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Smart operations. (preventing kidney disease) ( Diabetes Forecast ) 6/1/94

To the callow observer, the kidneys seem rather a bother. What do they do, really, except drip
urine into your bladder, so you end up in line for the bathroom at concerts?

No, you won't see the kidneys getting any standing ovations. Not like other major organs. Take
the heart. The way people go on about the heart, you'd think it was single-handedly keeping you
alive.

Fans of the kidney see things differently. To them, the heart is a big, dumb muscle, mindlessly
moving blood 'round and 'round. The heart doesn't seem to care what it pumps: clean blood,
dirty blood, it's all the same to the heart.

Luckily, your heart has two smart friends doing a lot of work behind the scenes.

Silent Filters

You've got about 6 quarts of blood circulating through your body. In 24 hours. 2,000 gallons of
blood pass through your heart.

While your heart is pumping your blood, you're eating, sleeping, working, and playing. All the
while, your cells work. They use energy and produce waste. The waste products get dumped in
the blood. There they would stay and build up to toxic levels were it not for your stalwart
kidneys: The 2,000 gallons of blood that go through your heart every day go through your
kidneys too, and there the blood gets filtered.

You have two kidneys, and they sit on either side of the small of your back. Each is made up of
about 1 million separate coiled tubes called nephrons. At the beginning of the nephron is a
filtering part called the glomerulus. It allows blood to hold on to red blood cells, white blood
cells, and platelets while permitting water, salt, and chemical wastes to flow into what will
become urine.

It's an elegant, efficient, and essential system deserving applause. And protection, too, especially
in people who have diabetes.

Diabetes can damage your kidneys. This damage results in diabetic nephropathy, or kidney
disease. This can lead to kidney failure (also called end-stage renal disease).

Kidney failure develops in about 30 percent of those with insulin- dependent (type I) diabetes,
and in 10 to 20 percent of those with noninsulin-dependent (type II) diabetes.

Kidney failure attacks people with diabetes unequally. A greater percentage of women than
men, and of Black Americans, Hispanics, and Native Americans than Caucasians develop
kidney disease.

It takes from 10 to 30 years for the kidneys to fail due to diabetes. Type I diabetes usually
develops before age 30; type II diabetes after age 40. If kidney failure occurs, it usually
happens before age 50 in people with type I diabetes, and by age 70 in people with type II
diabetes. Although type I and type II diabetes have different causes, and are really two different
diseases, they both cause changes in the kidneys that look the same under the microscope.

But things are looking up. The percentages above--10 to 30 percent of people with
diabetes--are historical figures. Included are people who first developed type I diabetes back
when it was treated with one shot of insulin a day and monitored with urine testing, back when
type II diabetes was treated with not much more than a shrug and an "eat less sugar." Those
ways of treating diabetes left people with high blood glucose levels much of the day. We now
know that high blood glucose levels are linked to the development of kidney disease.

Today, people have more knowledge and better equipment, so many can keep their blood
glucose levels closer to normal. In addition, new medications, such as the drug captopril, are
available to help slow the progress of kidney disease. We expect to see evidence of this better
blood glucose control and better treatments in the years to come, with fewer people developing
advanced kidney disease.

You can take advantage of better treatments now. Whether you have type I or type II, have had
diabetes for years or have just been diagnosed, whether your kidneys are healthy now or
already show some signs of damage, there are steps you can take to head off kidney disease.

Recycling

Your first step in preventing kidney disease is to keep your blood glucose levels as close to
normal as you can safely manage. Very strong evidence is now in hand to show that the reward
for keeping tight control of blood glucose from the start of type I diabetes is a sharp decrease in
complications. Adding to many previous trials done in Europe and the United States, the
carefully conducted Diabetes Control and Complications Trial (DCCT) has shown about a 60
percent reduction in the rate of kidney disease in people with tight control as compared with
ordinary diabetes management. We believe the same is probably true for those with type II
diabetes.

