Chronic Kidney Disease Overview

Chronic Kidney Disease Overview Normal Kidneys and Their 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 ¼ pound 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.

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 two 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 and drains into the tubule.

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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: •

Activate 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.

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

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Renin, which regulates blood volume and blood pressure.

What is the difference between kidney failure and kidney disease? Kidney failure •

Kidney failure occurs when the kidneys partly or completely lose their ability to carry out normal functions.

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This is dangerous because water, waste, and toxic substances build up that normally are removed from the body by the kidneys.

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It also causes other problems such as anemia, high blood pressure, acidosis (excessive acidity of body fluids), disorders of cholesterol and fatty acids, and bone disease in the body by impairing hormone production by the kidneys.

Unlike chronic kidney disease, acute kidney failure develops rapidly, over days or weeks. •

Acute kidney failure usually develops in response to a disorder that directly affects the kidney, its blood supply, or urine flow from it.

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Acute kidney failure usually does not cause permanent damage to the kidneys. With appropriate treatment of the underlying condition, it is often reversible, with complete recovery.

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In some cases, though, it may progress to chronic kidney disease.

For more, please read the Kidney Failure article. Table 1. Stages of Chronic Kidney Disease Stage

Description

GFR* mL/min/1.73m2

1

Slight kidney damage with normal or increased More than 90 filtration

2

Mild decrease in kidney function

60-89

3

Moderate decrease in kidney function

30-59

4

Severe decrease in kidney function

15-29

5

Kidney failure requiring dialysis or transplantation

Less than 15

*GFR is glomerular filtration rate, a measurement of the kidney's function. 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.

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

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

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

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Use of analgesics such as acetaminophen (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.

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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.

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Obstruction of the flow of urine by stones, an enlarged prostate, strictures (narrowings), or cancers may also cause kidney disease.

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

If you have any of the following conditions, you are at higher-than-normal risk of developing chronic renal disease. Your kidney functions may need to be monitored regularly. •

Diabetes mellitus type 1 or 2

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High blood pressure

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High cholesterol

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Heart disease

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Liver disease

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Kidney disease

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Amyloidosis

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Sickle cell disease

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Systemic Lupus erythematosus

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Vascular diseases such as arteritis, vasculitis, or fibromuscular dysplasia

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Vesicoureteral reflux (a urinary tract problem in which urine travels the wrong way)

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Problems of the joints or muscles that require regular use of anti-inflammatory medications

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If you have a family history of kidney disease.

Chronic kidney disease Most kidney problems, however, happen slowly. A person may have “silent” kidney disease for years. Gradual loss of kidney function is called chronic kidney disease (CKD) or chronic renal insufficiency. People with CKD may go on to develop permanent kidney failure. They also have a high risk of death from a stroke or heart attack. Chronic kidney disease is when one suffers from gradual and usually permanent loss of kidney function over time. This happens gradually over time, usually months to years. Chronic kidney disease is divided into five stages of increasing severity (see Table 1

below). Stage 5 chronic kidney failure is also referred to as end-stage renal disease, wherein there is total or near-total loss of kidney function and patients need dialysis or transplantation to stay alive. The term "renal" refers to the kidney, so another name for kidney failure is "renal failure." Mild kidney disease is often called renal insufficiency.

How Common is Chronic Kidney Disease? •

Chronic kidney disease is a growing health problem in the United States. A report by the Centers for Disease Control (CDC) determined that 16.8% of all adults above the age of 20 years have chronic kidney disease. Thus, one in six individuals have kidney disease, and over 400,000 patients are on dialysis or have received kidney transplants. About 67,000 people die each year because of kidney failure.

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The prevalence of chronic kidney disease has increased by 16% from the previous decade. The increasing incidence of diabetes mellitus, hypertension (high blood pressure), obesity, and an aging population have led to this increase in kidney disease.

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Chronic kidney disease is more prevalent among individuals above 60 years of age (39.4%).

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

Chronic Kidney Disease Symptoms 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. •

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

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Loss of appetite, nausea and vomiting

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Need to urinate frequently, especially at night

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Swelling of the legs and puffiness around the eyes (fluid retention)

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Itching, easy bruising, and pale skin (from anemia)

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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

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High blood pressure, chest pain due to pericarditis (inflammation around the heart)

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Shortness of breath from fluid in lungs

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Bleeding (poor blood clotting)

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Bone pain and fractures

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Decreased sexual interest and erectile dysfunction

When to Seek Medical Care Several signs and symptoms may suggest complications of chronic kidney disease. Call your healthcare provider if you notice any of the following symptoms: •

Change in energy level or strength

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

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Shortness of breath or change from normal breathing

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Nausea or vomiting

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Light-headedness

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Severe bone or joint pain

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Easy bruisability

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Itching

If you have diabetes, high blood pressure, or kidney problems, see your healthcare provider right away if you know or suspect that you are pregnant. See your health care provider as recommended for monitoring and treatment of chronic conditions such as diabetes, high blood pressure, and high cholesterol. Some signs and symptoms represent the possibility of a severe complication of chronic kidney disease and warrant a visit to the nearest hospital emergency department. •

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

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Fainting

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Chest pain

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Difficulty breathing

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Severe nausea and vomiting

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Severe bleeding (from any source)

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Severe weakness

Exams and Tests 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.

