Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as
creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an importa ...
and
urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
and free water from the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
when the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s are in a state of
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
kidney transplant
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
and
peritoneal dialysis
Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...
). An alternative method for extracorporeal separation of blood components such as plasma or cells is
apheresis
Apheresis ( ἀφαίρεσις (''aphairesis'', "a taking away")) is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation ...
.
Hemodialysis can be an
outpatient
A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health care ...
or
inpatient
A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health ca ...
therapy. Routine hemodialysis is conducted in a dialysis outpatient facility, either a purpose-built room in a
hospital
A hospital is a health care institution providing patient treatment with specialized health science and auxiliary healthcare staff and medical equipment. The best-known type of hospital is the general hospital, which typically has an emerge ...
or a dedicated, stand-alone clinic. Less frequently hemodialysis is done at
home
A home, or domicile, is a space used as a permanent or semi-permanent residence for one or many humans, and sometimes various companion animals. It is a fully or semi sheltered space and can have both interior and exterior aspects to it. H ...
. Dialysis treatments in a clinic are initiated and managed by specialized staff made up of nurses and technicians; dialysis treatments at home can be self-initiated and managed or done jointly with the assistance of a trained helper who is usually a family member.
Medical uses
Hemodialysis is the choice of
renal replacement therapy
Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney di ...
for patients who need dialysis acutely, and for many patients as maintenance therapy. It provides excellent, rapid clearance of solutes.
A
nephrologist
Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function ( ...
(a medical kidney specialist) decides when hemodialysis is needed and the various parameters for a dialysis treatment. These include frequency (how many treatments per week), length of each treatment, and the blood and dialysis solution flow rates, as well as the size of the dialyzer. The composition of the dialysis solution is also sometimes adjusted in terms of its sodium, potassium, and bicarbonate levels. In general, the larger the body size of an individual, the more dialysis he/she will need. In
North America
North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and the Car ...
and the UK, 3–4 hour treatments (sometimes up to 5 hours for larger patients) given 3 times a week are typical. Twice-a-week sessions are limited to patients who have a substantial residual kidney function. Four sessions per week are often prescribed for larger patients, as well as patients who have trouble with
fluid overload
Hypervolemia, also known as fluid overload, is the medical condition where there is too much fluid in the blood. The opposite condition is hypovolemia, which is too little fluid volume in the blood. Fluid volume excess in the intravascular comp ...
. Finally, there is growing interest in short daily home hemodialysis, which is 1.5 – 4 hr sessions given 5–7 times per week, usually at home. There is also interest in
nocturnal dialysis In medicine, nocturnal dialysis, refers to (renal) dialysis done at night. It usually is a reference to nocturnal hemodialysis, but could also refer to peritoneal dialysis which is typically done at night.
Nocturnal hemodialysis was conceived ...
, which involves dialyzing a patient, usually at home, for 8–10 hours per night, 3–6 nights per week. Nocturnal in-center dialysis, 3–4 times per week, is also offered at a handful of dialysis units in the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
.
Adverse effects
Disadvantages
*Restricts independence, as people undergoing this procedure cannot travel around because of supplies' availability
*Requires more supplies such as high water quality and electricity
*Requires reliable technology like dialysis machines
*The procedure is complicated and requires that care givers have more knowledge
*Requires time to set up and clean dialysis machines, and expense with machines and associated staff
Complications
Fluid shifts
Hemodialysis often involves fluid removal (through
ultrafiltration
Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in the ...
), because most patients with
renal failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
pass little or no urine. Side effects caused by removing too much fluid and/or removing fluid too rapidly include
low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...
,
fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, chest pains, leg-cramps,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and
headaches
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result of m ...
. These symptoms can occur during the treatment and can persist post treatment; they are sometimes collectively referred to as the dialysis hangover or dialysis washout. The severity of these symptoms is usually proportionate to the amount and speed of fluid removal. However, the impact of a given amount or rate of fluid removal can vary greatly from person to person and day to day. These side effects can be avoided and/or their severity lessened by limiting fluid intake between treatments or increasing the dose of dialysis e.g. dialyzing more often or longer per treatment than the standard three times a week, 3–4 hours per treatment schedule.
