INTRODUCTION

Acute renal dysfunction or failure is a common occurrence in the intensive care unit (ICU).

The reported incidence of acute renal failure in the ICU varies and is dependent upon several factors including:

Definition of acute renal failure (this will be discussed later) Case mix of patients Whether the reported series is from a secondary or tertiary referral centre.

The incidence of acutely impaired renal function is very high in those patients dying in the ICU with sepsis or multiple organ failure.

In critically ill patients the kidney is usually an innocent bystander whose function is disturbed by the systemic effects of a disease process remote from the kidney. In general, preservation of renal function is best achieved by restoring and maintaining normal organ perfusion, avoiding nephrotoxic drugs and instituting effective treatment for the primary disease process.

Renal replacement therapy is required when renal function has been so badly affected that recovery will take several days or weeks and the patient is at risk from the side effects of renal failure. The aim is to provide a substitute for renal function to allow removal of the waste products normally excreted by the kidney. There have been many developments over the last twenty-five years that have simplified renal replacement therapy for the ICU patient suffering from acute renal failure.

It is essential that the intensivist has a clear understanding of the pathophysiology of acute renal failure and the means by which it can be treated or, more importantly, prevented.

Reference to the website of the Acute Dialysis Quality Initiative will be of value to accompany this module, see reference below. This site aims to distil the current evidence regarding the management of patients at risk of or suffering from acute renal failure. There is a constant increase in the data available at this site.

Renal failure in the ICU is usually secondary to other pathology and not primary renal disease

It is usually associated with multiple insults, most often hypovolaemia, hypotension and nephrotoxic drugs

Rule out any cause outside the kidney

 1/ HOW TO DIAGNOSE ACUTE RENAL FAILURE

What is the definition of renal failure?The primary function of the kidney is to eliminate water-soluble waste products of metabolism and other potentially toxic substances (e.g. drugs).

Acute renal failure is the sudden (and usually reversible) failure of the kidneys to excrete nitrogenous and other waste products causing loss of homeostasis and retention of these products within the body.

The investigation of acute renal failure in the critically ill has been hampered by the lack of consensus concerning the definitions of the severity of renal impairment. Most studies have used different criteria, making comparisons of treatment regimens impossibly difficult.

Chronic renal failure is the irreversible loss of, or reduction in, the capacity of the kidney to excrete nitrogenous and other waste products causing retention of these products within the body. This is due to a permanent loss of functioning renal mass.

In some circumstances acute renal failure occurring in the ICU patient may rarely progress to severe or permanent chronic renal failure.

NOTEThere is a continuum of acute impairment of renal function from rapidly reversible oligo-anuria to established acute renal failure. Early detection of impending renal impairment and prompt correction of the cause or causes will reduce the chance of the development of established acute renal failure.See the PACT module on Oliguria and anuria   for more information on this topic.

Clinical history

There are few symptoms of acute renal failure, particularly in the early stages, but an accurate and comprehensive history is essential. In many situations in the ICU the history will have to be gained from family and friends, the patient's family doctor, or a comprehensive review of the medical and nursing notes.

Specific information should be sought about: Symptoms suggestive of pre-existing renal disease, e.g.

nocturia, periods of total anuria, haematuria, renal colic Recent surgical procedures, trauma Recent episodes of hypotension, infection, coma or

prolonged immobility Past medical history e.g. obstructive uropathy, cardiac

disease, hypertension, peripheral vascular disease, chronic renal impairment, diabetes mellitus, liver disease,

A good history is vital for patient management

radiological contrast medium exposure, cancer treatment or transplantation

Family history of renal disease (e.g. polycystic kidneys)

Prescribed medication :o Antihypertensives e.g. angiotensin-converting

enzyme (ACE) inhibitors, β-blockers, diureticso Analgesics e.g. non-steroidal anti-inflammatory

drugs (NSAIDs), paracetamol (acetaminophen)o Antibioticso Chemotherapy and immunosuppressives e.g.

ciclosporin, platinum compounds Non-prescribed medication e.g. laxatives, recreational

drugs, herbal remedies, analgesics (particularly NSAIDs)

Confirm the importance of a complete history, particularly in relation to drug ingestion

In the next 10 cases you see of acute oliguria/renal failure assess the value and relevance of obtaining a complete history.

Why might ACE inhibitors precipitate oliguria in the ICU patient ?

Physical examination

Physical examination is commonly unhelpful in providing evidence of acute renal failure but the presence of hypotension, salt and water depletion, vasculitic lesions, hypersensitivity rash, enlarged kidneys or bladder should be sought.

Urinalysis must not be forgotten as this may provide valuable clues as to the underlying cause of renal failure.

Always perform urinalysis

 

3/ HOW TO MANAGE THE PATIENT WITH ACUTE RENAL FAILURE

COMMUNICATION Intensive care units should develop protocols for the management of oliguria/acute renal failure, including the role of the nephrology service.

Renal perfusionFrom what has been discussed above, it should be obvious that restoration of optimal renal perfusion is the first and most important step. This requires:

Correcting any deficit in the circulating volume Ensuring that cardiac output is adequate for the individual

patient Restoring perfusion pressure to a level that will allow

The first priority is to correct circulatory deficits and restore renal perfusion

Relationship of serum creatinine to creatinine clearance

glomerular filtration in the presence of impaired autoregulation. This will vary depending on the patients' normal blood pressure.

Relieving abdominal tamponade In rare cases restoring the patency of the aorta or renal

arteries

These interventions must be carried out in the sequence described.

What might be the adverse effects of attempting to restore perfusion pressure with vasopressors prior to the restoration of an adequate circulatory volume?