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

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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 you to collect all of your 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 100140 mL/min in men and 85-115 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. 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 breakdown 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 your physician may calculate an estimated GFR using the information from your blood work. It is important to be aware of your estimated GFR and stage of chronic kidney disease. Your physician uses your stage of kidney disease to recommend additional testing and suggestions on management. 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 to excrete phosphorus by failing kidneys 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 and hemoglobin may be low (anemia). Some patients may also have iron deficiency 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 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 only 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.

Chronic Kidney Disease Treatment Self-Care at Home Chronic kidney disease is a disease that must be managed in close consultation with your healthcare provider. Self-treatment is not appropriate. •

There are, however, several important dietary rules you can follow to help slow the progression of your kidney disease and decrease the likelihood of complications.

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This is a complex process and must be individualized, generally with the help of your healthcare provider and a registered dietitian.

The following are general dietary guidelines: •

Protein restriction: Decreasing protein intake may slow the progression of chronic kidney disease. A dietitian can help you determine the appropriate amount of protein for you.

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Salt restriction: Limit to 4-6 grams a day to avoid fluid retention and help control high blood pressure.

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Fluid intake: Excessive water intake does not help prevent kidney disease. In fact, your doctor may recommend restriction of water intake.

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Potassium restriction: This is necessary in advanced kidney disease because the kidneys are unable to remove potassium. High levels of potassium can cause abnormal heart rhythms. Examples of foods high in potassium include bananas, oranges, nuts, and potatoes.

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Phosphorus restriction: Decreasing phosphorus intake is recommended to protect bones. Eggs, beans, cola drinks, and dairy products are examples of foods high in phosphorus.

Other important measures that you can take include: •

Carefully follow prescribed regimens to control your blood pressure and/or diabetes.

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Stop smoking

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Lose excess weight

In chronic kidney disease, several medications can be toxic to the kidneys and may need to be avoided or given in adjusted doses. Among over-the-counter medications, the following need to be avoided or used with caution: •

Certain analgesics - Aspirin; nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen [Motrin, for example])

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Fleets or phosphosoda enemas because of their high content of phosphorus

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Laxatives and antacids containing magnesium and aluminum such as Milk of Magnesia and Mylanta

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Ulcer medication H2-receptor antagonists - cimetidine (Tagamet), ranitidine (Zantac), (decreased dosage with kidney disease)

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Decongestants like pseudoephedrine (Sudafed) especially if you have high blood pressure

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Alka Seltzer, since this contains a lot of salt

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Herbal medications

If you have a condition such as diabetes, high blood pressure, or high cholesterol underlying your chronic kidney disease, take all medications as directed and see your healthcare provider as recommended for follow-up and monitoring.

Medical Treatment There is no cure for chronic kidney disease. The four goals of therapy are as follows: 1. To slow the progression of disease 2. To treat underlying causes and contributing factors 3. To treat complications of disease 4. To 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.

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Control of high blood pressure: This also slows progression of chronic kidney disease. It is recommended to keep your blood pressure below 130/80 mm Hg if you have 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.

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

The complications of chronic kidney disease may require medical treatment. •

Fluid retention can be treated with any of a number of diuretic medications, which remove excess water from the body. However, these drugs are not suitable for all patients.

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Anemia can be treated with erythropoiesis stimulating agents. Erythropoiesis stimulating agents are a group of drugs that replace the deficiency of erythropoietin, which is normally produced by healthy kidneys. Often, patients treated with such drugs require either to take iron by mouth or sometimes even intravenously.

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Bone disease develops in patients due to an inability to excrete phosphorus and a failure to form activated Vitamin D. In such circumstances, your physician may prescribe drugs binding phosphorus in the gut, and may prescribe active forms of vitamin D.

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

ialysis In end-stage renal disease, kidney functions can be replaced only by dialysis or by kidney transplantation. See the Transplant section for more information about transplants. There are two types of dialysis 1) hemodialysis and 2) peritoneal dialysis. Hemodialysis Hemodialysis involves circulation of blood through a filter on a dialysis machine. Blood is cleansed of waste products and excess water. The acid levels and the concentration of various minerals such as sodium and potassium in the blood are normalized. The blood is then returned to the body.

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Long-term dialysis requires access to a blood vessel so that the machine has a way to remove and return blood to the body. This may be in the form of a dialysis catheter or an arteriovenous fistula or graft.

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A catheter may be either temporary or permanent. These catheters are either placed in the neck or the groin into a large blood vessel. These catheters are prone to infection and may also cause blood vessels to clot or narrow.

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The preferred access for hemodialysis is an arteriovenous fistula wherein an artery is directly joined to a vein. The vein takes two to four months to enlarge and mature before it can be used for dialysis. Once matured, two needles are placed into the vein for dialysis. One needle is used to draw blood and run through the dialysis machine. The second needle is to return the cleansed blood.

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An arteriovenous graft is placed in patients who have small veins or in whom a fistula has failed to develop. The graft is made of artificial material and the dialysis needles are inserted into the graft directly.

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These venous access devices usually can be placed with local anesthesia on an outpatient basis.

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Hemodialysis typically takes three to five hours and is needed three times a week.

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You will need to travel to a dialysis center for hemodialysis.

