UAL

LYSI
S
FOR NURSING BASIC
CONCEPTS
INDEX PAGE

FOR NURSING BASIC CONCEPTS............................................................................2

PAGE.......................................................................................................................3
CHAPTER 1 – FUNCTIONS OF THE KIDNEY.......................................................4
B FUNCTION OF THE KIDNEY...............................................................................4
T(RE(G//LAR?....................................................................................................................6
SUMMARY:............................................................................................................7
& THE URINARY SYSTEM..................................................................................7
CHAPTER 2 – KIDNEY FAILURE.....................................................................10
& RENAL INSUFFICIENCY...............................................................................10
• TESTS AND EXAMS:........................................................................................11
g TREATMENT:...................................................................................................12
8 FORECAST........................................................................................................14
8 PREVENTION....................................................................................................15
CHAPTER 3 – KIDNEY TREATMENT..............................................................18
& KIDNEY THERAPY.........................................................................................18
& HEMODIALYSIS..............................................................................................21
8 HEMODIALYSIS: TREATMENT PRINCIPLES.............................................25
& SUMMARY OF PARAMETERS IN HEMODIALYSIS.................................26
CHAPTER 4 – PRINCIPLES OF TRANSPORTATION.....................................30
• DIFFUSION........................................................................................................30
& OSMOSIS..........................................................................................................31
& ULTRAFILTRATION:......................................................................................33
8 CONVECTION:..................................................................................................34
CHAPTER 5 – THE DIALYZER, DIALYSIS MACHINE..................................38
& THE DIALYZER...............................................................................................38
B DIALYZER DESIGN:........................................................................................39
B TYPES OF MEMBRANES:...............................................................................41
& MEMBRANE PERMEABILITY......................................................................42
• STERILIZATION METHODS...........................................................................45
8 CHOOSING THE SUITABLE DIALYZER:.....................................................47
8 DIALYSIS MACHINE.......................................................................................48
CHAPTER 6 – TREATMENT PREPARATIONS................................................52
& START OF TREATMENT:...............................................................................52
g PARAMETERS:.................................................................................................54
g ACUTE COMPLICATIONS:.............................................................................55
g ADEQUATE DIALYSIS....................................................................................57
CHAPTER 7 – VASCULAR ACCESS.................................................................60
9 Vascular access for hemodialysis........................................................................61
CHAPTER 8 – DIET.............................................................................................64
& DO I TAKE CARE OF MY DIET?...................................................................65
8 WHAT IS UREA?...............................................................................................65
& THE CARBOHYDRATES................................................................................66
& WHAT IS PHOSPHORUS?:.............................................................................66
• WHAT IS CALCIUM?........................................................................................67
& DO I WATCH THE POTASSIUM?..................................................................68
tr WHAT ARE VITAMINS?.................................................................................69
& WHAT IS SODIUM?.........................................................................................70
B THE LIQUIDS....................................................................................................71
B I AM IN PREDIALYSIS:...................................................................................72
® I AM IN HEMODIALYSIS...............................................................................74
B WHAT IF I GO OUT TO EAT OUT?...............................................................78
8 HOW DOES THE DOCTOR KNOW IF I HAVE AN ADEQUATE INTAKE?
................................................................................................................................80
CHAPTER 9 – EPO...............................................................................................82
& ANEMIA AND ERYTHROPOIETIN...............................................................83
8 THERAPEUTIC INDICATIONS.......................................................................83
g PHARMACOKINETICS AND PHARMACODYNAMICS.............................84
g GENERAL PRECAUTIONS..............................................................................88
& RESTRICTIONS ON USE DURING PREGNANCY AND
BREASTFEEDING...............................................................................................94
g SECONDARY AND ADVERSE REACTIONS................................................95
BIBLIOGRAPHY..................................................................................................98
 CHAPTER 1 – FUNCTIONS OF THE KIDNEY

B FUNCTION OF THE KIDNEY.

General characteristics of the kidneys:

^ Each kidney is 10 to 12 cm long, 5 to 6 cm wide and 3

to 4 cm thick (about the size of a closed fist)
^ They are found in the retroperitoneal region.
^ Each one weighs about 150 grams (without fluids
inside), around 300 -400 grams with the fluids ( blood -
urine).
^ They are surrounded by a thin renal capsule.
^ They are divided into three different areas: cortex, medulla and pelvis.
^ They are two glands in the shape of a tack.
^ They are dark red in color and are located on both sides of the spine.
^ At the top of each kidney are the adrenal glands .
^ The two most common diseases that can affect it are diabetes and
hypertension.

fibrous capsule
The kidneys are
vital organs for excretion of artery
renaland
vein
materials
waste from the body, but
they also regulate the
composition of the body's
fluids.

In addition, they constitute the site of production of some important hormones.

Therefore, its function is both excretory and secretory.

 Excretory function is necessary to maintain homeostasis in the body.

Kidney function is essential for the regulation of water and electrolyte (dissolved
salts) balance, as well as acid-base balance.

Metabolic waste products need to be removed from the blood. These include a
large number of substances, among which urea is the most important. Likewise, another
important waste material is creatinine.

Urea : A substance that contains a large amount of nitrogen and constitutes most
of the organic matter contained in urine in its normal state. It is very soluble in water,
crystallizable, odorless and colorless.

Creatinine : Organic substance, product of protein metabolism, which is eliminated

in the urine and is measured in the blood as an indicator of kidney function.

In addition to natural waste materials, the kidneys also excrete foreign substances,
for example alcohol and drugs.

The excretion product of the kidneys is urine. Its composition depends on the
internal balance of water, electrolytes and acids as well as the metabolic state of the body.

Normally urine is a somewhat acidic solution containing 96% water, 2% urea and
2% other substances, such as creatinine, salts and acids. Its yellowish color comes from
bile pigments.

The secretory or hormonal function of the kidneys includes the secretion of three
different hormones:

^ Renina.
^ Erythropoietin.
^ Vitamin D.

Renin is a hormone that has to do with the regulation of blood pressure. It is a

protein formed in the kidney tubules, which is released into the blood. Its hyperproduction,
which can occur in case of kidney failure, can cause high blood pressure. This is usually
compensated by administering antihypertensive medication.
 Erythropoietin stimulates the bone marrow to produce erythrocytes (red blood
cells). Erythropoietic therapy has led to a great improvement in the well-being of many
kidney patients, since it reverses the anemia that many of these patients have suffered.

Vitamin D is necessary for the absorption of calcium from food in the intestine. This
vitamin is supplied with the diet. In the kidney it undergoes a chemical modification in
which an active form of the vitamin is produced. Vitamin D deficiency causes reduced
calcium absorption, which eventually leads to bone fragility. For patients with kidney
failure, vitamin D has to be administered as a medicine.

T(RE(G//LAR?
 SUMMARY:

Excretory functions:

^ Remove waste materials.

^ Remove excess liquid.

^ Regulate the balance between acids-bases.

^ Regulate electrolyte levels.

Secretory functions:

^ Regulate blood pressure (renin).

^ Regulate the production of red blood cells (EPO).

^ Regulate the absorption of calcium (vitamin D).

& THE URINARY SYSTEM.

The kidneys are a pair of bean-shaped organs, each about the size of a fist. They
are located at the back of the abdomen, near the abdominal wall, one on each side of the
spine.

Each kidney is supplied with blood through a renal artery, which is a branch
of the aorta, the main trunk of the arterial circulatory system. Approximately 20% of
the blood flowing through the aorta bifurcates into the renal arteries.

Blood leaves the kidneys through the renal veins, which empty into the
inferior vena cava. This is the major vein that receives blood from the parts of the
body below the diaphragm and transports it back to the heart.

The urine produced in the kidneys is accumulated in the renal pelvis, which
functions like a funnel.

Urine continuously circulates through the ureters to the urinary bladder . The
bladder is a sac that acts as a reservoir for urine. When 200 to 300 ml of urine have
accumulated, the pressure stimulates the nervous system , resulting in the need to
release urine. However, the maximum content of the bladder is about 500 ml.

The urethra is a tubular structure that empties the bladder to the outside. The
urethra measures about 20 cm in men, while in women it measures only about 4 cm.
This explains women's higher risk of contracting infections in the urinary region.

The urinary system consists of the kidneys, ureters, bladder, and urethra.
 CHAPTER 2 – KIDNEY FAILURE

& RENAL INSUFFICIENCY.

When the kidney fails suddenly, in acute kidney failure, it may be a temporary
problem and the patient may recover after a short period of treatment.

Decreased blood flow to the kidneys or obstruction of urine flow can cause acute
kidney failure.

Traumatic injury to the kidneys, for example in a traffic accident, can also decrease
kidney function. Some types of kidney inflammation can appear suddenly and show rapid
development.

If acute kidney failure causes continually decreased kidney function, it is called

chronic kidney failure.

Chronic kidney failure can also be the result of a gradual decline in kidney function
over a long period of time. On these occasions, the kidneys are irreversibly damaged and
never regain their function.

When kidney function is deteriorating, this can be checked by measuring falling

creatinine clearance. As creatinine clearance decreases, the concentration of creatinine in
the blood will increase.

Patients suffering from end-stage renal failure have a glomerular filtration rate of
less than 5 ml/min and require renal replacement therapy, such as kidney transplant or
dialysis, to survive.

When the kidneys fail, urine production is reduced and the components of urine,
therefore water and waste materials, accumulate in the body.

As kidney function deteriorates, disorders can develop in most of the body's

important systems; a syndrome that is called uremia. Common symptoms are fatigue,
anorexia, nausea. A characteristic sign of severe uremia is “coffee-au-lait” colored skin. If
untreated, uremia can lead to death.

An important disease that can lead to chronic kidney failure is glomerulonephritis

(inflammation of the glomeruli). This term refers to a variety of inflammatory diseases that
affect the glomeruli.

Another important cause of kidney failure is old-fashioned diabetes mellitus, which

causes structural damage to the kidneys. To prevent these changes, careful control of
blood glucose levels is believed to be of great importance.

Apart from those mentioned, there are many other causes.

Infections that ascend through the urinary region can reach and attack the renal
pelvis in some cases, causing pyelonephritis.

Long-term hypertension can result in hardening of the small blood vessels in the
kidney, or nephrosclerosis.

Some congenital diseases lead to the destruction of the kidneys, for example,
polycystic kidney disease.

Major diseases leading to chronic kidney failure.

chronic pyelonephritis
Mellitus diabetes
• TESTS AND EXAMS:
High blood pressure is almost always present during all stages of kidney disease.

A neurological evaluation may show signs of nerve damage. The doctor can hear
abnormal heart or lung sounds with a stethoscope.

A urine test may reveal protein or other changes. These changes can appear
anywhere from 6 months to 10 years or more before symptoms appear.

Tests to check how well your kidneys are working include:

+ Creatinine levels.
+ BUN.
A- Creatinine clearance.

Chronic kidney disease changes the results of some other tests. Each patient
needs to have the following checked regularly, as often as every 2 to 3 months when
kidney disease worsens:

^ Potassium.
 ^ Sodium.
^ Albumin.
^ Phosphorus.
^ Calcium.
^ Cholesterol.
^ Magnesium.
^ Complete blood count (CBC).
^ Electrolytes.

The causes of chronic kidney disease can be seen in:

^ CT scan of the abdomen.

^ MRI of the abdomen.
^ Abdominal ultrasound.
^ Kidney scan.

This disease can also change the results of the following tests:

^ Erythropoietin.
^ PTH.
^ Bone density examination.

g TREATMENT:
Controlling blood pressure is the key to delaying further damage to the kidney.

^ Angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin

receptor blockers (ARBs) are most commonly used.
^ The goal is to maintain blood pressure at or below 130/80 mmHg.

Other tips to protect your kidneys and prevent heart disease and stroke:

^ No smoking.
^ Eat foods low in fat and cholesterol.
^ Get regular exercise (talk to your doctor or nurse before you start).
^ Take cholesterol-lowering drugs, if necessary.
^ Keep blood sugar under control.