The selection of the most appropriate fluids, inotropes and vasopressors is discussed elsewhere, see the PACT modules on Oliguria and anuria  , Hypotension  , Sepsis and MODS   and Heart failure  . The evidence would suggest that dobutamine and norepinephrine, either alone or in combination depending on the haemodynamic disturbance, are the agents of choice.

In many situations achieving these goals will result in the restoration of urine production by ensuring filtration in the face of impaired autoregulation.

ANECDOTE An example of this effect is seen (figure below) in this young adult with meningococcal sepsis whose mean arterial pressure, urinary output and metabolic acidosis were not corrected by volume replacement and antibiotics alone. Norepinephrine was commenced and titrated to increase the MAP. The metabolic acidosis resolved and urinary output increased, with a fall in serum creatinine.

Patency of lower urinary tractOnce circulatory abnormalities have been corrected the next step is to ensure that there is no obstruction of the lower urinary tract (e.g. bladder catheterisation, imaging of the lower urinary tract by ultrasound or CT scan.)

Infection within an obstructed urinary collecting system needs urgent drainage

 

COMMUNICATION Percutaneous nephrostomy may be required in the presence of ureteric obstruction. This can be performed in the intensive care unit under ultrasound guidance by an interventional radiologist.

Absolute anuria indicates an obstructed lower urinary tract until proven otherwise.

NOTEThe presence of infection within an obstructed collecting system requires emergency relief of the obstruction in addition to antimicrobial treatment. This is a surgical emergency and urological advice should be obtained without delay.

Without relief of the obstruction the kidney will be destroyed.

Relief of a chronically obstructed urinary tract may precipitate a massive diuresis. This is, in part, the result of an osmotic diuresis as retained solute is cleared, but more importantly is a consequence of damage to the distal nephron causing a salt and water losing state.

Haemofiltration processThis is a convective process in which a hydrostatic pressure gradient is used to filter plasma water and solute across a membrane. This fluid is then discarded. The properties of the membrane determine the size and charge of the solute that can be removed and the rate at which water will be filtered for any given driving pressure. This process mimics the function of the glomerulus. Excess water and essential solute that is lost in the filtrate must be replaced from a sterile source of fluid.

Convection describes a process by which solutes are transported across a semipermeable membrane together with the solvent by means of filtration driven by a transmembrane pressure gradient

 

Haemodialysis processThis is a diffusive process where blood is passed over a semi-permeable membrane which separates it from an electrolyte solution flowing in the opposite direction. The electrolyte solution contains essential solute present in plasma water and waste solute is removed by its movement down a concentration gradient from plasma water into the electrolyte compartment (this fluid is commonly referred to as dialysate).

Diffusion describes a process of solute transport across a semi-permeable membrane driven by a concentration gradient such that the solute will tend to an equal concentration in the available distribution space on both sides of the membrane

 

 

Diagram representing diffusion through a semi-permeable membrane on the left and convection on the right

 

Renal replacement systems may rely predominantly on haemofiltration (convection) or haemodialysis (diffusion) but there are also systems that combine the two methods.

Nomenclature of renal replacement therapy

There is a plethora of acronyms that have been generated to describe the various techniques that have been employed to provide renal replacement therapy (RRT). A consensus statement has been produced for continuous renal replacement therapy.

Renal replacement therapy may be Intermittent or Continuous and is described and differentiated by the prefix I or C respectively.

It must be remembered that true continuous treatment is an aspiration and that there are many reasons (planned and unplanned) why treatment may be interrupted for variable lengths of time in caring for the critically ill.

The type of extracorporeal circuit is then described e.g. arterio-venous AV and pumped veno-venous VV. This is followed by the method of blood purification e.g. haemofiltration H, haemodiafiltration HDF, haemodialysis HD. Therefore continuous veno venous haemodiafiltration would be represented by CVVHDF. Examples will be seen later in this task. For more information about the nomenclature, see the following reference.

When to start RRT?

Absolute indications Uncontrollable hyperkalaemia. Salt and water overload causing or exacerbating severe

pulmonary oedema, which is unresponsive to diuretics or other measures.

Severe metabolic acidaemia in the face of acute renal failure e.g. ethylene glycol or metformin toxicity.

Complications of a high blood urea (azotaemia) causing symptoms of the clinical syndrome of uraemia such as pericarditis, encephalopathy, neuromyopathy or bleeding disorders.

Severe electrolytic disorders associated with renal failure e.g. hypercalcaemia, severe hyponatraemia.

Renal replacement therapy should be instituted on the basis of both the individual patient's disease process and biochemical results

Removal of a dialysable toxin e.g. Lithium carbonate. Raised blood urea (azotaemia). The absolute value of blood urea at which treatment

should be started is not universally agreed. The level of blood urea at which the symptoms of the uraemia syndrome are evident varies considerably between patients and the rate of rise of blood urea. A blood urea of over 40 mmol/l in a patient with no evidence of recovering renal function despite standard treatment, as described in Task 4, should receive prompt renal replacement therapy. Most would accept an upper limit of 30 mmol/l while receiving renal replacement therapy although many would prefer the limit to be closer to 20 mmol/l.

In the situation of a critically ill patient with no evidence of recovery of renal function despite standard supportive measures following a major insult or sepsis, the threshold for renal replacement therapy is much lower. The rise in urea will be rapid and it is probably unwise to allow the urea to rise above 30 mmol/l before starting treatment.

Start renal replacement therapy early rather than late

 

Starvation or limitation of protein intake should not be used to delay the need for renal replacement therapy. It is better to provide appropriate nutritional intake and intervene with renal replacement therapy early.

Do not starve patients in an attempt to avoid renal replacement therapy results

 

 In what group of patients might you consider waiting longer before instituting renal replacement therapy?