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Home hemodialysis is possible in some situations. A care partner is needed to assist you with the dialysis treatments. A family member or close friend are the usual options, though occasionally patients may hire a professional to assist with dialysis. Home hemodialysis may be performed as traditional three times a week treatments, long nocturnal (overnight) hemodialysis, or short daily hemodialysis. Daily hemodialysis and long nocturnal hemodialysis offer advantages in quality of life and better control of high blood pressure, anemia, and bone disease.

Peritoneal dialysis Peritoneal dialysis utilizes the lining membrane (peritoneum) of the abdomen as a filter to clean blood and remove excess fluid. A catheter is implanted into the abdomen by a minor surgical procedure. Peritoneal dialysis may be performed manually or by using a machine to perform the dialysis at night. •

About 2 to 3 liters of dialysis fluid are infused into the abdominal cavity through this catheter. This fluid contains substances that pull wastes and excess water out of neighboring tissues.

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The fluid is allowed to dwell for two to several hours before being drained, taking the unwanted wastes and water with it.

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The fluid typically needs to be exchanged four to five times a day.

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Peritoneal dialysis offers much more freedom compared to hemodialysis since patients do not need to come to a dialysis center for their treatment. You can carry out many of your usual activities while undergoing this treatment. This may be the preferable therapy for children.

Most patients are candidates for both hemodialysis and peritoneal dialysis. There are little differences in outcomes between the two procedures. Your physician may recommend one kind of dialysis over the other based on your medical and surgical history. It is best to choose your modality of dialysis after understanding both procedures and matching them to your life style, daily activities, schedule, distance from the dialysis unit, support system, and personal preference.

Transplantation Kidney transplantation offers the best outcomes and the best quality of life. Successful kidney transplants occur every day in the United States. Transplanted kidneys may come from living related donors, living unrelated donors, or people who have died of other causes (cadaveric donors). In people with type I diabetes, a combined kidney-pancreas transplant is often a better option. However, not everyone is a candidate for kidney transplant. Patients need to undergo extensive testing to ensure their suitability for transplantation. Also, there is a shortage of organs for transplantation, requiring patients to wait months to years before getting a transplant. A person who needs a kidney transplant undergoes several tests to identify characteristics of his or her immune system. The recipient can accept only a kidney that comes from a donor who matches certain of his or her characteristics. The more similar the donor is in these characteristics, the greater the chance of long-term success of the transplant. Transplants from a living related donor generally have the best results. Transplant surgery is a major procedure and generally requires four to seven days in the hospital. All transplant recipients require lifelong immunosuppressant medications to prevent their bodies from rejecting the new kidney. Immunosuppressant medications require careful monitoring of blood levels and increase the risk of infection as well as some types of cancer. For more, please read the Kidney Transplant article.

Follow-up If you have chronic kidney disease, your health care provider will recommend a schedule of regular follow-up visits. •

At these visits, your underlying condition and your kidney status will be evaluated.

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You will have regular blood and urine tests and possibly imaging studies as part of this ongoing evaluation.

Prevention Chronic kidney disease cannot be prevented in most situations. You may be able to protect your kidneys from damage, or slow the progression of the disease by controlling your underlying conditions. •

Kidney disease is usually advanced by the time symptoms appear. If you are at high risk of developing chronic kidney disease, see your healthcare provider as recommended for screening tests.

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If you have a chronic condition such as diabetes, high blood pressure, or high cholesterol, follow the treatment recommendations of your healthcare provider. See your healthcare provider regularly for monitoring. Aggressive treatment of these diseases is essential.

Avoid exposure to drugs especially NSAIDs (nonsteroidal anti-inflammatory drugs), chemicals, and other toxic substances as much as possible.

Outlook 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.

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

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

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

Kidney and surrounding anatomy.

Synonyms and Keywords analgesic nephropathy, anemia, calcitriol, CAPD, chronic kidney failure, chronic kidney disease, chronic renal failure, chronic renal insufficiency, continuous ambulatory peritoneal dialysis, diabetes, diabetic nephropathy, dialysis, end-stage renal disease, endstage kidney disease, erythropoietin, hemodialysis, high blood pressure, hypertension, kidney transplant, kidney transplantation, kidneys, nephritis, peritoneal dialysis, renal disease, renal failure, renal insufficiency, renal osteodystrophy, renin, urine

Dialysis The two major forms of dialysis are hemodialysis and peritoneal dialysis. Hemodialysis uses a special filter called a dialyzer that functions as an artificial kidney to clean a person’s blood. The dialyzer is a canister connected to the hemodialysis machine. During treatment, the blood travels through tubes into the dialyzer, which filters out wastes, extra salt, and extra water. Then the cleaned blood flows through another set of tubes back into the body. The hemodialysis machine monitors blood flow and removes wastes from the dialyzer. Hemodialysis is usually performed at a dialysis center three times per week for 3 to 4 hours. A small but growing number of clinics offer home hemodialysis in addition to standard in-clinic treatments. The patient first learns to do treatments at the clinic, working with a dialysis nurse. Daily home hemodialysis is done 5 to 7 days per week for 2 to 3 hours at a time. Nocturnal dialysis can be performed for 8 hours at night while a person sleeps. Research as to which is the best method for dialysis is under way, but preliminary data indicate that daily dialysis schedules such as short daily dialysis or nocturnal dialysis may be the best form of dialysis therapy.

