Acute renAl fAilure

The management of acute renal failureAndrew Slack

Serene Ho

lui G forni

AbstractAcute renal failure is a commonly encountered condition in the hospital

setting. in many cases accurate history-taking, careful examination of the

patient and meticulous monitoring of volume balance may reverse this

process. However, acute renal failure presents a unique set of metabolic

derangements which, if untreated, will result in death. We outline the

initial management of acute renal failure as well as the specific treat-

ments that may be required. Some consideration is also given to the use

of renal replacement therapies.

Keywords acute renal failure; glomerular filtration rate; haemofiltration;

hyperkalaemia; metabolic acidosis; uraemic encephalopathy; uraemic

pericarditis

Acute renal failure (ARF) is a loss of glomerular filtration rate (GFR) occurring over days or weeks, resulting in a loss of the abil-ity to excrete soluble nitrogenous waste appropriately, together with impaired fluid and electrolyte homeostasis.1 The incidence of ARF is increasing, particularly in the elderly, although report-ing suffers from the lack of consensus regarding a precise defi-nition. UK-based population studies have estimated the annual incidence of ARF from 486–620 per million population, account-ing for about 1% of hospital admissions and complicating more than 7% of hospital inpatient admissions.2,3 ARF is a common finding on the critical care unit with as many as 35% of patients admitted to ICU requiring renal replacement therapy (RRT) and, when present as part of multiple organ failure, mortality is over 90% if four organs or more fail.4 More than 30 definitions of ARF are found within the literature prompting a recent collaboration between nephrologists and intensivists to decide on a uniform means of classifying ARF. This Acute Dialysis Quality Initiative group (ADQI) proposed the RIFLE classification encompassing

Andrew Slack MBBS BSc MRCP is a Specialist Registrar in Renal and

Intensive Care Medicine at Worthing and Southlands Hospitals Trust,

Worthing, West Sussex, UK. Competing interests: none declared.

Serene Ho MBBS BSc MRCP is a Senior House Officer in Renal and General

Medicine at Worthing and Southlands Hospitals Trust, Worthing, West

Sussex, UK. Competing interests: none declared.

Lui G Forni MBBS BSc PhD MRCPI is Consultant Physician and Intensivist

at Worthing and Southlands Hospitals Trust, Worthing, West Sussex,

UK, and Honorary Senior Lecturer at the Brighton and Sussex Medical

School, UK. Competing interests: none declared.

MeDicine 35:8 43

two separate criteria, the calculated GFR and urine output; it is covered in more detail elsewhere in this issue (pages 429–33).5 Although the RIFLE criteria may help in terms of defining ARF, practical problems remain with this definition, including the proposed calculation of the baseline creatinine as well as the lack of consensus regarding initiation of treatment.

At-risk populations

The two main in-hospital patient groups at increased risk of ARF are those with pre-existing renal impairment and associated co- morbidities, and those at risk of iatrogenic ARF. The first group includes elderly patients and those with underlying chronic renal impairment of any cause. Co-morbidities such as congestive cardiac failure and hepatic disease add to the increased risk of ARF following relatively mild insults. Those at risk of iatrogenic ARF include patients undergoing major surgery or radiological procedures involving intravenous contrast agents. Practically, in the hospital environment there is considerable overlap between the two groups.

Prevention of ARF

Simple measures may prevent ARF. These include the temporary omission of nephrotoxic drugs together with appropriate adjust-ment of drug doses for the estimated GFR. Pre-operative optimi-zation of a patient’s medical conditions should take place prior to elective surgery and attention paid to adequate volume replace-ment before, during and after surgery. Wherever possible during radiological investigation, non-ionic contrast agents should be used in patients at risk of ARF with adequate hydration prior to the procedure which may minimize the risk of contrast nephro-pathy. N-acetyl cysteine (NAC) has been proposed as a means by which the risk of contrast nephropathy may be reduced but its value in the prevention of contrast-induced nephropathy is debatable.6

Management of ARF

General managementEarly recognition and treatment of ARF saves nephrons and prevents further decline in the GFR. Importantly, the measured serum creatinine may not actually rise appreciably until GFR has fallen significantly. This is of particular relevance in indi-viduals of small build, vegetarians and the undernourished where a value in the normal range can be misleading. The mainstay of treatment in ARF is aimed at minimizing damage to surviving nephrons whilst providing support until the kidney recovers. This includes restoration of the circulating volume, relief of outflow obstruction if present, removal of tubular toxins and specific treatment of glomerular disease. Early restora-tion of renal perfusion in precipitant ARF due to acute tubular necrosis is essential. Recovery of GFR depends on the number of remaining functional nephrons, which increase their filtration to maintain GFR. However, continued hyperfiltration may lead to progressive glomerular sclerosis and nephron death leading to end-stage renal failure.