In the next 10 patients you see with a blood urea concentration greater than 30 mmol/l, record any features of the uraemia syndrome that are present. Try to relate these to the rate of rise of the urea concentration.

Relative indications

Control of severe hyperthermia or hypothermia is a relative indication.

A relative indication for the institution of renal replacement therapy in the form of high volume haemofiltration has been suggested to be the presence of severe sepsis. This treatment uses very large volume exchanges (of the order of 100 litres per day) and high permeability membranes. It has been found that inflammatory mediators may be removed by both filtration through and adsorption onto haemofilter membranes. It is postulated that removal of inflammatory mediators by this treatment may promote reversal of the haemodynamic and respiratory consequences of severe sepsis. Evidence in humans to support this concept is at present not available and there are potential deleterious effects of the removal of beneficial inflammatory and counter-inflammatory mediators. As the cut off limit for permeability rises to increase the removal of mediators there is an increasing loss of albumin which is undesirable.

There are also potential problems with high volume changes over short periods of time and the systems used must have very accurate volume measurement and control with very low tolerance limits.

The simplistic view that isovolaemic high volume exchange will not result in significant net solute change has been challenged by the findings of significant net changes in small molecular weight solute over the course of large volume exchange treatment with no net volume change. The net change in solute transfer was dependent upon the proportion of replacement fluid returned pre filtration or post filtration.

There are major logistical problems of handling and storing such large volumes of replacement fluid if online production of fluid is not available.

What methods are available?

Peritoneal dialysis

This technique uses the peritoneal lining as a semi-permeable membrane to allow equilibration of solute waste with dialysate introduced into the peritoneal cavity, the volume of dialysate used being dependent upon the patient's size (normally 2 litres in an average adult). This fluid is left in the peritoneal cavity for a period of time ('dwell time'), then drained and replaced by fresh dialysate. Good clearance of solute can be obtained by this method but it suffers from a number of disadvantages, particularly in the critically ill patient and currently is seldom used in the adult ICU. The technique is used more commonly in paediatric practice. One potential advantage is that peritoneal dialysis does not require the use of anticoagulants.

Complications of peritoneal dialysis.

Technical

Perforation of viscus Perforation of blood vessel Failure to enter peritoneal cavity

Clinical

Peritonitis Diaphragmatic splinting/ increase in intra-abdominal pressure Hydrothorax Electrolyte disturbance Hyperglycaemia

What advantages or indications can you list for peritoneal dialysis?

Haemodialysis

Haemodialysis is the traditional method of acute and chronic renal replacement therapy introduced into clinical practice by Kolff. Blood is passed, via an extracorporeal circuit, through a haemodialyser containing a semi-permeable membrane. This allows adequate exchange of small molecular weight solutes into the dialysate and hence their removal from the body. The efficiency of the process is affected by several factors :

Rate of blood flow through the haemodialyser Membrane properties (high or low flux) Rate of flow of dialysate Membrane surface area

Size dependent free diffusion coefficients of solutes in water and various membranes

Relationship of movement of solute by diffusion according to molecular weight (x-axis) and membrane permeability (y-axis). The diffusion co-efficient is inversely related to the molecular weight of a molecule.The three coloured lines represent this relationship as it applies in water at 37° C and membranes of different permeability (flux). Reference molecules are shown at their respective molecular weight.

 

High flux haemodialysis

In this technique high flux dialysers are utilised in a continuous haemodialysis circuit with continuous ultrafiltration volume control. Since the spontaneous filtration occurring in the hollow fibre dialyser would be much greater than the desired fluid loss, a positive pressure is automatically applied to the dialysate compartment and the transmembrane pressure gradient is reduced significantly. This in turn results in a very special pressure profile inside the dialyser. Large amounts of filtration and consequently of convective transport are maintained in the proximal part of the haemodialyser in spite of a moderate net filtration. The net fluid balance is obtained thanks to a significant amount of backfiltration of fresh dialysate in the distal portion of the dialyser. In this mechanism diffusion and convection are conveniently combined. A modification of this technique is continuous high flux dialysis where continuous treatment is used rather than the more common intermittent form.

In general, haemodialysis is effective for the removal of small molecular weight solutes and becomes increasingly less efficient as molecular weight rises above a thousand daltons (see diagram).

A=artery / V=vein / P=pump / Di=dialysate in / Do=dialysate out / Qb=blood flowQf=ultrafiltration rate / Qd=dialysate flow / h=heparin

Schematics describing continuous haemodialysis driven by arterio-venous AV, pumped Veno-venous VV and continuous VV high flux dialysis

Representative values for blood flow, filtration rate and dialysate flow are given

 

Clearance of solute is most rapid at the institution of treatment when the concentration gradient for solute is at its highest. Anticoagulation of the circuit is required.

Haemofiltration

Haemofiltration has found most favour in European and Australasian intensive care practice over the past 20 years. Blood is circulated through an extracorporeal circuit and a haemofilter. The rate of fluid removal is determined by :

Rate of blood flow Hydraulic conductance (permeability) of the membrane Hydrostatic pressure gradient across the membrane Surface area of the haemofilter membrane

Ultrafiltration (UF) rate versus TMP impact of membrane permeability

Effect of membrane composition on permeability and ultrafiltration rate. For a given transmembrane pressure (TMP) the higher the membrane permeability (Kf) the more fluid is filtered per unit time

 

Replacement fluid is returned to the circuit either before (pre dilution) or after the haemofilter (post dilution) at a rate that will maintain the desired overall fluid balance.

Pre dilution reduces the risk of clotting in the filter by reducing the haematocrit but diminishes the clearance of urea and creatinine by diminishing the concentration of both compounds in the filtered volume.

The amount of solute clearance per unit time is dependent on the volume of fluid exchanged in that time.

