Acute Kidney Injury and the Critically Ill Patient
Hugh avies PhD, MHM, BNurs, PostGradDip(Intensive Care)
Gavin eslie PhD, BAppSc, PostGradDip (Clinical Nursing),

Dimensions of Critical Care Nursing
June 2012 
Volume 31  Number 3
Pages 135 - 152

Acute kidney injury (AKI) is a serious complication for the critically ill patient. The term has been increasingly adopted over recent years as efforts have been made to capture and better define mild to severe renal dysfunction. Persistent AKI can lead to the subsequent development of renal failure recognized as an important determinant of morbidity and mortality in the critically ill patient. This article explores the clinical implications of AKI for the critically ill patient and how this can have a profound influence on the principal presenting disease and expected outcome.

Acute kidney injury (AKI) represents the entire spectrum of renal insufficiency and refers to a pathological event that causes functional or structural changes to occur in the kidneys.1 The term has been adopted in an attempt to reach a consensus on a common quantitative definition and classification of factors associated with acute renal failure. The change of emphasis away from the terminology of describing only failure is also in recognition of observations that have shown small decreases in renal function are predictive of a worse outcome when compared with patients who sustain no injury.2 The development of AKI is a major complication that if left unresolved can be detrimental to the management of the critically ill patient. The loss of renal function affects the ability of the body to maintain normal physiological processes and interrupts the activity of other organ systems of the body.3

Observational studies suggest critically ill patients who incur single or multiple episodes of AKI and subsequently develop acute renal failure are older patients, who have more comorbidities, are more likely to have sepsis because of severe infection, and have greater severity of illness and organ dysfunction.4-6 The development of AKI has also been shown to be associated with higher patient mortality and increased hospital length of stay and cause a rise in health care expenditure.7 This article reports on efforts made by intensivists and nephrologists to reach consensus on a quantitative definition of AKI. This is followed by a description of pathological conditions that can occur because of the sudden loss of kidney function where the effects may lead to serious derangements in the body's internal environment. The implementation of supportive measures and the incorporation of pharmacological strategies are discussed, which may provide the critically ill patient protection against injury or reduce the extent of damage sustained by the kidneys.

A MEDLINE and CINAHL search plan was conducted from 1970 to November 2010 limited to the English language using the key search words: acute renal failure, acute kidney injury, protection strategies, and critical illness. Studies were assessed according to the levels of evidence presented and practice recommendations based on Australian guidelines proposed by the National Health and Medical Research Council for clinical intervention.8 The level of evidence and grades of recommendations are shown in Table 1.

Table 1 - Click to enlarge in new window   TABLE 1 Levels of Evidence and Grades of Recommendations


Acute kidney injury is characterized by a sudden loss of renal function whereby the organ is unable to adequately excrete metabolic waste products, maintain fluid and electrolyte homeostasis, and regulate acid-base balance.9-11 A summary of the main functions of the kidney is shown in Table 2. Quantitative definitions of AKI are based on verifiable clinical measurements routinely undertaken that reflect some of the physiological functions of the kidney. Although the measurement of urine output and the monitoring of serum creatinine (SCr) levels identify changes in kidney function, both markers do not accurately reflect the extent of injury that has occurred to the kidneys. Several urinary and serum markers (neutrophil gelatinase-associated lipocalin and interleukin 18) have instead been identified as possible indicators of renal injury before the presence of a decline in kidney function.12 Until these new biomarkers have been validated in clinical practice as being reliable indicators of damage, the development of oliguria in the absence of inadequate intravascular volume and/or an increase in the concentration of SCr continues to be used as markers of AKI in the critically ill patient.13-16

Table 2 - Click to enlarge in new window   TABLE 2 Main Functions of the Kidney

The variety of different quantitative definitions that have been used in clinical trials to report the loss of renal function can lead to difficulties when attempts are made to investigate the incidence of AKI or make comparisons on patient outcomes when using alternative treatment strategies. As shown in Figure 1, the Risk Injury Failure Loss End-Stage (RIFLE) kidney disease classification system has been developed by the Acute Dialysis Quality Initiative group in an effort to reach a consensus on a quantitative definition of AKI.17 The condition is classified into 3 severity categories according to the degree of risk, injury, and failure. Classification of the severity in each category is met either through changes in SCr or urinary output or both. The other 2 clinical categories measure outcome according to the duration in loss of renal function and the development of end-stage renal disease. The degree of sensitivity to injury increases with milder forms of renal failure, but the detection of renal dysfunction is less specific, whereas specificity increases with moderate to severe renal dysfunction but is not as sensitive to the detection of increased loss in renal function. In recognition of reduced sensitivity to changes in renal function the proposed Acute Kidney Injury Network criteria18 introduces several stages to the RIFLE classification system in the measurement of SCr levels to reflect more accurately the degree of renal impairment sustained. The definition and classification of AKI using the RIFLE classification system have achieved wide acceptance as a useful predictor of patient outcomes following validation in a number of clinical trials.19-21 An upsurge in the use of a standard definition is likely to see RIFLE and refinements to the classification system adopted as the diagnostic reference point for investigations of AKI.