Always talk to your nephrologist before taking any over-the-counter medications,

vitamins, or herbal supplements. Make sure all the doctors you see know that you have
chronic kidney disease.
 Other treatments may include:

^ Special medications called phosphate bonds, to help prevent phosphorus

levels from becoming too high.
^ Treatment for anemia, such as extra iron in the diet, iron tablets, special
injections of a medicine called erythropoietin, and blood transfusions.
^ Extra calcium and vitamin D (always talk to your doctor before taking them)

You may need to make some changes to your diet. See: diet for chronic kidney
disease for more details.

^ It may be necessary to limit fluid intake.

^ Your doctor may recommend a low-protein diet.
^ You may need to restrict salt, potassium, phosphorus, and other electrolytes.
^ It is important to get enough calories if you are losing weight.

There are different treatments available for problems with sleep or restless leg
syndrome.

Patients with chronic kidney disease should keep important vaccinations up to date,
such as:

^ Pneumococcal polysaccharide vaccine (PPV)

English).
^ Flu vaccine.
^ H1N1 (swine flu) vaccine.
^ Hepatitis B vaccine.

^ Hepatitis A vaccine.

When the loss of kidney function becomes more severe, you will need to prepare
for dialysis or a kidney transplant.

^ The timing of starting dialysis depends on different factors, including

laboratory test results, severity of symptoms, and readiness status.
^ You should start preparing for dialysis before it is absolutely necessary.
Preparation includes learning about dialysis and the types of dialysis
therapies, as well as placing a dialysis access.
^ Even those who are candidates for a kidney transplant will need dialysis while
 they wait for a kidney to become available.

8 FORECAST
Many people are not diagnosed with chronic kidney disease until they have lost
much of their kidney function.

There is no cure for chronic kidney disease. Without treatment, it usually

progresses to end-stage kidney disease. Lifelong treatment can control the symptoms of
this disease.

Possible complications

^ Possible complications.
^ Anemia.
^ Bleeding from the stomach or intestines.
^ Bone, joint or muscle pain.
^ Changes in blood sugar.
^ Damage to the nerves in the legs and arms (peripheral neuropathy).
^ Dementia.

^ Fluid buildup around the lungs (pleural effusion).

^ Cardiovascular complications.
o Congestive heart failure.
o Coronary artery disease
o High blood pressure.
or Pericarditis.
o Stroke.
^ High levels of phosphorus.
^ High potassium levels.
^ Hyperparathyroidism.
^ Increased risk of infections.
^ Liver damage or failure.
^ Malnutrition.
^ Spontaneous abortion and sterility.
^ Seizures.
^ Weakening of bones and increased risk of fractures.
8 PREVENTION.
Treating the condition that is causing the problem can help prevent or slow chronic
kidney disease. Diabetics should control their blood sugar levels and blood pressure, as
well as refrain from smoking.
 CHAPTER 3 – KIDNEY TREATMENT

& KIDNEY THERAPY.

Before 1960 all patients suffering from chronic kidney failure died of uremia. In
recent decades, different therapies have been developed successfully.

When kidney function has decreased to 10% of its normal capacity, the patient may
be prescribed a diet with reduced protein, sodium and potassium content.

Low protein diet means less nitrogenous waste products in the blood, such as urea
and creatinine. The buildup of sodium and potassium in the body can lead to fluid retention
and cardiac arrhythmia. Maintaining a strict diet can delay the start of dialysis treatment.

Other components of this type of conservative treatment are antihypertensive

medications to control blood pressure and bicarbonate medication to correct acidosis or
ion exchange resin powders to prevent hyperkalemia.

When only 5% of kidney function is finally left, it will be necessary to start dialysis
treatment, either with hemodialysis (HD), or peritoneal dialysis (PD), or provide a new
kidney for transplant.

In hemodialysis treatment, blood is purified outside the body (extracorporeally) by

an artificial kidney. In principle, blood flows along one side of a thin membrane, through
which waste products pass into a stream of liquid on the other side.

Normally hemodialysis is carried out three times a week for 3 to 5 hours. The
variations of this treatment are hemofiltration (HF) and hemodiafiltration (HDF).
 In peritoneal dialysis, the membrane that lines the abdominal cavity (the
peritoneum) serves as a substitute for the kidney. Normally, about 2 liters of fluid are
instilled through a catheter into the abdominal cavity. Waste materials from the blood pass
into solution by diffusion.

After a certain time the liquid is drained and replaced with new solution.

In contrast to hemodialysis, peritoneal dialysis is almost always a continuous

therapy (continuous ambulatory peritoneal dialysis), that is, the patient carries the dialysis
fluid in the abdominal cavity all the time.

After a successful kidney transplant, the patient can return to an almost normal life.

The problems they present are mainly the difficulties in finding a suitable kidney,
and the risk of rejection.

The kidney can be taken from a living donor, preferably a close relative, or from a
deceased person (cadaver kidney). What is truly decisive is that the donor kidney is
accepted by the recipient's body.

As in the case of blood transfusions, it is important to match the blood type, but
also that the tissue type corresponds as exactly as possible.

After the operation the recipient's immune system has to be suppressed, otherwise
it will be strongly activated by the presence of the foreign tissue, and rejection will most
likely occur.

Strongly immunosuppressive medications are normally used, such as cyclosporine

A and steroids.

The graft is placed in the lower front part of the abdomen, outside the peritoneum,
an apposition that is easily accessible for surgery and examinations. The vessels are
connected to the pelvic vessels, and the ureter is connected to the urinary bladder.

The patient's kidneys are frequently left in their usual place.

Currently, kidney transplants are almost always successful with one-year graft
survival of more than 90% with kidneys from living donors and 70% with cadaveric kidneys.

In the case of a kidney transplant, the graft is placed in the lower front part of the abdomen,
a location easily accessible for surgery and examinations. The patient's own kidneys can be left in
place.
& HEMODIALYSIS.

a) Hemodialysis concept.

HD is based on the physical and chemical laws that

govern the dynamics of solutes through semipermeable
membranes, taking advantage of the exchange of solutes
and water through a membrane of this type.

In this way by transportation

ultrafiltration, the volume of body fluids will be adjusted,
thus replacing the excretory function of the kidney. The rest
diffusive and convective, are extracted the retained solutes and through
of the functions of which there is a progressive knowledge, they must try to replace in
another way, since only the transplant can fully perform them.

b) History of hemodialysis.

If anyone deserves to be considered the father of dialysis, there is no doubt that

that honor must fall to a Scottish researcher Thomas Graham, (1830) who at the age of 25
was appointed professor of chemistry at Anderson University in Glasgow and 7 years later
to University College London.

Graham laid the foundation for what later became colloid chemistry and among
other things demonstrated that plant-based parchment acted as a semipermeable
membrane. He stretched this parchment over a cylindrical wooden frame and placed it
over a container of water; Then he placed a liquid containing crystalloids and colloids in it,
like a sieve, and was able to verify after time that only the crystalloids passed through the
parchment.

In another similar experiment he used urine, he showed that the crystalloid matter
of this urine was filtered into the water, since after evaporating it, a white powder that
looked like urea remained at the bottom.

Graham gave the name DIALYSIS to this phenomenon.

It was not until 50 years after Thomas Graham's experiments that the practical
clinical application of his discovery took place.
 In 1913 John Abel and his collaborators performed the first dialysis in animals and
described a series of experiences with a primitive device that they called ARTIFICIAL
KIDNEY.

But it was Dr. George Haas who, applying the ideas of Abel and colleagues,
managed to practice the first dialysis in a human being in 1926. The dialysis lasted 35
minutes and apart from a febrile reaction, the patient tolerated the procedure well. Logically
it had no therapeutic effects.

Subsequently, Haas would perform another 2 dialysis sessions, with 2 uremic

patients and precisely using the heparin recently discovered by Howell and Holt, although
with great problems in its purification.

It was in the 1940s with the appearance of Koll's rotary kidney and that developed
by Murray, that HD became an accepted procedure for clinical application.

But despite Koll's success, HD was not widely disseminated because its
implementation presented numerous technical problems, since effective anticoagulation
had not been achieved, numerous infections appeared and, above all, there was no
effective and stable vascular access that would allow apply HD as another replacement
treatment.

In 1955 HD was only applied in a few hospitals and in exceptional cases since
many considered it a laborious, expensive and dangerous experimental procedure.
However, the successful use of this technique in numerous cases of ARF provided a new
impetus for its development.

The HD. In patients with CKD, it was necessary to wait until 1960, although Quinton
and Scribner implanted the first external shunt, built with thin Teflon walls to be inserted
into the radial artery and the cephalic vein of the

patients, made possible repeated access to their circulation and the birth in 1961 of the
first HDP program, the first outpatient HD unit in history being created in Seattle (at the
University of Washington hospital).

From this moment on, the natural evolution of CKD would no longer be the same,
because a procedure had been standardized to replace the purifying function of the kidney
and prevent the death of these patients. The treatment of CKD with HDP was born. The
diffusion of this therapeutic procedure was extraordinary and in a few years numerous HD
units were created.

This Scribner shunt had the advantage of being used immediately after insertion
and of being used repeatedly for relatively long periods of time, which allowed the birth of
the HDP program.

Despite this, the problem of finding adequate vascular access had not been
completely resolved since this shunt limited the patient's movements, required meticulous
cleaning care, and presented frequent infections and thrombosis.

In 1966, a historic event occurred when Cimino and Brescia described the internal
arteriovenous fistula (IAVF), which resolved the problems that had remained pending with
the Scribner shunt, since it allows obtaining adequate blood flow, presents low incidence of
infectious and thrombotic processes and is well tolerated by the patient.

c) Indication for hemodialysis.

To carry out treatment with HDP, it must be previously decided when to start said
treatment, to whom it should be applied and how the patient should be managed before
starting treatment.

Currently, the indication to begin treatment with HD is clear in those cases in which
conservative treatment fails.

control the symptoms of IR and the patient feels unable to lead a normal life.

Problems arise when the patient with CKD does not present clear symptoms of
uremia. For this reason, Creatinine Clearance has been sought as the objective parameter
to define the ideal time to start HD.

We, like the majority, estimate that HD should begin when creatinine clearance is
between 5 and 10 ml/minute, choosing the appropriate moment in each case, according to
the clinical situation and the presence or absence of uremic symptoms. .

The second problem to be resolved is the indication or contraindication of HD

treatment, and the decision must be made as to whether or not it should be included in the
HD program.

Currently, the relaxation of criteria is almost absolute and HD is considered

indicated in almost all patients with CKD.
 This has led to an increase in the total number of patients who begin HD treatment
annually and an increase in the number of those who present clear limitations in their
health status and who cannot be transplanted, which represents a percentage increase in
the so-called high-risk patients. risk.

d) Patient management before starting hemodialysis.

When the patient with CKD has a creatinine clearance of less than 20 ml/min. It is
necessary to take extreme controls to know the evolution of kidney function, monitor the
possible appearance of factors that may aggravate it, but that may be potentially
reversible, and avoid the administration of nephrotoxic drugs.

In this situation, it is advisable for the patient to be informed of their situation and
the future evolution of their disease, making them aware of the possibility of being treated
with HD in the future.

You should be informed of the reality of HD and reassured that HD can offer you a
long, and despite the limitations, reasonably comfortable life. This information should help
the patient better understand the present and future reality and achieve a better
psychological adaptation to it.

During this phase it is advisable to allow the patient to lead a lifestyle that is as
normal as possible without any limitations other than those required by the patient's clinical
symptoms or when it comes to activities that may entail special risks in themselves.

The diet should tend to cover the patient's caloric and protein needs. You should
receive a normocaloric diet and an amount of protein, around 1G/Kg of weight/day to avoid
malnutrition.

The main problem during this period is providing the patient with effective and
stable vascular access. The most suitable is the FAVI. As it takes several weeks to mature,
it is advisable to do it in advance of the scheduled date to start HD.