Hemodialysis. In peritoneal dialysis, a fluid called dialysis solution is put into the abdomen. This fluid captures the waste products from a person’s blood. After a few hours when the fluid is nearly saturated with wastes, the fluid is drained through a catheter. Then, a fresh bag of fluid is dripped into the abdomen to continue the cleansing process. Patients can perform peritoneal dialysis themselves. Patients using continuous ambulatory peritoneal dialysis (CAPD) change fluid four times a day. Another form of peritoneal dialysis, called continuous cycling peritoneal dialysis (CCPD), can be performed at night with a machine that drains and refills the abdomen automatically.

Peritoneal dialysis.

Transplantation A donated kidney may come from an anonymous donor who has recently died or from a living person, usually a relative. The kidney must be a good match for the patient’s body. The more the new kidney is like the person receiving the kidney, the less likely the immune system is to reject it. The immune system protects a person from disease by attacking anything that is not recognized as a normal part of the body. So the immune

system will attack a kidney that appears too “foreign.” The patient will take special drugs to help trick the immune system so it does not reject the transplanted kidney. Unless they are causing infection or high blood pressure, the diseased kidneys are left in place. Kidneys from living, related donors appear to be the best match for success, but kidneys from unrelated people also have a long survival rate. Patients approaching kidney failure should ask their doctor early about starting the process to receive a kidney transplant.

Kidney transplantation.

Controlling Blood Pressure People with reduced kidney function and high blood pressure should control their blood pressure with an ACE inhibitor or an ARB. Many people will require two or more types of medication to keep their blood pressure below 130/80. A diuretic is an important addition when the ACE inhibitor or ARB does not meet the blood pressure goal.

Changing the Diet People with reduced kidney function need to be aware that some parts of a normal diet may speed their kidney failure. Protein. Protein is important to the body. It helps the body repair muscles and fight disease. Protein comes mostly from meat but can also be found in eggs, milk, nuts, beans, and other foods. Healthy kidneys take wastes out of the blood but leave in the protein. Impaired kidneys may fail to separate the protein from the wastes.

Some doctors tell their kidney patients to limit the amount of protein they eat so the kidneys have less work to do. But a person cannot avoid protein entirely. People with CKD can work with a dietitian to create the right food plan. Cholesterol. Another problem that may be associated with kidney failure is high cholesterol. High levels of cholesterol in the blood may result from a high-fat diet. Cholesterol can build up on the inside walls of blood vessels. The buildup makes pumping blood through the vessels harder for the heart and can cause heart attacks and strokes. Sodium. Sodium is a chemical found in salt and other foods. Sodium in the diet may raise a person’s blood pressure, so people with CKD should limit foods that contain high levels of sodium. High-sodium foods include canned or processed foods like frozen dinners and hot dogs. Potassium. Potassium is a mineral found naturally in many fruits and vegetables, such as oranges, potatoes, bananas, dried fruits, dried beans and peas, and nuts. Healthy kidneys measure potassium in the blood and remove excess amounts. Diseased kidneys may fail to remove excess potassium. With very poor kidney function, high potassium levels can affect the heart rhythm.

Pathophysiology (http://www.merck.com/mmpe/sec17/ch233/ch233c.html) CKD can be roughly categorized as diminished renal reserve, renal insufficiency, or renal failure (end-stage renal disease). Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance (renal functional adaptation); a loss of 75% of renal tissue produces a fall in GFR to only 50% of normal. Decreased renal function interferes with the kidneys' ability to maintain fluid and electrolyte homeostasis. Changes proceed predictably, but considerable overlap and individual variation exist. The ability to concentrate urine declines early and is followed by decreases in ability to excrete phosphate, acid, and K. When renal failure is advanced (GFR ≤ 10 mL/min/1.73 m2), the ability to dilute urine is lost; thus urine osmolality is usually fixed close to that of plasma (300 to 320 mOsm/kg), and urinary volume does not respond readily to variations in water intake. Plasma concentrations of creatinine and urea (which are highly dependent on glomerular filtration) begin a nonlinear rise as GFR diminishes. These changes are minimal early on. When the GFR falls below 10 mL/min/1.73 m2 (normal = 100 mL/min/1.73 m2), their levels increase rapidly and are usually associated with systemic manifestations (uremia).

Urea and creatinine are not major contributors to the uremic symptoms; they are markers for many other substances (some not yet well defined) that cause the symptoms. Despite a diminishing GFR, Na and water balance is well maintained by increased fractional excretion of Na and a normal response to thirst. Thus, the plasma Na concentration is typically normal, and hypervolemia is infrequent unless dietary intake of Na or water is very restricted or excessive. Heart failure can occur from Na and water overload, particularly in patients with decreased cardiac reserve. For substances whose secretion is controlled mainly through distal nephron secretion (eg, K), adaptation usually maintains plasma K at normal levels until renal failure is advanced or K-sparing diuretics, ACE inhibitors, β-blockers, NSAIDs, cyclosporine Some Trade Names NEORAL SANDIMMUNE Click for Drug Monograph , tacrolimus Some Trade Names PROGRAF Click for Drug Monograph , or angiotensin II receptor blockers are used. Abnormalities of Ca, phosphate, parathyroid hormone (PTH), vitamin D metabolism, and renal osteodystrophy can occur. Decreased renal production of calcitriol contributes to hypocalcemia. Decreased renal excretion of phosphate results in hyperphosphatemia. Secondary hyperparathyroidism is common and can develop in renal failure before abnormalities in Ca or phosphate concentrations occur. For this reason, monitoring PTH in moderate chronic kidney disease, even prior to hyperphosphatemia occurs, has been recommended. Renal osteodystrophy (abnormal bone mineralization resulting from hyperparathyroidism, calcitriol deficiency, elevated serum phosphate, or low or normal serum Ca) usually takes the form of increased bone turnover due to hyperparathyroid bone disease (osteitis fibrosa) but can also involve decreased bone turnover due to adynamic bone disease (with increased parathyroid suppression) or osteomalacia. Calcitriol deficiency may cause osteopenia or osteomalacia. Moderate acidosis (plasma HCO3 content 15 to 20 mmol/L) and anemia are characteristic. The anemia of CKD is normochromic-normocytic, with an Hct of 20 to 30% (35 to 50% in patients with polycystic kidney disease). It is usually caused by deficient erythropoietin production due to a reduction of functional renal mass (see Anemias Caused by Deficient Erythropoiesis). Other causes include deficiencies of iron, folate, and vitamin B12.

