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Each year in the United States, more than 50,000 people are diagnosed with end-stage
renal disease (ESRD), a serious condition in which the kidneys fail to rid the body
of
wastes. ESRD is the final stage of a slow deterioration of the kidneys, a process
known as
nephropathy.
Primary Diagnoses (Causes) for ESRD (1991)
35.9 percent Diabetes
28.8 percent High Blood Pressure
18.1 percent Other Causes
11.4 percent Glomerulonephritis
2.9 percent Polycystic Kidney Disease
2.9 percent Interstitial Nephritis
Diabetes is the most common cause of ESRD, resulting in about one-third of new ESRD
cases. Even when drugs and diet are able to control diabetes, the disease can lead
to
nephropathy and ESRD. Most people with diabetes do not develop nephropathy that is
severe enough to cause ESRD. About 15 million people in the United States have diabetes,
and about 50,000 people have ESRD as a result of diabetes.
ESRD patients undergo either dialysis, which substitutes for some of the filtering
functions
of the kidneys, or transplantation to receive a healthy donor kidney. Most U.S. citizens
who develop ESRD are eligible for federally funded care. In 1994, the Federal
Government spent about $9.3 billion on care for patients with ESRD.
African Americans and Native Americans develop diabetes, nephropathy, and ESRD at
rates higher than average. Scientists have not been able to explain these higher
rates. Nor
can they explain fully the interplay of factors leading to diabetic nephropathy--factors
including heredity, diet, and other medical conditions, such as high blood pressure.
They
have found that high blood pressure and high levels of blood sugar increase the risk
that a
person with diabetes will progress to ESRD.
In diabetes--also called diabetes mellitus, or DM--the body does not properly process
and
use certain foods, especially carbohydrates. The human body normally converts
carbohydrates to glucose, the simple sugar that is the main source of energy for
the body's
cells. To enter cells, glucose needs the help of insulin, a hormone produced by the
pancreas. When a person does not make enough insulin, or the body is unable to use
the
insulin that is present, the body cannot process glucose, and it builds up in the
bloodstream. High levels of glucose in the blood or urine lead to a diagnosis of
diabetes.
Most people with diabetes have a form known as noninsulin-dependent diabetes
(NIDDM), or Type II diabetes. Many people with NIDDM do not respond normally to
their own or to injected insulin--a condition called insulin resistance. NIDDM occurs
more
often in people over the age of 40, and many people with NIDDM are overweight. Many
also are not aware that they have the disease. Some people with NIDDM control their
blood sugar with diet and an exercise program leading to weight loss. Others must
take
pills that stimulate production of insulin; still others require injections of insulin.
A less common form of diabetes, known as insulin-dependent diabetes (IDDM), or Type
I
diabetes, tends to occur in young adults and children. In cases of IDDM, the body
produces little or no insulin. People with IDDM must receive daily insulin injections.
NIDDM accounts for about 95 percent of all cases of diabetes; IDDM accounts for about
5
percent. Both types of diabetes can lead to kidney disease. IDDM is more likely to
lead to
ESRD. About 40 percent of people with IDDM develop severe kidney disease and ESRD
by the age of 50. Some develop ESRD before the age of 30. NIDDM causes 80 percent
of
the ESRD in African Americans and Native Americans.
The deterioration that characterizes kidney disease of diabetes takes place in and
around the
glomeruli, the blood-filtering units of the kidneys. Early in the disease, the filtering
efficiency diminishes, and important proteins in the blood are lost to the urine.
Medical
professionals gauge the presence and extent of early kidney disease by measuring
protein
in the urine. Later in the disease, the kidneys lose their ability to remove waste
products,
such as creatinine and urea, from the blood.
Symptoms related to kidney failure usually occur only in late stages of the disease,
when
kidney function has diminished to less than 25 percent of normal capacity. For many
years
before that point, kidney disease of diabetes exists as a silent process.
Scientists have described five stages in the progression to ESRD in people with diabetes.
They are as follows:
Stage I. The flow of blood through the kidneys, and therefore through the
glomeruli,
increases--this is called hyperfiltration--and the kidneys are larger than normal.
Some
people remain in stage I indefinitely; others advance to stage II after many years.
Stage II. The rate of filtration remains elevated or at near-normal levels,
and the glomeruli
begin to show damage. Small amounts of a blood protein known as albumin leak into
the
urine--a condition known as microalbuminuria. In its earliest stages, microalbuminuria
may come and go. But as the rate of albumin loss increases from 20 to 200 micrograms
per
minute, microalbuminuria becomes more constant. (Normal losses of albumin are less
than
5 micrograms per minute.) A special test is required to detect microalbuminuria.
