By Stephen Z. Fadem, MD,
Chronic kidney disease (CKD) is
common, affecting approximately 20 million (one out of every nine)
people in the United States. In the majority of cases, it is the
result of hypertension or diabetes. Nearly three years ago, the
National Kidney Foundation (NKF) published a simple classification
system and method of estimating kidney function. Thus making it
easier to screen, identify and classify high-risk persons. What is
not easy, however, is to accept and hear for the first time that
you have kidney disease.
This article will identify and discuss three objectives to keep in
mind when facing CKD:
1) Delaying the progression of disease.
2) Maintaining the quality of life.
3) Decreasing morbidity.
Delaying the progression of disease
Studies in the last 12 years have
shown us that we can delay the onset of renal failure. The top
three measures are controlling blood
pressure, using a converting enzyme inhibitor or angiotensin
receptor blocker medications and strict control of diabetes.
Maintaining the quality of life
Quality of life can be measured
and quantified by several tests. The most popular and useful is
the Kidney Disease Quality of Life (KDQOL). In essence, it relates
to ones energy level and exercise tolerance and sense of
Anemia is a major factor in determining quality of life. In
anemia, there is a decrease in red blood cells (the little
elements containing iron and hemoglobin that carry oxygen to
tissues and take carbon dioxide products away). Medications that
stimulate this production alleviate anemia and drastically improve
quality of life. They also improve severe heart failure.
Malnutrition and inflammation are both related to feeling badly,
but can also be symptoms of underlying diseases.
In the late stages of kidney disease, the development of
malnutrition usually responds to dialysis the removal of the
acids and waste products. Thus, patients at this stage often feel
better after initiating dialysis. In addition, quality of life is
related to the presence of pain, such as bone and joint pain,
coexistence of neuropathy (nerve injury from diabetes and uremia),
limit ambulation and preoccupy patients leading to a decrease in
the quality of life.
Complications require evaluation and therapy. Heart disease and
failure can be aggressively treated, but must first be assessed.
In my experience, any kidney patient who has persisting fatigue
should be evaluated for underlying coronary artery disease, and
should have tests to determine cardiac function. Treating bone and
calcium disease associated with kidney disease can be done with
vitamin D analog supplements control of serum phosphorus.
Proactive and preventive care are ideal. The chemical
abnormalities begin in early stage three kidney disease when the
GFR is around 60 cc/min. These laboratory abnormalities persist
for months to years before leading to symptoms, and thus ample
time to aggressively prevent progression to symptomatic disease.
However, what is more compelling is research showing that the same
abnormalities that eventually cause bone disease also lead to
calcium deposits inside the walls of blood vessels. This is fast
becoming recognized as a major contributor to the late morbidity
and mortality in kidney patients.
The major cause of death in CKD is
cardiovascular disease. This is related to a combination of
hypertension, atherosclerosis and vascular calcification. It is
becoming apparent that the earlier we begin to manage these
entities, the better chance we have of lowering the risk of a
cardiovascular event. Blood pressure is one of the major problems
that we must deal with, and it is prudent to start as early as
possible in managing this disease. It challenges the health of 65
million Americans, and is a major promoter of kidney disease.
Controlling blood pressure is the major means by which patients
can decrease morbidity, prolong the life of their kidneys and
enjoy a higher quality of life. Thus, it is important to
understand something about hypertension.
The heart is a pump, and beats
with pressure. The top number of our blood pressure is a
measurement of the direct action of the heart against the blood
pressure. It is systolic because the segment of the heart rhythm
where blood is squeezed out the heart is systole. The bottom
number is the measure of the residual pressure in the blood
vessels when the heart is resting between beats that resting
period is called diastole. The normal blood pressure is around
120/80. Interestingly, in primitive cultures where free salt
ingestion is not part of the diet, blood pressures are much lower.
If the pressure with which the heart beats is greater than 120/80,
the blood vessel cells undergo changes that make them thicker.