According to the construction of the membrane, solute of high (up to 50 000 daltons) molecular weight can be filtered. There are reports of this being of benefit in the critically ill.

There is no current information on the clearance of drugs during high volume haemofiltration at the current suggested levels of 35 ml/kg/hr

Anticoagulation of the circuit is required.

A=artery / V=vein / P=pump / Uf=ultrafiltrate / Ufc=ultrafiltration controllerR=replacement fluid / Qb=blood flow / Qf=ultrafiltration rate / h=heparin

Schematic of continuous haemofiltration driven by arterio-venous (CAVH) or veno-venous (CVVH) circuits

In the examples replacement fluid is given after the filter i.e. post dilution

 Haemodiafiltration

This process combines the two processes of diffusion and convection by introducing a countercurrent flow of dialysate into the non-blood containing compartment of the haemodiafilter. This increases the efficiency of clearance of small molecular weight solute over that of standard haemofiltration. This technique was originally introduced to increase the limited clearance of urea and other small molecular weight solute in non-pumped arterio-venous haemofiltration systems dependent on the patient's own circulation.

Anticoagulation of the circuit is required.

Schematic of arterio-venous and veno-venous haemodiafiltration (CAVHDF and CVVHDF) and the typical operational parameters used for these techniques

 

A=artery / V=vein / P=pump / R=replacement fluid / Di=dialysate in / Do=dialysate outQb=blood flow / Qf=ultrafiltration rate / Qd=dialysate flow / h=heparin

Requirements for RRT

Extracorporeal circuit

For all methods requiring an extracorporeal circuit, the current preferred system is to have a pump driven blood circuit with vascular access established by the insertion of a large double lumen venous catheter, a veno-venous circuit. These circuits are now components of increasingly sophisticated machines that control blood flow, ultrafiltration rate and the rate of fluid replacement during haemofiltration. These machines allow the running of the circuit with appropriate safety systems and precise control of volume removal and replacement, thereby minimising the risk of the major volume errors which could occur with the older more primitive systems. They also help to control the temperature of the fluid returning to the patient and thus limit the development of hypothermia.

The Prisma, the Equasmart and the Aquarius machines

The easy interface makes them suitable for most of the CRRT techniques available at present

The Prisma, The Equasmart, The Aquarius

The older arterio-venous circuits, which required vascular access via a formal Scribner shunt or large percutaneous catheters inserted into both the femoral artery and vein, are now seldom used. It is now unusual for the extracorporeal circuit to be driven by the patient's circulation. The establishment of satisfactory vascular access is essential for the efficient functioning of all of the extracorporeal systems. Poor vascular access and low blood flow are the most common causes of circuit clotting.

Passive, patient driven extracorporeal circuits are generally unsatisfactory and now rarely used

 

Example of a typical patient driven CAVH extracorporeal circuit

 

There is a risk of infection as is the case for any central venous indwelling catheter.

Attempts have been made to define an appropriate policy for catheter replacement.

A recent report has suggested that catheter replacement on the basis of clinical indication allows for significantly fewer catheter insertions over the course of an individual's acute RRT course, without any increase in catheter sepsis rate.

Why are patient driven, non-pumped systems no longer favoured?

Anticoagulation

The extracorporeal circuit will normally require anticoagulation (in the critically ill the associated coagulopathy may allow the circuit to run without anticoagulant). Traditionally this has been achieved using unfractionated heparin with tight control of APPT or ACT as there is a significant risk of bleeding (10%). In situations of high bleeding risk or heparin-induced thrombocytopenia (HIT), heparinoids, prostacyclin or sodium citrate may be used. Further experience is being gained with the use of low molecular weight heparin and hirudin and argatroban.

In the next 10 cases you see of extracorporeal circuit clotting in patients receiving haemofiltration, list the potential causes and the measures taken to reduce the risk of further clotting.

Buffering agentsFor chronic haemodialysis the traditional buffer in dialysate fluid was acetate which was metabolised to bicarbonate. Acetate has been shown to cause vasodilatation and should be avoided in the critically ill. The most common buffer currently used is lactate, which is converted in muscle and the liver to bicarbonate. Lactate is suitable for all patients other than those with established impaired hepatic function or with severe sepsis where lactate metabolism is significantly impaired. The buffer of choice is bicarbonate but the ability to produce on line replacement fluid is still limited. New commercially available replacement fluid preparations containing bicarbonate have recently appeared on the market. The two major electrolytes that are not present in these fluids are potassium and phosphate. Potassium may be added according to the patient's current blood level but phosphate is incompatible with the solution.

The ideal buffer for renal replacement therapy in the critically ill is bicarbonate

 

Serum phosphate may become significantly reduced with large volume haemofiltration or intensive dialysis and usually requires separate replacement. When sodium citrate is used as the anticoagulant no added buffer is required as citrate is converted into bicarbonate by the patient. Specially designed replacement fluid is available with no buffer and a low sodium to compensate for the large sodium load administered as sodium citrate.

Phosphate depletion is a common complication of continuous renal replacement therapy

 

 Why is bicarbonate so difficult to use as the buffer in dialysate/replacement fluid?

 What are the potential adverse effects of a low serum phosphate?

For more information on hypophosphataemia see the following reference.

Which method for critically ill patients?Attempts have been made to demonstrate the superiority of haemofiltration over haemodialysis in several studies. It is extremely difficult to conduct randomised controlled trials in a heterogeneous patient population as the methods for controlling for all the potential variables are probably still not sufficiently sophisticated.

As yet the ideal RRT regimen for the treatment of acute renal failure in the critically ill is not established

 

There is as yet no clear-cut evidence of superiority of one process over the other in the critically ill. Uncertainty also remains regarding the place of continuous versus intermittent treatment in the critically ill. Homeostasis is better maintained by continuous treatment with apparent improved haemodynamic stability but at the risk of the complications of long term anticoagulant exposure.