ntroduction Background Chronic kidney disease (CKD) is a worldwide public health problem and is now recognized as a common condition that is associated with an increased risk of cardiovascular disease and chronic renal failure (CRF). The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) defines chronic kidney disease as either kidney damage or a decreased kidney glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for 3 or more months. Whatever the underlying etiology, the destruction of renal mass with irreversible sclerosis and loss of nephrons leads to a progressive decline in GFR. The different stages of chronic kidney disease form a continuum in time; prior to February 2002, no uniform classification of the stages of chronic kidney disease existed. At that time, K/DOQI published a classification of the stages of chronic kidney disease, as follows: • • • • •

Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m2) Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2) Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2) Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2) Stage 5: Kidney failure (GFR <15 mL/min/1.73 m2 or dialysis)

In stage 1 and stage 2 chronic kidney disease, GFR alone does not clinch the diagnosis. Other markers of kidney damage, including abnormalities in the composition of blood or urine or abnormalities in imaging tests, should also be present in establishing a diagnosis of stage 1 and stage 2 chronic kidney disease. The K/DOQI definition and the classification of chronic kidney disease allow better communication and intervention at the different stages.

Pathophysiology Approximately 1 million nephrons are present in each kidney, each contributing to the total GFR. Regardless of the etiology of renal injury, with progressive destruction of nephrons, the kidney has an innate ability to maintain GFR by hyperfiltration and compensatory hypertrophy of the remaining healthy nephrons. This nephron adaptability allows for continued normal clearance of plasma solutes so that substances such as urea and creatinine start to show significant increases in plasma levels only after total GFR has decreased to 50%, when the renal reserve has been exhausted. The plasma creatinine value will approximately double with a 50% reduction in GFR. A rise in plasma creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still within the reference range, actually represents a loss of 50% of functioning nephron mass.

The residual nephron hyperfiltration and hypertrophy, although beneficial for the reasons noted, has been hypothesized to represent a major cause of progressive renal dysfunction. This is believed to occur because of increased glomerular capillary pressure, which damages the capillaries and leads initially to focal and segmental glomerulosclerosis and eventually to global glomerulosclerosis. This hypothesis has been based on studies of five-sixths nephrectomized rats, which develop lesions that are identical to those observed in humans with chronic kidney disease. Factors other than the underlying disease process and glomerular hypertension that may cause progressive renal injury include the following: • • • • • • • •

Systemic hypertension Acute insults from nephrotoxins or decreased perfusion Proteinuria Increased renal ammoniagenesis with interstitial injury Hyperlipidemia Hyperphosphatemia with calcium phosphate deposition Decreased levels of nitrous oxide Smoking

Frequency

United States In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. Kidney disease is the ninth leading cause of death in the United States. Data from the United States Renal Data System (USRDS) indicated that there has been an increase of 104% in the prevalence of chronic renal failure (CRF) between the years 1990-2001. There is an even higher prevalence of the earlier stages of chronic kidney disease. According to the Third National Health and Nutrition Examination Survey, it was estimated that 6.2 million people (ie, 3% of total US population) older than 12 years had a serum creatinine value above 1.5 mg/dL; 8 million people had a glomerular filtration rate (GFR) of less than 60 mL/min, the majority of them being in the Medicare senior population (5.9 million people). Therefore, for the first time, the US Surgeon General's mandate for America's citizenry, Healthy People 2010, contains a chapter focused on chronic kidney disease. The objectives of this chapter are to articulate goals and to provide strategies to reduce the incidence, morbidity, mortality, and health costs of chronic kidney disease in the United States. The burden of chronic kidney disease can be assessed by multiple criteria, all of which underscore the need for improved detection, treatment, and monitoring of clinical and fiscal outcomes. Reducing renal failure will require additional public health efforts, including effective preventive strategies and early detection and treatment of chronic kidney disease.

Because of the nonuniform definition of kidney disease prior to February 2002, among other factors, most patients with earlier stages of chronic kidney disease have not been recognized or adequately treated. The Third National Health and Examination Survey (NHANES III) estimated that the prevalence of chronic kidney disease in adults in the United States was 11% (19.2 million): 3.3% (5.9 million) had stage 1, 3% (5.3 million) had stage 2, 4.3% (7.6 million) had stage 3, 0.2% (400,000) had stage 4, and 0.2% (300,000) had stage 5. Furthermore, the prevalence of chronic kidney disease stages 1-4 increased from 10% in 1988-1994 to 13.1% in 1999-2004. This increase is partially explained by the increase in the prevalence of diabetes and hypertension, the two most common causes of chronic kidney disease.

