Dr. MJ Bazos MD,
Disease in Diabetes
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
- 35.9% diabetes
- 28.8% high blood pressure
- 18.1% other causes
- 11.4% glomerulonephritis
- 2.9% polycystic kidney disease
- 2.9% 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.
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.
Most people with diabetes have a form
known as noninsulin-dependent diabetes (NIDDM), or type 2 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
A less common form of diabetes, known
as insulin-dependent diabetes (IDDM), or type 1 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% of all cases
of diabetes; IDDM accounts for about 5%. Both types of diabetes can lead to
kidney disease. IDDM is more likely to lead to ESRD. About 40% 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% of the ESRD in African Americans and
The Course of
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
Symptoms related to kidney
failure usually occur only in late stages of the disease, when kidney function
has diminished to less than 25% 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.
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
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
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% 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
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. 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 1 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.
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.
The DCCT, conducted from 1983 to 1993,
involved 1,441 participants who had IDDM. Researchers found a 50% 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
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 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
- 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
- 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. 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