Despite these efforts, diabetes may still affect your kidneys. When the glomeruli (the filters) are
damaged, substances that should be recycled are allowed to pass out with the urine, while some
waste products are kept in the blood.

One of the substances that should be recycled is protein. When it' s not, and when the kidneys
allow it to pass into the urine, that' s a sign that the kidneys are damaged. Many people who
show small amounts of the protein albumin in their urine (microalbuminuria) after 5 years with
diabetes go on to develop diabetic kidney disease many years later.

You should have your kidney function checked regularly. After you have had diabetes for 5
years, you should have a microalbuminuria test run on your urine every year. (If you were
diagnosed at a very young age, you should begin having this annual test after you go through
puberty.) Should 10 years go by without finding microalbuminuria, it's highly likely that
nephropathy will not develop. If your urine is negative for microalbuminuria beyond 10 years,
the risk of your ever developing nephropathy is minimal, but you should continue to get
microalbuminuria tests.

If you have microalbuminuria, you should redouble your efforts to keep near-normal blood
glucose levels. Tighter control may slow, or even stop, the progress of kidney disease.

Kidney Disease

In most people who have microalbuminuria, after 10 or more years of diabetes the amount of
protein in the urine increases. This is proteinuria. It's a sign of definite kidney disease.

At this stage, the kidneys are losing so much protein that the liver can't manufacture enough to
replace it. The level of albumin in the blood falls. Body water that is normally held within blood
by the albumin then leaks into tissue and fills the abdomen and chest cavities. This is called the
nephrotic syndrome. People in the midst of nephrotic syndrome often have swollen ankles,
bloating by fluid, and difficulty breathing.

Healthy kidneys should get rid of excess salt and water. When the kidneys aren't functioning
well, the body retains excess salt and water, which raises blood pressure to unhealthy levels
(hypertension). Hypertension and an increased blood volume may lead to bleeding in the retinas,
congestive heart failure, or a stroke.

Further decrease in kidney function, after years of proteinuria, can be detected with blood tests.
When protein loss is at a certain high level, your doctor should refer you to a kidney specialist
(nephrologist). The nephrologist will check to see if there is another cause other than diabetes
for the protein in the urine. He or she may do a kidney biopsy: While you are under local
anesthesia, a small snip of kidney tissue is taken, which is studied under the microscope.

At first, the nephrologist is seen only once or twice yearly. Later, the nephrologist may become
the leader of the diabetes-care team with visits as often as every week or two.

By drawing a graph of the amount of kidney function present at each visit, the doctor can see
the rate of loss of function and predict the approximate date when therapy such as dialysis will
be required. This gives the patient and family the time to plan for the next stage of diabetic
nephropathy.

Kidney Failure

The final stage of diabetic nephropathy begins when waste products in the blood rise to toxic
levels. This is called uremia, meaning urine in the blood. Signs of uremic poisoning include
nausea, loss of appetite, restless legs, easy bruising, a foul taste in the mouth, and an inability to
sleep at night and stay awake during the day.

The person with this level of kidney damage suffers drastic weight loss. Especially serious is a
decrease in muscle mass. At this point in the illness, the patient and family meet with the medical
team to decide on a plan for end-stage renal disease therapy.

This is how kidney disease progresses from the development of microalbuminuria to the onset
of uremia in people with type I diabetic nephropathy. Although few reports tell what happens to
the kidneys of people with type II diabetes, the stages in loss of kidney function are probably
the same as that which take place in people with type I diabetes.

In practice, there is no substantial difference between how the doctor manages kidney disease
in people with type I or type II. The exception is pancreatic transplantation. A pancreas
transplant can cure type I diabetes and help kidney disease, but pancreas transplants are not
recommended for people with type II diabetes.

Treatment

Before complete kidney failure, you can take steps to slow the progress of the disease.

* Blood Pressure Control

High blood pressure puts undue pressure on the small blood vessels of the kidneys. No matter
what your kidney function is now, if you have high blood pressure, you need to get it down to
the normal range of 130/80 or lower. Your doctor may advise diet changes, exercise, weight
loss, and possibly medication.