International The incidence rates of end-stage renal disease (ESRD) have increased steadily internationally since 1989. The United States has the highest incident rate of ESRD, followed by Japan. Japan has the highest prevalence per million population, with the United States taking second place.

Mortality/Morbidity Chronic kidney disease is a major cause of morbidity and mortality, particularly at the later stages. Although the diabetic population is at highest risk, in the United States, the general hemodialysis and peritoneal dialysis populations have 2 hospital admissions per patient per year; patients who have a renal transplant have an average of 1 hospital admission per year. The 5-year survival rate for a patient undergoing chronic dialysis in the United States is approximately 35%. This is approximately 25% in patients with diabetes. The most common cause of death in the dialysis population is cardiovascular disease. Among patients with ESRD aged 65 years and older, the mortality rates are 6 times higher than in the general population. In 2003, over 69,000 dialysis patients enrolled in the ESRD program died (annual adjusted mortality rate of 210.7 per 1000 patient-years at risk for the dialysis population, which represents a 14% decrease since peaking at 244.5 per 1000 patient-years in 1988). The highest mortality rate is within the first 6 months of initiating dialysis, which then tends to improve over the next 6 months, before increasing gradually over the next 4 years. The mortality rates associated with hemodialysis are striking and indicate that the life expectancy of patients entering into hemodialysis is markedly shortened. At every age, patients with ESRD on dialysis have significantly increased mortality when compared with nondialysis patients and individuals without kidney disease. At age 60 years, a healthy person can expect to live for more than 20 years, whereas the life expectancy of a 60-year-old patient starting hemodialysis is closer to 4 years.

Race •

Chronic kidney disease affects all races, but, in the United States, a significantly higher incidence of ESRD exists in blacks as compared to whites; the incident rate for blacks is nearly 4 times that for whites.

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In NHANES III, the distribution of estimated GFRs for the chronic kidney disease stages was similar in both sexes. Nonetheless, the USRDS 2004 Annual Data Report reveals that the incident rate of ESRD cases is higher for males with 409 per million population in 2002 compared to 276 for females.

Age Chronic kidney disease is found in persons of all ages. The normal annual mean decline in the GFR with age from the peak GFR (approximately 120 mL/min/1.73 m2) attained during the third decade of life is approximately 1 mL/min/y/1.73 m2, reaching a mean value of 70 mL/min/1.73 m2 at age 70 years. Nonetheless, in the United States, the highest incidence rate of ESRD occurs in patients older than 65 years. As per NHANES III data, the prevalence of chronic kidney disease was 37.8% among patients older than 70 years. Besides diabetes mellitus and hypertension, age is an independent major predictor of chronic kidney disease. The geriatric population is the most rapidly growing kidney failure (chronic kidney disease stage 5) population in the United States. The biologic process of aging initiates various structural and functional changes within the kidney. Renal mass progressively declines with advancing age. Glomerulosclerosis leads to a decrease in renal weight. Histologic examination is notable for a decrease in glomerular number of as much as 30-50% by age 70 years. Ischemic obsolescence of cortical glomeruli is predominant, with relative sparing of the renal medulla. Juxtamedullary glomeruli see a shunting of blood from the afferent to efferent arterioles, resulting in redistribution of blood flow favoring the renal medulla. These anatomical and functional changes in renal vasculature appear to contribute to an age-related decrease in renal blood flow. Renal hemodynamic measurements in aged human and animals suggest that altered functional response of the renal vasculature may be an underlying factor in diminished renal blood flow and increased filtration noted with progressive renal aging. The vasodilatory response is blunted in the elderly when compared to younger patients. However, the vasoconstrictor response to intrarenal angiotensin is identical in both young and older human subjects. A blunted vasodilatory capacity with appropriate vasoconstrictor response may indicate that the aged kidney is in a state of vasodilatation to compensate for the underlying sclerotic damage. Given the histologic evidence for nephronal senescence with age, a decline in the GFR is expected. However, a wide variation in the rate of decline in the GFR is reported because of measurement methods, race, gender, genetic variance, and other risk factors for renal

dysfunction. Because of these anatomical and physiological changes, elderly patients with chronic kidney disease may behave differently, in terms of progression and response to pharmacological treatment, than younger patients. Therefore, a serum creatinine value of 1.2 mg/dL in a 70-kg, 25-year-old man versus a 70-kg, 80-year-old man represents an eGFR of 74 mL/min/1.73m2 and 58 mL/min/1.73m2, respectively. What can appear as only mild renal impairment in a 70-kg, 80-year-old man with a pathologically elevated serum creatinine of 2 mg/dL actually represents severe renal impairment when the eGFR is calculated to be 32 mL/min/1.73m2. Therefore, an eGFR must be determined simply by using the Modification of Diet in Renal Disease (MDRD) equation (see Other Tests) in elderly people so that appropriate drug dosing adjustments can be made and nephrotoxins can be avoided in patients who have more extensive chronic kidney disease than would be suggested by the serum creatinine value alone.

