Introduction
Dialysis has prolonged life of many patients with Acute Renal failure and Chronic Kidney Disease (CKD) owing to irreversible nature of the disease and renal transplant not being an open option for all patients. Let us first understand brief about Acute Renal Failure and Chronic Renal Failure.
Acute Renal Failure (ARF) is a syndrome which is characterized by declining glomerular filtration rate which may extend to hours to weeks, as a result of which accumulation of nitrogenous waste products, and disturbance in extracellular fluid, and acid base balance takes place. Of all hospital admissions 5 percent are in ARF. Generally a patient presents with oligourea (less than 400mL/day) and recent increase in urea and creatinine. ARF can be outcome of hypoperfusion of kidney tissue, damage to parenchymal tissue of kidney, or urinary tract obstruction.
ARF is reversible therefore urgent management of it leads to almost complete recovery of kidney function (BRADY HR et al: 1996).
Renal injury of prolonged duration leads to irreversible destruction of kidney tissue. As a result of this remaining kidney tissue enlarges and predisposes kidneys to sclerosis of remaining glomerular tissue. Most common causes of Chronic Kidney Disease (CKD) are diabetes mellitus, hypertension and glomerulonephritis (ANDERSON S, BRENNER BM: 1989).
Uremia refers to clinical manifestations that accrue due to loss of renal mass. It pertains to accumulation of urea and other metabolities which are normally excreted in urine. In early stages of CKD, when glomerular filtration is lost to about 35 to 50 percent of normal- overall function is still sufficient to keep patient symptoms free. At renal function of 20 percent and below a patient develops overt renal failure at which stage medical intervention can save life of patient from myriad of infections and complications of the disease.
Patients with End Stage Renal Disease eventually require some type of dialysis or kidney transplant if that is indicated.
Dialysis
Dialysis is also called as renal replacement therapy because it is considered as artificial replacement of kidneys. Dialysis is indicated for ARF or patients with CKD. As indicated above derangement of functions due to loss of functions of kidney can be prevented on equilibrium water and minerals. Although dialysis cannot replenish overall functions of kidney specially endocrine functions(production of erythropoietin and 1,25-dihydroxycholecalciferol) yet it rids of toxins that are lethal to our body tissues.
Dialysis is a process of removing blood from a patient whose kidney function is impaired so that nitrogenous waste products remain in blood thereby filling circulatory system with toxins and waste products of metabolism. Generally, dialysis should not be initiated in CKD if the patient is totally asymptomatic, yet it should be indicated if risk of complication of this debilitating disease overweigh risks of dialysis.
There are two main principles involved in dialysis: diffusion of solutes and ultra filtration of fluid on semipermeable membranes. Concentration of undesired solutes such as urea and creatinine are removed from blood. Similarly concentration of a substance which is greater in blood is kept at low on the side of dialysate to remove it from blood by the process of diffusion. For biocarbonate it is set at higher levels on the side of dialysate to increase its concentration on blood side of semipermeable membrane. It should be remembered that biocarbonate is necessary for maintanence of acid base balance in body (Graham T 1854).
In other patients risk to benefit ratio should be proportionated. Relation of Uremia symptoms to Renal functions tests varies from patient to patient depending upon the cause of disease such as diabetes mellitis, muscle mass; more muscular a patient more time it tolerates high levels of Azotemia, diet and nutritional status.
Who requires dialysis
Those patients require dialysis when amount of toxins in their bodies become high and they become debilitated. This is quite a slow process. About 20 percent of kidney function relative to normal remain when patient start to enter into azotemia. Two major chemical indicators are blood urea nitrogen(BUN) and creatinine. Escalating levels of these chemicals indicate that renal tissue is unable to excrete toxins from body. The ‘ creatinine clearance test’ is done when patient is asked to collect his urine for whole day. Then creatine is measured in blood and in urine. Therefore, when creatinine clearance falls to 10-12 cc/minute, the patient needs dialysis. If creatine clearance has not fallen to this level but the patient complains of problems in any major organ system, heart , lungs or blood, tingling sensation in legs even then dialysis may be indicated.