Access-related
Since hemodialysis requires access to the circulatory system, patients undergoing hemodialysis may expose their circulatory system to
microbes
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
, which can lead to
bacteremia
Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. Blood is normally a sterile environment, so the detection of microb ...
, an infection affecting the heart valves (
endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
) or an infection affecting the bones (
osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
). The risk of infection varies depending on the type of access used (see below). Bleeding may also occur, again the risk varies depending on the type of access used. Infections can be minimized by strictly adhering to
infection control
Infection prevention and control is the discipline concerned with preventing healthcare-associated infections; a practical rather than academic sub-discipline of epidemiology. In Northern Europe, infection prevention and control is expanded fro ...
best practices.
Venous needle dislodgement
Venous needle dislodgement (VND) is a fatal complication of hemodialysis where the patient experiences rapid blood loss due to a faltering attachment of the needle to the venous access point.
Anticoagulation-related
Unfractioned heparin (UHF) is the most commonly used anticoagulant in hemodialysis, as it is generally well tolerated and can be quickly reversed with
protamine sulfate
Protamine sulfate is a medication that is used to reverse the effects of heparin. It is specifically used in heparin overdose, in low molecular weight heparin overdose, and to reverse the effects of heparin during delivery and heart surgery. ...
. Low-molecular weight heparin (LMWH) is however, becoming increasingly popular and is now the norm in western Europe. Compared to UHF, LMWH has the advantage of an easier mode of administration and reduced bleeding but the effect cannot be easily reversed. Heparin can infrequently cause a low platelet count due to a reaction called heparin-induced thrombocytopenia (HIT). In such patients, alternative anticoagulants may be used. The risk of HIT is lower with LMWH compared to UHF. Even though HIT causes a low platelet count it can paradoxically predispose thrombosis. In patients at high risk of bleeding, dialysis can be done without anticoagulation.
First-use syndrome
First-use syndrome is a rare but severe
anaphylactic reaction
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
to the
artificial kidney
Artificial kidney is often a synonym for hemodialysis, but may also refer to the other renal replacement therapies (with exclusion of kidney transplantation) that are in use and/or in development. This article deals mainly with bioengineered kid ...
. Its symptoms include sneezing, wheezing, shortness of breath, back pain, chest pain, or sudden death. It can be caused by residual sterilant in the artificial kidney or the material of the membrane itself. In recent years, the incidence of first-use syndrome has decreased, due to an increased use of gamma irradiation, steam sterilization, or electron-beam radiation instead of chemical sterilants, and the development of new semipermeable membranes of higher
biocompatibility
Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...
. New methods of processing previously acceptable components of dialysis must always be considered. For example, in 2008, a series of first-use type of reactions, including deaths, occurred due to heparin contaminated during the manufacturing process with oversulfated
chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ove ...
neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
and various forms of
heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
. Increasing the frequency and length of treatments has been shown to improve fluid overload and enlargement of the heart that is commonly seen in such patients.
Vitamin deficiency
Folate deficiency
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folate ...
can occur in some patients having hemodialysis.
Electrolyte imbalances
Although a dyalisate fluid, which is a solution containing diluted electrolytes, is employed for the filtration of blood, haemodialysis can cause an electrolyte imbalance. These imbalances can derive from abnormal concentrations of potassium (
hypokalemia
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
,
hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
), and sodium (
hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
,
hypernatremia
Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and b ...
). These electrolyte imbalances are associated with increased cardiovascular mortality.
Mechanism and technique
The principle of hemodialysis is the same as other methods of dialysis; it involves
diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
of solutes across a semipermeable membrane. Hemodialysis utilizes counter current flow, where the dialysate is flowing in the opposite direction to
blood flow
Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously m ...
in the extracorporeal circuit. Counter-current flow maintains the concentration gradient across the membrane at a maximum and increases the efficiency of the dialysis.
Fluid removal (
ultrafiltration
Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in the ...
) is achieved by altering the
hydrostatic pressure
Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body "fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an imme ...
of the dialysate compartment, causing free water and some dissolved solutes to move across the membrane along a created pressure gradient.