Clinical History Patients with chronic kidney disease stages 1-3 (GFR >30 mL/min) are generally asymptomatic and do not experience clinically evident disturbances in water or electrolyte balance or endocrine/metabolic derangements. Generally, these disturbances clinically manifest with chronic kidney disease stages 4-5 (GFR <30 mL/min). Uremic manifestations in patients with chronic kidney disease stage 5 are believed to be primarily secondary to an accumulation of toxins, the identity of which is generally not known. The ability to maintain potassium (K) excretion at near normal levels is generally maintained in chronic kidney disease patients as long as both aldosterone secretion and distal flow are maintained. Another defense against potassium retention in patients with chronic kidney disease is increased potassium excretion in the GI tract, which also is under control of aldosterone. Therefore, hyperkalemia usually develops when the GFR falls to less than 20-25 mL/min because of the decreased ability of the kidneys to excrete potassium. It can be observed sooner in patients who ingest a potassium-rich diet or if serum aldosterone levels are low, such as in type IV renal tubular acidosis commonly observed in people with diabetes or with use of angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal antiinflammatory drugs (NSAIDs). Hyperkalemia in chronic kidney disease can be aggravated by an extracellular shift of potassium, such as that occurs in the setting of acidemia or from lack of insulin. Hypokalemia is uncommon but can develop among patients with very poor intake of potassium, gastrointestinal or urinary loss of potassium, diarrhea, or diuretic use. Metabolic acidosis often is mixed, normal anion gap and increased anion gap, the latter observed generally with chronic kidney disease stage 5 but with the anion gap generally not higher than 20 mEq/L. In chronic kidney disease, the kidneys are unable to produce

enough ammonia in the proximal tubules to excrete the endogenous acid into the urine in the form of ammonium. In chronic kidney disease stage 5, accumulation of phosphates, sulphates, and other organic anions are the cause of the increase in anion gap. Metabolic acidosis has been shown to have deleterious effects on protein balance, leading to a negative nitrogen balance, increased protein degradation, increased essential amino acid oxidation, reduced albumin synthesis, and a lack of adaptation to a low protein diet. Hence, this is associated with protein-energy malnutrition, loss of lean body mass, and muscle weakness. The mechanism for reducing protein may include effects on ATPdependent ubiquitin proteasomes and increased activity of branched chain keto acid dehydrogenases. In the NHANES III prevalence study, hypoalbuminemia (a marker of protein-energy malnutrition and a powerful predictive marker of mortality in dialysis patients as well as in the general population) was independently associated with low bicarbonate as well as the inflammatory marker C reactive protein. Metabolic acidosis is a factor in the development of renal osteodystrophy, as bone acts as a buffer for excess acid, with resultant loss of mineral. Acidosis may interfere with vitamin D metabolism, and patients who are persistently more acidotic are more likely to have osteomalacia or low-turnover bone disease. The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no randomized controlled trials in pre-ESRD patients, none in children, and only 3 small trials in dialysis patients. These trials suggest that there may be some beneficial effects on both protein metabolism and bone metabolism, but the trials were underpowered to provide robust evidence. Experts recommend alkali therapy to maintain the serum bicarbonate concentration above 22 mEq/L. Inflammation and hemostasis may increase the risk of kidney function decline, but prospective studies are lacking. The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort, observed markers of inflammation and hemostasis in 14,854 middle-aged adults.1 The risk for decreased kidney function associated with the inflammatory and hemostasis markers was examined, using data from 1787 cases of chronic kidney disease (CKD) that developed between 1987 and 2004. After adjusting for various factors, such as demographics smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction (MI), antihypertensive use, and alcohol use, the study revealed that the risk for chronic kidney disease rose with increasing quartiles of white blood cell (WBC) count, fibrinogen, von Willebrand factor, and factor VIIIc. The investigators found a strong inverse association between serum albumin level and chronic kidney disease risk. The study's findings suggested that inflammation and hemostasis are antecedent pathways for chronic kidney disease. Salt and water handling by the kidney is altered in patients with chronic kidney disease. Extracellular volume expansion and total-body volume overload results from failure of sodium and free water excretion. This generally becomes clinically manifested when the GFR falls to less than 10-15 mL/min, when compensatory mechanisms have become exhausted. As kidney function declines further, sodium retention and extracellular volume expansion lead to peripheral and, not uncommonly, pulmonary edema and hypertension. At a higher GFR, excess sodium and water intake could result in a similar

picture if the ingested amounts of sodium and water exceed the available potential for compensatory excretion. Normochromic normocytic anemia principally develops from decreased renal synthesis of erythropoietin, the hormone responsible for bone marrow stimulation for red blood cell (RBC) production. It starts early in the course of disease and becomes more severe as the GFR progressively decreases with the availability of less viable renal mass. No reticulocyte response occurs. RBC survival is decreased, and tendency of bleeding is increased from the uremia-induced platelet dysfunction. Other causes of anemia in chronic kidney disease patients include chronic blood loss, secondary hyperparathyroidism, inflammation, nutritional deficiency, and accumulation of inhibitors of erythropoiesis. Anemia is associated with fatigue, reduced exercise capacity, impaired cognitive and immune function, and reduced quality of life. Anemia is also associated with the development of cardiovascular disease, the new onset of heart failure, or the development of more severe heart failure. Anemia is associated with increased cardiovascular mortality. Renal bone disease is a common complication of chronic kidney disease and results in both skeletal complications (eg, abnormality of bone turnover, mineralization, linear growth) and extraskeletal complications (eg, vascular or soft tissue calcification). Different types of bone disease occur with chronic kidney disease, as follows: (1) high turnover bone disease due to high parathyroid hormone (PTH) levels; (2a) low turnover bone disease (adynamic bone disease); (2b) defective mineralization (osteomalacia); (3) mixed disease; and (4) beta-2-microglobulin associated bone disease. Secondary hyperparathyroidism develops because of hyperphosphatemia, hypocalcemia, decreased renal synthesis of 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D, or calcitriol), intrinsic alteration in the parathyroid gland that give rises to increased PTH secretion as well as increased parathyroid growth, and skeletal resistance to PTH. • •

