Renal Replacement Therapy

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Introduction

The different types of renal replacement therapies include haemodialysis, peritoneal dialysis, haemofiltration, and renal transplation.

Haemodialysis (HD)

This can be carried out on an outpatient or an inpatient basis. In the context of this explanation it is considered as an inpatient procedure.

Haemodialysis involves diffusion of solutes across a semi-permeable membrane, i.e. the process normally carried out in the kidneys to remove waste products from blood. The dialysis machine utilises counter current flow whereby the dialysis solution flows in opposite direction to blood flow in an external circuit. The counter current process helps to maintain the maximum possible gradient across the semi-permeable membrane, thus increasing the efficiency of the dialysis.

The dialysis solution,called dialysate,contains low concentrations of urea, potassium and phosphate to allow these substances to diffuse out of the blood. The concentration of sodium and chloride are similar to that in plasma so as to prevent the loss of these electrolytes. There is often a higher amount of bicarbonate and glucose in dialysate than that present in the blood to help correct acidosis and provide energy respectively.

Blood flow during dialysis is usually 200-300 ml/min, whilst dialysate flow is 500 ml/min.

Synthetic membranes allow for a faster rate of dialysis than cellulose-based membranes.

All patients are treated with heparin during dialysis to prevent formation of clots against the foreign surface.

Access

Adequate access requires blood flow of at least 200 ml/min.

There are three main modes of access. The modality used depends on the predicted length of treatment, and the condition of the patient’s vasculature. The three types of access are cannulation, arteriovenous (AV) fistula and synthetic graft. Often initially a cannula is used, whilst an implanted AV fistula or graft matures.

Catheter, aka cannula

This is sometimes called a CVC, i.e. central venous catheter. A large vein is used – usually the vena cava, internal jugular or femoral vein. The catheter has two lumens, or sometimes two catheters are used, one to withdraw the blood and the other to deliver it back to the body from the dialysis machine. With this method, the level of blood flow is never as good as that that can be obtained from a fistula or graft.

There are two types of catheter – tunnelled and non-tunnelled. Non-tunnelled tend to be used in the short term, for up to 10 days, but usually only for one session of dialysis. This type of catheter exits the skin at the site of the catheter. It may be used for emergency haemodialysis. The tunnelled variety are often inserted into the internal jugular vein, and travel a long way under the skin before entering the vein in order to reduce the risk of infection travelling to the site of the vein. Tunnelled catheters are for more long-term use and so are usually used in ARF where the patient is expected to recover within a few weeks’ time.

Infection and venous stenosis are potential risks of catheterisation. Stenosis occurs due to inflammation of the vein at the catheter entrance site. This can lead to occlusion and scarring of the vein, rendering it useless due to poor blood flow. Stenosis may also mean that this vein can’t be used for future access, and this can be a major problem in some patients who run out of access sites, translating into a fatal situation.

AV fistula

This is the preferred access method. A surgeon needs to join an artery and a vein together to allow this type of access. This then means that blood by-passes capillaries, and as a result the blood flow rate is markedly increased. The ‘thrill’ of blood flow can be palpated by running a finger over the fistula site.

The fistula is usually created in the non-dominant arm, and is usually inserted between the radial artery and cephalic vein, resulting in a radiocephalic fistula. It is usually visible on the anterior surface of the wrist. The fistula will take several, i.e. 4-8, weeks to mature before it can be used for haemodialysis. And after it has matured, two needles will be inserted into the vein side of the access site, one to remove blood, and the other to return it to the body. The advantages of a fistula are:

Increased rate of flow of blood, thereby:
- Increasing the effectiveness of haemodialysis
- Reducing the risk of thrombosis
Reduced risk of inflammatory reaction through the avoidance of foreign grafts or cannulas.

Generally, there aren’t any complications, but sometimes “steal syndrome” can occur. This is the result of blood travelling through the fistula, and straight into the vein and back out of the arm, bypassing the arm capillaries. This leads to cold extremities, cramps, and sometimes even tissue damage.