The dialysis solution that is used may be a sterilized solution of mineral ions and is called dialysate.
Urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
and other waste products including
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
, and
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
diffuse into the dialysis solution. However, concentrations of
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
and chloride are similar to those of normal
plasma
Plasma or plasm may refer to:
Science
* Plasma (physics), one of the four fundamental states of matter
* Plasma (mineral), a green translucent silica mineral
* Quark–gluon plasma, a state of matter in quantum chromodynamics
Biology
* Blood pla ...
to prevent loss.
Sodium bicarbonate
Sodium bicarbonate (IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda, is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cation ( Na+) and a bicarbonate anion ( HCO3−) ...
is added in a higher concentration than plasma to correct blood acidity. A small amount of glucose is also commonly used. The concentration of electrolytes in the dialysate is adjusted depending on the patient's status before the dialysis. If a high concentration of sodium is added to the dialysate, the patient can become thirsty and end up accumulating body fluids, which can lead to heart damage. On the contrary, low concentrations of sodium in the dialysate solution have been associated with a low blood pressure and intradialytic weight gain, which are markers of improved outcomes. However, the benefits of using a low concentration of sodium have not been demonstrated yet, since these patients can also develop cramps, intradialytic hypotension and low sodium in serum, which are symptoms associated with a high mortality risk.
Note that this is a different process to the related technique of
hemofiltration
Hemofiltration, also haemofiltration, is a renal replacement therapy which is used in the intensive care setting. It is usually used to treat acute kidney injury (AKI), but may be of benefit in multiple organ dysfunction syndrome or sepsis. During ...
.
Access
Three primary methods are used to gain access to the blood for hemodialysis: an intravenous catheter, an
arteriovenous fistula
An arteriovenous fistula is an abnormal connection or passageway between an artery and a vein. It may be congenital, surgically created for hemodialysis treatments, or acquired due to pathologic process, such as trauma or erosion of an arterial ...
(AV) and a synthetic graft. The type of access is influenced by factors such as the expected time course of a patient's renal failure and the condition of their vasculature. Patients may have multiple access procedures, usually because an AV fistula or graft is maturing and a catheter is still being used. The placement of a catheter is usually done under light sedation, while fistulas and grafts require an operation.
Types
There are three types of hemodialysis: conventional hemodialysis, daily hemodialysis, and nocturnal hemodialysis. Below is an adaptation and summary from a brochure of The Ottawa Hospital.
Conventional hemodialysis
Conventional hemodialysis is usually done three times per week, for about three to four hours for each treatment (Sometimes five hours for larger patients), during which the patient's blood is drawn out through a tube at a rate of 200–400 mL/min. The tube is connected to a 15, 16, or 17 gauge needle inserted in the dialysis fistula or graft, or connected to one port of a dialysis
catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
. The blood is then pumped through the dialyzer, and then the processed blood is pumped back into the patient's bloodstream through another tube (connected to a second needle or port). During the procedure, the patient's blood pressure is closely monitored, and if it becomes low, or the patient develops any other signs of low blood volume such as nausea, the dialysis attendant can administer extra fluid through the machine. During the treatment, the patient's entire blood volume (about 5000 cc) circulates through the machine every 15 minutes. During this process, the dialysis patient is exposed to a week's worth of water for the average person.
Daily hemodialysis
Daily hemodialysis is typically used by those patients who do their own dialysis at home. It is less stressful (more gentle) but does require more frequent access. This is simple with catheters, but more problematic with fistulas or grafts. The "buttonhole technique" can be used for fistulas requiring frequent access. Daily hemodialysis is usually done for 2 hours six days a week.
Nocturnal hemodialysis
The procedure of nocturnal hemodialysis is similar to conventional hemodialysis except it is performed three to six nights a week and between six and ten hours per session while the patient sleeps.
Equipment
The hemodialysis machine pumps the patient's blood and the dialysate through the dialyzer. The newest dialysis machines on the market are highly computerized and continuously monitor an array of safety-critical parameters, including blood (QB) and dialysate QD) flow rates; dialysis solution conductivity, temperature, and pH; and analysis of the dialysate for evidence of blood leakage or presence of air. Any reading that is out of normal range triggers an audible alarm to alert the patient-care technician who is monitoring the patient. Manufacturers of dialysis machines include companies such as
Nipro
is a Japanese medical equipment manufacturing company. Founded in 1954, the company is headquartered in Osaka and is listed on the Tokyo Stock Exchange and the Osaka Securities Exchange.
