

shortness of breath or change from normal breathing;

nausea or vomiting;


bone or joint pain;

easy bruising; or


If a woman has known kidney problems, she should see a health care professional right
away if she knows or suspects that she is pregnant.

See a health care practitioner as recommended for monitoring and treatment of chronic
conditions such as diabetes, high blood pressure, and high cholesterol.
The following signs and symptoms represent the possibility of a severe complication of
chronic kidney disease and warrant a visit to the nearest hospital emergency

Change in level of consciousness -- extreme sleepiness or difficult to awaken

Severe fatigue

Chest pain

Difficulty breathing

Severe nausea and vomiting

Severe bleeding (from any source)

Muscle weakness Continue Reading

Chronic Kidney Disease Diagnosis

Chronic kidney disease usually causes no symptoms in its early stages. Only lab tests
can detect any developing problems. Anyone at increased risk for chronic kidney
disease should be routinely tested for development of this disease.

Urine, blood, and imaging tests (X-rays) are used to detect kidney disease, as well as to follow
its progress.

All of these tests have limitations. They are often used together to develop a picture of the nature
and extent of the kidney disease.

In general, this testing can be performed on an outpatient basis.

Urine tests
Urinalysis: Analysis of the urine affords enormous insight into the function of the
kidneys. The first step in urinalysis is doing a dipstick test. The dipstick has reagents
that check the urine for the presence of various normal and abnormal constituents
including protein. Then, the urine is examined under a microscope to look for red and
white blood cells, and the presence of casts and crystals (solids).
Only minimal quantities of albumin (protein) are present in urine normally. A positive
result on a dipstick test for protein is abnormal. More sensitive than a dipstick test for

protein is a laboratory estimation of the urine albumin (protein) and creatinine in the
urine. The ratio of albumin (protein) and creatinine in the urine provides a good estimate
of albumin (protein) excretion per day.
Twenty-four hour urine tests: This test requires the patient to collect all of their urine
for 24 consecutive hours. The urine may be analyzed for protein and waste products
(urea nitrogen, and creatinine). The presence of protein in the urine indicates kidney
damage. The amount of creatinine and urea excreted in the urine can be used to
calculate the level of kidney function and the glomerular filtration rate (GFR).
Glomerular filtration rate (GFR): The GFR is a standard means of expressing overall
kidney function. As kidney disease progresses, GFR falls. The normal GFR is about 100
to 140 mL/min in men and 85 to 115 mL/min in women. It decreases in most people with
age. The GFR may be calculated from the amount of waste products in the 24-hour
urine or by using special markers administered intravenously. An estimation of the GFR
(eGFR) can be calculated from the patient's routine blood tests. Patients are divided into
five stages of chronic kidney disease based on their GFR (see Table 1 above).
Blood tests
Creatinine and urea (BUN) in the blood: Blood urea nitrogen and serum creatinine
are the most commonly used blood tests to screen for and monitor renal disease.
Creatinine is a product of normal muscle breakdown. Urea is the waste product of
breakdown of protein. The level of these substances rises in the blood as kidney
function worsens.
Estimated GFR (eGFR): The laboratory or physician may calculate an estimated GFR
using the information from a patient's blood work. It is important to be aware of one's
estimated GFR and stage of chronic kidney disease. The physician uses the patient's
stage of kidney disease to recommend additional testing and provide suggestions on
Electrolyte levels and acid-base balance: Kidney dysfunction causes imbalances
in electrolytes, especially potassium, phosphorus, and calcium. High potassium
(hyperkalemia) is a particular concern. The acid-base balance of the blood is usually
disrupted as well.
Decreased production of the active form of vitamin D can cause low levels of calcium in
the blood. Inability of failing kidneys to excrete phosphorus causes its levels in the blood
to rise. Testicular or ovarian hormone levels may also be abnormal.
Blood cell counts: Because kidney disease disrupts blood cell production and
shortens the survival of red cells, the red blood cell count andhemoglobin may be low
(anemia). Some patients may also have irondeficiency due to blood loss in their

gastrointestinal system. Other nutritional deficiencies may also impair the production of
red cells.
Other tests
Ultrasound: Ultrasound is often used in the diagnosis of kidney disease. An ultrasound
is a noninvasive type of imaging test. In general, kidneys are shrunken in size in chronic
kidney disease, although they may be normal or even large in size in cases caused by
adult polycystic kidney disease, diabetic nephropathy, and amyloidosis. Ultrasound may
also be used to diagnose the presence of urinary obstruction, kidney stones and also to
assess the blood flow into the kidneys.
Biopsy: A sample of the kidney tissue (biopsy) is sometimes required in cases in which
the cause of the kidney disease is unclear. Usually, a biopsy can be collected with local
anesthesia by introducing a needle through the skin into the kidney. This is usually done
as an outpatient procedure, though some institutions may require an overnight hospital
stay. Continue Reading
Chronic Kidney Disease Treatment

There is no cure for chronic kidney disease. The four goals of therapy are to:
1. slow the progression of disease;
2. treat underlying causes and contributing factors;
3. treat complications of disease; and
4. replace lost kidney function.