In most patients, the most appropriate time to perform AVF is when the patient has
a creatinine clearance of around 10 ml/min. However, it should be performed earlier in
those patients who have difficulties achieving a good fistula. , in which a more rapid
deterioration of renal function can be presumed and in which an earlier start with HD is
advised.
8 HEMODIALYSIS: TREATMENT PRINCIPLES.
The goal of dialysis is to replace the excretory function of the kidneys. Through
artificial means we wish to eliminate excess fluid and superfluous solutes from the body.

During a hemodialysis treatment, the patient's blood is circulated outside the body
through an artificial kidney, the dialyzer. In principle, a dialyzer contains two chambers
separated by a membrane, one of them flooded with blood and the other with a special
dialysis fluid. The membrane is semipermeable, thus allowing the passage of water and
solutes up to a certain size. Extracorporeal circulation is controlled by a dialysis machine,
which also prepares the dialysis fluid.

When treatment begins, the patient's blood contains excess fluid and waste
products. To remove the liquid, a pressure gradient is applied across the membrane in the
dialyzer. This forces water to leave the blood, penetrate the membrane, and enter the
dialysis fluid through the process of ultrafiltration.

The amount of ultrafiltered fluid during the entire treatment session should
correspond to the excess volume.

As the dialysis fluid is freed of waste products, a concentration gradient is created

across the membrane. This causes waste products to diffuse from the blood through the
membrane and into the dialysis fluid.

The result of the treatment is that the blood volume is adjusted, and waste products
are eliminated from it. The two processes of liquid removal (ultrafiltration) and solute
removal (diffusion) normally take place simultaneously.

This flow chart shows the extracorporeal circuit during a hemodialysis treatment. In the blood circuit
(left) blood is pumped through the dialyzer. In the fluid circuit (right) dialysis fluid is prepared and
pumped through the dialyzer.
& SUMMARY OF PARAMETERS IN HEMODIALYSIS.
To carry out an effective hemodialysis session, sufficient removal of fluid and
solutes must be ensured. These two processes are controlled by different treatment
parameters.

Liquid removal is determined by the following two parameters:

4- Total pressure gradient:
The ultrafiltration rate is directly proportional
to the total pressure gradient across the membrane,
i.e., the true transmembrane pressure.
Fluid removal rate The fluid removal
rate during a hemodialysis treatment is
determined by the following parameters: •
Total pressure gradient.
• Dialyzer characteristics.

The total pressure gradient consists of the

hydrostatic pressures in the blood and dialysis fluid
compartments of the dialyzer, as well as the osmotic
pressure exerted by plasma proteins in the blood (oncotic pressure).

+ Dialyzer Features:

Different membranes have different ultrafiltration capacities, which is why they

require very different pressure gradients to offer the same liquid removal.

Membrane type and surface area are the most important determinants.

The rate of solute removal by diffusion is determined by the following four

parameters:

^ Blood flow, Qs:

In standard hemodialysis, the Qs is normally 200-300 ml/min.

By increasing Qs, greater clearance is achieved, especially of small molecules,

such as urea and creatinine. For larger molecules an increased Qs has little effect on
clearance.

^ Dialysis fluid flow, Qd:

 For optimal solute removal, the Qd should be approximately twice the blood flow
rate. Almost all dialysis machines are graduated to offer a Qd of 5oo ml/min, which in
practice is sufficient for blood flows of up to 300-350 ml/min.

^ Concentration gradient:

For small molecules, diffusive transport is directly proportional to the concentration

gradient across the membrane.
The gradient is maintained by the flow of blood and dialysis fluid.

^ Dialyzer Features:

Different dialyzers have different performance characteristics.

Membrane type, thickness and area are the most important determinants of
diffusive solute removal.
The dialyzer flow geometry and flow distribution also affects solute transport.
The solute elimination rate by diffusion during a
hemodialysis treatment is determined by the
following parameters:
• Blood flow rate, Qs.
• Dialysis fluid flow rate, Qd.
• Concentration gradient between blood and
dialysis fluid.
• Dialyzer characteristics.
Finally, solute removal by convection is
determined by the ultrafiltration rate and
sieving properties of the membrane. This is
usually of minor importance in standard
hemodialysis.
 CHAPTER 4 – PRINCIPLES OF TRANSPORTATION

• DIFFUSION.
The molecules of a gas mixture or solution are never at rest, but are vibrating,
pushing and colliding. This proper motion, which does not require external forces but is
dependent on temperature, is called Brownian motion.

As a consequence, a certain component of a solution that is abundant in one area

will diffuse to other areas where the concentration is lower. There is simply a tendency in
the composite body to spread as evenly as possible throughout the defined space.

This phenomenon is known as diffusion.

In solutions, the term diffusion is used to describe the physical process in which
dissolved solutes move from an area of high solute concentration to another area of lower
solute concentration in order to eventually reach equilibrium.

The driving force is the concentration gradient, and net transport continues until
equilibrium has been reached and the solute concentration is the same everywhere.

The degree of diffusion depends greatly on the size of the solute. Large molecules
move more slowly than small ones, so their rate of diffusion is slower. We can conclude
that the larger the solute, the longer it takes until equilibrium is reached.

Diffusion is a very rapid process over distance. However, when it comes to a

distance of a few centimeters it is an extremely slow process, requiring days or more to
level out a concentration gradient.

Suppose we create two separate compartments of liquid by introducing a

membrane that offers no obstacles to small molecules but excludes large ones. A
selectively permeable membrane is called semipermeable.

Then we can observe that the small solutes move freely between the
compartments, behaving as if the membrane did not exist. The process is analogous to
diffusion in a solution without a membrane, and the driving force is the concentration
gradient.

Medium-sized molecules are slowed down by the membrane and large solutes are
completely excluded from the other compartment.

The movement of solutes will continue until the concentration gradient is

maintained.
 If the liquid on the low concentration side of the membrane is continually replaced
with fresh solution, the process will continue indefinitely.

This process, in which solutes diffuse through a semipermeable membrane,

illustrates the original meaning of the word dialysis, although this limited definition of the
word is rarely used today.

Diffusion: the movement of solutes from an area of high concentration of

solute to one of lower concentration.

Diffusion is
defined as the
movement of solutes
from an area of high
concentration of

solute to one of lower concentration. A membrane that is completely permeable to the solute has
little effect on diffusion. These containers, in which the solutes are represented by black dots,
schematically illustrate the principle. Note how the initial concentration gradient is gradually
eliminated as the solutes spontaneously diffuse into the liquid.

& OSMOSIS.
We have two solutions separated by a semipermeable membrane. The solutions
are quite different, as one contains solutes that are too large to pass through the
membrane and the other contains pure water. Since large solutes cannot move across the
membrane, the only way to balance the solutions is for water to move.

Osmosis is the name of this physical process in which water moves from an area of
high concentration of water (that is, of low concentration of solutes) to an area of low
concentration of water (that is, of high concentration of solutes). ).

The water concentration of a solution depends on the total concentration of solutes,

regardless of the type of solutes. To describe the total concentration of solute particles in a
solution, we use the term osmolarity (osmol/liter).

A high osmolarity means a low concentration of water.

Osmotic pressure is the hydrostatic pressure needed to prevent fluid flow caused
by the osmolarity gradient; The greater the difference in osmolarity, the greater the osmotic
pressure.

A solution that contains more solutes than a living cell is defined as hypertonic; A
cell placed in a hypertonic solution will shrink as water flows out of it.

A hypotonic solution has a concentration of solute particles that is lower than that
of a cell, so a cell placed in such a solution will swell and sometimes even burst.

When the concentration of solutes is equal on both sides of the membrane, the
solution is isotonic.

Osmosis can be observed whenever the solutes are so large that their transport across the
membrane is prevented or simply

hindered (the so-called non-permeable solutes). As long as there is a water concentration

gradient across a membrane, water will tend to move. If we have a system in which solutes
cross the membrane freely, the concentration gradient will be balanced by solute diffusion
rather than water transport.

Inverse osmosis:

It is a process used for water purification, in which it can be said that osmosis has
been reversed. The impurified water is separated from the purified water by a membrane
with very small pores. A hydrostatic pressure that is greater than the osmotic pressure is
applied on the impurified water side, that is, on the side with low water concentration. In
this way, water is forced from an area of low water concentration to an area of higher water
concentration, the result being highly purified water.

Osmosis: The movement of water across a membrane from an area of high concentration to an
area of low water concentration.

When a solute is too large to pass through a semipermeable membrane, the other component of the
solution, i.e. water, will move instead. This will continue to occur until the hydrostatic pressure of the
water column formed equals the osmotic pressure.

Osmotic pressure P is defined as the hydrostatic pressure needed to prevent the flow of
water.
& ULTRAFILTRATION:
Ultrafiltration is a physical process in which a liquid is transported through a
semipermeable membrane. The driving force is a pressure gradient across the membrane.
The pressure gradient can be applied in three different ways.

A hydrostatic pressure, created for example by a piston or a pump, can be either

positive or negative.

A positive hydrostatic pressure is created when liquid is forced through the

membrane and a negative hydrostatic pressure is created when liquid is absorbed through
the membrane.

In hemodialysis, the combination of the two positive (blood side) and negative
(dialysis fluid side) pressures constitute the total pressure gradient over the membrane.
This pressure gradient, known as transmembrane pressure (TMP), is used to remove
excess water.

The third alternative is to create an osmotic pressure. By adding a high molecular

weight solute, that is, a non-permeable solute, to the “suction side” of the membrane, the
liquid will move from the high water concentration compartment to the low water
concentration compartment. This principle is used to remove fluid in peritoneal dialysis, in
which glucose is the solute that provides osmotic pressure.

Ultrafiltration: The movement of liquid across a membrane caused by a pressure gradient.

Ultrafiltration is the process in which liquid is transported through a semipermeable

membrane. The driving force is a pressure gradient across the membrane that can be created in
different ways.

a) A positive pressure: on the left, represented by the large arrow, will push the liquid
through the membrane.
 b) A negative pressure: in the right behavior, it will draw liquid through the membrane.
c) Non-permeable solutes create osmotic pressure. In such a case, water will move
from an area of high water concentration to the area of low water concentration.

8 CONVECTION:
Suppose we put a cube of sugar into a cup of coffee, in which it dissolves to the
bottom. If we waited for the sugar to diffuse into the cup by diffusion alone, the coffee
would certainly cool down. So, to quickly achieve a uniform concentration of sugar in the
cup, we use a teaspoon to stir the coffee, causing the liquid to move in a turbulent manner.
In this case, the sugar molecules do not move by diffusion, but are transported by the
movement of the solvent, water.

This same phenomenon can be observed when a solution passes through a

semipermeable membrane, dragging along the dissolved substances. Convection is the
term used to describe the movement of solutes across the membrane caused by the
passage of solvent. Hence the term “solvent carryover”.

Solute transport is directly proportional to solvent transport, and solvent transport

depends on the pressure gradient.

For the displacement of very large solutes, but for which the degree of diffusion is
extremely slow, convection is the only transport principle.

Depending on the size of the membrane pores, solutes of different molecular

weight will pass through it to a different extent.

Small solutes, not impeded by the membrane, will cross the membrane in a certain
proportion and thus in a concentration equal to that of the original solution. However, for
large solutes the membrane will act as a sieve, and certain large solutes will not be able to
pass through the membrane at all.

Convection: the movement of solutes with a flow of water, solvent entrainment, that is, the
movement of solutes permeable to membranes with ultrafiltered water.
When a solution moves, the solutes dissolved in it will circulate, a process known as convection.
This phenomenon can be observed during ultrafiltration, in which membrane-permeable solutes will
accompany the ultrafiltered water through the membrane.
CHAPTER 5 – THE DIALYZER, DIALYSIS MACHINE

& THE DIALYZER.

The first disposable artificial kidney was built in the mid-1960s.

Currently the term dialyzer is used in preference to artificial kidney.

The dialyzer is a device through which blood and dialysis fluid flow, separated by a
semipermeable membrane.

Some type of support structure is also needed, as well as an exterior covering. A

modern dialyzer is so small that it can be held in your hand.

There are two basic types in use: plate and capillary.

The most essential quality of a dialyzer is its performance, that is, how effectively it
purifies the blood. Another property is its compatibility, that is, that contact between blood
and foreign materials in the dialyzer does not cause any type of clinically important
adverse reactions.