As of 2013 the company has 58 subsidiaries in Japan, As ...
, Fresenius, Gambro, Baxter, B. Braun, NxStage and Bellco. QB to QD flow rates have to reach 1:2 ratio where QB is set around 250 ml/min and QD is set around 500 ml/min to ensure good dialysis efficiency.
Water system
An extensive
water purification
Water purification is the process of removing undesirable chemicals, biological contaminants, suspended solids, and gases from water. The goal is to produce water that is fit for specific purposes. Most water is purified and disinfected for hu ...
system is critical for hemodialysis. Since dialysis patients are exposed to vast quantities of water, which is mixed with dialysate concentrate to form the dialysate, even trace mineral contaminants or bacterial
endotoxins
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer me ...
can filter into the patient's blood. Because the damaged kidneys cannot perform their intended function of removing impurities, molecules introduced into the bloodstream from water improperly purified water can build up to hazardous levels, causing numerous symptoms or death.
Aluminum
Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. It has ...
,
chlorine
Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...
and or
chloramines
Chloramines refer to derivatives of ammonia and organic amines wherein one or more N-H bonds have been replaced by N-Cl bonds. Two classes of compounds are considered: inorganic chloramines and organic chloramines.
Inorganic chloramines
Inorgan ...
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
, and
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
, as well as bacterial fragments and
endotoxins
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer me ...
, have all caused problems in this regard.
For this reason, water used in hemodialysis is carefully purified before use. A common water purification system includes a multi stage system.
The water is first softened. Next the water is run through a tank containing activated charcoal to adsorb organic contaminants, and chlorine and chloramines. The water may then be temperature-adjusted if needed. Primary purification is then done by forcing water through a membrane with very tiny pores, a so-called
reverse osmosis
Reverse osmosis (RO) is a water purification process that uses a partially permeable membrane to separate ions, unwanted molecules and larger particles from drinking water. In reverse osmosis, an applied pressure is used to overcome osmotic pre ...
membrane. This lets the water pass, but holds back even very small solutes such as electrolytes. Final removal of leftover electrolytes is done in some water systems by passing the water through an
electrodeionization
Electrodeionization (EDI) is a water treatment technology that utilizes electricity, ion exchange membranes, and resin to deionize water and separate dissolved ions (impurities) from it. It differs from other water purification technologies in ...
(EDI) device, which removes any leftover anions or cations and replace them with hydroxyl and hydrogen ions, respectively, leaving ultrapure water.
Even this degree of water purification may be insufficient. The trend lately is to pass this final purified water (after mixing with dialysate concentrate) through an ultrafiltration membrane or absolute filter. This provides another layer of protection by removing impurities, especially those of bacterial origin, that may have accumulated in the water after its passage through the original water purification system.
Dialysate
Once purified water is mixed with dialysate (also called dialysis fluid) concentrate consisting of:
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
,
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
,
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
,
magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
and dextrose mixed in an acid solution; this solution is mixed with the purified water and a chemical buffer. This forms the dialysate solution, which contains the basic electrolytes found in human blood. This dialysate solution contains charged ions that conducts electricity. During dialysis, the conductivity of dialysis solution is continuously monitored to ensure that the water and dialysate concentrate are being mixed in the proper proportions. Both excessively concentrated dialysis solution and excessively dilute solution can cause severe clinical problems.
Chemical buffers such as bicarbonate or lactate can alternatively be added to regulate the pH of the dialysate. Both buffers can stabilize the pH of the solution at a physiological level with no negative impacts on the patient. There is some evidence of a reduction in the incidence of heart and blood problems and high blood pressure events when using bicarbonate as the pH buffer compared to lactate. However, the mortality rates after using both buffers do not show a significative difference.