Strategies for slowing progression and treating conditions underlying chronic kidney
disease include the following:

Control of blood glucose:Maintaining good control of diabetes is critical. People with diabetes
who do not control their blood glucose have a much higher risk of all complications of diabetes,
including chronic kidney disease.

Control of high blood pressure: This also slows progression of chronic kidney disease. It is
recommended to keep blood pressure below 130/80 mm Hg if one has kidney disease. It is often
useful to monitor blood pressure at home. Blood pressure medications known as angiotensin
converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) have special benefit in
protecting the kidneys.

Diet: Diet control is essential to slowing progression of chronic kidney disease and should be
done in close consultation with a health care practitioner and a dietitian. For some general guidelines,
see the Chronic Kidney Disease Self-Care at Homesection of this article.

The complications of chronic kidney disease may require medical treatment.

Fluid retention is common in kidney disease and manifests with swelling. In late phases, fluid
may build up in the lungs and cause shortness of breath.

Anemia is common with CKD. The two most common causes of anemia with kidney disease are
iron deficiency and the lack of erythropoietin. If one is anemic, the doctor will run tests to determine if
the anemia is secondary to kidney disease or due to alternative causes.

Bone disease develops in kidney disease. The kidneys are responsible for excreting
phosphorus from the body and processing Vitamin D into its active form. High phosphorus levels and
lack of vitamin D cause blood levels of calcium to decrease, causing activation of the parathyroid
hormone (PTH). These and several complex changes cause the development of metabolic bone
disease. Treatment of metabolic bone disease is aimed at managing serum levels of calcium,
phosphorus, and parathyroid hormone.

Metabolic acidosis may develop with kidney disease. The acidosis may cause breakdown of
proteins, inflammation, and bone disease. If the acidosis is significant, the doctor may use drugs such
as sodium bicarbonate (baking soda) to correct the problem.

Chronic Kidney Disease Medications

Common adverse drug reactions include hypotension (low blood pressure), cough,
hyperkalemia (high potassium), headache,dizziness, fatigue, nausea, skin rash and a
metallic taste. In some patients, the medication may cause a further decline in kidney
function. Rarely, patients may develop angioedema, which is swelling of the
subcutaneous and submucosal tissue and may lead to difficulty in breathing. This may
be a life-threatening condition and needs immediate medical attention.

Common adverse drug reactions include dizziness, headache, and hyperkalemia. Other
side effects include hypotension, rash, diarrhea, dyspepsia, abnormal liver
function, muscle cramps, myalgia, back pain, insomnia, anemia, and worsening of
kidney function. Instances of angioedema are also reported with ARBs.

Common adverse effects include frequent urination, dehydration, muscle cramps,

weakness, heart rhythm abnormalities, electrolyte abnormalities, lightheadedness, and

allergic reactions. Diuretics may also cause a decline in kidney function especially if
fluid is removed rapidly from the body.

Angiotensin converting enzyme inhibitors (ACE-Is): ACE-Is are drugs commonly used in the
treatment of hypertension. Some examples of these drugs
include captopril (Capoten),enalapril (Vasotec), lisinopril (Zestril,
Prinivil), ramipril (Altace), quinapril(Accupril), benazepril (Lotensin) andtrandolapril (Mavik). These
drugs decrease blood pressure by reducing production of angiotensin-II (a hormone that causes blood
vessels to constrict) and aldosterone (a hormone that causes sodium retention). Besides reducing
blood pressure, these drugs have additional effects that affect progression of kidney disease including
reducing pressure inside the glomerulus and decreasing scarring in the kidney.

Angiotensin receptor blockers (ARBs): ARBs are drugs that block the action of angiotensin 2
on its receptors. These drugs, like ACE-I, have a protective effect on the kidneys and slow the
progression of kidney failure. Drugs included in this category
include losartan(Cozaar), valsartan (Diovan), irbesartan (Avapro), candesartan(Atacand)
and olmesartan (Benicar).