  Avoid intermittent therapy and rapid solute removal in conditions associated with cerebral oedema

In situations where there is haemodynamic instability or cerebral oedema continuous treatment is preferred to minimise sudden osmotic shifts of body water. It is also important to avoid major cardiovascular instability, which can be caused by short duration, high efficiency intermittent treatment as it is felt that this will delay renal recovery in the presence of impaired autoregulation.

Modern management in the ICU is normally achieved using a pumped system to achieve adequate blood flow and therefore allows a sufficient daily exchange volume during haemofiltration/haemodiafiltration to maintain satisfactory levels of urea and creatinine. As patients recover there is scope to use the most convenient method that allows proper rehabilitation. The technique of providing renal replacement therapy should be tailored to the clinical situation and may change from continuous to intermittent and from predominantly convective to diffusive. Any method used must be performed by a team skilled in its use.

 What are the potential disadvantages of continuous renal replacement therapy?

Does the filtration/dialysis membrane play a part in patient outcome?Older membrane materials such as the cellophane-based membranes (Cuprophan) have been shown to activate the complement system. It has been proposed that the newer membranes such as those based on polyacrylonitrile (PAN), polysulphone and polycarbonate confer a survival advantage when used in the critically ill compared with cellophane based membranes. Studies have been published which both support and refute this hypothesis.

The newer artificial membranes allow easier passage of higher molecular weight solutes ('middle molecules') which seem to play an important role in the toxicity of uraemia. They also allow for a higher hydraulic conductance and high filtration rates and are generally preferred for haemofiltration in the critically ill. High volume (approx 6 l/hr exchange) requires the use of high hydraulic conductance membranes.

What level of blood urea and creatinine?There is no clear evidence from the literature that maintaining urea and creatinine levels lower than 30 mmol/l for intermittent treatment or less than 20 mmol/l for continuous treatment results in a better patient outcome.

Conversion factors from SI to conventional units: Creatinine x 0.0113 mg/dLUrea x 2.8 mg/dL

Others have claimed that the urea clearance in relation to the time of treatment and volume of distribution (Kt/V) should be estimated and that this value correlates with mortality rate. However this has not as yet been confirmed.

 

Similarly it has been suggested that haemofiltration with a higher daily exchange volume and therefore a lower average level of circulating solute waste improved patient outcome. The results of the trial by Ronco et al can be found in the reference below.

In a study of early high volume (72-96 l/day) versus early and late low volume (24-36 l/day) however no difference was found in outcome (survival and recovery of function).

The Acute Dialysis Quality Initiative has been set up to try to establish the appropriate level of renal replacement therapy that will result in the best patient outcomes. This may be visited at the following website.

How long should RRT be continued? As the renal tubular cells regenerate and re-establish a normal tubular membrane, glomerular filtration will re-commence and urine output will

increase. Once clearance of solute waste is sufficient to maintain urea at less than 30 mmol/l, treatment can be discontinued, remembering that care must be taken to avoid further insults (e.g. hypotension or hypovolaemia) to the kidneys as they recover and regain their normal intrarenal compensatory capacity. In the elderly critically ill patient recovery may take up to three months and on occasions even longer.

What complications can occur during haemofiltration/haemodialysis?Vascular access

Vascular damage causing occlusion or haemorrhage Infection

Renal replacement therapy is not without risk and must be carried out and supervised by

Insertion complications e.g. pneumothorax trained personnel

Processo Dysequilibration (more common with short duration intermittent haemodialysis)o Hypotension

ECF loss through membrane/by accident or design Hypersensitivity to membrane Acetate buffer Pyrogens

o Haemorrhage Circuit disconnection Anticoagulation

o Haemolysiso Electrolyte disturbanceo Air embolism

CONCLUSION

The outcome for recovery of renal function is good in the vast majority of the critically ill with previously normal renal function. By six months they will normally have recovered greater than 90% of their pre insult function. There is a small but significant incidence of non-recovery of function such that chronic renal replacement therapy is needed. This is most common in the elderly, and those with a vasculitis or pre-existing renal disease. Cortical necrosis in adults secondary to obstetric disaster is now a very rare event in western medicine.

The direct effect of acute renal failure on survival in the critically ill is still not entirely clear

Survival of critically ill patients with acute renal failure is highly dependent upon the cause of the underlying acute disease and other comorbidities. The mortality for those presenting to the intensive care unit with established acute renal failure requiring renal replacement therapy is better than for those who develop acute renal failure at a later date despite critical care management. This latter group is usually those who have progressive multiple organ failure with its known poor outcome.

With modern forms of renal support, death from renal failure alone should not occur. Survival rates for acute renal failure are generally reported to be around 40-50%. As multi organ failure involves more organ systems mortality rate steadily increases. It has been suggested using observational data that acute renal failure per se has an effect on mortality. However as acute renal failure is not a specific disease process rather a syndrome secondary to other disease states it is difficult to separate the effects of the primary disease process, the length of time of the insult prior to initiation of appropriate treatment (e.g. restoration of adequate tissue perfusion) and the individual patient's response to the primary disease from the effect of the acute renal failure. Although scoring systems are increasing in sophistication it is debateable whether they have achieved the discrimination necessary to resolve this issue.