To achieve these selected properties, several aspects have had to be considered.

The vital component of the dialyzer is the membrane, of which its permeability and
compatibility properties constitute the first priority.

In order to achieve the best performance from a membrane, a dialyzer design will
be chosen that perfects the exchange process between blood and dialysis fluid, and
provides adequate membrane surface area. The internal liquid volume and flow resistance,
as well as the size and weight of the apparatus should be reduced to a minimum.

The final product of the manufacturing process must not contain any particles or
residues of unhealthy substances, such as sterilization agents.
 The performance of each individual dialyzer will be in reproducible accordance with
the specification.

Considering that a hemodialysis patient is dialyzed about 150 times a year, the final
cost of the dialyzer is also of interest, although this generally represents less than 10% of
the total cost of the treatment.

The different characteristics of the dialyzer

interact to determine its specific performance.

The same properties act reciprocally to

offer the dialyzer some compatibility in its
interaction with the human body.

B DIALYZER DESIGN:
Over the years, several different dialyzer designs have been studied and tested in
order to refine performance.

Two different types are used today:

• The capillary dialyzer.

• The plate dialyzer.

They have four external connectors, two for the entry and exit of the dialysis fluid
and two for the entry and exit of the blood.

All dialyzers share the same basic characteristics.

 Blood and dialysis fluid circulate in different channels separated by a membrane.
The geometry of these flow paths must be designed so that the blood and dialysis fluid are
in contact with a large area of the membrane surface. It is important that the flow
resistance in both parts is low.

Blood and dialysis fluid flow in opposite directions, countercurrent flow. Thus, in this
way, the blood always finds a less dirty dialysate. This maintains the concentration
gradient from start to finish throughout the dialyzer.

The internal volume (especially that of the blood compartment) has to be small
since the volume of blood outside the body must be minimized. The volume of blood
needed to fill the blood compartment is called the priming volume, normally amounting to
75-100 ml. in normal size dialyzers.

Residual blood volume is the amount of blood remaining in the dialyzer after
treatment and following a final saline rinse. This volume is negligible in modern dialyzers.

In the capillary dialyzer, also called hollow fiber dialyzer, the dialysis membrane is
in the shape of a bundle of thousands of fine capillaries.

The rigid wall of the fibers prevents them from being distensible; their internal
volume is fixed and independent of pressure. The bundle of fibers is fixed and secured at
both ends of the casing, separating the blood from the dialysis fluid. For this, a fixing
material is used, usually polyurethane (PUR).

The plate dialyzer is more complex in design than the capillary dialyzer, although it
is similar in size and weight. Pairs of layers
membranes, are stratified in a block with support plates in between.

Blood is distributed to the space between each pair of membranes, surrounded by

dialysis fluid. The entire block is pressed together into an airtight structure within the
container; Very little fixing material is needed.

The support plates have a surface structure that creates a specific flow pattern in
the dialysis fluid and blood channels. This non-laminar flow causes “internal agitation” that
ensures good transport properties in the dialyzer.

The plate dialyzer is distensible, its internal volume adapts to the pressure
conditions.

Clinical experiences also show that the tendency to clot is reduced in plate
dialyzers.

Cross sections of roads

of blood in plate dialyzers.

And capillary dialyzers.

B TYPES OF MEMBRANES:
A membrane is defined as a thin film of a natural or synthetic material that is
semipermeable, allowing certain substances to pass through but not others. An example in
nature is the glomerular basement membrane in the nephron.

To produce an ideal membrane for hemodialysis, the permeability properties for

solutes and fluids should resemble those of the natural kidney. Waste products of varying
molecular weights could easily penetrate while essential plasma proteins, such as albumin,
would not be allowed to escape from the bloodstream.
 The membrane does not have to contain materials or additives from the
manufacturing process or other dangerous substances. To avoid breakage, high
mechanical resistance is also needed.

Dialysis membranes consist of polymers. A polymer can be described chemically

as a repeating structure of one or more small molecules (monomers), in the same way that
a chain consists of links.

Many polymers can be found in nature, for example cellulose, which is a plant
material that can be converted into paper, cotton fabric or cellophane.

The units of cellulose are glucose molecules, which are linked together in a chain.

Synthetic polymers are what we normally call “plastics”. These represent a wide
range of chemical structures and can show very different properties.

Dialysis membranes are divided in frequency into two different groups:

• Cellulosic membranes, for which the raw material is cotton. “Cuprophane” is a

widely used dialysis membrane. In some cellulosic membranes, the basic
cellulose is chemically modified in order to create new surface and
permeability properties, for example cellulose acetate and Hemophan.
d Synthetic membranes, which represent many different chemical
compositions.

Some types, so-called copolymers, have not just one but two molecular
units, selected to combine certain properties of two different polymers in a
single membrane, for example “Gambrane”.

& MEMBRANE PERMEABILITY.

The permeability properties of a membrane are described by the thickness of the
membrane and the size and number of its pores.

More and larger pores, as well as a thinner membrane, offer greater permeability.

Diffusive permeability describes the rate of diffusion across a membrane in

response to a certain concentration gradient across the membrane. The larger the solute
and the more compact the membrane, the slower the diffusion.
 An important parameter is also the thickness of the membrane: the longer the
distance that the solute has to travel through the membrane material, the longer it takes to
pass.

Hydraulic permeability describes the rate of water transport (ultrafiltration) through

the membrane in response to a certain pressure gradient (PTM) across the same
membrane.

The relationship between UF and PTM is most often linear in the clinical operating
range of UF. It can be easily described in mathematical terms by a coefficient, the UF
coefficient, for which the unit is normally ml/h, mmHg, m2.

Most membranes can be classified into one of these two groups:

^ Low flow membranes with low water permeability. The UF coefficient is

between 2 and 10 ml/h. The membranes of this group are for example
“Cuprophan” and “Gambrane”.
 ^ High flow membranes with much higher hydraulic permeability. The UF
coefficient is between 20 and 50 ml/h. Examples of these membranes are
“AN 69” and polyamide.

Low flux and high flux membranes with completely different properties, made from
the same membrane material. Examples are polysulfone and PMMA.

The sieving properties of a membrane describe the permeability to solutes during

ultrafiltration, that is, during convective transport.

Solutes that are smaller than the pores of the membrane pass through it without
problems. Permeability decreases with increasing molecular weight.

The cutoff point of the membrane is defined as the molecular weight at which only
10% of the solutes cross it. This value provides an estimate of the upper limit of membrane
permeability.

The thinner the membrane, the lower the

resistance for a solute

can spread through it.

low flow

Schematic comparison of a low flux

membrane and a high flux membrane.
• STERILIZATION METHODS.
The internal parts of a dialyzer are in direct contact with the blood. It is important
that the dialyzer be sterile, that it does not contain living microorganisms.

The manufacturing process of sterile equipment has to include practical hygienic

production to reduce the total number of microorganisms, followed by effective destruction
or elimination of all remaining living organisms.

The most common way to sterilize disposable medical equipment is to use the
bactericidal gas ethylene oxide, EtO. This method is considered safe and economical, and
is based on long-term experiences. The environmental problems of EtO have been solved
by using a mixture of 10% EtO in carbon dioxide, which after being used, is transformed
into a harmless waste product through a purification process.

EtO gas is capable of penetrating all areas of the dialyzer, even if it is packaged
before sterilization. It is then quarantined for a period of time, usually 1 to 2 weeks, during
which deaeration takes place.

It has been shown that, despite deaeration, some EtO residues can remain in the
dialyzer for a long time, especially in the fixation material (polyurethane, PUR) in capillary
dialyzers.

In a sensitized patient, the small amount of EtO that may escape from the dialyzer
into the blood during treatment may be enough to cause an allergic reaction. For plate
dialyzers the risk of such hypersensitivity associated with EtO is considerably lower, since
they do not contain fixation material, so they retain less EtO.

Hypersensitivity reactions to materials sterilized with EtO are very rare, as long as
rinsing is carried out according to the manufacturer's instructions before the patient is
connected to the blood lines and dialyzer.

Alternatives to EtO sterilization are becoming more common. Sterilization by means

of gamma radiation is also easily achievable, also for prepackaged dialyzers. It is possible
to carry out an immediate release of the product. However, there have been reports that
the high energy of radiation has induced the formation of reactive chemicals or caused the
decomposition of polymeric materials. To minimize these effects, the dialyzer is almost
always filled with water before proceeding with gamma sterilization.

Steam sterilization (autoclave) is carried out at high temperature and high pressure.
Since no chemicals are used, this process is non-toxic and allows the immediate release of
the product. It is considered to be more complicated and expensive than EtO sterilization.

Many dialyzer membranes and other materials cannot withstand high temperatures,
so steam sterilization can destroy them or modify their performance.

Three methods are used for dialyzer sterilization:

Typical symptoms of a hypersensitivity reaction probably caused by ethylene oxide (EtO).

sneezing )) suffocation

chest pressure i lack of breathing

warmth sensation

itch
8 CHOOSING THE SUITABLE DIALYZER:
Today a wide variety of dialyzers of different designs, sizes and membrane
materials are available.

To make the ideal choice for each individual patient, it is necessary to make a
careful needs analysis.

The performance and compatibility of a dialyzer depend on the reciprocal

relationship between membrane material and structure, dialyzer design, and sterilization
mode.

They are highly dependent on the patient's condition and other treatment factors
such as blood flow, dialysis fluid composition and temperature, dialyzer flushing procedure,
and heparinization.

Consequently, the choice and handling of the dialyzer will have to be done with
caution and care.
8 DIALYSIS MACHINE.
The dialysis machine is sometimes called “the artificial kidney.”

The artificial kidney would be the dialyzer, since it is in this where blood purification
takes place.

The dialysis machine is necessary to carry out hemodialysis. If the dialyzer is the
kidney, the machine could be said to correspond to the rest of the body, supplying blood to
the kidney and controlling the entire process.

There are many types of dialysis machines commercially available, and although
some have different techniques, they all have the same function.

The functions of the dialysis machine can be divided into three categories:
 • Basic functions:

They are responsible for the circulation of blood and dialysis fluid through the
dialyzer. This can be accomplished with relatively simple equipment.

Blood should flow through the extracorporeal circuit in a controlled manner. The
dialysis fluid will be prepared with the correct composition and temperature and then
pumped through the fluid compartment of the dialyzer at a certain flow rate and pressure.

• Security features:

They monitor and control all processes to offer patient safety. Rigorous safety
requirements currently determine the use of the advanced high technology of a modern
dialysis machine.

When the alarm limits indicated for the different parameters are exceeded, the
machine will normally give an alarm signal, while the patient is automatically disconnected
from the system.

• Optional features:

Additional functions according to the specific needs of each operator, for example
an extra pump for single needle dialysis.

When examining the functions of the dialysis machine we will first describe the
blood circuit and then the fluid circuit. These functions are almost always integrated into a
machine, sometimes they are separated into a blood monitor and a fluid monitor.
 CHAPTER 6 – TREATMENT PREPARATIONS

The dialysis machine is in standby status after a disinfection process.

The nurse starts it and connects the concentrate. The dialysis fluid passes through
the fluid circuit for a period of time in order to achieve stable conductivity and temperature.

The dialyzer and blood lines are then connected to the machine.

The arterial end of the blood line is connected to a saline bag, hanging on its
holder, and the venous end of the blood line to a waste bag.

This is followed by filling and flushing the dialyzer and blood lines, sometimes
called the priming procedure. The liquid circuit is also connected to the dialyzer for
countercurrent flow. This may be done before or after the start of priming, depending on
the instructions for the specific dialyzer used and the unit's routines.

During this procedure the blood lines and dialyzer are filled with saline, if additional
saline is necessary to remove air and debris.

Air bubbles can cause clotting and also block the blood path in the dialyzer, which
can lead to a reduction in effective surface area.

An optimal preparation may vary between different dialyzers; The manufacturer's

recommendations should always be followed.