People
with NIDDM and IDDM may remain in stage II for many years, especially if they have
normal blood pressure and good control of their blood sugar levels.
Stage III. The loss of albumin and other proteins in the urine exceeds 200
micrograms per
minute. It now can be detected during routine urine tests. Because such tests often
involve
dipping indicator strips into the urine, they are referred to as "dipstick methods."
Stage III
sometimes is referred to as "dipstick-positive proteinuria" (or "clinical
albuminuria" or
"overt diabetic nephropathy"). Some patients develop high blood pressure.
The glomeruli
suffer increased damage. The kidneys progressively lose the ability to filter waste,
and
blood levels of creatinine and urea-nitrogen rise. People with IDDM and NIDDM may
remain at stage III for many years.
Stage IV. This is referred to as "advanced clinical nephropathy."
The glomerular filtration
rate decreases to less than 75 milliliters per minute, large amounts of protein pass
into the
urine, and high blood pressure almost always occurs. Levels of creatinine and
urea-nitrogen in the blood rise further.
Stage V. The final stage is ESRD. The glomerular filtration rate drops to
less than 10
milliliters per minute. Symptoms of kidney failure occur.
These stages describe the progression of kidney disease for most people with IDDM
who
develop ESRD. For people with IDDM, the average length of time required to progress
from onset of kidney disease to stage IV is 17 years. The average length of time
to
progress to ESRD is 23 years. Progression to ESRD may occur more rapidly (5-10 years)
in people with untreated high blood pressure. If proteinuria does not develop within
25
years, the risk of developing advanced kidney disease begins to decrease. Advancement
to
stages IV and V occurs less frequently in people with NIDDM than in people with IDDM.
Nevertheless, about 60 percent of people with diabetes who develop ESRD have NIDDM.
High blood pressure, or hypertension, is a major factor in the development of kidney
problems in people with diabetes. Both a family history of hypertension and the presence
of hypertension appear to increase chances of developing kidney disease. Hypertension
also accelerates the progress of kidney disease where it already exists.
Hypertension usually is defined as blood pressure exceeding 140 millimeters of
mercury-systolic and 90 millimeters of mercury-diastolic. Professionals shorten the
name
of this limit to "140 over 90." The terms systolic and diastolic refer
to pressure in the
arteries during contraction of the heart (systolic) and between heartbeats (diastolic).
Hypertension can be seen not only as a cause of kidney disease, but also as a result
of
damage created by the disease. As kidney disease proceeds, physical changes in the
kidneys lead to increased blood pressure. Therefore, a dangerous spiral, involving
rising
blood pressure and factors that raise blood pressure, occurs. Early detection and
treatment
of even mild hypertension are essential for people with diabetes.
Scientists have made great progress in developing methods that slow the onset and
progression of kidney disease in people with diabetes. Drugs used to lower blood
pressure
(antihypertensive drugs) can slow the progression of kidney disease significantly.
One
drug, an angiotensin-converting enzyme (ACE) inhibitor, has proven effective in
preventing progression to stages IV and V.1 Calcium channel blockers, another class
of
antihypertensive drugs, also show promise.
An example of an effective ACE inhibitor is captopril, which the Food and Drug
Administration approved for treating kidney disease of Type I diabetes. The benefits
of
captopril extend beyond its ability to lower blood pressure; it may directly protect
the
kidney's glomeruli. ACE inhibitors have lowered proteinuria and slowed deterioration
even in diabetic patients who did not have high blood pressure.
Some, but not all, calcium channel blockers may be able to decrease proteinuria and
damage to kidney tissue. Researchers are investigating whether combinations of calcium
channel blockers and ACE inhibitors might be more effective than either treatment
used
alone. Patients with even mild hypertension or persistent microalbuminuria should
consult
a physician about the use of antihypertensive medicines.
A diet containing reduced amounts of protein may benefit people with kidney disease
of
diabetes. In people with diabetes, excessive consumption of protein may be harmful.
Experts recommend that most patients with stage III or stage IV nephropathy consume
moderate amounts of protein.
Antihypertensive drugs and low-protein diets can slow kidney disease when significant
nephropathy is present, as in stages III and IV. A third treatment, known as intensive
management or glycemic control, has shown great promise for people with IDDM,
especially for those with early stages of nephropathy.
Intensive management is a treatment regimen that aims to keep blood glucose levels
close
to normal. The regimen includes frequently testing blood sugar, administering insulin
on
the basis of food intake and exercise, following a diet and exercise plan, and frequently
consulting a health care team.
A number of studies have pointed to the beneficial effects of intensive management.
Two
such studies, funded by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) of the National Institutes of Health, are the Diabetes Control and
Complications Trial (DCCT)2 and a trial led by researchers at the University of Minnesota
Medical School.3
The DCCT, conducted from 1983 to 1993, involved 1,441 participants who had IDDM.