Powerful drugs are available to drop blood pressure, some of which need to be taken only once
a day. True, there can be unhappy side effects of the drugs used to treat hypertension including
dizziness, dry mouth, cough, and depressed sexual function in men. You'll probably have to try
several drug combinations before finding the one that works best for you. There is no question
that the payoff for putting up with antihypertensive drugs is a slowing in loss of kidney function.

Diuretics are drugs that cause the kidneys to put out extra salt and water. These drugs can help
lower blood pressure as well as regulate the extra water kept in the body in the nephrotic
syndrome.

Getting blood pressure down is important in people who have microalbuminuria as well as those
with definite kidney disease. In some people, once a normal blood pressure is established,
kidney function remains rock stable for 5 or more years.

One type of antihypertensives, the angiotensin converting enzyme (ACE) inhibitors, may slow
the progress of kidney disease, even in people who don't have high blood pressure (see
Forecast, "ACE In The Hole," November 1993, pp. 24-27).

In January, the ACE inhibitor captopril was approved by the Food and Drug Administration for
the treatment of kidney disease in people who have type I diabetes. According to the FDA,
treatment with captopril should be offered to people who have two signs of kidney disease: high
levels of protein in the urine and abnormalities in the blood vessels of the eyes. (Diabetes affects
both the large and small blood vessels. Damage to the small blood vessels results in eye disease
and kidney disease. Damage can be detected in the eyes earlier than in the kidneys, so signs of
eye disease are a sign of small blood vessel damage, which would also affect the kidneys.)

* Diet

If you have persistent microalbuminuria, that is, microalbuminuria for several months, you should
eat less protein. The theory is that the breakdown of the protein in food produces more waste
products than the breakdown of carbohydrates. These waste products must be eliminated by
the kidneys. This isn't a problem for healthy kidneys, but it taxes kidneys that aren't
functioning perfectly.

Foods from the Milk and Meat Exchanges lists in the American Diabetes Association, the
American Dietetic Association Exchange Lists for Meal Planning are high in protein. These
include meat, fish, poultry, eggs, milk, and cheese. Keep in mind that some foods that are
predominantly starch, such as soybeans and lentils, contain significant amounts of protein as well.

Studies have shown that people with diabetic nephropathy who are able to put up with a dietary
protein allowance of only 40 grams daily will be rewarded with a slower rate of loss of kidney
function.

As an example, if you ate 3 ounces of meat (21 grams of protein), a half cup of milk (4 grams
protein), 4 Starch/Bread Exchanges (12 grams protein), and 2 Vegetable Exchanges (4 grams
protein), that would be about 40 grams of protein. You could eat other foods that day, but they
would need to be foods that don't contain protein, such as fruit.

It can be very hard to plan a diet that is so restricted in protein. Contact a dietitian. He or she
will work out how many grams of protein you can have and help you plan meals, taking into
consideration your weight and how many calories you need to consume in a day. Don't start a
low-protein diet without first consulting with your health-care team.

* Blood Glucose Control

Yep, this again. Tight blood glucose control cannot only help prevent kidney disease, it can
slow it once it starts. True, the value of strict control is still unproven in those who have
advanced kidney damage. And there is a down side of strict control (among those taking
insulin): an increase in episodes of severe low blood glucose. Still, after reviewing both sides of
tight control, nearly all doctors accept that the benefits outweigh the drawbacks and advise a
program of strict glucose management.

* Team Approach

Diabetic complications often come in sets. Many people who have kidney disease also have
other complications, such as retinopathy (diabetic eye disease), foot ulcers, nerve disease of the
bladder (cystopathy) and stomach (gastroparesis), and coronary artery disease. These
complications may sap the strength of patients trying to cope with worsening nephropathy. It is
usual, therefore, to apply a team approach to managing patients with failing kidneys.

Substitutes For Kidneys

If kidney disease progresses and your kidneys fail, your blood will need to be artificially
filtered. Today, there are three satisfactory ways to do this: maintenance hemodialysis; peritoneal
dialysis; and kidney transplantation (with or without a pancreas transplant in people with type
I diabetes).