PATIENT CHALLENGES

A 72-year-old woman, Mrs A, is admitted to your hospital as an emergency with a two day history of abdominal pain of sudden onset. She has a history of hypertension and angina treated with enalapril, diuretics and a β-blocker. Her exercise tolerance is normally good. Her admission pulse rate was 124 beats/min, BP 110/65 mmHg. She was noted to have peritonism and there was free gas under the diaphragm. She was taken for laparotomy after fluid resuscitation. Preoperatively her urea was 15 mmol/l and creatinine 195 mmol/l. Arterial blood gases showed good oxygenation but a pCO2 of 4.1 kPa, pH of 7.29 and BE of −9 mmol/l. At operation gross faecal peritonitis was discovered secondary to perforation of the sigmoid colon which was severely affected by diverticular disease. A Hartmann's procedure (resection of diseased colon, end colostomy and closure of rectal stump) was performed.

Learning issues

 

 Clinical history

Postoperatively she was cold but her BP was 175/80 and her urine output was 75 ml/hr. Three hours later you are asked to see her in the recovery room with a view to ICU admission. She is intubated and being ventilated. Her pulse rate is 140/min, sinus rhythm, BP 100/60 mmHg, CVP +6 mmHg, core temperature 37.7 °C with marked vasodilatation. Urinary output has been 40 ml over the past three hours. Arterial blood gases pO2 9.6 kPa, FiO2 0.5, pCO2 6.2 kPa, pH 7.15, BE −12 mmol/l. She is receiving tazobactam as broad spectrum antibiotic cover and morphine as an analgesic. 

 What are the initial management imperatives to restore urinary output?

Learning issues  

 Restoration of the circulation

What are your goals for blood pressure and cardiac output and why?

NOTEIn the previously hypertensive patient a higher mean arterial pressure (MAP) may be necessary for adequate organ perfusion

Learning issues  

 PACT module on Hypertension

Mrs A responds well to fluids and a vasopressor. Her MAP rises to 90 with normalisation of her ST segments, improvement in her urinary output and correction of her metabolic acidosis. She requires a considerable volume of fluid over the next two days as her abdomen distends. On the third day her gas exchange deteriorates and despite an increase in cardiac output her perfusion pressure falls, requiring an increase in the norepinephrine support. Renal function deteriorates with worsening oliguria despite restoring the circulation. On examination the colostomy was ischaemic. Mrs A was taken for exploration of her colostomy, which was found to be devascularised to 15 cm proximal to the skin margin. The ischaemic section of bowel was removed and a new colostomy refashioned. Over the next few hours Mrs A's urinary output improves and her renal function recovers.

Learning issues  

 Metabolic acidosis

 PACT module on Homeostasis

 Secondary versus primary renal insult

Oliguria PACT module on Oliguria & anuria Underlying causes

A visiting trainee asks why dopamine was not chosen in a renal dose as he has witnessed in other hospitals. What is your reaction?

Learning issues

 Specific treatments

Mrs A develops a Methicillin Resistant Staphylococcus aureus (MRSA) infection of her abdominal wound and her respiratory tract. She is treated with teicoplanin and rifampicin. At day 12 as she is recovering from her respiratory failure and is being weaned from her vasoactive drugs Mrs A develops a fever 39.6 °C, a florid maculapapular rash, neutropenia and diminishing renal function with a rising urea and creatinine.

Rash developing 9 days after commencement of antibiotics

Learning issues  

 PACT module on Severe infection

What should be the response to Mrs A's further deterioration in renal function?

Learning issues  

 Renal perfusion

 Causes of acute renal failure

 Renal replacement therapy

Mrs A is found to have no circulatory deficit or urinary tract obstruction. No new infectious or other occult pathological processes are discovered. Ultrasound shows enlarged echogenic kidneys consistent with acute renal failure. Urinalysis showed 2+ proteinuria.

Learning issues  

 Imaging

 PACT module on Clinical imaging

What is the likely cause of the renal dysfunction?

Learning issues  

 Interstitial nephritis (1) Interstitial nephritis (2)

 Renal biopsy

 Multiprofessional collaboration (1) Multiprofessional collaboration (2) Multiprofessional collaboration (3) Multiprofessional collaboration (4)

How would you treat the presumed interstitial nephritis and would you do so without having performed a renal biopsy?Explain your answer.

NOTEDo not feel compelled to initiate unproven treatments because there is no other specific therapy availableDo no further harm!

In Mrs A's case, the risks of steroid treatment are felt to far outweigh the unproven benefits and therefore withheld. Mrs A's renal function deteriorates such that she requires renal replacement therapy (RRT) despite prompt discontinuation of her antibiotics. She becomes very drowsy and then unresponsive with small pupils. She is treated by haemofiltration and her renal function recovers to

a point that she no longer requires RRT after 10 days.

Learning issues  

 Renal replacement therapy

 Haemofiltration

Why might Mrs A have become so drowsy and what should be done?

Learning issues

 

 Opiate toxicity

Mrs A gradually recovers normal consciousness over four days and is extubated a week after starting renal replacement therapy.

She asks if she will require kidney treatment permanently. What do you tell her?

Learning issues

 

 Outcome

Now that Mrs A no longer requires renal replacement therapy, why does she require continued detailed attention to her renal function?

NOTERemember that the kidney's ability to maintain fine control of electrolyte and water balance will take some weeks to recover

Mrs A recovers from her septic state and her drug induced interstitial nephritis. She is discharged home five weeks after her emergency surgery, with a creatinine of 125 mmol/l. Her creatinine had returned to 80 mmol/l when seen at the follow-up clinic six months later. 

A 25-year-old man, Mr B, is admitted to hospital unconscious. He had started working on his

car with the engine running in a closed garage. He had taken the precaution of leaving only a small quantity of fuel in the tank and the engine had stopped by the time he was found several hours later.

On admission he was hypothermic (34.5 °C), shocked PR 140/min, BP 80/50 with a severe metabolic acidaemia (BE −20) and carboxyhaemoglobin level of 35%. The serum creatinine was 256 µmol/l and urea 9 mmol/l. There were red marks over his left shoulder, lower leg and buttock corresponding to the position in which he had been found lying on the floor.