Researchers found a 50-percent decrease in both development and progression of early
diabetic kidney disease (stages I and II) in participants who followed an intensive
regimen
for controlling blood sugar levels. The intensively managed patients had average
blood
sugar levels of 150 milligrams per deciliter--about 80 milligrams per deciliter lower
than
the levels observed in the conventionally managed patients.
In the Minnesota Medical School trial, researchers examined kidney tissues of long-term
diabetics who received healthy kidney transplants. After 5 years, patients who followed
an
intensive regimen developed significantly fewer lesions in their glomeruli than did
patients
not following an intensive regimen. This result, along with findings of the DCCT
and
studies performed in Scandinavia, suggests that any program resulting in sustained
lowering of blood glucose levels will be beneficial to patients in the early stages
of diabetic
nephropathy.
When people with diabetes reach ESRD, they must undergo either dialysis or a kidney
transplant. As recently as the 1970's, medical experts commonly excluded people with
diabetes from dialysis and transplantation, in part because the experts felt damage
caused
by diabetes would offset benefits of the treatments. Today, because of better control
of
diabetes and improved rates of survival following treatment, doctors do not hesitate
to
offer dialysis and kidney transplantation to people with diabetes.
Currently, the survival of kidneys transplanted into diabetes patients is about the
same as
survival of transplants in people without diabetes. Dialysis for people with diabetes
also
works well in the short run. Even so, people with diabetes who receive transplants
or
dialysis experience higher morbidity and mortality because of coexisting complications
of
the diabetes--such as damage to the heart, eyes, and nerves.
If you have diabetes:
Ask your doctor about the DCCT and how its results might help you.
Have your doctor measure your glycohemoglobin regularly. The HbA1c test
averages your level of blood sugar for the previous 1-3 months.
Follow your doctor's advice regarding insulin injections, medicines, diet,
exercise, and monitoring your blood sugar.
Have your blood pressure checked several times a year. If blood pressure is
high, follow your doctor's plan for keeping it near normal levels.
Ask your doctor whether you might benefit from receiving an ACE inhibitor.
Have your urine checked yearly for microalbumin and protein. If there is
protein in your urine, have your blood checked for elevated amounts of waste
products such as creatinine.
Ask your doctor whether you should reduce the amount of protein in your
diet.
The incidences of both diabetes and ESRD caused by diabetes have been rising. Some
experts predict that diabetes soon might account for half the cases of ESRD. In light
of the
increasing morbidity and mortality related to diabetes and ESRD, patients, researchers,
and
health care professionals will continue to benefit by addressing the relationship
between the
two diseases. The NIDDK is a leader in supporting research in this area.
Several areas of research supported by NIDDK hold great potential. Discovery of ways
to
predict who will develop kidney disease may lead to greater prevention, as people
with
diabetes who learn they are at risk institute strategies such as intensive management
and
blood pressure control. Discovery of better anti-rejection drugs will improve results
of
kidney transplantation in patients with diabetes who develop ESRD. For some people
with
IDDM, advances in transplantation--especially transplantation of insulin-producing
cells of
the pancreas--could lead to a cure for both diabetes and the kidney disease of diabetes.
1. Lewis, E.J., et al., The effect of angiotensin-converting-enzyme inhibition on
diabetic
nephropathy. New England Journal of Medicine, Vol. 329, No. 20, pp. 1456-1462,
1993.
2. Diabetes Control and Complications Trial [fact sheet], August 1994. National Diabetes
Information Clearinghouse, 1 Information Way, Bethesda, MD 20892-3560.
3. Barbosa, J., et al., Effect of glycemic control on early diabetic renal lesions.
Journal of
the American Medical Association, Vol. 272, No. 8, pp. 600-606, 1994.
National Kidney and Urologic Diseases Information
Clearinghouse
3 Information Way
Bethesda, MD 20892-3580
(301) 654-4415
E-mail: nkudic@info.niddk.nih.gov
The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) is a
service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The NIDDK is part of the National Institutes of Health under the U.S. Public Health
Service. Established in 1987, the clearinghouse provides information about diseases
of the
kidneys and urologic system to people with kidney and urologic disorders and to their
families, health care professionals, and the public. NKUDIC answers inquiries; develops,
reviews, and distributes publications; and works closely with professional and patient
organizations and Government agencies to coordinate resources about kidney and urologic
diseases.
Publications produced by the clearinghouse are carefully reviewed for scientific
accuracy,
content, and readability.
This e-text is not copyrighted. The clearinghouse encourages users of this e-pub
to
duplicate and distribute as many copies as desired.
NIH Publication No. 97-3925
July 1995
e-text posted: 12 February 1998
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