Figure 1 - Click to enlarge in new window   Figure 1. The RIFLE classification system. Based on information obtained from Bellomo et al.

The condition is classified into 3 severity categories according to the degree of risk, injury, and failure.


The causes of AKI can be divided into 3 categories, depending on the area of the kidney where the damage has occurred.22 As shown in Box, the site of injury indicates whether the problem is the result of prerenal, intrarenal, or postrenal causes of insufficiency in the renal system. The nature of critical illness exposes the patient to a greater incidence of injury from prerenal or intrarenal causes, which can result in the temporary or permanent loss of kidney function. Prerenal injury occurs in response to conditions such as hypovolemia that result in hypoperfusion of the kidney and can be considered a precursor to ischemic intrarenal injury. Approximately 20% to 25% of cardiac output (CO) is distributed to the kidneys delivering a blood flow rate of 1000 to 1200 mL/min. This large supply of blood exceeds the metabolic and oxygen requirements of the kidneys necessary for the organ to maintain the body's normal internal environment. As shown in Figure 2, the filtration of arterial blood occurs through the glomerular capillary network and is driven by hydrostatic pressure regulated by the afferent and efferent arteriole of the glomerulus. The peritubular network of capillaries surrounding the renal tubular system facilitates reabsorption, secretion, and excretion. As shown in Figure 3, the modification of glomerular filtrate takes place along different segments of the tubular system. The greatest uptake of oxygen occurs within the ascending portion of the loop of Henle where modification of tubular fluid requires the release of energy for active transport. The supply of oxygen through this section of the tubular system is particularly sensitive to changes in perfusion pressure.23 The restoration of blood flow is essential to prevent injury to the infrastructure of the renal tubules.

Figure 2 - Click to enlarge in new window   Figure 2. Microcirculation of the nephron. Based on information obtained from Marieb EN, Hoehn K.
Figure 3 - Click to enlarge in new window   Figure 3. Segments of the tubular system. Based on information obtained from Marieb EN, Hoehn K.

A reduction in blood flow to the kidneys may initially go unrecognized when not associated with a dramatic drop in blood pressure. The intrarenal response to hypovolemia relies on the autoregulation system shown in Figure 4 to detect a reduction in perfusion pressure. In addition to the autoregulation system, the renin-angiotensin mechanism shown in Figure 5 is able to temporarily maintain normal blood flow and glomerular filtration rate (GFR), despite a fall in systolic blood pressure. The release of aldosterone will also improve circulatory volume by increasing the reabsorption of sodium and water. Although perfusion pressure is restored by vasoconstriction, and the loss of intravascular fluid reduced following a decrease in urinary output, the normal physiological responses to changes in blood flow are unable to protect the kidney from injury indefinitely.

BOX. The causes of a... - Click to enlarge in new window   BOX. The causes of acute kidney injury (AKI) according to the area of insult. Based on information obtained from Lameire
Figure 4 - Click to enlarge in new window   Figure 4. Autoregulation of renal blood flow. Based on information obtained from Marieb EN, Hoehn K.
Figure 5 - Click to enlarge in new window   Figure 5. Renin-angiotensin mechanism. Based on information obtained from Marieb EN, Hoehn K.

Controversy surrounds the use of the term acute tubular necrosis to describe the pathophysiology of AKI because the presence of necrotic tubular cells has not been a consistent defining feature observed during histological examination. Evidence from renal biopsies undertaken on ischemic injury has shown the presence of only limited necrosis despite the existence of marked functional impairment. The death of renal tubules is suspected to instead occur by apoptosis, a form of cell death where the damaged cell undergoes a cascade of intracellular changes.24 Once damaged, the cell is broken down, and cellular debris removed by phagocytosis. The process is often underestimated because of changes that are difficult to detect in histology tissue samples. Consequently, the physiological derangement caused by AKI is not necessarily reflected by a profound alteration in renal tubule pathology.