When the dialyzer and dialysis machine are ready for the patient, the entire system
can be left on standby with saline in the blood lines and dialysis fluid flowing through the
fluid circuit.

Immediately before the patient is connected, it is important that the blood circuit be
flushed again with a small volume of saline.

& START OF TREATMENT:

In hemodialysis, two identical fistula needles are typically used, one for the arterial
blood line and one for the venous blood line. Their plastic fins make them easier to hold
and keep in place with a piece of tape at the puncture site.

There are four sizes, from 17 gauge (the smallest 9) to 14 gauge (the largest),
indicated with a color key.

The use of large gauge needles can be difficult for the patient and staff. On the
other hand, small needles can limit the effectiveness of the treatment since they do not
allow high blood flows to be achieved.

To reduce the number of needle sticks, single-needle dialysis is sometimes used.

To prevent blood clotting in the extracorporeal circuit, an anticoagulant is needed,

the most common being heparin.

This is administered intravenously before and during treatment.

A single large dose, bolus, may be sufficient for the entire session. An alternative is
the administration of several small doses during the session, or so-called intermittent
administration. Another option is continuous administration via a heparin pump.

Low heparinization can lead to clotting in the dialyzer and subsequent blood loss.
High heparinization can cause side effects, such as internal bleeding or long-term
osteoporosis.
g PARAMETERS:
The volume of liquid that must be eliminated, the volume of UF (ultrafiltration), is
calculated based on the increase in weight since the last treatment, to which we must add
the volume of the drink consumed during the session as well as the volume of liquids. that
can be infused.

To limit the load on the cardiovascular system, the weight gained between
treatments should not exceed, if possible, 3% of body weight, about 2 kg.

Excess fluid in the body will cause high blood pressure, hypertension.

The liquid ingested should be limited to approximately 1 liter per day, including
water from food.
 A deprivation that constitutes a
difficulty for all patients with kidney failure.

The weight that must be achieved for

a patient is called dry weight. This is the
weight the patient would have if they had
normal fluid regulation. Estimation of dry
weight is difficult and depends mainly on the
experience and clinical observations of
healthcare personnel.

An overestimated dry weight (too

high) implies constant overhydration. This
can aggravate the general regulation of blood
pressure, normally associated with kidney
failure.

Furthermore, underestimated dry

weight can lead to problems with acute
episodes of low blood pressure (symptomatic
hypotension) in response to ultrafiltration.

When the UF volume is adjusted, the

machine can calculate the required UF rate
considering the treatment time, usually
between 3.5 and 5 hours. The duration of
treatment is determined by trying to combine practical and social considerations, and the
physiological limits of the rate of liquid and solute elimination.

To achieve effective solute removal, blood flow (Qs) should be kept high.

Care must be taken to ensure that the fistula can provide the chosen blood flow
without collapsing.

Another problem is that with higher Qs, recirculation can occur in the fistula, the
purified blood can find a shortcut and re-enter the arterial line instead of returning to the
body. This causes reduced solute removal.

g ACUTE COMPLICATIONS:
The most common complication during a hemodialysis session is symptomatic
hypotension, a sudden drop in blood pressure accompanied by nausea, vomiting and even
dizziness, which usually occurs late during treatment.

In these situations, the nurse usually tilts the chair or bed to place the patient's
head lower than the heart. Saline infusion rapidly increases blood volume and is usually
very helpful. The UF rate should be reduced.

For the preservation of blood pressure, the main factors are blood volume and flow
resistance in the peripheral arteries.

To avoid a drastic reduction in blood volume in connection with ultrafiltration it is

important that vascular refilling takes place simultaneously, that extravascular fluid enters
the blood.

It is essential to have a moderate UF rate, achieved, if possible, using the volume

control.

The slower the fluid removal, the lower the risk of symptomatic hypotension. To
promote vascular filling we must avoid a low concentration of sodium in the dialysis fluid,
that is, below the physiological level.

The higher the sodium level, the easier it is to eliminate

liquid, although it should be avoided since it causes thirst and therefore
excessive fluid intake.

Peripheral resistance depends on the constriction of peripheral arteries. Dialysis

with bicarbonate is superior in this regard, as acetate dilates blood vessels.

The experience of convective therapies, such as hemofiltration and isolated

ultrafiltration, shows that during these treatments peripheral resistance is maintained better
than hemodialysis.

Other acute complications are cramps and imbalance, the latter being a situation of
physiological imbalance that occurs when the elimination of small solutes is too efficient,
causing dizziness, nausea, etc.

Acute reactions result from hypersensitivity to the membrane or something else in

the dialyzer. Although very rare, they can occur early during the session, often being the
result of poor dialyzer flushing.
g ADEQUATE DIALYSIS.
To carry out a satisfactory dialysis treatment, two things must be achieved:

• Proper removal of excess liquid.

• The proper elimination of unwanted solutes.

Although it is not known what substances cause uremia, it has been seen that the
effective elimination of urea is related to satisfactory clinical results. Urea is not harmful in
itself, but it is believed to be a marker for unknown low molecular weight uremic toxins,
meaning that when urea is removed, the toxins are also removed.

The easiest way to track urea elimination is to analyze and compare blood urea
concentrations before and after dialysis.

The Ktv index is widely used for treatment planning and monitoring. The formula
consists of urea clearance, treatment time and the volume of water in the body.

The recommended Ktv for an adequate dialysis session has been much debated,
currently a minimum of 1.2 is recommended.

The Ktv index is precisely a tool to understand the relationship between patient
size, clearance and treatment time.

The best indication of the quality of the dialysis session is the patient's sense of
well-being, frequently expressed by their appetite.

Microglobulin, a small protein that accumulates in the body of patients with kidney
failure and is deposited in certain tissues as protein grains or amyloid. These deposits
cause problems in the form of pain and disability, for example in the wrist (carpal tunnel
syndrome) or in the knees and shoulders. This disease is called dialysis-related
amyloidosis.

In contrast to urea, which is efficiently removed by diffusion, microglobulin is a large

solute that is best removed by convective transport.
 CHAPTER 7 – VASCULAR ACCESS

A prerequisite for hemodialysis treatment is to conduct a portion of the patient's

blood through an extracorporeal circuit, outside the body.

For this it is necessary to have good access to the bloodstream.

The best and most used vascular access for hemodialysis is the arteriovenous
fistula.

If a peripheral artery is “shorted” and connected directly to a vein, the vein will
develop thick walls as internal pressure and flow increase; the vein becomes arterialized.

The thick walls of the vessel allow for repeated punctures with large-gauge
needles.

The blood flow in the fistula is considerable and reaches up to 1000 ml/min. From a
good fistula it would be possible to obtain an extracorporeal flow of up to 400 ml/min.
without any problem for the patient.

The most common place to construct a fistula is in the forearm, where one of the
two arteries that supply the hand is surgically connected to a superficial vein.

For the arterialization process, a maturation period of four weeks or more is

needed.

In the most favorable cases, an arteriovenous fistula can last for 10 or 15 years.

Many patients however have problems with fistula; for example constriction of the
fistula by gradual hardening and narrowing of the walls (stenosis) or obstruction by blood
clots (thrombosis). In many cases, reconstructive surgery or the creation of a new fistula in
another limb is necessary.
 In some cases the patient's blood vessels are so fragile that they do not make it
possible to create an arteriovenous fistula.

In such a case, a synthetic graft can be used to form a connection between an

artery and a vein, which can be punctured in exactly the same way as
a natural fistula but one that has a shorter duration.

For acute treatments, temporary

access is created by inserting catheters into
deep veins.

Catheters can be grafted into the

groin or neck. In this last position it can
remain for a long period of time and serve as permanent access, when there are no other
possible alternatives.

9 Vascular access for hemodialysis.

What is vascular access?

Before starting hemodialysis, there must be a way to remove blood from the body
(a few ounces at a time) and reintroduce it. The arteries and veins are typically too small;
That is why it is necessary to perform a surgical intervention to create vascular access.

There are three types of vascular access:

^ FISTULA (also called "arteriovenous fistula or AV fistula"), which is created by

joining an artery and a vein under the skin of the arm. (In most cases the
radial artery joins the cephalic vein.) When the artery and vein join, the
pressure inside the vein increases, strengthening the walls of the vein. The
strengthened vein is then able to receive the needles used in hemodialysis.
The AV fistula typically takes about 3 or 4 months to be ready for use in
hemodialysis. The fistula can be used for many years.

^ The GRAFT (also called an arteriovenous graft or AV graft), which is created

by joining an artery and a vein in the arm with a plastic tube. The plastic
tube is placed to form a U-shaped bridge under the skin to join the radial
artery to a vein near the elbow. The graft can typically be used about three
weeks after surgery. AV grafts are generally not as durable as AV fistulas,
but a well-cared for graft can last several years.
^ The CATHETER , which is inserted into a vein in the neck or under the
collarbone for temporary use, until the AV fistula or AV graft is ready for
use. The catheter is not used as a permanent access.
 You will most likely need to have some special tests so doctors can determine the
best type of vascular access for you and the best location for the access. The most
common studies are phlebography and ultrasound or Doppler ultrasound.

Life after surgical creation of a vascular access: Patients should not lift heavy
things. An injury to your arm could cause it to bleed. When you go to the doctor, do not let
anyone take your blood pressure, start an IV, or draw blood from the arm with the AV
fistula or graft.

If you have an AV graft, don't wear anything tight on your arms or wrists. Tight
clothing and jewelry can reduce blood flow to the graft, which can lead to blood clots
forming within the graft. Also do not lie down or sleep on your arm.

You should always be able to feel the vibration of blood flow as it passes through the AV
graft. This sensation is called a thrill. You may also feel a slight vibration in the graft when
you place your fingers on the skin above the graft.
 CHAPTER 8 – DIET

A kidney patient needs a carefully planned diet.

Your protein and energy intake must be balanced during the different phases of
your illness.

During the time after kidney failure has been diagnosed until dialysis begins, the
patient may be prescribed a special low-protein diet, which has been shown to reduce the
symptoms of uremia.

When a patient with kidney failure begins to receive dialysis, the conditions are very
different. In addition to an increased need for protein, many valuable nutrients are lost
during dialysis treatment and need to be replaced.

All dialysis patients are prescribed a diet with a high amount of protein. A high
protein intake improves the patient's health, and the waste products produced are removed
by dialysis.

Dietary habits almost always need to be discussed and supervised by a dietitian,

since your appetite may be suppressed by the underlying illness and by the many
medications you have to take.

Calcium and phosphorus are important substances in the body that are carefully
balanced in a healthy person. In kidney failure they are affected: phosphorus accumulates
(hyperphosphatemia), while calcium decreases (hypocalcemia).

Compensatory physiological processes ultimately cause bone diseases, for

example decalcification of bone tissue (osteodystrophy), resulting in bone fragility.

The disturbed calcium/phosphorus balance can be compensated in different ways.

The diet does not have to contain excessive amounts of phosphorus. A

phosphorus-binding medication, for example calcium carbonate, must be prescribed.
Active vitamin D improves the assimilation of calcium by the intestines.
& DO I TAKE CARE OF MY DIET?
High amounts of:

J Urea.
J Phosphorus.
J Potassium.

They are GARBAGE for the body since they can cause many imbalances because
our kidneys cannot assimilate them when we are sick.

If there is a lot in our body we notice: SOMETHING IS VERY WRONG!!!

8 WHAT IS UREA?
It's PROTEIN garbage. These proteins are found in: Eggs (95%), human milk
(95%), cow's milk (84%), fish (80%), meats (70-80%), cereals and legumes (65-75%) .

Urea: It is eliminated by the kidney but

when it is sick it cannot handle so much
“garbage” so the amounts of protein must be
respected.
EI
T

Bt¡SuRA./
OREA
& THE CARBOHYDRATES

They are found in cereals (70%), legumes (50-60%), vegetables and fruits in
smaller quantities.

And they have very important functions in our body:

^ They provide energy.

^ They regulate insulin and glycemia metabolism (blood sugar).
^ They participate in the metabolism of triglycerides and cholesterol and dietary
fiber.