Throughout a period of many years, the thickening worsens,
damaging blood vessels that supply organs like the kidney and
brain. Thick blood vessels are narrow, and have a high resistance
to the flow of blood, forcing the heart to have to pump with an
increased pressure to get the same amount of blood to tissues.
When the heart works at a higher level for a long period, heart
failure may develop. Meanwhile, the higher pressure against the
tissue causes damage to the walls of the filters, which may lead
to kidney disease.
In May 2004, NKF published Clinical Practice Guidelines for
hypertension in CKD patients. The goal to keep blood pressure at
130/80 or lower was based upon clinical trials showing blood
pressures at this level were less likely to damage the kidney.
Higher blood pressures associated with GFR (the glomerular
filtration rate a means of measuring kidney function and
classifying kidney disease) loss around 13 cc/min per year.
Patients should reduce their sodium intake to less than 2.4 grams
per day. In addition, patients were encouraged to modify their
lifestyle. The main stay of therapy is the use of antihypertensive
therapy. Preferably, kidney patients should be on either an
angiotensin receptor blocker (ARB) or a converting enzyme
inhibitor (CEI) medications. In addition to reducing the blood
pressure, these types of medicine relax or widen the blood vessels
in the kidney. This reduces the pressure that is placed on the
kidney filter (glomerulus). Increased pressure on any tissue,
especially kidney blood vessels will result in damage over a
period of years. In diabetics, there are studies that show that
both these types of medication slow deterioration of renal
Controlling hypertension will often require several medications.
Since hypertension is associated not only with kidney failure, but
also with stroke and heart failure, it is important to screen
patients at risk for CKD very early starting with those who
have known risk factors.
One of the mainstays of managing
CKD, is to try to reduce proteinuria. Remember, the filters in the
kidney are designed to hold back proteins and red blood cells,
while letting waste products pass through. Studies with
angiotensin converting enzyme inhibitors (ACE inhibitors or CEIs,
such as lisinopril) and the angiotensin receptor blockades (ARBs,
such as losartan) show these classes of medication are effective
in reducing the amount of protein that leaks across the filter.
This preserves renal function. It may be necessary to use these
medications in larger doses to lower protein losses. Proteinuria
is associated with worsening renal function because proteins harm
the glomerular filter as they leak across it. While these classes
seem to work independent of controlling blood pressure that is
they work directly on the kidney filter blood vessels the
study Modification of Diet in Renal Disease (MDRD), demonstrated
that lowered blood pressure to less than a systolic of 130 and a
diastolic of less than 75 in patients with reduced kidney function
and proteinuria would help slow the decline in kidney function.
CKD is common in the later stages
of diabetes, especially if the disease is not aggressively managed
early. Type 1 diabetics generally have progressive kidney disease
that manifests concurrently with microalbuminuria small traces
of protein leaking into the urine. While one-third of type 2
diabetics have proteinuria when their disease is diagnosed, it
coexists with cardiovascular disease, hypertension and obesity. A
major study, conducted more than 10 years ago, show the value of
reducing blood sugar level and normalizing the HgbA1C a
measure of diabetes management. The second important step in
controlling kidney disease in diabetes is to keep the blood
pressure under control again 130/80 is the recommendation.