Learning issues  

 PACT module on Homeostasis

On arrival he was intubated and ventilated with 100% oxygen and resuscitated with intravenous fluid which restored his blood pressure to 110/70 mmHg. His CVP continued to fall after each fluid challenge. As his perfusion improved the urine obtained via the urinary catheter was noticed to be brown (see image below), contained obvious sediment and was strongly positive for haem on dipstick testing. Microscopy revealed no red cells in the spun sediment.

Learning issues  

Intubation PACT module on Airway management Renal perfusion

Microscopy PACT module on Oliguria & anuria

What is the likely cause of the urine changes and the high creatinine?

The history of unconsciousness with the presence of pressure marks

should cause immediate suspicion of rhabdomyolysis

What confirmatory investigations are appropriate?

Why is this young man requiring such large volumes of fluid to maintain his circulating volume?

NOTEThe major threat to renal function in rhabdomyolysis is the severe extracellular fluid depletion combined with the toxic effects of the products of muscle breakdown

The SCPK of Mr B is found to be very high at 124 000 iu/l confirming the diagnosis of rhabdomyolysis. By this time the left buttock and shoulder have begun to swell very obviously.

Severe swelling of the buttock following pressure induced muscle necrosis

Learning issues

 

 Rhabdomyolysis

NOTEIf you suspect rhabdomyolysis you must act quickly

What measures must be taken to prevent the development of established acute renal failure ?

NOTECirculation, Circulation, Circulation

NOTEMultiprofessional collaboration

Mr B's circulation is maintained as his muscles swell. He requires a positive fluid balance of 12 litres over the first 36 hours. His urine is alkalinised using isotonic sodium bicarbonate infusion as part of his resuscitation fluid. His carboxyhaemoglobin rapidly falls and his conscious level improves. The surgical team assesses his muscle injuries and he is taken for fasciotomy of his lower leg compartments. No muscle resection is required. His urinary output is established at greater than 100 ml/hr and his creatinine peaks at 48 hours at a level of 358 µmol/l before returning to normal. He makes a good functional recovery. 

What complications of rhabdomyolysis would be likely to develop in this patient in the short term?

Learning issues

 Treating complications

 PACT module on Homeostasis

Mr C, aged 68, is brought to the emergency department unconscious, hypotensive and in respiratory distress. His arterial blood gases on admission show PaO2 7.9 kPa on an FiO2 PaCO25.2 kPa, pH 7.01 and BE −24 mmol/l. His potassium is 9.8 mmol/l. His ECG is as shown (classic hyperkalaemia with bradycardia, absence of p wave and QRS almost a sign wave). You have been called to see him to assist and just as you arrive he vomits, aspirates and has a respiratory arrest.

Learning issues  

 ECG changes of hyperkalaemia Management of acute hyperkalaemia

What are your priorities?

NOTEEnsure adequate oxygenation and hyperventilation in the presence of a severe metabolic acidaemia

Learning issues  

 Treatment of hyperkalaemia

As his resuscitation is proceeding more history is obtained. Mr C has been having nocturia 3-4 times per night and is due to see the urologists. He has been taking diclofenac for bone pain for the last three months. This has been thought to be due to an osteoid osteoma, which was to be dealt with by the orthopaedic surgical service next month. Just then his urea is reported to be 96 mmol/l and his creatinine 1783 µmol/l. Blood sugar is normal. Blood lactate is 2.5 mmol/l.

What other features of the physical examination might you concentrate upon in view of this information?

Learning issues  

 Lower urinary tract patency (1) Lower urinary tract patency (2)

What procedure will you do next?

What are the possible reasons for Mr C's uraemia and metabolic upset?

Learning issues  

 Obstructive uropathy (1) Obstructive uropathy (2) Obstructive uropathy (3)

 Actions of common nephrotoxic drugs

Mr C is catheterised successfully and 1800 ml of urine is obtained. By this time he is being ventilated (MV 15 l/min) with adequate oxygenation on a high FiO2. His circulation has improved after the administration of 3 litres of fluid, partial correction of his hyperkalaemia to 6.6 mmol/l and support from dobutamine and norepinephrine. His circulation is being monitored with the aid of a pulmonary artery catheter. Broad-spectrum antibiotics have been given. Urinary output is 150 ml in the past hour. He is transferred to the ICU.

How would you begin to manage his renal failure? Would you institute immediate renal replacement therapy? Why?

Learning issues  

 Indications for instituting renal replacement therapy

 Correction of metabolic acidaemia

NOTECorrect the metabolic acidaemia gradually, as in obstructive uropathy the kidney cannot eliminate non-volatile hydrogen ions

Mr C increases his urine volume over the next two hours to 350 ml/hr and his urea and creatinine begin to fall. He requires a positive balance of six litres over the next 48 hours and his urea and creatinine steadily fall. His acidaemia is corrected over the next 48 hours. E. coli is grown from his urine and blood. He steadily improves and his respiratory failure corrects over the next 15 days. He is eventually discharged from hospital with an indwelling catheter, to return for prostatic resection once he has recovered his muscle mass. Investigation of his lower urinary tract showed dilation of the ureters and hydronephrosis. His creatinine has stabilised at 215 µmol/l and urea at 12 mmol/l.

What do you think the likelihood is that Mr C's renal function will return to normal with time?

Learning issues  

 Long term effects of obstructive uropathy (1) Long term effects of obstructive uropathy (2)

Mr C's creatinine never fell below 210 mmol/l over the next three years.

