Kidney Disease of Diabetes
End Stage Renal Disease
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.
What Is The Cause?
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.
Who Gets It?
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.
Primary Diagnoses (Causes) for ESRD (1991)
2.9 percent Interstitial Nephritis
2.9 percent Polycystic Kidney Disease
11.4 percent Glomerulonephritis
18.1 percent Other Causes
28.8 percent High Blood Pressure
35.9 percent Diabetes
Two Types of Diabetes
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.
NIDDM
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.
IDDM
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 Course of Kidney Disease
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.
Five Stages
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.
Effects of High Blood Pressure
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.
Preventing and Slowing Kidney Disease
Blood Pressure Medicines
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.
Low-Protein Diets
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.
Intensive Management
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.
Dialysis and Transplantation
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.
Good Care Makes a Difference
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.
Looking to the Future
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.
NIH Publication No. 95-3925
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