As there is no specific therapy for ARF, management should be focused on addressing the causes as well as correcting metabolic

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Acute renAl fAilure

and volume derangements. This should be allied to optimal nutritional support ensuring adequate calorific intake whilst limiting nitrogenous waste production and potassium intake. Sepsis should be treated aggressively and ulcer prophylaxis with proton pump inhibitors should be initiated.

Addressing the causeClassically the major causes of ARF are grouped into three general categories: pre-renal causes, intrinsic renal causes and obstruction. Pre-renal failure is responsible for up to 60–70% of ARF and is due in most cases to hypovolaemia, relative hypoten-sion or renal hypoperfusion.7 In keeping with prevention of ARF, potential nephrotoxins should be avoided and restoration of the circulation should be attempted through careful volume resusci-tation and/or through vasopressors. Intrinsic renal disease and its management is beyond the scope of this review.

Histologically, acute tubular necrosis remains the most com-mon cause.1,7 Although post-renal causes account for only 5–15% of cases of ARF, it is important to recognize as prompt interven-tion may result in complete recovery of renal function. Clinical assessment should include assessment for an enlarged bladder, and prostate examination where applicable, and in the catheter-ized patient the urinary catheter should be changed if obstruction is suspected. The investigation of choice is an abdominal ultra-sound. Relief of obstruction may lead to a significant diuresis, which may lead to volume depletion and consequent worsening of renal function. Therefore careful monitoring of fluid balance is mandatory (see also pages 420–22).

Specific problems

Volume resuscitationIn hypovolaemia, volume expansion is recommended. However, uncontrolled volume substitution may result in clinical deterio-ration and should be avoided. Isotonic crystalloids remain the mainstay of volume replacement therapy correcting sodium depletion as well as restoring solute and water diuresis. Crystal-loids expand plasma volume by about 25% of the infused vol-ume however, large-volume saline infusion can be associated with a ‘hyperchloraemic acidosis’ which may be associated with renal vasoconstriction and gut hypoperfusion.8 Colloids, which include albumin, gelatins and hydroxyethyl starch, result in vol-ume expansion approximate to the infused volume. These should be used with caution in ARF due to the associated risk of osmotic nephrosis (osmotic tubular damage) if administered in isolation, although a recent study comparing the use of 4% albumin com-pared to saline failed to demonstrate any significant differences in outcome.9 The hydroxyethyl starches are highly polymerized sugars characterized by their molecular weight, grade of substitu-tion and concentration. They are degraded through hydrolytic cleavage, the remnants of which are excreted by the kidney, and should be avoided in ARF particularly when due to sepsis.

Volume overloadThe volume status of a patient with ARF needs to be assessed carefully. Although somewhat unfashionable, careful bedside examination including assessment of the venous pressure, capil-lary refill time, pulse and postural blood pressure changes are elementary tool for assessing volume status. Hourly urine-output

MeDicine 35:8 43

and fluid-input charts need to include all fluid losses, including estimated insensible losses as well as drain/stoma output and nasogastric losses where appropriate. If possible, daily weight measurement should be undertaken. Ideally, a central venous catheter and an arterial cannula are required, particularly where multiorgan failure (MOF) is precipitant. In established MOF, fur-ther invasive monitoring may be required as absolute measure-ment of central venous pressure may be misleading especially in the ventilated patient where high intrathoracic pressures may be present.