Types of dialysis
Hemodialysis
In this process patients blood is pumped through blood compartment of dialyzer, to a semipermeable membrane. Purified blood is returned to body after that. Negative pressure is developed on the dialysate side to allow ultrafiltration , which filtrates water and other solutes. Hemodialysis can be performed in hospital setting as well as in home. Typically home dialysis is easy to carry out for patients.
Peritoneal dialysis
Peritoneal dialysis like home dialysis can be performed in many settings. In this type of dialysis peritoneal membrane works as a semipermeable membrane. Dialysate is left in peritoneal cavity to allow exchange of fluid and solutes , then it is drained back to exterior. In this procedure a more concentrated fluid is used such as glucose , which cause osmosis of fluid from blood to dialysate. This procedure was developed in 1978, a concept called continous peritoneal lavage with prolonged dwell times.
Permanent peritoneal catheter –tenck hoff catheter is used for chronic peritoneal dialysis. Patients are treated for 2 to 3 times a week for total of upto 40 hours. Advantage of peritoneal dialysis include avoidance of heparinization and vascular surgery. It is good for self treatment. Disadvantages of this system is longer duration of treatment times. (Keane WF:1991)
Hemofiltration
In this process no dialysate is used but only blood is passed through hemofilter, then pressure gradient is applied which cause movement of fluid from blood side to another side of the membrane. Substitution fluid is given in exchange to fluid filtered by this procedure.
Hemodialysis
Process of hemodialysis involves diffusion across semipermeable membrane to remove unwanted substances from blood such as potassium and urea as well as free water from blood when kidneys are functionless i.e. renal failure it also involves addition of desirable components to blood. Hemodialysis can be done in hospital or at home. In hospital setting it requires proper staff to look after proceedings and careful monitoring of blood chemistry.
Principles of hemodialysis are essentially same as of dialysis; Blood flow is constantly provided from one side of the membrane and on the other side of it a cleansing solution called dialysate is placed, which allows removal of waste products by the process of diffusion and convection.
Dr. Willem Kolff was the first person to make working dialyzer in 1943. It was used for acute renal failure. In 1962 Scribner started first outpatient dialysis facility.
With composition of dialysate, method of exposure of blood, type and surface area of semipermeable membrane and frequency and duration of exposure, patients can be safely managed in healthy state.
Access to blood to be dialyzed
There are three routes to get access to blood. An ateriovenous fistula, synthetic graft, or intravenous(internal jugular vein). Due to many complications of each procedure usually a multiple access may be desirable to help prevent complications.
AV fistula are preferred over other methods. A fistula is created by anastomosing artery with vein. Depending on the location of fistula and arteries and veins emplyed for the use, they are named as snuffbox’ fistula, radiocephalic fistula in which radial artery is anastomosed with cephalic vein, brachiocephalic fistula, in which brachial artery is united with cephalic vein. Reason for creating fistula is to establish fast flow of blood since it needs to be at 300 to 450 mL/min to be effectively dialyzed in hemodialysis process. Main advantages of AV fistula are high blood flow rates, lowered incidence of infection.
AV graft is achieved by placing artificial vessel made of polytetrafluroethylene (PTFE). These are set when AV fistula can not be setup due to phlebitis, fibrosis of veins due to repeated needling or due to any other reason. PTFE are set between an artery and a nearby vein as a bridge. There is often risk of clotting or thrombosis. It can also get infected very easily.
Intravenous Catheter is made up of plastic with two lumens. The catheter is inserted into a large vein such as internal jugular vein or the femoral vein. It is noted that blood flow of intravenous catheter is comparatively lower than fistula or graft.
Venous stenosis is a major complication of catheter use perhaps because catheter initiates inflammatory response in venous walls.