On reflection, you have been presented with three challenging cases of critically ill patients with acute renal failure. In each patient the cause was a pathological process outside the kidney, rather than primary renal disease (as is usually the case in clinical practice). These cases emphasise that the aetiology of acute renal failure in critically ill patients is frequently multifactorial, that the cause may not be immediately obvious, that treatment decisions may be complex and that collaboration with a nephrologist is therefore essential.

Thinking about the management of these three patients, what are the key messages you

have learned about how best to preserve or restore renal function? Q1. 'Renal dose' dopamine has been shown in large RCTs to Your answers

A. Reduce the risk of the development of acute renal failure in critically ill patients

The correct answer is :

False

B. Reduce the requirement for dialysis treatment in the critically ill with acute renal impairment

The correct answer is :

False

C. Increase urine volume and sodium excretion (produce a diuresis)

The correct answer is :

True

D. Have significant cardiovascular effects

The correct answer is :

True

-

Low dose dopamine has been shown to increase cardiac output in critically ill patients with acute renal failure.

E. Be less efficient in protecting against radiocontrast induced acute renal injury in the diabetic patient than salt loading

The correct answer is :

True -

Studies have shown that administration of dopamine to diabetics as prophylaxis against radiocontrast induced renal impairment produced a higher incidence of renal dysfunction than patients who were saline loaded.

Your total score is 0/5

Q2. A previously hypertensive patient is admitted to the ICU after an emergency laparotomy, colonic resection and defunctioning colostomy, following an anastomotic leak after an anterior resection for carcinoma of the upper rectum. Initially he was hypertensive, hypothermic and peripherally shutdown in the recovery room. Now he has become vasodilated with BP 95/39 mmHg, heart rate 140 b/min, CI 3.4 l/m2, PCWP +4 mmHg, SVR 400 dynes/cm/sec -5, oliguria and Base Excess of -9 mmol/l, Hb 14g/dl, pO2 9.5 kPa, pCO2 5.1 kPa. He has just arrived and is being ventilated in the ICU. The following actions would be appropriate to restore his renal function. Put also them in order of implementation. Your answers

A. Administration of a vasopressor agent e.g. norepinephrine

The correct answer is :

True -

In view of the low systemic vascular resistance and low blood pressure in a previously hypertensive individual, raising the renal perfusion pressure would be appropriate ZiBaliseOuvrantehiZiBaliseFermantebut only after correcting the circulating volume deficit suggested by the low PCWP.ZiBaliseOuvrante/hiZiBaliseFermante

B. Mannitol

The correct answer is : False - Mannitol might transiently increase the circulating volume but is likely to cause an osmotic diuresis thus making the circulating volume deficit worse. Mannitol has never been convincingly shown to prevent acute renal failure and has produced acute renal failure when given in high dose.

C. Frusemide

The correct answer is :

False -

Frusemide might cause a transient diuresis but will make any hypovolaemia worse. It will not improve renal function.

D. Circulating volume expansion with appropriate fluid

The correct answer is : True - This is the first action that should be taken. The haemodynamic data suggest a circulating volume deficit which is due to systemic vasodilatation secondary to the septic insult and the sequestration of fluid into the bowel and peritoneal cavity, combined

with a generalised increase in microvascular permeability.

E. Administration of a β-adrenergic agonist e.g. dobutamine

The correct answer is : True - Administration of dobutamine as a β-agonist might be appropriate if this patientâs cardiac index did not improve with restoration of an appropriate ��circulating volume. Care would be required as the vasodilating effects of these agents may cause a further drop in perfusion pressure despite increasing cardiac output.

Your total score is 0/5

Q3. In obstructive uropathy Your answers

A. Patients are normally fluid overloaded

The correct answer is : False - The effect of obstruction upon the distal nephron causes a water and salt losing defect. Most patients with obstruction are therefore salt depleted.

B. Ultrasound will always demonstrate a dilated collecting system

The correct answer is : False - In a small proportion of patients in the very early stages of obstruction it may be too early to demonstrate urinary tract dilatation.

C. Infection behind the obstruction can be safely left for several days without drainage, provided antibiotics are given

The correct answer is : False - This is a true urological emergency and drainage of the obstructed system must be performed as soon as it is demonstrated.

D. Absolute anuria makes this the presumptive diagnosis

The correct answer is : True

E. Bilateral ureteric obstruction is most commonly and easily relieved by retrograde placement of ureteric stents via a cystoscope

The correct answer is : False - Percutaneous nephrostomy is the most convenient way of dealing with the obstructed upper collecting system.

Your total score is 0/5

Q4. Renal replacement therapy Your answers

A. Must always be started when the blood urea exceeds 30 mmol/l

The correct answer is : False - Treatment must be tailored to the individual patient.

B. Haemodialysis is more efficient at removing potassium than haemofiltration

The correct answer is : True

C. There is no place for peritoneal dialysis in critically ill patients

The correct answer is : False

D. High volume haemofiltration has been proven to improve survival of patients suffering from severe sepsis in the absence of acute renal failure

The correct answer is : False - While inflammatory mediators may be removed and there is some animal work suggesting benefit, there is as yet no convincing human data to support this contention.

E. Is more efficient when driven by the patient's own circulation

The correct answer is : False - Pump driven systems are generally more efficient.

Your total score is 0/5

Q5. Acute renal failure in the intensive care unit Your answers

A. Cannot be present if the patient is passing more than 50 ml of urine per hour

The correct answer is : False - It depends on solute clearance not simply urine volume.

B. Has a high mortality if present as a single organ failure

The correct answer is : False - Mortality is very low.

C. Is not normally caused by primary renal disease

The correct answer is : True

D. Can be caused by interstitial nephritis

The correct answer is : True

E. Is often associated with cortical necrosis

The correct answer is : False

Your total score is 0/5