Diuretics: The doctor may prescribe diuretics (water pills) to controledema (swelling), blood
pressure and/or potassium levels. There are several classes of diuretics, including loop diuretics
(furosemide,ethacrynic acid, bumetanide, torsemide), thiazides
(hydrochlorothiazide, chlorthalidone, indapamide), and potassium-sparing diuretics
(spironolactone, eplerenone, amiloride, triamterene). Diuretics differ in their potential to eliminate salt
and water

More Chronic Kidney Disease Medications

ESAs may have serious side effects. These include the risk of strokes, heart attacks,
and blood clots. Worsening hypertension and seizures as well as serious allergic
reactions are other side effects.
The calcium-based binders may causehypercalcemia. Lanthanum and sevelamerdo not
contain calcium. While non-calcium based binders are much more expensive, the doctor
may favor these if a patient's blood calcium levels are high. All phosphate binders may
cause constipation, nausea, vomiting, bowel obstruction, and fecal impaction.
Phosphate binders may interfere with the absorption of other medications if these are
taken together. Always check with the doctor to confirm the suitability of taking these
medications together with other drugs.
As kidney disease progresses, activated forms of vitamin D may be prescribed. These
drugs include Calcitriol (Rocaltrol),Paricalcitol (Zemplar), or doxercalciferol(Hectorol).
These drugs are prescribed to control secondary hyperparathyroidismwhen the
correction of nutritional vitamin D deficiency, administration of calcium supplementation,
and control of serum phosphate have been ineffective.

The use of activated vitamin D may cause hypercalcemia (high calcium levels). The
symptoms of hypercalcemia include feeling tired, difficulty thinking clearly, loss of
appetite, nausea, vomiting, constipation, increased thirst, increased urination,
andweight loss. Other side effects include diarrhea, nausea, swelling, allergic reactions,
viral infections, high blood pressure, inflammation of the throat and nose, and dizziness.
The doctor will recommend regular blood tests to follow the patient's kidney function,
calcium, phosphorus, and parathyroid hormone levels.

Erythropoiesis-stimulating agents (ESAs): Patients with chronic kidney disease often develop
anemia due to a lack of erythropoietin produced by the kidneys. Anemia is a condition with too few red
cells and is characterized by fatigue and tiredness. After excluding other causes of anemia, the doctor
may prescribe erythropoiesis-stimulating agents (ESAs) such as Procrit (erythropoietin), Aranesp
(darbepoetin), or Omontys (peginesatide). ESAs stimulate the bone marrow to produce red cells and
reduce the need for blood transfusions.

Phosphate binders: The doctor may recommend a diet low in phosphorus if one's serum
phosphorus levels are high. If dietary restriction of phosphorus is unable to control the phosphorus
levels, the patient may be started on phosphate binders. When taken with meals, binders combine with
dietary phosphate and allow for elimination without absorption into the bloodstream. Binders are
divided into large classes, including calcium-based binders such as Tums (calcium carbonate) and
PhosLo (calcium acetate) and non-calcium based binders like Fosrenol (lanthanum carbonate),
Renagel (sevelamer hydrochloride) and Renvela (sevelamer carbonate).

Vitamin D: Vitamin D deficiency is very common in patients with chronic kidney disease. The
first step in treating metabolic bone disease is to ensure that there are adequate reserves of vitamin D
in the body. The doctor may prescribe over-the-counter vitamin D or prescription-strength vitamin D
(Drisdol) based on the patient's vitamin D levels.

Chronic Kidney Disease Prevention and Prognosis

Chronic kidney disease cannot be prevented in most situations. The patient may be
able to protect their kidneys from damage, or slow the progression of the disease by
controlling their underlying conditions such as diabetes mellitus and high blood

Kidney disease is usually advanced by the time symptoms appear. If a patient is at high risk of
developing chronic kidney disease, they should see their health care practitioner as recommended for
screening tests.

If a patient has a chronic condition such as diabetes, high blood pressure, or high cholesterol,
they should follow the treatment recommendations of their health care practitioner. The patient should
see their health care practitioner regularly for monitoring. Aggressive treatment of these diseases is

The patient should avoid exposure to drugs especially NSAIDs (nonsteroidal antiinflammatory drugs), chemicals, and other toxic substances as much as possible.
Chronic Kidney Disease Prognosis
There is no cure for chronic kidney disease. The natural course of the disease is to
progress until dialysis or transplant is required.

Patients with chronic kidney disease are at a much higher risk than the general population to
develop strokes and heart attacks.

People undergoing dialysis have an overall 5-year survival rate of 32%. The elderly and those
with diabetes have worse outcomes.

Recipients of a kidney transplant from a living related donor have a 2-year survival rate greater
than 90%.

Recipients of a kidney from a donor who has died have a 2-year survival rate of 88%.