The development of intracellular changes within the tubular system is the most common intrarenal injury observed in the intensive care unit. As shown in Figure 6, the pathophysiology of tubular cell death can be either the result of ischemia25 or exposure to nephrotoxic substances26 or due to sepsis representing a mixed aetiology.27 The Beginning and Ending Supportive Therapy kidney study investigated the development of AKI in the critically ill patient.28 Of the conditions diagnosed as AKI, the authors observed that 47.5% was associated with sepsis; 34%, after patients had undergone major surgery; in 27% of cases related to cardiogenic shock, hypovolemia occurred in 26% of patients; and 19%, as the result of exposure to nephrotoxic drugs. These observations suggest that the causes of renal damage to the tubular system are multifactorial, with the prevalence of severe infection leading to septic shock a major reason for AKI in the critically ill patient.

Figure 6 - Click to enlarge in new window   Figure 6. Pathophysiology of intracellular changes as a result of injury within the renal tubular system.


The physiological consequences of AKI in the critically ill patient derive from the important role the kidneys play in maintaining water and electrolyte balance, in the excretion of metabolic waste products, and in the regulation of acid-base balance. The adverse physiological effects that develop during AKI include volume overload, electrolyte disorders, retention of organic compounds, and metabolic acidosis. The severity of complications associated with AKI depends on the number and severity of renal insults that have occurred and the preexisting functional status of the kidney.

Volume Overload

The administration of intravenous fluid and liquid nutrition is often required in the management of the critically ill patient. This can lead to the accumulation of fluid as the result of AKI when there is deterioration in renal function and the development of oliguria. A reduction in urinary output or complete cessation (anuria) is a predictor of worsening clinical outcome in comparison with nonoliguric patients who have instead been shown to have fewer complications, shorter hospital stays, and lower mortality.29

Several reasons might explain why volume overload can reduce survival in patients who are oliguric. The accumulation of fluid in lung tissue places the patient at risk of hypoxia when gas exchange within the alveoli is reduced, and the requirement for mechanical ventilation increases the potential for the respiratory tract to become a source of infection.30 The impact of existing cardiac failure or altered protein capillary permeability due to sepsis can also lead to the presence of excess fluid volume.31 The resolution of volume overload in the management of AKI is now recognized as being an important pathological factor that has the potential to improve patient survival and reduce the severity of organ dysfunction.32


Regular observations of urinary output can detect a decline in measured volumes and identify possible changes in GFR that may suggest a reduction in renal blood flow and perfusion pressure has occurred.

The accurate recording of a daily fluid balance chart allows the patient's fluid input and output to be monitored and minimizes the potential for volume overload in those patients at risk of AKI.

Visual inspection of the patient may provide evidence of volume overload by the appearance of peripheral edema with the accumulation of fluid causing the face, hands, and feet to become swollen.

A record of body weight changes over several days can detect the cumulative effect of intravenous fluid administration and liquid nutrition that may indicate changes in body weight are the result of excess fluid volume.

Electrolyte Disorders

The development of electrolyte disorders can lead to a range of clinical disorders when AKI affects the balance of electrolytes important for cellular metabolism and membrane potentials of muscle and nerve cells.33 Hyponatremia is a common feature of patients with renal insufficiency when oliguria causes the retention of water and the dilution of sodium ions within the extracellular fluid compartment.34 The presence of hyponatremia leads to swelling of the cells due to an osmotic gradient differential causing water to shift from the extracellular to the intracellular fluid compartment. In response to these changes, the normal functioning of the central nervous system is interrupted, and the possibility of seizure activity is a major complication of hyponatremia.

Failure of the kidneys to excrete sufficient quantities of potassium is another electrolyte imbalance that can have serious life-threatening consequences for the patient.35 The elevation of serum levels will also occur when the transfer of potassium from the intracellular to the extracellular fluid compartment is increased because of alterations in acid-base balance caused by the retention of organic anions, or after potassium is released into the bloodstream following extensive tissue damage.36 Other disturbances also develop in nerve and muscular tissue when renal insufficiency disrupts the absorption or excretion of magnesium, chloride, calcium, and phosphate.37


The appearance of abnormal neurological nerve responses and the development of cardiac arrhythmias are signs of renal insufficiency when the normal regulation of electrolytes is disrupted by injury to the tubular system.

The sampling of urine can indicate whether the integrity of the tubular system has been compromised with the ability of the collecting tubule to concentrate urine impaired. A low urine osmolarity with high concentrations of urinary sodium suggests damage has occurred to the tubular system.

The taking of regular blood samples can identify electrolyte disorders and prompt the nurse to instigate appropriate measures that correct the abnormality and restore the correct balance of electrolytes circulating in the body.

Hyponatremia is a common feature of patients with renal insufficiency when oliguria causes the retention of water and the dilution of sodium ions within the extracellular fluid compartment.