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Calcium and calcitriol are primary feedback inhibitors; hyperphosphatemia is a stimulus to PTH synthesis and secretion. Phosphate retention begins in early chronic kidney disease; when the GFR falls, less phosphate is filtered and excreted, but serum levels do not rise initially because of increased PTH secretion, which increases renal excretion. As the GFR falls toward chronic kidney disease stages 4-5, hyperphosphatemia develops from the inability of the kidneys to excrete the excess dietary intake. Hyperphosphatemia suppresses the renal hydroxylation of inactive 25hydroxyvitamin D to calcitriol, so serum calcitriol levels are low when the GFR is less than 30 mL/min. Increased phosphate concentration also effects PTH concentration by its direct effect on parathyroid gland (posttranscriptional effect). Hypocalcemia develops primarily from decreased intestinal calcium absorption because of low plasma calcitriol levels and possibly from calcium binding to elevated serum levels of phosphate.

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Low serum calcitriol levels, hypocalcemia, and hyperphosphatemia have all been demonstrated to independently trigger PTH synthesis and secretion. As these stimuli persist in chronic kidney disease, particularly in the more advanced stages, PTH secretion becomes maladaptive and the parathyroid glands, which initially hypertrophy, become hyperplastic. The persistently elevated PTH levels exacerbate hyperphosphatemia from bone resorption of phosphate. If serum levels of PTH remain elevated, a high bone turnover lesion, known as osteitis fibrosa, develops. This is one of several bone lesions, which as a group are commonly known as renal osteodystrophy. These lesions develop in patients with severe chronic kidney disease and are common in those with ESRD. The prevalence of adynamic bone disease in the United States has increased, and it has been described before the initiation of dialysis in some cases. The pathogenesis of adynamic bone disease is not well defined, but several factors may contribute, including high calcium load, use of vitamin D sterols, increasing age, previous corticosteroid therapy, peritoneal dialysis, and increased level of Nterminally truncated PTH fragments. Low turnover osteomalacia in the setting of chronic kidney disease is associated with aluminum accumulation and is markedly less common. Dialysis-related amyloidosis from beta-2-microglobulin accumulation in patients who have required chronic dialysis for at least 8-10 years is another form of bone disease that manifests with cysts at the ends of long bones.

Other manifestations of uremia in ESRD, many of which are more likely in patients who are inadequately dialyzed, include the following: • • • • • • • • • •

Pericarditis - Can be complicated by cardiac tamponade, possibly resulting in death. Encephalopathy - Can progress to coma and death Peripheral neuropathy Restless leg syndrome GI symptoms - Anorexia, nausea, vomiting, diarrhea Skin manifestations - Dry skin, pruritus, ecchymosis Fatigue, increased somnolence, failure to thrive Malnutrition Erectile dysfunction, decreased libido, amenorrhea Platelet dysfunction with tendency to bleeding

Physical The physical examination often is not very helpful but may reveal findings characteristic of the condition underlying chronic kidney disease (eg, lupus, severe arteriosclerosis, hypertension) or complications of chronic kidney disease (eg, anemia, bleeding diathesis, pericarditis).

Causes

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Vascular disease - Renal artery stenosis, cytoplasmic pattern antineutrophil cytoplasmic antibody (C-ANCA)–positive and perinuclear pattern antineutrophil cytoplasmic antibody (P-ANCA)–positive vasculitides, antineutrophil cytoplasmic antibody (ANCA)–negative vasculitides, atheroemboli, hypertensive nephrosclerosis, renal vein thrombosis Primary glomerular disease - Membranous nephropathy, immunoglobulin A (IgA) nephropathy, focal and segmental glomerulosclerosis (FSGS), minimal change disease, membranoproliferative glomerulonephritis, rapidly progressive (crescentic) glomerulonephritis Secondary glomerular disease - Diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, Goodpasture syndrome, Wegener granulomatosis, mixed cryoglobulinemia, postinfectious glomerulonephritis, endocarditis, hepatitis B and C, syphilis, human immunodeficiency virus (HIV), parasitic infection, heroin use, gold, penicillamine, amyloidosis, light chain deposition disease, neoplasia, thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), HenochSchönlein purpura, Alport syndrome, reflux nephropathy Tubulointerstitial disease - Drugs (eg, sulfa, allopurinol), infection (viral, bacterial, parasitic), Sjögren syndrome, chronic hypokalemia, chronic hypercalcemia, sarcoidosis, multiple myeloma cast nephropathy, heavy metals, radiation nephritis, polycystic kidneys, cystinosis Urinary tract obstruction - Urolithiasis, benign prostatic hypertrophy, tumors, retroperitoneal fibrosis, urethral stricture, neurogenic bladder

http://en.wikipedia.org/wiki/Chronic_kidney_disease