Diabetic Nephropathy
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Each year in the United States, nearly 100,000 people are
diagnosed with kidney failure, a serious condition in which the
kidneys fail to rid the body of wastes. Kidney failure is the final
stage of a slow deterioration of the kidneys, a process known as
nephropathy.
Diabetes is the most common cause of kidney failure, accounting
for more than 40 percent of new cases. Even when drugs and diet are
able to control diabetes, the disease can lead to nephropathy and
kidney failure. Most people with diabetes do not develop nephropathy
that is severe enough to cause kidney failure. About 17 million
people in the United States have diabetes, and over 100,000 people
are living with kidney failure as a result of diabetes.
People with kidney failure 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 kidney failure are eligible for federally
funded care. In 2000, care for patients with kidney failure cost the
Nation nearly $20 billion.
African Americans, American Indians, and Hispanic Americans
develop diabetes, nephropathy, and kidney failure 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 glucose increase
the risk that a person with diabetes will progress to kidney
failure.
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There are two types of diabetes. In patients with either type,
the body does not properly process and use food. The human body
normally converts food 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 does not respond to
the insulin that is present, the body cannot process glucose, and it
builds up in the bloodstream. High levels of glucose in the blood
lead to a diagnosis of diabetes. Both types of diabetes can lead to
kidney disease.
Only about 1 in 20 people with diabetes has type 1 diabetes,
which tends to occur in young adults and children. Type 1 used to be
known as insulin-dependent diabetes mellitus (IDDM) or juvenile
diabetes. In type 1 diabetes, the body stops producing insulin.
People with type 1 diabetes must take daily insulin injections or
use an insulin pump. They also control blood glucose levels with
meal planning and physical activity. Type 1 diabetes is more likely
to lead to kidney failure. Twenty to 40 percent of people with type
1 diabetes develop kidney failure by the age of 50. Some develop
kidney failure before the age of 30.
About 95 percent of people with diabetes have type 2 diabetes,
once known as noninsulin-dependent diabetes mellitus (NIDDM) or
adult-onset diabetes. Many people with type 2 diabetes do not
respond normally to their own or to injected insulin--a condition
called insulin resistance. Type 2 diabetes occurs more often in
people over the age of 40, and many people with type 2 are
overweight. Many also are not aware that they have the disease. Some
people with type 2 control their blood glucose with meal planning
and physical activity. Others must take pills that stimulate
production of insulin, reduce insulin resistance, decrease the
liver's output of glucose, or slow absorption of carbohydrate from
the gastrointestinal tract. Still others require injections of
insulin. Between 1993 and 1997, more than 100,000 people in the
United States were treated for kidney failure caused by type 2
diabetes.
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Diabetic kidney disease takes many years to develop. In some
people, the filtering function of the kidneys is actually higher
than normal in the first few years of their diabetes. This process
has been called hyperfiltration.
Over several years, people who are developing kidney disease will
have small amounts of the blood protein albumin begin to leak into
their urine. At its first stage, this condition has been called
microalbuminuria. The kidney's filtration function usually remains
normal during this period.
As the disease progresses, more albumin leaks into the urine.
Various names are attached to this interval of the disease such as
overt diabetic nephropathy or macroalbuminuria. As the amount of
albumin in the urine increases, filtering function usually begins to
drop. The body retains various wastes as filtration falls.
Creatinine is one such waste, and a blood test for creatinine can
measure the decline in kidney filtration. As kidney damage develops,
blood pressure often rises as well.
Overall, kidney damage rarely occurs in the first 10 years of
diabetes, and usually 15 to 25 years will pass before kidney failure
occurs. For people who live with diabetes for more than 25 years
without any signs of kidney failure, the risk of ever developing it
decreases.
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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.
In the past, hypertension was defined as blood pressure exceeding
140 millimeters of mercury-systolic and 90 millimeters of
mercury-diastolic. Professionals shorten the name of this limit to
140/90 or "140 over 90." The terms systolic and diastolic refer to
pressure in the arteries during contraction of the heart (systolic)
and between heartbeats (diastolic).
