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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.
• 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:
• Erythropoietin (EPO), which stimulates the bone marrow to produce red blood
cells.
Kidney failure
• Kidney failure occurs when the kidneys partly or completely lose their ability to
carry out normal functions.
• This is dangerous because water, waste, and toxic substances build up that
normally are removed from the body by the kidneys.
• 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 does not cause permanent damage to the kidneys.
With appropriate treatment of the underlying condition, it is often reversible, with
complete recovery.
• In some cases, though, it may progress to chronic kidney disease.
GFR*
Stage Description
mL/min/1.73m2
Slight kidney damage with normal or increased
1 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
Kidney failure requiring dialysis or
5 Less than 15
transplantation
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.
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.
• High cholesterol
• Heart disease
• Liver disease
• Kidney disease
• Amyloidosis
• Vesicoureteral reflux (a urinary tract problem in which urine travels the wrong
way)
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.
• 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.
• 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.
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.
• Swelling of the legs and puffiness around the eyes (fluid retention)
• High blood pressure, chest pain due to pericarditis (inflammation around the
heart)
Several signs and symptoms may suggest complications of chronic kidney disease. Call
your healthcare provider if you notice any of the following symptoms:
• Increased water retention (puffiness or swelling) in the legs, around the eyes or in
other parts of the body
• Nausea or vomiting
• Light-headedness
• Easy bruisability
• 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.
• Chest pain
• Difficulty breathing
• Severe weakness
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.
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 100-
140 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.
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
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.
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.
• This is a complex process and must be individualized, generally with the help of
your healthcare provider and a registered dietitian.
• Salt restriction: Limit to 4-6 grams a day to avoid fluid retention and help
control high blood pressure.
• Fluid intake: Excessive water intake does not help prevent kidney disease. In
fact, your doctor may recommend restriction of water intake.
• Stop smoking
• 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:
Strategies for slowing progression and treating conditions underlying chronic kidney
disease include the following:
• 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
• These venous access devices usually can be placed with local anesthesia on an
outpatient basis.
• Hemodialysis typically takes three to five hours and is needed three times a week.
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.
• The fluid is allowed to dwell for two to several hours before being drained, taking
the unwanted wastes and water with it.
• The fluid typically needs to be exchanged four to five times a day.
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.
• 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.
• 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.
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.
• People undergoing dialysis have an overall five 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 two year
survival rate greater than 90%.
• Recipients of a kidney from a donor who has died have a two year survival rate of
88%.
Kidney and surrounding anatomy.
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, end-
stage 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.
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.
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.
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.
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.
Sex
• 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.
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 anti-
inflammatory 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 ATP-
dependent ubiquitin proteasomes and increased activity of branched chain keto acid
dehydrogenases.
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.
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.
Other manifestations of uremia in ESRD, many of which are more likely in patients who
are inadequately dialyzed, include the following:
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
• 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), Henoch-
Schönlein 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