Hemodialysis machine
Hemodialysis machine basically consist of three main parts- the blood delivery system, the composition and delivery system of the dialysate, and the dialysate itself. Blood flow through the system is kept at 300 to 450 mL/min. desirable ultrafilteration can be achieved by adjusting dialysate negative hydrostatic pressure. Ultrafiltration coeffiecient refers to how many mL of blood is removed per mmHg/min, this coefficient is variable for different dialysis membranes. The dialysate, of which composition is similar to plasma, is delivered to the dialyzer from a storage tank which prepares dialysate when required. In different types of machines , dialysate passes one time across membrane, countercurrent to blood flow at rate of 500 mL/min. The composition of dialysate may be altered depending on the need. Concentration of potassium is varied most often, whereas that of calcium, chloride, and biocarbonate is maintained at same level in each unit. Sodium modeling can be changed to improve removal of fluid. A single blinded, crossover study conducted in 10 hemodialysis patients with previous history of itradialytic hypotension suggested that number of hypotensive signs and symptoms was lowered with sodium modeling procedure. Use of sodium modeling was supported as first line treatment for hypotension associated with dialysis. Ultrafiltration removes fluid from blood which causes fluid from tissues to be reimbursed to blood vessels, with it electrolytes are also lost; if fluid loss is great enough it can cause cramps and low blood pressure. Sodium modeling is done to prevent this from happening. It increases amount of fluid in dialysate because sodium draws more water but it keeps sodium in blood to remain in it (Sunita dheenan and William L Henrich:2000)
Presence of water purification system is essential feature of hemodialysis. Aim of this is to prevent any infection or contaminant to gain entry into patients blood. pH of water is adjusted by adding acid or base. Water is purified by passing it through very tiny pored membrane so that any solute in it may be left over on other side of the water. Then ion exchange resins may be used to remove anions or cat-ions. Conductivity of dialysis solution is in strict check to see water and dialysate mix in proper amounts.
Modern dialysis machines have safety critical parameters. Blood flow and dialysate flow rates, temperature, pH may be shown on the machine.
Most common dialyzer in United States is Capillary Dialyzer or hollow fiber variety. A cylindrical bundle of hollow fibers is attached with potting compound. This is in turn placed into a clear plastic cylindrical shell with four openings.
The membrane has several thousand capillaries with blood flowing through them while dialysate is circulated on outside of this membrane. These membranes are of different pore sizes, small pored let only small molecules pass through, therefore they are called as low flux. Membrane with large pore are called as high flux.
Type of the membrane used, and its surface area determine ultrafiltration and clearance. This is also important with respect to its biocompatibility. Polyacrynitrile, polymethymethacrylate, and polysulphon are porous and biocompatible as compared with cupra ammonium cellophane and cellulose acetate which are tighter membranes with less diffusive and ultrafiltrative ablities.
Current dialysis techniques require at least 9 to 12 hours of dialysis per week, divided into multiple sessions. Variable time is due to residual renal function, dietary intake, any other illness, rate of metabolism. Dialysis duration, frequency of treatment, type and size of dialyzer, dialysate composition can all be adjusted to meet individual needs.
It is currently recommended that high flux membranes be used since these remove beta-2-microglobulin accumulation. Accumulation of beta 2 microglobulin has many complications, which will be discussed under the heading complications of hemodialysis below (Maldague B, Jamart J :1991).
Dialyzer can be reused provided it is sufficiently disinfected. If dialyzers are reused with precautions, then similar outcomes to single use dialyzers may be achieved. (Küchle C, Fricke H, Held E, Schiffl H (1996).
Desirable values for hemodialysis
Patient on hemodialysis should have atleast URR (Urea Reduction Ratio) of 65 percent. This can be measured by pre and postdialysis urea sample. It is noted that reduction of dialysis time without accompanying reduction in URR increases mortality rate and patient complications.
Complications of hemodialysis
Complications of hemodialysis are due to the procedure, unresolved uremia, direct complications of clearance and ultrafiltration, and complication due to longer duration of treatment.
Blood flow of 300 to 450 mL/min is required for effective hemodialysis. As this blood is not possible with blood flowing in veins, and repeated puncture of artery is not useful, therefore anastomosing a superficial artery to a nearby vein is achieved to create fistula. If vein is not available due to any reason, or fibrosis then venous graft made of PTFE may be bridged between vein and artery. This fistula can be complicated by infection and aneurysms. Aneurysm is a bulging in the wall of the vein where its smooth muscle is weakened. Careful needling techniques may prevent this complication.