Where volume overload is encountered in the setting of ARF, symptoms can be alleviated with high-flow oxygen or, where nec-essary, non-invasive ventilation by continuous positive airway pressure ventilation (CPAP) where pulmonary oedema is refrac-tory to pharmacological management whilst preparing the patient for urgent RRT. The use of diuretics, such as frusemide and man-nitol, as well as ‘low-dose’ dopamine in ARF have yielded incon-sistent results when subject to rigorous scrutiny.10,11 Although loop diuretics may promote diuresis in oliguric renal failure there is little evidence that they influence outcome.12 Furthermore, the large doses of frusemide often required for diuresis in ARF can result in ototoxicity. Similarly, the use of dopamine does not reduce mortality or accelerate the recovery of renal function and, in the critically ill, dopamine use is not without risk.

HyperkalaemiaThis life-threatening complication requires immediate treatment and arises through cellular shifts of potassium or release from lysed cells together with decreased renal excretion of potassium. Acidosis, hyponatraemia and hypocalcaemia all potentiate the deleterious effects of hyperkalaemia on cardiac function and hence must also be corrected. Presentation is non-specific, mus-cle weakness may be present, which if severe can lead to flaccid paralysis, although symptoms rarely manifest until the plasma potassium concentration exceeds 7.0 mmol/l. The most serious concern is the effect on cardiac conduction, which classically presents as a shortened QT interval with a tall peaked T wave on the electrocardiograph (ECG). Progressive lengthening of the QRS duration and the PR interval without treatment ultimately progresses to a ‘sine wave’ followed by ventricular standstill or fibrillation. A variety of other conduction disturbances may occur including bundle-branch block (left or right), bifascicu-lar block and advanced atrioventricular block. All patients with ARF should have continuous cardiac monitoring and immediate therapy is warranted if ECG changes or neuromuscular abnor-malities occur. Asymptomatic patients with a plasma potassium concentration of less than 6.5 mmol/l or whose ECG does not manifest signs of hyperkalemia can be treated with a cation exchange resin, such as calcium resonium, and a low potassium diet. Additional sources of potassium intake should be stopped and any potentiating drugs discontinued.

Specific treatment of hyperkalaemia is directed at removing excess potassium, shifting extracellular potassium into the cells or antagonizing its membrane effects. Calcium directly antago-nizes the actions of hyperkalaemia and, although short-lived, the effect begins within minutes. Hyperinsulinaemia can be achieved through giving insulin and glucose intravenously which stimu-lates Na/K-ATPase activity, causing a shift of potassium into cells. Effective therapy usually leads to a 0.5–1.5 mmol/l fall in

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Acute renAl fAilure

the plasma potassium concentration within 15 minutes, and the maximal effect is observed after approximately 60 minutes. Similar effects can be achieved with sodium bicarbonate solutions and although this can correct acidosis its use may be limited in ARF given the potential problems with volume balance. ß2-adrenergic agonists may also act directly on Na/K-ATPase activity and may also be used effectively to treat hyperkalaemia but should be avoided in patients with known active coronary disease. If these conservative measures are ineffective and/or the hyperkalaemia is severe then RRT should be employed.

AcidosisMetabolic acidosis in ARF results from increased acid produc-tion, increased acid retention and decreased renal reabsorption of bicarbonate. Acidosis is exacerbated by sepsis, malnutri-tion and some drugs. Mild acidosis (pH > 7.2) can usually be reversed with adequate volume resuscitation. Sodium bicarbon-ate either intravenously or orally may be used if the acidosis is severe (pH <7.2 or HCO3 10–15mmol/l). Although some authors express caution with regard to the generation of a ‘paradoxical acidosis’ on bicarbonate administration, in clinical practice this is not a problem. The argument stems from the observation that on addition of sodium bicarbonate to a weakly acidified solution CO2 is generated. Since there is no significant gradient between intracellular and extracellular CO2 it is argued that this results in an increase in intracellular CO2, thus worsening the acidosis. The evidence for this comes from in vitro work far removed from the physiological, as well as animal work where predetermined ven-tilatory restraints were imposed. In effect these studies have used a ‘closed’ system whereas in spontaneously breathing patients, or indeed one being adequately mechanically ventilated, the sys-tem is ‘open’ allowing for CO2 removal.13,14 However, if large volumes of isotonic sodium bicarbonate in ARF are employed, they should be used with caution due to observed volume expan-sion and development of hypernatraemia.