& WHAT IS PHOSPHORUS?:

It is a mineral that in our body has functions of:

• Reserve, warehouse.
• Make structures.
JY regulation.

Together with calcium, they form bones and the two must be in balance in the
blood and in the intake because their uncontrolled intake can be responsible for anomalies
in the bones and arteries.

They have a lot of PHOSPHORUS and should

be avoided:

• Viscera, legumes.

• Chocolate, cocoa. (22387

• Refreshments.
Nuts.
Some fish.
J Charcuterie.
J Be careful, with some milk and derivatives.
• WHAT IS CALCIUM?
Calcium is another of the mineral elements essential for life, since it is present in the
blood, tissues, teeth and bones of our body.

While in the blood and tissues the amount of calcium is constant; In the bones it is
continually renewed since it participates in its formation and destruction.

Calcium ingested through the diet plays a very important role in this bone renewal.

In patients with Chronic Kidney Failure, daily intakes of 1000-2000 mg of Calcium are
recommended. But we must not forget that foods rich in calcium are also rich in phosphorus.

Calcium and phosphorus are 2 mineral salts that must be in continuous balance in the
blood.

There does not have to be more of one compared to the other, since this
decompensation would begin to generate
numerous bone diseases that in patients with
CKD are included under the name RENAL
OSTEODYSTROPHY.

HOW TO PREVENT RENAL OSTEODYSTROPHY?

• Add foods that are rich in calcium to our diet.

• Exposure to the sun in moderation to synthesize vitamin D, which is
responsible for absorbing calcium from the intestines and passing it into the
bloodstream and also helps fix calcium in the bones.
• Moderate physical activity.
• Absence of bad habits such as alcohol and tobacco.
• Periodic controls by blood analysis of phosphorus, calcium and parathormone
levels.
 • Control of blood glucose in diabetics.
• Pharmacological contribution under medical prescription of phosphorus binders
that sequester that phosphorus that is free/only in the blood and eliminate it
through the feces, so that this phosphorus does not go to the bone store and
steal the calcium from there

& DO I WATCH THE POTASSIUM?

Increased potassium can cause:

HEART ATTACK

Foods rich in PHOSPHORUS are usually rich in POTASSIUM:

FOODS RICH IN POTASSIUM:

Vegetable
s
Fruit

Chocolate

Cocoa

I Meat/fish concentrate

I Powdered milk

fresh
mushrooms
Tomato

Nuts

Legumes

Potato bags
HOW DO I DECREASE POTASSIUM?

3 WAYS:

1) SOAK: vegetables, fruit, potatoes, legumes. Cut into pieces, leave in water for
8 hours and discard the water.
2) BOILED: halfway through cooking, throw away the water and then cook
again.
3) FREEZING: the food loses potassium.

tr WHAT ARE VITAMINS?

Vitamins are essential compounds for the normal functioning of the body. Man cannot
manufacture them, which is why their contribution to the diet is important.

Vitamins can be of two types:

• Water soluble.
• Liposoluble.

Water-soluble vitamins: they are those that are soluble in water, and they are vitamins.
of group B and C. They are found in most foods, especially fruits, vegetables, cereals and
legumes.

Fat-soluble vitamins: are those that are transported through the fat in foods. They are
the vits: A, D, E and K. They are present in: oils, meats, fish, eggs and dairy products.

They serve to carry out the regulation of all the processes that occur in the body (they
are enzymatic cofactors). They do not provide energy.

All foods contain vitamins. There is no one that contains all of them, which is why it is
important to have a balanced and varied diet within our limitations.

Vitamin D is very important because it acts as a hormone and, together with other
substances, regulates calcium and phosphorus levels in the blood.
 Its deficiency can cause calcium loss in the bones and this leads to a greater risk of
breakage and bone pain.

SIGNS OF VITAMIN DEFICIENCY:

Vitamin B1

Beriberi, edema, ataxia, cardiomegaly

Vitamin B2

Conjunctivitis, glossitis, dermatitis, keratosis.

Vitamin C

Delayed healing, spongy and bleeding gums, scurvy, petechiae.

Vitamin A

Night blindness, incidence of infections…

Vitamin D

Rickets, osteomalacia, tetanus

Vitamin E

Neuronal degeneration, hemolytic anemia, hemorrhages, thrombocytosis, Edema.

B12 vitamin

Anemia, stomatitis, glossitis, polyneuropathy.

Vitamin K

Hemorrhages

& WHAT IS SODIUM?

The main source of sodium is common salt (sodium chloride).

Salt produces thirst, which increases fluid intake and also raises blood pressure.

It is recommended to eliminate salt from meals or reduce them as much as possible

depending on blood pressure figures.

They are foods rich in salt: sausages, salted meats, concentrated broth cubes, canned
foods, seafood...
 To enrich the flavor of your meals and as a substitute for salt, we advise you to use
spices and aromatic herbs. Do not use diet salts, most are rich in potassium.

B THE LIQUIDS.
Water is an extremely important molecule for life, both because it appeared and
evolved within it and because it is the most abundant molecule in all living beings.

It represents 60% of the body weight of a human being, a percentage that varies
depending on sex and age.

But the concept of WATER should not be understood only as that element that Mother
Nature gives us that: waters our crops, decorates our landscapes, we use it to practice sports
such as fishing or rowing and that is present in all homes by simply opening it. the tap.

For kidney patients, WATER will be any element that is liquid and moist.

Therefore, the concept of water will also encompass soups, fruit, purees, milk, coffee,
tea, gazpachos, consommés, legume broths, ice cubes, alcoholic beverages...

The amount of fluid recommended in a kidney patient will depend on the residual
diuresis (amount that is urinated in one day) and the renal replacement treatment.
 The kidney transplant patient will drink significant amounts of fluid to maintain a good
state of hydration.

The patient on peritoneal dialysis will not require control over fluid intake unless there
are fluid retention problems or high blood pressure, for which the nephrologist will limit this
intake.

While the patient who undergoes hemodialysis will have to strictly and rigorously
control his or her fluid intake throughout the day, nursing will play a very important role here,
since it will try to educate the patient in trying to understand and lead to the Practice the
advice and good habits.

B I AM IN PREDIALYSIS:
My doctor tells me that my kidneys are bad, and I want to do everything I can to delay
the progression of the disease, prevent urea from damaging my body (uremic toxicity) and be
well nourished.

During this time, urine output is normally maintained or even higher than normal, so
we will not have to worry about limiting fluid intake.

Yes, we must control the volume of diuresis (urine over 24-48 hours...it depends on
medical indications) because it will indicate the water requirements (need for liquid), which will
be the volume of diuresis plus approximately 500-1000 ml.

But a low-sodium diet (low in salt) is important, especially for

the hypertensive.

FOODS NOT RECOMMENDED IN THE DIET WITH SODIUM

RESTRICTION:

1- Cooking and table salt, sea salt, iodized salt.

4- Salted, smoked and cured meats. i Smoked and dried fish, crustaceans,
mollusks, caviar.
+ Delicatessen.
i- Cheeses in general.
i- Bread and biscuits with salt.
+ Olives.
i- Soup packets, instant purees, cubes, potatoes in packets.
+ Packaged vegetable juices.
i- Industrial pastry.
 + Salted butter, salted margarine.
i- Sparkling water, carbonated drinks.
+ Salty condiments (mustard, pickles,…)
+ Preserves in general.

As for proteins, we should not become obsessed because the important thing is to
prevent urea levels in the blood from rising, and this is controlled by the doctor with what we
call creatinine and urea clearance.

It is true that low protein diets prevent kidney function, but without falling into
malnutrition.

The kidney is the main route of elimination of potassium. If it accumulates, it can cause
damage to the heart (arrhythmias). We must be careful if we are diabetic or take drugs called
ACE inhibitors (angiotensin converting enzyme inhibitors, they serve to regulate blood
pressure). ) because we will already have high blood potassium (hyperkalemia).
® I AM IN HEMODIALYSIS.
The diet should be: personalized, varied and balanced.
MEATS
ALLOWED PROHIBITED

^ Veal • Meat in sauce

^ Ox • Smoked
^ Duck • Bacon
^ Goose • sausages
^ Pig • meat broth
^ Lamb
^ Rabbit
^ Chicken

Be careful with the sausage

FISH
ALLOWED PROHIBITED

^ Hake • Trout
^ Sepia • Swordfish
^ Monkfish • Seafood
^ Golden • smoked cod
^ Sole • Smoked salmon
^ Sardine • canned fish
^ Bream
^ Anguilla
^ Cod
^ Salmon
^ Grouper
^ Boqueron
^ Sea bass
^ Squid
^ Whiting
^ Turbot
 OILS AND BUTTERS
ALLOWED PROHIBITED

^ Olive oil • Butter

^ Butter oil
^ Sunflower oil
^ Vegetable margarine

RICE, PASTA AND EGGS

ALLOWED PROHIBITED

^ Pasta • Oatmeal
^ Rice • Rye
^ Wheat flour • Cornmeal

^ Cereals • wheat semolina

^ Eggs (3 per week if there is no

cholesterol problem)

FRUIT
ALLOWED PROHIBITED

^ Apple • Grapes
^ Watermelon • Banana
^ Pear • Melon
^ Macedonia • Cherries
^ Tangerine • Apricot
^ Strawberries • Figs
^ Peach • Kiwi
^ Pineapple • Avocado
^ Orange • Mango
• Olive
• Nuts

BREAD AND PASTRY

ALLOWED PROHIBITED

^ White bread • Wholemeal bread

^ Biscottes • Rye bread
^ Milk-free muffins
^ Cookies
 VEGETABLE
ALLOWED (ALWAYS BOILED) PROHIBITED

^ Col • Brussels sprouts

^ Carrot (can) • Spinach
^ Chard • Celery
^ Lettuce • Beet
^ Zucchini • French fries (bag)
^ Lombarda • Mashed potatoes in flakes
^ Eggplants
^ Mushroom (can)
^ Green beans (can)
^ Cucumber
^ Green pepper

LESS THAN 100 GR ALLOWED.

^ Cauliflower
^ Peas (can)
^ Asparagus
^ Green beans
^ Corn
^ Potatoes
^ Tomatoes
^ Carrots

LESS THAN 50 GR ALLOWED.

^ Artichokes
^ Leeks
^ Natural tomato
 SWEETS AND CONDIMENTS
ALLOWED PROHIBITED

^ White sugar • Brown sugar

^ Desserts with cream • Molasses
^ Jams • Chocolate
^ Honey • Cocoa
^ Biscuits • Ketchup
^ Marzipan • Pastille broths
^ Nougat • Sauces
^ Species
^ Aromatic herbs
^ Onion
^ Vinegar
^ Mustard

MILK AND DERIVATIVES

ALLOWED PROHIBITED

^ Skim milk • Milk powder

^ Plain yogurt • Condensed milk
^ Fruit yogurt • Rice pudding
^ Yogurt mouse • pudding
^ Cheeses
or Burgos
or Camembert
or Gervais
or cottage cheese
or sliced
or White
 B WHAT IF I GO OUT TO EAT OUT?
Eating out will be a pleasant experience despite
your dietary limitations. It is enough to choose what is
appropriate, moderating the intake with the combination of
foods.

Generally, restaurants offer us a wide variety of

foods to make it easier for us to choose the menu. In
addition, most of them are used to preparing special
dishes, all due to the health and nutrition awareness of the
current population.

ITALIAN FOOD:

Italian restaurants normally present their dishes with foods

seasoned with their corresponding sauce, since this is high in
sodium, phosphorus and potassium. Order it separately, in order
to control the amount of your intake.

Pizza is high in salt, phosphorus and potassium in this

order, a slice or two is preferable, instead of a whole one, and better with ground meat and
some vegetables such as pepper or onion instead of ordering one with pepperoni, chorizo,
olives and extra cheese.

ORIENTAL FOOD

Oriental dishes usually consist of meat, fish or chicken combined with vegetables
high in potassium.

Ask for white rice (less sodium) and not fried.

Avoid the famous: Soy Sauce or other typical oriental

sauces.