The American Diabetes Association and the National Heart, Lung,
and Blood Institute recommend that people with diabetes keep their
blood pressure below 130/80.
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.
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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. Two
types of drugs, angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs), have proven effective in
slowing the progression of kidney disease. Many people require two
or more drugs to control their blood pressure. In addition to an ACE
inhibitor or an ARB, a diuretic is very useful. Beta blockers,
calcium channel blockers, and other blood pressure drugs may also be
needed.
An example of an effective ACE inhibitor is captopril, which
doctors commonly prescribe for treating kidney disease of 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.
An example of an effective ARB is losartan, which has also been
shown to protect kidney function and lower the risk of
cardiovascular events.
Any medicine that helps patients achieve a blood pressure target
of 130/80 or lower provides benefits. Patients with even mild
hypertension or persistent microalbuminuria should consult a
physician about the use of antihypertensive medicines.
In people with diabetes, excessive consumption of protein may be
harmful. Experts recommend that people with kidney disease of
diabetes consume the recommended dietary allowance (RDA) for
protein, but avoid high-protein diets. For people with greatly
reduced kidney function, a diet containing reduced amounts of
protein may help delay the onset of kidney failure. Anyone following
a reduced-protein diet should work with a dietitian to ensure
adequate nutrition.
Antihypertensive drugs and low-protein diets can slow kidney
disease when significant nephropathy is present. A third treatment,
known as intensive management of blood glucose or glycemic control,
has shown great promise for people with type 1 and type 2 diabetes,
especially for those in early stages of nephropathy.
Intensive management is a treatment regimen that aims to keep
blood glucose levels close to normal. The regimen includes testing
blood glucose frequently, administering insulin frequently
throughout the day on the basis of food intake and exercise,
following a diet and exercise plan, and consulting a health care
team frequently. Some people use an insulin pump to supply insulin
throughout the day.
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) and a trial led by researchers at the
University of Minnesota Medical School. A third study, conducted in
the United Kingdom, is the U.K. Prospective Diabetes Study
(UKPDS).
The DCCT, conducted from 1983 to 1993, involved 1,441
participants who had type 1 diabetes. Researchers found a 50 percent
decrease in both development and progression of early diabetic
kidney disease in participants who followed an intensive regimen for
controlling blood glucose levels. The intensively managed patients
had average blood glucose 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 people with long-standing diabetes 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.
The UKPDS--a 20-year trial conducted in England, Ireland, and
Scotland--tested the effects of intensive glucose and blood pressure
control in people with type 2 diabetes and found similar benefits
for this group.
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When people with diabetes experience kidney failure, they must
undergo either dialysis or a kidney transplant. As recently as the
1970s, 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 patients
with diabetes 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.
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If you have diabetes:
- Have your doctor measure your A1C level at least twice a
year. The test provides a weighted average of your blood
glucose level for the previous 3 months. Aim to keep it at
less than 7 percent.
- Work with your doctor regarding insulin injections,
medicines, meal planning, physical activity, and blood
glucose monitoring.
- 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. Aim to keep it at less than
130/80.
- Ask your doctor whether you might benefit from taking an
ACE inhibitor or ARB.
- 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. The doctor should provide you with an estimate
of your kidney's filtration based on the blood creatinine
level.
- Ask your doctor whether you should reduce the amount of
protein in your diet. Ask for a referral to see a registered
dietitian to help you with meal planning.
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The incidences of both diabetes and kidney failure caused by
diabetes have been rising. Some experts predict that diabetes soon
might account for half the cases of kidney failure. In light of the
increasing morbidity and mortality related to diabetes and kidney
failure, patients, researchers, and health care professionals will
continue to benefit by addressing the relationship between the two
diseases. 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 kidney failure. For some
people with type 1 diabetes, 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.
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