Dialyzer
The dialyzer is the piece of equipment that actually filters the blood. Almost all dialyzers in use today are of the hollow-fiber variety. A cylindrical bundle of hollow fibers, whose walls are composed of semi-permeable membrane, is anchored at each end into potting compound (a sort of glue). This assembly is then put into a clear plastic cylindrical shell with four openings. One opening or blood port at each end of the cylinder communicates with each end of the bundle of hollow fibers. This forms the "blood compartment" of the dialyzer. Two other ports are cut into the side of the cylinder. These communicate with the space around the hollow fibers, the "dialysate compartment." Blood is pumped via the blood ports through this bundle of very thin
capillary
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
-like tubes, and the dialysate is pumped through the space surrounding the fibers. Pressure gradients are applied when necessary to move fluid from the blood to the dialysate compartment.
Membrane and flux
Dialyzer membranes come with different pore sizes. Those with smaller pore size are called "low-flux" and those with larger pore sizes are called "high-flux." Some larger molecules, such as beta-2-microglobulin, are not removed at all with low-flux dialyzers; lately, the trend has been to use high-flux dialyzers. However, such dialyzers require newer dialysis machines and high-quality dialysis solution to control the rate of fluid removal properly and to prevent backflow of dialysis solution impurities into the patient through the membrane.
Dialyzer membranes used to be made primarily of cellulose (derived from cotton linter). The surface of such membranes was not very biocompatible, because exposed hydroxyl groups would activate
complement
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-clas ...
in the blood passing by the membrane. Therefore, the basic, "unsubstituted" cellulose membrane was modified. One change was to cover these hydroxyl groups with acetate groups (cellulose acetate); another was to mix in some compounds that would inhibit complement activation at the membrane surface (modified cellulose). The original "unsubstituted cellulose" membranes are no longer in wide use, whereas cellulose acetate and modified cellulose dialyzers are still used. Cellulosic membranes can be made in either low-flux or high-flux configuration, depending on their pore size.
Another group of membranes is made from synthetic materials, using
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
polyamide
A polyamide is a polymer with repeating units linked by amide bonds.
Polyamides occur both naturally and artificially. Examples of naturally occurring polyamides are proteins, such as wool and silk. Artificially made polyamides can be made through ...
,
polyvinylpyrrolidone
Polyvinylpyrrolidone (PVP), also commonly called polyvidone or povidone, is a water-soluble polymer made from the monomer ''N''-vinylpyrrolidone. PVP is available in a range of molecular weights and related viscosities, and can be selected accor ...
,
polycarbonate
Polycarbonates (PC) are a group of thermoplastic polymers containing carbonate groups in their chemical structures. Polycarbonates used in engineering are strong, tough materials, and some grades are optically transparent. They are easily work ...
, and
polyacrylonitrile
Polyacrylonitrile (PAN), also known as polyvinyl cyanide and Creslan 61, is a synthetic, semicrystalline organic polymer resin, with the linear formula (C3H3N)n. Though it is thermoplastic, it does not melt under normal conditions. It degrades bef ...
. These synthetic membranes activate complement to a lesser degree than unsubstituted cellulose membranes. However, they are in general more hydrophobic which leads to increased adsorption of proteins to the membrane surface which in turn can lead to complement system activation. Synthetic membranes can be made in either low- or high-flux configuration, but most are high-flux.
Nanotechnology is being used in some of the most recent high-flux membranes to create a uniform pore size. The goal of high-flux membranes is to pass relatively large molecules such as beta-2-microglobulin (MW 11,600 daltons), but not to pass albumin (MW ~66,400 daltons). Every membrane has pores in a range of sizes. As pore size increases, some high-flux dialyzers begin to let albumin pass out of the blood into the dialysate. This is thought to be undesirable, although one school of thought holds that removing some albumin may be beneficial in terms of removing protein-bound uremic toxins.