Over time, the vein side of the fistula may turn into an aneurysm through the frequent insertion of needles. This can be avoided by using careful needle insertion technique and rotating needle placement sites. Another technique, known as the “buttonhole technique”, involves sticking a blunt needle in the same place each time.

AV graft

This is used when either anatomical variation doesn’t allow for the easy creation of an AV fistula, or when there is arterial disease, such as in diabetes mellitus. The graft is usually made of the synthetic material PTFE, although sometimes a vein from an animal is used. It will join an artery and a vein in the same way a fistula does. Grafts do not take as long to mature as fistulas, but they do cause more complications. The vein joined to the graft tends to narrow, and this predisposes the patient to clot formation, as does the fact that foreign material has been inserted into the body.

Two-year graft patency is only 50-60%.

In the case of CKD that requires dialysis, HD is normally carried out about 3 times a week for 4 hours at a time.

Recall that bicarbonate is used at the buffer in the dialysate.

Complications of HD

The most common complication as a result of dialysis is hypotension. This is caused by excessive removal of fluid during the process, as well as left ventricular hypertrophy and abnormalities of venous tone.

Rarely, patients may have an anaphylactic reaction to ethylene oxide which is used to sterilise dialysis machines.

Haemolytic reactions, air embolus and “hard water syndrome” in areas where the local water supply has a high concentration of calcium, are other potential complications. In the last scenario, the water used to make up the dialysate is not softened, thereby causing nausea, hypertension, headache, confusion, memory loss, and sometimes seizures.

The symptoms of underdialysis are vague and include insomnia, itching, fatigue despite adequate correction of anaemia, peripheral sensory neuropathy and “restless legs”. Optimum results from dialysis are seen when long dialysis sessions, >8 hours in length, are carried out. This allows for better removal of small molecules such as urea. Recall that the kidneys carry out this function 24/7, but on dialysis this is only achieved for a few hours each week.

Haemodialysis is the best way of achieving quick filtration and balancing solute concentration in the blood.

In ill patients with multi-organ disease, HD can upset normal haemodynamic balance, resulting in nausea, vomiting, restlessness, headache, hypertension, and even coma and seizures. All of this is caused by sudden plasma imbalance causing cerebral oedema. The life-threatening nature of cerebral oedema has lead to the development of alternative treatments.

Peritoneal dialysis (PD)

In this procedure, dialysate is placed in the peritoneal cavity and the peritoneal membrane serves as the surface across which filtration occurs. As the peritoneal membrane is well-perfused by many blood vessels, the dialysate readily draws out water and certain solutes from circulation. The dialysate used in PD has a very high concentration of glucose or glucose polymer, i.e. icodextrin, which creates a high osmotic pressure, helping to draw waste products out of the blood.

PD is considered a “low-tech” methodcompared to haemodialysis. The fluid enters and exits the abdomen through a permanent catheter that has to be placed surgically. In this way the catheter can be used for many years.

PD is less effective than HD; therefore, it needs to be carried out over a longer period of time.

The treatment is carried out at home, not in an in-patient or even outpatient setting, requiring significant motivation on behalf of the patient. Some patients enjoy the freedom from a medical facility because PD can be carried out wherever and whenever as it requires a minimal amount of equipment. Many patients also prefer it to HD because it does not involve any needles. PD is considered a “gentler” treatment as the dialysis process is undertaken over a longer period of time. Some researchers have used this point to argue that patients undertaking PD therefore have a better long-term prognosis due to preservation of kidney function. Continuous PD treatments reduce the risk of cardiovascular effects, as opposed to intermittent ones.