Uraemic pericarditisUraemic pericarditis is observed in 6–10% of patients with advanced renal failure resulting from inflammation of both the visceral and parietal membranes of the pericardial sac. Pericar-ditis in ARF presents with fever and pleuritic chest pain charac-teristically worse in the recumbent position and a pericardial rub may be heard on auscultation, although the ECG does not show the typical diffuse ST and T wave elevations observed with other causes of acute pericarditis. The development of pericarditis in a patient with ARF is an indication to institute RRT unless there are signs of cardiac tamponade due to a pericardial effusion. Under such conditions, heparin-free hemodialysis or haemofiltration should be used due to the risk of increased bleeding into the pericardial sac with anticoagulation.

Uraemic encephalopathyUraemic encephalopathy together with uraemic pericarditis tends to be related to the degree of uraemia. Early clinical features include rambling speech, disorientation, lethargy, irritability and hallucinations and, more rarely, coma. Commonly encountered signs include tremor, myoclonus, and asterixis which tend to occur with deterioration in mental status. Rarely, transient focal signs may occur such as hemiparesis or reflex asymmetry but

MeDicine 35:8 43

resolve with treatment, although mental state may not improve for up to 48 hours. If the signs do not resolve then other pathologies need to be excluded.

Renal replacement therapyRenal replacement therapy (RRT) does not cure acute renal failure but it is a safe and efficient way of replacing renal function while the kidneys recover from disease or injury. Historically, single-organ ARF has been treated with either peritoneal or haemodialy-sis which are the mainstay of chronic renal replacement therapy. Hospitals with acute nephrology services will perform haemodi-alysis in haemodynamically stable patients although acutely, RRT is most commonly performed in a level 2 or 3 facility employing either haemodialysis or more commonly haemofiltration. Although superficially similar the mechanisms by which the composition of the blood is altered, differ markedly.15–17 In haemodialysis, blood flows along one side of a semipermeable membrane as a solution of crystalloids, the dialysis fluid, is pumped against the direction of the blood flow along the other side of the membrane (see pages 461–65). Molecules diffuse across the membrane from higher to lower concentrations driven by the law of mass action. The composition of the dialysis fluid allows as near normalization of the plasma as possible. The dialysis-fluid compartment is under lower pressure and this generates a transmembrane pressure gra-dient enabling the removal of salt and water. Haemofiltration in its simplest form involves the passage of blood under pressure passing down one side of a highly permeable membrane allowing water and other molecules up to a size of c. 20 kD to pass through the membrane through convection. Thus filtrate is discarded and replaced by an idealized buffered replacement fluid the crystal-loid components of which are at physiological levels. Although the technique of haemofiltration has been refined and is also being used in the treatment of sepsis using so-called ‘high-flux’ systems, the basic principles remain the same.18

Indications for renal replacement depend on the clinical and biochemical derangements outlined above and, although these are general indications, use will be guided by the clinical situa-tion. In the intensive care unit, for example, treatment may begin before the absolute indications are reached with uncertainty sur-rounding the optimal timing of the initiation of renal support. There is some evidence that in the critically ill intensive, early treatment may result in improved outcomes but to date no randomized clinical trials have specifically addressed this question (Table 1).

Practical aspects of renal replacement therapyIn both haemodialysis and haemofiltration access to the circula-tion is required and a variety of double-lumen vascular cath-eters are commercially available allowing blood flow rates up to 200 ml/min. Adequate venous access is critical in preventing technical difficulties with blood flow from the patient and poten-tial problems with clotting leading to a loss of the extracorporeal circuit. In most cases anticoagulation is required, with unfraction-ated heparin being commonly used to prime the circuits, and a continuous infusion is maintained through the inflow side of the circuit. If the patient is thrombocytopenic then alternative anti-coagulants can be used, including saline, citrate or prostacyclin, but care must be taken with the latter given its vasodilatatory effects.

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Acute renAl fAilure

Continuous haemofiltration is a highly effective system for the replacement of renal function in patients with ARF. Although only a few trials have compared continuous versus intermittent techniques as yet no evidence exists to favour one technique over the other. Where studies have been performed these unfor-tunately have not supplied the answer due to problems in study design.19,20 The relative ease of continuous veno-venous hae-mofiltration (CVVH) together with its minimal haemodynamic effects make it the treatment of choice in acute renal failure especially when complicated by other organ failure. ◆

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