Membrane flux and outcome
Whether using a high-flux dialyzer improves patient outcomes is somewhat controversial, but several important studies have suggested that it has clinical benefits. The NIH-funded HEMO trial compared survival and hospitalizations in patients randomized to dialysis with either low-flux or high-flux membranes. Although the primary outcome (all-cause mortality) did not reach statistical significance in the group randomized to use high-flux membranes, several secondary outcomes were better in the high-flux group. A recent Cochrane analysis concluded that benefit of membrane choice on outcomes has not yet been demonstrated. A collaborative randomized trial from Europe, the MPO (Membrane Permeabilities Outcomes) study, comparing mortality in patients just starting dialysis using either high-flux or low-flux membranes, found a nonsignificant trend to improved survival in those using high-flux membranes, and a survival benefit in patients with lower serum albumin levels or in diabetics.
Membrane flux and beta-2-microglobulin amyloidosis
High-flux dialysis membranes and/or intermittent internal on-line hemodiafiltration (iHDF) may also be beneficial in reducing complications of beta-2-microglobulin accumulation. Because beta-2-microglobulin is a large molecule, with a molecular weight of about 11,600 daltons, it does not pass at all through low-flux dialysis membranes. Beta-2-M is removed with high-flux dialysis, but is removed even more efficiently with IHDF. After several years (usually at least 5–7), patients on hemodialysis begin to develop complications from beta-2-M accumulation, including carpal tunnel syndrome, bone cysts, and deposits of this amyloid in joints and other tissues. Beta-2-M amyloidosis can cause very serious complications, including
spondyloarthropathy
Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebra ...
, and often is associated with shoulder joint problems. Observational studies from Europe and Japan have suggested that using high-flux membranes in dialysis mode, or IHDF, reduces beta-2-M complications in comparison to regular dialysis using a low-flux membrane.
Dialyzers and efficiency
Dialyzers come in many different sizes. A larger dialyzer with a larger membrane area (A) will usually remove more solutes than a smaller dialyzer, especially at high blood flow rates. This also depends on the membrane permeability coefficient ''K0'' for the solute in question. So dialyzer efficiency is usually expressed as the ''K0A'' – the product of permeability coefficient and area. Most dialyzers have membrane surface areas of 0.8 to 2.2 square meters, and values of ''K0A'' ranging from about 500 to 1500 mL/min. ''K0A'', expressed in mL/min, can be thought of as the maximum clearance of a dialyzer at very high blood and dialysate flow rates.
Reuse of dialyzers
The dialyzer may either be discarded after each treatment or be reused. Reuse requires an extensive procedure of high-level disinfection. Reused dialyzers are not shared between patients. There was an initial controversy about whether reusing dialyzers worsened patient outcomes. The consensus today is that reuse of dialyzers, if done carefully and properly, produces similar outcomes to single use of dialyzers.
Dialyzer Reuse is a practice that has been around since the invention of the product. This practice includes the cleaning of a used dialyzer to be reused multiple times for the same patient. Dialysis clinics reuse dialyzers to become more economical and reduce the high costs of "single-use" dialysis which can be extremely expensive and wasteful. Single used dialyzers are initiated just once and then thrown out creating a large amount of bio- medical waste with no mercy for cost savings. If done right, dialyzer reuse can be very safe for dialysis patients.
There are two ways of reusing dialyzers, manual and automated. Manual reuse involves the cleaning of a dialyzer by hand. The dialyzer is semi-disassembled then flushed repeatedly before being rinsed with water. It is then stored with a liquid disinfectant(PAA) for 18+ hours until its next use. Although many clinics outside the USA use this method, some clinics are switching toward a more automated/streamlined process as the dialysis practice advances. The newer method of automated reuse is achieved by means of a medical device that began in the early 1980s. These devices are beneficial to dialysis clinics that practice reuse – especially for large dialysis clinical entities – because they allow for several back to back cycles per day. The dialyzer is first pre-cleaned by a technician, then automatically cleaned by machine through a step-cycles process until it is eventually filled with liquid disinfectant for storage. Although automated reuse is more effective than manual reuse, newer technology has sparked even more advancement in the process of reuse. When reused over 15 times with current methodology, the dialyzer can lose B2m, middle molecule clearance and fiber pore structure integrity, which has the potential to reduce the effectiveness of the patient's dialysis session. Currently, as of 2010, newer, more advanced reprocessing technology has proven the ability to eliminate the manual pre-cleaning process altogether and has also proven the potential to regenerate (fully restore) all functions of a dialyzer to levels that are approximately equivalent to single-use for more than 40 cycles. As medical reimbursement rates begin to fall even more, many dialysis clinics are continuing to operate effectively with reuse programs especially since the process is easier and more streamlined than before.