With fistula there is always risk that blood may be diverted to general circulation without first passing into capillaries from which it would normally flow, resulting into cold extremities, cramping pain and if severe can lead to necrosis.
Additionally, there is always risk of septicemia and septic embolism. Infection with staphylococcus aureus is common with indweling intravenous catheter.
With dialysis rapid changes may lead to disruption of ions leading to arrhthymia. As indicated above hyptension is a common complication of dialysis. There are many factors which may lead towards it, such as degree of ulfiltration, changes in serum osmolality, the size of extracorporeal circulation, removal of catecholamines, concomitant use of antihypertensive drug therapy.
Occurrence of dialysis dementia (indicated by decreasing mental function with seizure activity and abnormal electroencephalogram), low turnover osteomalacia, and microcytic anemia may be secondary to aluminum hydroxide. These complications have lessened in recent year due to awareness.
Incidence of hepatitis B surface antigen (HBS Ag) and hepatitis C(Anti HCV) is due to increased rate of transfusion. It should be noted that as kidney function deteriorate in Chronic Kidney Disease, and so does endocrinal functions associated with kidney. Erythropoietin which is necessary for production of blood cells is absent which leads to anemia. Therefore multiple transfusions and patient is thereby exposed to great risk of hepatitis.
Mechanical and iatrogenic complications such as hemolysis, air embolus, blood leaks, and contaminated equipment. There can be membrane induced adverse reactions, as indicated by complement mediated leukopenia and hypoxemia. Some times bronchospasm and anaphylatic shock can occur.
It is noted that these cytokines along with decreased excretion of B2-microglobulin lead to the dialysis related amyloidosis- this syndrome include myriad of other diseases and syndromes : carpal tunnel syndrome, destructive spondyloarthropathy, cervicooccipital psuedotumors, cyst formation in the femoral head and neck, carpal bones, and humoral head, scapulohumoral periarthritis and visceral involved with amyloidosis.(Sprague SM: 1995) Use of more biocompatible membranes like polycrilonitrile, polysulfone has been suggested to have overall beneficial effects. There is disadvantage of their high cost however it can be cost effective if they are reused after proper disinfection.
Heparin is necessary during hemodialysis. But it has risks of its own: subdural hematoma, gastrointestinal bleeding.
Major cause of death in patients with CKD receiving dialysis remains to be cardiovascular disease. This is due to inadequate treatment of hypertension and due to persistent hyperlipidemia.
There is risk of malnutrition in patients on dialysis; it could be due to loss of excessive amino acids with membrane filtration, so there should be more aggressive feeding of these patients. It should contain meat, chicken, and fish. Simultaneously foods rich in potassium should be avoided such as bananas, oranges, and nuts. Too much potassium in circulation can cause arrhythmia.
In view of above complications, and risks of hemodialysis risk to benefit ratio of patient should be evaluate for the use of dialysis therapy. In comparison to peritoneal dialysis hemodialysis offers good prospects.
References
- BRADY HR et al: Acute renal failure, in The Kidney, 5th edition., BM Brenner(ed). Philadelphia, Sauners, 1996, pp 1200-1252
- ANDERSON S, BRENNER BM: Progressive renal disease: A disorder of adaptation. Q J Med 70:185. 1989
- Graham T: The Bakerian lecture—on osmotic force. Philos Trans RSoc Lond 1854, 144:177–228.
- Hemodialysis. Web.
- Keane WF et al: peritoneal dialysis related peritonitis treatment recommendations,1993 update, perit dial int 13:14, 1993
- van Ypersele de Strihou C, Jadoul M, Malghem J, Maldague B, Jamart J (1991). “Effect of dialysis membrane and patient’s age on signs of dialysis-related amyloidosis. The Working Party on Dialysis Amyloidosis“. Kidney Int.39 (5): 1012–9. Web.
- Küchle C, Fricke H, Held E, Schiffl H (1996). “High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis“. Am. J. Nephrol.16 (6): 484–8. Web.
- Preventing dialysis hypotension: A comparison of usual protective maneuvers Sunita Dheenan and William L Henrich
- +7. SPRAGE SM, POPOVTZER MM: Is B2- microglobulin a mediator of bone disease? Kidney Int 47:1, 1995