MEXICAN FOOD:

MEXi
C
 It is of poor quality and high in sodium and phosphorus.

A dish of choice would be a Taco with meat, lettuce and white rice.

Avoid Beans.

“QUICK” PREPARED FOODS: BURGERS:

You can order the food without added salt and without
other condiments.

Avoid French fries as they are high in potassium (remember these have not been
soaked before).

Better fried onion rings with potatoes.

Avoid ketchup and mustard.

IN SUMMARY FOLLOW THESE TIPS:

1. AS FOR PROTEINS:

Control portions. You can order half or share the whole thing with another diner.

Be careful with “hidden” proteins that are usually found in cheese, creamy sauces…

2. DRINKS:

Choose lemonade, cold tea or water, instead of fruit juices, large cola drinks….

3. SALT:

Ask not to add it to your food if its consumption is totally restricted.

4. POTASSIUM:

Better small salads, with lettuce, cabbage and grated carrots, instead of one with a
large variety of vegetables.
 Fruit; For dessert, better an apple or canned fruit but without eating the syrup, instead
of kiwi, grapes, banana or dishes with a variety of fresh fruit.

5. AVOID:

Snacks, nuts and popcorn due to their phosphorus, potassium and salt content.

6. DO NOT ADD TYPICAL SAUCES:

From the restaurant where you are going to eat (soy sauce, tomato sauce, ketchup,
mustard or the typical Argentine sauce called “chimichurri”…)

We believe that by knowing how to choose and planning ahead, you will know how to
enjoy mealtime.

8 HOW DOES THE DOCTOR KNOW IF I HAVE AN ADEQUATE

INTAKE?
Every month or every two, depending on the center where you are undergoing
dialysis, your doctor will perform a control analysis and the results will be compared with the
normal values of each parameter and with your previous analysis.

One of the parameters that are observed, apart from interviews with the doctor about
his diet, his weight, height, arm circumference, skin folds... to know if he is well nourished, is:

1) Serum albumin: (albumin in the blood) is a protein and tells us the protein
reserves we have.

It is a very important sign of well-being in patients. A serum albumin analysis between

3.0-4.0 is a sign of being well nourished. Below 3.0 is worrying and your doctor will look for
solutions by analyzing your diet with you.

2) BUN concentrations:

Low concentrations of plasma urea nitrogen (BUN) will also indicate that malnutrition
exists.
 CHAPTER 9 – EPO

The greatest contribution to the well-being of patients with kidney failure has
probably been erythropoietin, EPO.

This hormone is produced by the kidneys and controls the production of red blood
cells in the bone marrow. Today it can be manufactured through genetic engineering.

In most forms of kidney failure, EPO production is impaired, leading to anemia.

This means that the number of red blood cells in the body and the concentration of
hemoglobin in the blood are below normal.

45% hematocrit would be a normal value, it means that 45% of the blood volume
consists of red blood cells. Before the introduction of EPO, dialysis patients typically had
hematocrits of 20 to 25%, and frequent blood transfusions were required to maintain these
values. Nowadays with EPO, hematocrit levels are always above 30%.

Administration of EPO may follow different guidelines. It can be administered to

patients intravenously, through the venous needle at the end of each treatment. It can also
be administered as a subcutaneous injection, placed in the thigh or belly, which is usually
done one to three times a week in connection with dialysis.

The cost of EPO is high.

To benefit from EPO treatment, the patient also needs the administration of iron.
& ANEMIA AND ERYTHROPOIETIN
Anemia is a condition in which the volume of red blood cells is low. Red blood cells
carry oxygen to the body's cells. Without oxygen, cells cannot use energy from food, so
someone with anemia may feel tired and look pale. Anemia can also contribute to heart
problems.

Anemia is common among those with kidney disease because the kidneys produce
the hormone erythropoietin (EPO), which stimulates the bone marrow to produce red blood
cells. Diseased kidneys often do not make enough EPO and so the bone marrow makes
fewer red blood cells. EPO is marketed and commonly administered to patients on dialysis.

Today several commercially known names of erythropoietin are used: EPREX,

DARBOPOETIN ALFA, ARANESP….

They are all an artificial protein that stimulates erythropoiesis, which can be
administered subcutaneously or intravenously.

8 THERAPEUTIC INDICATIONS
EPREX® can be used in the treatment of anemia related to chronic kidney failure in
pediatric and adult patients on hemodialysis and peritoneal dialysis.

EPREX® can be used for the treatment of severe anemia of renal origin
accompanied by clinical symptoms in adult patients with renal failure who have not yet
undergone dialysis.

EPREX® can be used in the treatment of anemia and reduction of transfusion

requirements in adult cancer patients (with non-myeloid neoplasms) receiving or not
receiving chemotherapy.

EPREX® can be used in the treatment of anemia in HIV-infected adults who have
received treatment with zidovudine and have endogenous erythropoietin levels □ 500
mU/ml.

EPREX® can be used to facilitate the collection of autologous blood in a pre-

deposit program and decrease the risk of receiving allogeneic blood transfusions in
patients with moderate anemia (hematocrit of 33 39%, hemoglobin [Hb] 10-13 g/dl, [6.2-8.1
mmol/l], no iron deficiency) who are scheduled for major elective surgery and are expected
to require more blood than can be obtained at through autologous blood collection
techniques in the absence of epoetin alfa. Treatment should only be given to patients if
blood is unavailable or insufficient when major elective surgery requires a large volume of
blood (4 or more units of blood in women or 5 or more units in men).

EPREX® can be used to increase erythropoiesis in the presurgical period to reduce

allogeneic blood transfusions and correct postoperative anemia in adult patients with non-
iron deficient anemia scheduled for major elective orthopedic surgery. Use should be
restricted to patients with moderate anemia (e.g., Hb 10-13 g/dL) who are not on
autologous predonation programs and moderate blood loss, 900 to 1,800 ml, is expected.
Good blood management practices should always be used in the pre-surgical stage.

g PHARMACOKINETICS AND PHARMACODYNAMICS

Epoetin alfa is a purified glycoprotein hormone that stimulates erythropoiesis. It is
produced from mammalian cells into which the gene that codes for human erythropoietin
has been inserted.

Epoetin alfa obtained by genetic technology is identical in its amino acid sequence
to erythropoietin isolated from the urine of anemic patients. The protein fragment
represents about 58% of the molecular weight and consists of 165 amino acids. The four
carbohydrate chains are attached to the protein by three N-glycosidic bonds and one O-
bond.

glycosidic. The molecular weight of erythropoietin is approximately 32,000 to 40,000

daltons.

Intravenous administration: Measurement of epoetin alfa levels after intravenous

administration of a multiple dose of 50 to 100 IU/kg to healthy subjects indicates a half-life
of approximately 4 hours and longer, approximately 5 hours, in patients with renal failure
after doses of 50, 100 and 150 IU/kg. In children, a half-life of approximately 6 hours has
been reported. With at least 4 days of sampling after intravenous administration of doses of
667 and 1,500 IU/kg of EPREX®, half-life values in the range of 20.1 to 33 hours were
observed in cancer patients.
 Subcutaneous (SC) administration: Serum concentrations after subcutaneous
administration were lower than after intravenous administration. Serum levels increase
slowly and reach peak level 12 to 18 hours after subcutaneous administration. Peak serum
concentrations are below the peak seen with the intravenous route (approximately 1/20 of
the value).

There is no accumulation effect, serum levels remain the same, whether collected
after 24 hours after the first administration or 24 hours after the last administration. The
concentration-time profiles of EPREX® at weeks 1 and 4 were similar to those obtained
with multiple doses of 600 IU/kg/once a week in healthy individuals.

Pharmacokinetic data indicate no apparent differences in half-life between adult

patients older or younger than 65 years.

A Study of 7 Very Low Birth Weight Premature Neonates and 10 Healthy Adults On
IV Erythropoietin suggested that the volume of distribution was approximately 1.5 to 2
times greater in premature neonates than in healthy adults and clearance was
approximately 3 times greater in premature neonates than in healthy adults.
 The half-life of subcutaneous administration is approximately 24 hours. With
multiple doses of 150 IU/kg three times a week and 40,000 IU/ml once a week, mean half-
life values of 19.4 ± 8.1 and 15.0 ± 6.1, respectively, were found.

In a study that compares the administration of 40,000 IU S.C. a

once a week and 150 IU/kg SC 3 times a
th
week of EPREX® with human albumin in Cmax (MUI/ml) Cmln (MUI/ml) (h)
healthy individuals, the following 150U.Lkg
3/week (n = 24) 191 (100.1) 39(17.9) 31.8
parameters were calculated using the 40,000 Ul
predose-corrected data of endogenous 1/week (n = 22)
785 (427.3) 13 (9.5) 39.3
erythropoietin concentrations during the Cmax = Maximum plasma concentration
Cmin = Minimum plasma concentration. t =
fourth week:
Half life .
Data from the EPO-PHI-370 study

Based on the comparison of AUC (Areas Under the Curve), the relative
bioavailability of EPREX® after a dosing schedule of 40,000 IU/once a week compared to a
dosing schedule of 150 IU/kg three times a week It was 176%.

In a study comparing the administration of 40,000 IU S.C. once a week vs 150 IU/kg
SC 3 times a week and of EPREX® free of human albumin in healthy individuals, the
following parameters were calculated using the data corrected for the predose of the
concentrations of endogenous erythropoietin during the fourth week:

Based on the comparison of AUC the t

Cmax (MUI/ml) Cmln (MUI/ml) (h)
relative bioavailability of EPREX® after a 150 Ul/kg 3/week (n =
17) 40,000 Ul
dosing regimen of 40,000 IU/week compared 1/week (n = 17)
143 (54.2) 18(9.3) 19.4

to a dosing schedule of 150 IU/kg three 861 (445.1) 3.8 (4.27) 15.0
Cmax = Maximum plasma concentration
times a week was 239%.
Cmin = Minimum plasma concentration. t =

Half life.

Data from the EPO-PHI-373 study

The bioavailability of EPREX® by subcutaneous route after a dose of 120 IU/kg is

much lower than by intravenous route, approximately 20%.

The pharmacokinetic parameters of EPREX® with human albumin were estimated

in healthy individuals and in anemic cancer individuals receiving cycles of chemotherapy
and dosing schedules of 150 IU/kg 3 times a week and 40,000 IU/ml once a week. . The
pharmacokinetic parameters of anemic cancer individuals were different from those
observed in healthy individuals during the first week (when anemic cancer individuals were
receiving chemotherapy) but were similar during the third week (when anemic cancer
individuals were not receiving chemotherapy). receiving chemotherapy).

The pharmacokinetics of human albumin-free EPREX® were studied in anemic

cancer individuals receiving cycles of chemotherapy following dosing schedules of 150
IU/kg 3 times a week and 40,000 IU/ml once a week.

Overall, there was a high degree of variability associated with pharmacokinetic

parameters in anemic cancer individuals.

The pharmacokinetic profile of EPREX® during the first week (when anemic cancer
individuals were receiving chemotherapy) showed a higher Cmax (maximum plasma
concentration), an increase in half-life; and a decrease in clearance, than the second
pharmacokinetic profile of weeks 3 and 4 (when anemic cancer individuals were not
receiving chemotherapy).

Pharmacodynamics: Erythropoietin is a mitosis-stimulating factor and a

differentiation hormone which stimulates erythropoiesis. Considering its biological
properties, epoetin alfa cannot be distinguished from human erythropoietin.

The biological efficacy of epoetin alfa has been demonstrated in vivo in several
animal models (healthy and anemic rats and polycythemic mice).

After the administration of EPREX®, the erythrocyte and reticulocyte count,

hemoglobin values and iron incorporation increase.

It could be demonstrated with the help of bone marrow cell cultures that EPREX®
specifically stimulates erythropoiesis and does not affect leukopoiesis. It stimulates the
proliferation, maturation and differentiation of erythroid precursors in the bone marrow, in
an identical manner to endogenous human erythropoietin. EPREX® has been shown to
stimulate erythropoiesis in healthy volunteers, in patients with chronic renal failure and in
HIV-infected patients with endogenous erythropoietin levels less than 500 MU/ml, through
intravenous or subcutaneous administration and with a dose-related erythropoietic
response.