Tight glucose and blood pressure control reduces cardiovascular
events, according to a large study published in the United Kingdom
around seven years ago. Diabetes is associated with a two to four
fold risk in cardiovascular mortality, and lifestyle changes that
include increasing activity and reducing the smoking of cigarettes
are necessary. The third step in controlling diabetes is to use an
ACE or ARB. Screening for small traces of albumin in the urine is
easy, and very useful in predicting who will develop kidney
disease. These patients, especially, should be treated with ACEs
or ARBs or perhaps both, together, as some research is now
suggesting. The fourth step in controlling diabetes is to control
weight. One-half of people in the U.S. have criteria for obesity,
based upon the calculation of the body mass index. It is
recommended that patients with CKD work with a dietitian so that
their diet will also help reduce cardiovascular risks. The diet
may need to be tailored to the patients food preferences and
Heart failure is associated with
the later stages of CKD. It is related to many factors, but most
heavily linked to hypertension. Anemia is also associated with
heart failure. Left ventricular hypertrophy (LVH) is the
consequence of the heart having to work harder than usual to make
blood circulate through vessels that are now thickened from
hypertension. Any muscle that works harder requires more oxygen,
and the requirement for this increase in oxygen is one of many
signals that stimulate the formation of new blood vessels. In
kidney disease, it is shown that muscles thicken, but the new
blood vessels do not form fast enough. Thus, it is not surprising
that around five years ago, a study was published showing risk of
sudden death from LVH was associated with wall thickness,
confirming what has been observed for years in clinical practice.
Large clinical trials tried to resolve this problem and showed
that death or the development and persistence of LVH could be
significantly reduced by lowering blood pressure with an ACE
To add insult to injury, the
tendency of late stage kidney patients to accumulate phosphorus
causes changes in the blood vessel wall leading to vascular
calcification. This is independent of the forces that cause
hypertensive vascular disease and compounded. It is being
extensively studied now, but it is very important that kidney
patients follow the guidelines for bone disease.
Lipids and inflammation
It is difficult to imagine a link
between delicious but fattening food usually associated with
pleasurable events with inflammation usually associated with
pain and swelling. But, both inflammation and hyperlipidemia have
a common dark side. All cells in the body will either change their
shape, grow, die or release little hormones known as cytokines,
when exposed to stress factors. One of those stress factors is the
appropriately named oxygen radical. These radical oxidizing agents
too often come from eating quantities of foods that our bodies
have not yet adapted. When changes occur in the blood vessel
walls, they cannot make enough of the nitrogen-containing
substance nitric oxide to stay dilated. This begins the story of
atherosclerosis. Damaged blood vessels recruit inflammatory cells
to repair themselves. These cells see that excess fat (LDL
cholesterol) has been oxidized and is foreign to the body and try
to devour it. Engorged with oxidized fat, these cells die and
stimulate the cascade of events that lead to plaque formation or
atherosclerosis. Thus, the therapy for atherosclerosis is not only
to reduce LDL (bad) cholesterol and those fat-containing foods
that metabolize to LDL cholesterol, but also to reduce
inflammation. It appears that statin medications (atorvastatin or
simvastatin) appear to do both and long term clinical studies are
underway to determine how to better-reduce inflammation and
cholesterol in kidney patients. These studies are not being done
in patients without abnormally high cholesterol. In the later
stages of kidney disease, metabolism is altered and the serum
measurement of cholesterol is lower than expected. Yet, the
presence of atherosclerosis in the renal population cannot be
denied. There is now a question of what cholesterol level should
be for the general population, and additionally, what the balance
between the good HDL and bad LDL cholesterol should be. Our diet
is higher in lipids than that of pre-agricultural ancestors, and
we will never exercise as ancestors did before the domestication
of animals for transportation. Studies of primitive populations
who do not share our diet and who ambulate as a means of
transportation show that their LDL cholesterols were comparatively
lower and HDL cholesterol levels higher than those following the
traditional western diet.
The management of reduced kidney
function creates a series of challenges that have to be handled in
a systematic and orderly fashion. Chronic disease patients should
keep these three goals in mind; delay the progression of disease,
maintain the quality of life and decrease morbidity/mortality. In
CKD, the major steps revolve around the control of blood pressure,
reduction of cardiac risk factors, controlling underlying
diseases, such as diabetes, and accompanying diseases, such as
Stephen Z. Fadem, MD, FACP serves as a member of the AAKP
Medical Advisory Board and a Vice President of the AAKP Board of
Directors. Dr. Fadem is a practicing nephrologist in Houston.
This article originally appeared in the November 2004
issue of aakpRENALIFE, Vol. 20, No. 3.