Epidemiology
Hemodialysis was one of the most common procedures performed in U.S. hospitals in 2011, occurring in 909,000 stays (a rate of 29 stays per 10,000 population). This was an increase of 68 percent from 1997, when there were 473,000 stays. It was the fifth most common procedure for patients aged 45–64 years.
History
Many have played a role in developing dialysis as a practical treatment for renal failure, starting with Thomas Graham of
Glasgow
Glasgow ( ; sco, Glesca or ; gd, Glaschu ) is the most populous city in Scotland and the fourth-most populous city in the United Kingdom, as well as being the 27th largest city by population in Europe. In 2020, it had an estimated popul ...
, who first presented the principles of solute transport across a semipermeable membrane in 1854. The artificial kidney was first developed by
Abel
Abel ''Hábel''; ar, هابيل, Hābīl is a Biblical figure in the Book of Genesis within Abrahamic religions. He was the younger brother of Cain, and the younger son of Adam and Eve, the first couple in Biblical history. He was a shepherd ...
, Rountree, and Turner in 1913, the first hemodialysis in a human being was by Haas (February 28, 1924) and the artificial kidney was developed into a clinically useful apparatus by
Kolff
Kolff (also: Van Santen Kolff, Kolff van Oosterwijk and Van Breda Kolff) is the name of a Dutch patrician family originating from the provinces of Holland and Gelderland in the Netherlands.
History
First known Kolffs are Wouter, Aernt Woutersz., W ...
in 1943 – 1945. This research showed that life could be prolonged in patients dying of
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
.
Willem Kolff
Willem Johan "Pim" Kolff (February 14, 1911 – February 11, 2009) was a pioneer of hemodialysis, artificial heart, as well as in the entire field of artificial organs. Willem was a member of the Kolff family, an old Dutch patrician fam ...
was the first to construct a working dialyzer in 1943. The first successfully treated patient was a 67-year-old woman in uremic coma who regained consciousness after 11 hours of hemodialysis with Kolff's dialyzer in 1945. At the time of its creation, Kolff's goal was to provide life support during recovery from acute renal failure. After
World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
ended, Kolff donated the five dialyzers he had made to hospitals around the world, including
Mount Sinai Hospital, New York
Mount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. It is located in East Harlem in the New York City borough of Manhattan, on the eastern border of Central Park stretching along Madis ...
. Kolff gave a set of blueprints for his hemodialysis machine to George Thorn at the
Peter Bent Brigham Hospital
Brigham and Women's Hospital (BWH) is the second largest teaching hospital of Harvard Medical School and the largest hospital in the Longwood Medical Area in Boston, Massachusetts. Along with Massachusetts General Hospital, it is one of the two f ...
in
Boston
Boston (), officially the City of Boston, is the state capital and most populous city of the Commonwealth of Massachusetts, as well as the cultural and financial center of the New England region of the United States. It is the 24th- mo ...
. This led to the manufacture of the next generation of Kolff's dialyzer, a
stainless steel
Stainless steel is an alloy of iron that is resistant to rusting and corrosion. It contains at least 11% chromium and may contain elements such as carbon, other nonmetals and metals to obtain other desired properties. Stainless steel's corros ...
Kolff-Brigham dialysis machine.
According to McKellar (1999), a significant contribution to renal therapies was made by Canadian surgeon
Gordon Murray
Ian Gordon Murray (born 18 June 1946 in Durban, Union of South Africa), is a South African-born British designer of Formula One racing cars and the McLaren F1 road car. He is the founder and CEO of Gordon Murray Automotive.
Early life
Born t ...
with the assistance of two doctors, an undergraduate chemistry student, and research staff. Murray's work was conducted simultaneously and independently from that of Kolff. Murray's work led to the first successful artificial kidney built in North America in 1945–46, which was successfully used to treat a 26-year-old woman out of a uraemic coma in Toronto. The less-crude, more compact, second-generation "Murray-Roschlau" dialyser was invented in 1952–53, whose designs were stolen by German immigrant Erwin Halstrup, and passed off as his own (the "Halstrup–Baumann artificial kidney").