You need to understand the pros and cons of each kind of treatment, and you should participate
in selecting a treatment option. If things don't work out well with one therapy, you can change to
another until a satisfactory long-term plan is worked out.

* Hemodialysis

For most people (80 percent of people with kidney failure), maintenance hemodialysis is the
only treatment that they will ever get.

During hemodialysis, blood is pumped to a filtering machine outside the body. Unfiltered blood
is taken from an artery, usually in the arm. It goes into the filtering machine, where waste
products pass through a membrane into a washing solution. The filtered blood is returned to the
body through a vein. The amount of blood outside the body at any one time is small--about 1
pint.

The typical hemodialysis treatment plan requires three weekly treatments lasting 3 to 6 hours
each. This is usually done in a clinic, but motivated people can be trained to perform
selfhemodialysis at home in 1 to 2 months. This gives them freedom in scheduling treatments.
People doing home hemodialysis rank at the top in survival, rehabilitation, and selfesteem.
Although hemodialysis is a good way to rid the body of waste chemicals, salt, and water, it still
leaves the person low on certain hormones that are normally produced by healthy kidneys, and
these will need to be replaced.

About 80 percent of hemodialysis patients will live through the first year; 50 percent will be alive
after 3 years. Because of recent improvements in dialysis care, today's patients are likely to
survive for even longer periods.

* Peritoneal Dialysis

The peritoneum is the sac-like lining of your abdominal cavity. In continuous ambulatory
peritoneal dialysis (CAPD), the peritoneum is used as the filtering site, rather than a machine
outside the body. Patients change the rinsing solution in the peritoneum three to five times daily.

To prepare for CAPD, a catheter that leads from the outside to the peritoneal cavity is sewn in
place a day or so before the first dialysis. To do CAPD, the person uncaps the catheter and
removes or adds rinsing solution.

Patients, including those who are blind, are usually able to learn to perform CAPD at home
within 10 to 15 days. Insulin, antibiotics, and other drugs can be added by the patient to each
dialysate exchange. This method of dialysis means freedom from a machine. Because CAPD is
always going on, the patient is free to travel, attend events, or sit on the couch and watch
television. Another advantage is that the blood never leaves the body, eliminating some potential
problems.

Peritonitis, an infection of the lining inside the abdomen, is the major complication of CAPD and
occurs about once a year. Antibiotics usually clear up the peritonitis, but sometimes an infection
becomes life-threatening.

Approximately 12 percent of patients will be treated by CAPD or other types of peritoneal
dialysis. Survival on CAPD is about the same as on hemodialysis. To help you decide, go see
both in progress at a nearby dialysis center. Remember, you can switch methods if you have
trouble with the first one you try.

* Kidney Transplantation

Without question, rehabilitation in a person given a functioning kidney transplant (you only need
one working kidney) is far better than with dialysis. We recommend a kidney transplant as the
favored treatment to all people with diabetic kidney failure who are under the age of 60.

Either a living donor (usually from the immediate family) or a cadaver donor can be used for the
needed kidney; patient survival rates are slightly higher when the donor is related than when the
donor kidney comes from an unrelated cadaver. More than half of kidney transplant recipients
live for more than 3 years, and they return to work, school, and home responsibilities.

The addition of a pancreas transplant to a kidney transplant provides a marvelous chance for
people with type I diabetes to achieve a cure for both uremia and diabetes. Because the
problem in type II diabetes is not too little insulin, a pancreas transplant is not likely to be of
benefit.

About 8 percent of people with type I diabetes whose kidneys fail opt for a kidney transplant.

Future Therapies

Controlling blood glucose is one way we know to slow or prevent complications. Researchers
continue to search for other ways. We know that the kidney and other organs are changed
chemically in diabetes. Researchers are seeking ways to attack the problem of complications
with a chemical approach that does not rely solely on control of blood glucose levels.