Types of PD

Continuous ambulatory peritoneal dialysis (CAPD) – dialysate remains in the peritoneal cavity continuously and exchanges of the dialysate are made 3 to 5 times a day, taking about 20-40 minutes per exchange. This type of treatment tends to be used in the hospital setting in end-stage renal failure.
Automated peritoneal dialysis (APD) – a machine exchanges the dialysate during the night while the patient is sleeping. Often the fluid may be left in the peritoneal cavity during the day to increase the effectiveness of the dialysis. NIPD can lead to peritonitis, as well as infection of the cannula site. And after many years of treatment the peritoneum may lose its ability to perform this job, necessitating a switch to HD.
Tidal peritoneal dialysis (TPD) – another intermittent technique; consists of fluid exchanges in which the peritoneal cavity always contains at least some dialysate, improving comfort and facilitates drainage in some patients.

Complications

Peritonitis – bacterial peritonitis is the most serious complication. This generally presents as abdominal pain of varying severity where guarding and rebound tenderness are unusual. There is also always a cloudy effluent from the cavity, and its presence is necessary for diagnosis. If the peritonitis is severe it may be accompanied by vomiting, nausea and paralytic ileus. Peritonitis will occur once every two patient-years in those on CAPD.
- Analyse the peritoneal fluid to establish to the causatory organism, and check for a neutrophil count >100 cells/ml to confirm diagnosis. Until positive identification is received use a wide-spectrum antibiotic.
- Continuous re-infection with the same organism suggests that the Tenckhoff catheter, i.e. the site where fluid enters the abdominal cavity, has become colonised. This requires replacement of the catheter.
- If both Gram-negative and anaerobic organisms are present, this is highly suggestive of bowel perforation, an indication for laparotomy.
- Sometimes, fungal infection follows the bacterial peritonitis, and this can be particularly difficult to get rid of.
Local infection around the catheter site is very common. This should be treated aggressively with local and systemic antibiotics to avoid spread.
Other complications
- Constipation – this is associated with CAPD and can be troublesome at it impairs the flow of dialysate.
- Pleural effusion – this is occurs when dialysate leaks through a diaphragmatic defect into the thoracic cavity. This can be differentiated from a true pleural effusion usually by examining the glucose content of the fluid. It is also possible for fluid to leak into the scrotum.
- Failure of peritoneal membrane function –this tends to occur in many patients over the longer term with continued CAPD. It reduces the effectiveness of dialysis. The more hypertonic the dialysate used, the worse this issue tends to be.
- Sclerosing peritonitis –the peritoneal membrane becomes thickened and there is also a high risk of adhesions and strictures. This is a potentially fatal complication. It can turn the small bowel into loops of matted mess thereby causing small bowel obstruction. It is caused by recurrent peritonitis and exposure of the peritoneum to high levels of glucose. When this occurs CAPD should be stopped, although the situation can improved with the administration of prednisolone or azathioprine.

Older patients, and those in end-stage renal failure with cardiovascular complications have a higher morbidity and mortality on CAPD than on HD; young patients tend to do better on CAPD.

Those with abdominal hernias should have them repaired prior to PD as raising intra-abdominal pressure can cause problems later on.

Patients with stomas are not encouraged to undertake PD.

Active intra-abdominal sepsis, such as that seen in diverticular disease is also likely to be an issue for this treatment; however this does not mean that patients with known diverticulae should be prevented from having it.

In terms of removal of waste products, this treatment isn’t as effective as HD. In particular, the treatment is inadequate once renal function declines to zero.

Haemofiltration

It is similar to haemodialysis but it is used almost completely in the intensive care setting, i.e. it is only indicated in acute renal failure! In this procedure, dialysate is not used. Sessions last between 12 to 24 hours and are usually performed daily, requiring a large amount of fluid exchange, up to 22 litres, at one time.

During haemofiltration, the patient’s blood is mechanically passed through a filtration circuit, i.e. a set of tubing, to a semi-permeable membrane, i.e. the filter, where waste products and water are removed. Replacement fluid is then added and the blood is returned to the patient.

There is still a “blood compartment” and a “filtrate’ compartment”, however the filtrate compartment is empty before the procedure begins, and blood products, including water and electrolytes, are driven out across the semi-permeable membrane and drained away. In this method, larger solutes tend to be left in the blood, whilst smaller ones are filtered out.