The pharmacodynamic responses to EPREX® free of human albumin, change in

the percentage of reticulocytes, hemoglobin and total red cell counts and the AUC of these
pharmacodynamic parameters, were similar between two dosing schedules, 150 IU/kg
subcutaneously (SC ) 3 times a week at 40,000 IU/ml SC once a week.
 The changes in the percentage of reticulocytes, hemoglobin and total red cell count,
as well as the respective AUC of these pharmacodynamic parameters, were similar
between the two dosing schedules of EPREX® with human albumin (150 IU/kg SC 3 times
a week and 40,000 IU/ml SC once a week), both in healthy individuals and anemic cancer
patients. The increase in hemoglobin AUC and reticulocyte count was lower in anemic
cancer subjects than in healthy subjects.

The effect of EPREX® on energy level and the ability to conduct daily activities has
been evaluated in multicenter, double-blind, placebo-controlled studies and in two open-
label studies with anemic cancer patients receiving chemotherapy.

In a large, double-blind study, patients treated with EPREX® compared to patients

treated with placebo had significant improvements in energy, daily activity levels, and
fatigue.

Small, randomized, open-label studies support these improvements in quality of life

parameters that were observed in association with increases as small as 1 g/dL in
hemoglobin.

g GENERAL PRECAUTIONS
Blood pressure should be adequately controlled before starting treatment with
EPREX®.

Blood pressure should be carefully monitored and controlled when necessary in all
patients treated with EPREX®. EPREX® should be used with caution in the presence of
untreated, inadequately treated or poorly controlled hypertension.

Particular attention should be paid to the development of unusual headaches or an

increase in headaches as a possible warning sign.

During therapy with EPREX® it may be necessary to initiate or increase

antihypertensive treatment. Treatment with EPREX® should be discontinued if blood
pressure cannot be controlled.

EPREX® should be used with caution in patients with a history of seizures and in
those with epilepsy and chronic liver failure.

Hemoglobin levels should be closely monitored in all patients due to a potential

increased risk of thromboembolic events and fatal outcome when patients are treated at
levels above that established by indication.

The safety and effectiveness of EPREX® have not been established in patients with
hematological diseases (hemolytic anemia, sickle cell anemia, thalassemia and porphyria).

The safety of EPREX® in patients with hepatic dysfunction has not been
established. Due to the decrease in metabolism, patients with hepatic dysfunction may
have an increase in erythropoiesis with EPREX®.

A moderate dose-dependent increase in platelet count within the normal range may
occur during treatment with EPREX®.

This returns during the course of continuing therapy. Additionally, thrombocytopenia

above normal ranges has been reported. It is recommended that platelet counts be
monitored regularly during the first 8 weeks of therapy.

Pure red cell aplasia: Antibody-mediated pure red cell aplasia has been reported
rarely after months to years of subcutaneous treatment with EPREX®.

In patients who present with a sudden lack of efficacy, defined as a decrease in

hemoglobin (1 to 2 g/d month) and an increased need for transfusions, a reticulocyte count
should be performed and typical causes of non-response investigated ( for example, iron,
folic acid or vitamin B12 deficiency, aluminum poisoning, infection or inflammation, blood
loss and hemolysis).

If the reticulocyte count corrected for anemia (e.g., reticulocyte index) is low (<
20,000/mm³ or < 20,000/uL or < 0.5%), the platelet count and white blood cell count are
normal and if there are no other causes of loss If no effect can be found, antierythropoietin
antibodies should be determined and a bone marrow examination should be considered for
the diagnosis of pure red cell aplasia (PRCA).

If APCR is suspected, EPREX® therapy should be discontinued immediately. No

other therapy can be started due to the risk of cross-reaction. Blood transfusions can be
performed in patients for whom it is indicated.
 Patients with renal failure: In patients with chronic renal failure the rate of increase
in hemoglobin should be approximately 1 g/dl (0.62 mmol/l)/month and should not exceed 2
g/dl (1.2 mmol/l) month. to reduce the risk of an increase in hypertension. The dose should
be reduced when hemoglobin reaches 12 g/dl.

In patients with chronic renal failure, the hemoglobin concentration should not
exceed the recommended upper limit. Hemoglobin levels greater than 12 g/dl may be
associated with an increased risk of cardiovascular events including death.

In patients with chronic renal failure on EPREX®, hemoglobin concentration should

be measured at least once a week until a stable level is achieved and periodically
thereafter.

In order to ensure an optimal response to EPREX®, adequate iron stores must be

available, folic acid and vitamin B12 deficiencies must be excluded before starting therapy.
In most patients with chronic renal failure, cancer, and HIV infection, plasma ferritin
concentrations decrease simultaneously with the increase in cell package volume.

Therefore, iron supplementation is recommended e.g. 200 300 mg/day of oral iron
(100-200 mg/day for pediatric patients) is recommended for patients with chronic renal
failure with serum ferritin levels below 100 ng/ml.

Based on the information available to date, the use of EPREX® in predialysis

patients (final stage of renal failure) does not accelerate the degree of progression of renal
failure.

As a result of an increase in cell packet volume, hemodialysis patients receiving

EPREX® frequently require an increase in the dose of heparin during dialysis. If
heparinization is not optimal, occlusion of the dialysis system is possible.

In some patients with chronic renal failure, menstruation has resumed after
continuing therapy with EPREX®, the possibility of potential pregnancy should be
discussed and the need for contraceptive use evaluated.

Exacerbation of porphyria has rarely been observed in patients with chronic renal
failure treated with EPREX®. EPREX® should be used with caution in patients with
porphyria.

Cancer Patients: Cancer patients treated with EPREX® should have hemoglobin
levels measured on a regular basis until a stable level is reached and periodically
thereafter.

9
 In cancer patients receiving chemotherapy, the increase in hemoglobin must
exceed 1 g/dL for 2 weeks or 2 g/dL per month or the hemoglobin concentration reaches
12 g/dL or the hemoglobin concentration exceeds 13 g/dL .

Dose adjustment should be continued to minimize the potential risk of thrombotic

events.

Because an increased incidence of vascular thrombotic events (VTEs) has been

observed in cancer patients receiving erythropoietic agents, this risk must be carefully
weighed against the benefit derived from treatment (with EPREX®), particularly in cancer
patients with greater risk factors for vascular thrombotic events, such as obesity and a
history of EVTs (e.g., deep vein thrombosis or pulmonary embolism).

In order to ensure an optimal response to EPREX®, adequate iron stores must be

available, folic acid and vitamin B12 deficiencies must be excluded before starting therapy.

In most patients with chronic renal failure, cancer, and HIV infection, plasma ferritin
concentrations decrease simultaneously with the increase in cell package volume.
 Therefore, iron supplementation is recommended for example 200 300 mg/day oral
iron (100-200 mg/day for pediatric patients) for cancer patients with serum ferritin levels
below 100 ng/ml.

EPREX® is a growth factor that primarily stimulates the production of red cells.
Erythropoietin receptors are also present on the surface of some malignant cell lines and
tumor cells obtained by biopsy or surgical resection. However, it is unknown whether these
receptors are functional.

Clinical studies with epoetin have not provided sufficient information to establish
whether the use of epoetin products has adverse effects on tumor progression or tumor
progression-free survival.

Until information is available, it is recommended that the hemoglobin level does not
exceed 12 g/dl in men and women.

In cancer patients receiving chemotherapy, when evaluating whether treatment with

EPREX® is appropriate (patient at risk of being transfused) the 2 and 3 weeks delay
between the administration of EPREX® and the appearance of induced red blood cells
should be considered. erythropoietin.

Patients with HIV: In patients who do not respond or do not maintain the response
to treatment with EPREX®, other etiologies for anemia, including iron deficiency, should be
considered and evaluated.

Patients on autologous blood donation programs: All special precautions and

warnings should be observed in patients initiating epoetin alfa supplementation associated
with autologous blood donation programs, especially routine volume replacement.

Pre-surgical patients (without autologous blood donation): In patients scheduled for

orthopedic surgery, the cause of anemia must be

established and treated, if possible, before starting treatment with EPREX®.

In patients scheduled for major elective orthopedic surgery, thrombotic events may
be a risk and their possibility must be carefully weighed against the benefit derived from
treatment in this group of patients.

Because thrombotic and vascular events can occur in surgical patients, especially
those with undiagnosed cardiovascular disease, patients scheduled for major elective
orthopedic surgery should receive appropriate antithrombotic prophylaxis.

Additionally, special precautions should be taken in patients with a predisposition to

develop deep vein thrombosis.

Furthermore, in patients with a baseline hemoglobin of > 13 g/dl (8.1 mmol/l), the
possibility that epoetin alfa treatment may be associated with an increased risk of
postoperative thrombotic/vascular events cannot be ruled out. Therefore, it should not be
used in patients with baseline hemoglobin > 13 g/dl (8.1 mmol/l).

The use of EPREX® is not recommended in pre-surgical patients with a baseline

hemoglobin > 13 g/dl.

Incompatibility: Should not be diluted or transferred to another container. It should

not be administered by intravenous infusion or together with other medicinal solutions.

Effects on the ability to drive and use machinery: Due to the risk of increased
hypertension during the initial phase of treatment with EPREX®, patients with chronic
kidney disease should use caution when engaging in potentially hazardous activities, such
as driving or operating machinery, until that the optimal maintenance dose with EPREX®
has been established.

& RESTRICTIONS ON USE DURING PREGNANCY AND

BREASTFEEDING
Pregnancy: In animal studies, EPREX® has been shown to induce a decrease in
fetal body weight, delay in ossification and increase in fetal mortality, at weekly doses of
approximately 20 times the recommended weekly dose for humans. These changes are
interpreted as secondary to the decrease in maternal weight gain. There are no adequate
and well-controlled studies in pregnancy. In patients with chronic renal failure, EPREX®
should be used in pregnancy if the benefits justify the potential risks to the fetus.

Breastfeeding: Erythropoietin is present in milk, however, it is unknown whether

EPREX® is distributed in human milk. EPREX® should be used with caution during
breastfeeding. The use of EPREX® is not recommended in pregnant or lactating women
participating in autologous blood predonation programs.
g SECONDARY AND ADVERSE REACTIONS.
Data from clinical studies: The most common adverse reaction during treatment
with EPREX® is a dose-dependent increase in blood pressure or worsening of pre-existing
hypertension. Blood pressure should be monitored, particularly at the start of treatment.

Other common adverse reactions that have been observed in clinical studies of
EPREX® are diarrhea, nausea, headache, flu-like illness, pyrexia, rash and vomiting. At
the beginning of treatment there may be flu-like illness including headache, joint pain,
myalgia and pyrexia.

Serious adverse reactions include venous and arterial thrombosis and embolism
(including some with fatal results), such as deep vein thrombosis, pulmonary embolism,
arterial thrombosis, retinal thrombosis and thrombosis of fistulas (including dialysis
equipment).

In a cumulative analysis of 10 double-blind, randomized, placebo-controlled clinical

trials in cancer subjects receiving chemotherapy, deep vein thrombosis was reported in
2.1% and pulmonary embolism in 1.2% of 1,564 subjects receiving EPREX®. compared
with 1.2% and 1.2%, respectively of 1,207 subjects exposed to placebo.

Additionally, cerebral vascular accidents (including strokes and cerebral

hemorrhages) and transient ischemic attacks have been reported in clinical studies of
EPREX®.

Hypersensitivity reactions have occurred, including cases of rash, urticaria,

anaphylactic reactions, and angioneurotic edema.

Hypertensive crises with encephalopathy and seizures, requiring immediate

medical attention and intensive medical care, have occurred during treatment with
EPREX® in patients with normal or low blood pressure.

Particular attention should be paid to cases of sudden onset migraine as a possible

warning sign.

The overall safety profile of EPREX® was evaluated in 142 subjects with chronic
renal failure and in 765 subjects with cancer who participated in registered, placebo-
controlled, double-blind clinical studies.
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