By the 1950s, Willem Kolff's invention of the dialyzer was used for acute renal failure, but it was not seen as a viable treatment for patients with stage 5 chronic kidney disease (CKD). At the time, doctors believed it was impossible for patients to have dialysis indefinitely for two reasons. First, they thought no man-made device could replace the function of kidneys over the long term. In addition, a patient undergoing dialysis developed damaged veins and arteries, so that after several treatments, it became difficult to find a vessel to access the patient's blood.
The original Kolff kidney was not very useful clinically, because it did not allow for removal of excess fluid. Swedish professor
Nils Alwall
Nils Alwall (1904, Kiaby – 1986) was a Swedish professor at Lund University, Sweden. He was a pioneer in hemodialysis and the inventor of one of the first practical dialysis machines. Alwall pioneered the technique of ultrafiltration and in ...
encased a modified version of this kidney inside a stainless steel canister, to which a negative pressure could be applied, in this way effecting the first truly practical application of hemodialysis, which was done in 1946 at the
University of Lund
, motto = Ad utrumque
, mottoeng = Prepared for both
, established =
, type = Public research university
, budget = SEK 9 billion Holger Crafoord to found one of the key companies that would manufacture dialysis equipment in the past 50 years, Gambro. The early history of dialysis has been reviewed by
Stanley Shaldon
Stanley Shaldon (8 November 1931 – 20 December 2013) was a British nephrologist who pioneered several techniques in haemodialysis, including venous access, reuse of dialysis machines, and home haemodialysis.
Life and career
Shaldon was born i ...
.
Belding H. Scribner
Belding Hibbard Scribner (January 18, 1921 – June 19, 2003) was an American physician and a pioneer in kidney dialysis.
Biography
Scribner received his medical degree from Stanford University in 1945. After completing his postgraduate s ...
, working with the biomechanical engineer
Wayne Quinton Wayne Everett Quinton (January 4, 1921 – January 22, 2015) was a developer of over 30 biomedical devices, including the Quinton catheter. He also invented a lightweight treadmill, for cardiac stress testing - the prototype of those used in fitne ...
, modified the glass shunts used by Alwall by making them from
Teflon
Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer of tetrafluoroethylene that has numerous applications. It is one of the best-known and widely applied PFAS. The commonly known brand name of PTFE-based composition is Teflon by Chemou ...
. Another key improvement was to connect them to a short piece of silicone elastomer tubing. This formed the basis of the so-called Scribner shunt, perhaps more properly called the Quinton-Scribner shunt. After treatment, the circulatory access would be kept open by connecting the two tubes outside the body using a small U-shaped Teflon tube, which would shunt the blood from the tube in the artery back to the tube in the vein.
In 1962, Scribner started the world's first outpatient dialysis facility, the Seattle Artificial Kidney Center, later renamed the
Northwest Kidney Centers
Northwest Kidney Centers is a regional, not-for-profit community-based provider of kidney dialysis, public health education, and research into the causes and treatments of chronic kidney disease. Established in Seattle in 1962, it was the world's ...
. Immediately the problem arose of who should be given dialysis, since demand far exceeded the capacity of the six dialysis machines at the center. Scribner decided that he would not make the decision about who would receive dialysis and who would not. Instead, the choices would be made by an anonymous committee, which could be viewed as one of the first
bioethics
Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...
committees.
For a detailed history of successful and unsuccessful attempts at dialysis, including pioneers such as Abel and Roundtree, Haas, and Necheles, see this review by Kjellstrand.Kjellstrand CM. History of Dialysis, Men and Ideas. Talk given to the Nordic Nephrology Days Symposium, Lund, 1997 as archived on HDCN. /ref>
See also
*
Dialysis disequilibrium syndrome
Dialysis disequilibrium syndrome (DDS) is the collection of neurological sign (medicine), signs and symptoms, attributed to cerebral edema, during or following shortly after intermittent hemodialysis or CRRT.
Classically, DDS arises in individua ...
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...