After this process, a solution containing necessary solutes is then put into the blood. This solution must be pure because it is infused directly into the patient’s blood.

Much of the equipment is very expensive and is also disposable; therefore not many patients are managed using this method on the NHS. However, in the ITU setting, the overall cost is reduced, as ITU nurses can operate the equipment without holding a qualification in renal dialysis.

The treatment can also be combined with haemodialysis to give haemodiafiltration. There is some early evidence to suggest that this is more effective than either of the two treatments on their own.

Adverse cardiovascular effects are reduced in haemofiltration when compared with haemodialysis.

Bicarbonate is not used as the buffer, as is the case in HD, in the haemofiltration dialysate. Instead, lactate is used. This is because bicarbonate can react with acetate when it is rapidly infused, resulting in the formation of crystals of calcium carbonate.

Continual Renal Replacement Therapy (CRRT)

The patient’s own blood pressure, or a small pump, draws the patient’s blood out of a dual-lumen catheter placed in the jugular, cubclavian or femoral vein, and runs it through a small filter. The treatment is continuous, thereby producing a better filtering effect than intermittent treatments.

Evidence suggests that there is no improvement in mortality between HD and CRRT, and thus there is no “best option”. Traditionally, most patients are on HD. In patients unsuited to HD, CRRT is usually the alternative choice.

Filtration membranes

There are two basic types – cellulose-based, or synthetic. Neither one offers a clear benefit with regard to improving the remaining kidney function; however, the synthetic variety does offer significantly better biocompatibility. This means that the body doesn’t recognise the substance as foreign, thus overall survival rates are enhanced using synthetic membranes.

Acute renal failure in the intensive care setting

Many renal failure patients with co-existing conditions such as multi-organ failure, sepsis and cardiovascular instability are treated in intensive care. In this setting, considerable benefits are derived from using constant as opposed to intermittent therapies. These benefits are as follow:

Reduced disturbance of cardiovascular system
Ability to generate “spare” fluid for administration later, e.g. in cases of hypovolaemia
Removal of potentially harmful substances, such as inflammatory cytokines through the larger filtration slits of haemofiltration membranes

General complications of long-term dialysis

Most patients will die from cardiovascular disease and sepsis. The causes of fatal sepsis tend to be Staphylococcus aureusinfections in patients with permanent access routes for haemodialysis, and peritonitis in patients with peritoneal dialysis.
Dialysis amyloidosis – this is the accumulation of amyloid protein as a result of dialysis. Celluose dialysis membranes do not allow the large β2-microglobulin protein to pass through their membranes, as would happen in normal filtration. Thus these proteins build up, and in a non-enzymatic glycosylation reaction, these proteins form amyloid deposits which can cause nerve compression, leading to pain in most joints, and possibly carpal tunnel syndrome. This condition rapidly improves after transplantation – owing to both the transplant itself, and the steroid therapy that goes along with it; prednisolone alone is beneficial.

Indications for Renal Replacement Therapy

In CKD

When to start dialysis in CKD a contentious issue. A rough guide would be:

eGFR <10 ml/minute, OR
eGFR <15 ml/minute in patient with diabetes

There is no evidence that early dialysis improves outcomes. However, late dialysis often results in marked malnutrition (perhaps due to protein loss).

Refer patients to a renal specialist when eGFR <30 ml/minute to consider their options

In AKI

Dialysis is also frequently used in AKI. In this circumstance, the on of the main indications is the potassium level (usually >6.5mmol/L for AKI, but 7.0 mmol/L in CKD). In AKI, other considerations include:

Sodium >155 mmol/L or <120 mmol/L
Severe acidosis (pH <7.0) – not responsive to bicarbonate
Severe renal failure – e.g. creatinine >500, urea >30 mmol/L
Drug toxicity with drugs than can be dialysed

Prognosis

Prognosis in AKI is worse if oliguria is present. Mortality is dependent on the cause:

80% in those with burns
60% in those having trauma/surgery
30% in those with medical illness
10% in those with poisoning