Retention of Organic Compounds

Urea is an organic solute normally found in the bloodstream following the metabolism of protein, and along with SCr levels, the blood urea nitrogen (BUN) level is used as a marker to represent the removal of nitrogenous waste products and other toxins that are normally excreted by the kidneys.38 In the presence of AKI, a variety of biochemical and physiological changes occur in response to the retention of urea and other organic compounds including platelet dysfunction and neurological deterioration, particularly if urea accumulation is rapid. The adverse consequences of uremic syndrome due to renal insufficiency are well documented in patients who have end-stage renal disease.39 The syndrome can also occur as the result of AKI, but rather than a gradual manifestation over several years, the loss of kidney function is rapid, with uremia developing over days to weeks.


The mental capacity of patients at risk of AKI should be monitored closely, and regular blood sampling undertaken in case there is a sudden rise in BUN levels due to a decline in renal function.

Metabolic Acidosis

A common manifestation of AKI in critically ill patients is the development of a metabolic acidosis caused by the accumulation of organic anions and a decrease in the production of bicarbonate affecting the buffering capacity of the kidneys. The magnitude of the metabolic acidosis is also influenced by nonrenal causes, such as anaerobic metabolism and the buildup of lactic acid, or an elevated anion-gap due to diabetic ketoacidosis, or as the result of ingesting toxins and the formation of acid metabolites.40


The taking of arterial blood gas samples will allow the nurse to monitor blood pH levels and, as the result of tubular damage, the severity of the metabolic acidosis due to the loss of bicarbonate production.


Management of the critically ill patient with AKI should be directed at the preservation of existing renal function and in the prevention of irreversible damage to the kidneys. The physiological causes of inadequate blood flow to the kidneys have been suggested as the basis for the instigation of protective strategies in reducing injury to the renal tubular infrastructure. These strategies include the replacement of lost intravascular volume, support of CO, and the maintenance of renal perfusion pressure.41

Intravascular Fluid Expansion

Lack of intravascular volume caused by acute hemorrhage and increased capillary leakage are examples of conditions commonly associated with the critically ill patient. The development of injury occurs when compensatory mechanisms such as the renin-angiotensin system are overwhelmed and unable to prevent a reduction in blood flow. The loss of intravascular volume that is not able to be replaced causes the development of hypovolemia and a reduction in blood supply to the kidneys.42

The administration of fluid is used to safeguard the patient against the adverse effects of hypovolemia, but there are no recommendations in regard to a specific intravascular volume that is more protective of renal function. The restoration and maintenance of intravascular volume are a frequent activity undertaken by the critical care nurse. In many situations, the administration of fluid will require the monitoring of central venous pressure (CVP) to measure right ventricular intravascular volume. The task of fluid resuscitation is made more difficult to manage in patients when the development of AKI is associated with other organ failures. The use of a liberal approach to fluid administration (CVP, 10-14 mm Hg) was shown in 1 randomized study of patients with acute lung injury to increase the duration of mechanical ventilation when compared with patients who instead received a conservative fluid management strategy (CVP, <10 mm Hg).43 The measurement of CVP values can nevertheless be misleading in patients who are receiving positive-pressure ventilation with the "artificial" elevation of intrathoracic measurements masking the depletion of intravascular volume. Observations made by the nurse of marked "swings" in arterial pressure tracings along with physical inspection may instead provide a better indicator that intravascular fluid expansion is required.44 A fine balance is often required to achieve adequate replacement of intravascular volume sufficient to sustain renal function but avoid the risk of fluid overload should AKI develop.

The practice of intravascular fluid expansion has been shown in some cases to protect the kidneys from injury and is recommended in patients with rhabdomyolysis or when exposed to radiocontrast agents. In the management of traumatic rhabdomyolysis, a protective effect on renal function has been observed when patients receive early and aggressive fluid resuscitation.45,46 The administration of extra volume can reduce the development of hypovolemia when damaged muscles become swollen and, as a consequence of muscular injury, expose the patient to large quantities of myoglobin when allowed to accumulate in the body. A forced alkaline diuresis using intravascular fluid expansion containing sodium bicarbonate attempts to protect the kidneys by minimizing the harmful effects of myoglobin and wash out excess myoglobin to prevent the formation of casts causing obstruction in the renal tubules. The administration of intravenous fluids before and after diagnostic procedures47 and the selection of isotonic rather than hypotonic hydration48 have also been shown to protect the kidneys against the harmful effects of nephrotoxic substances present in radiocontrast agents. A summary of studies investigating the use of intravenous fluid expansion in the management of patients with rhabdomyolysis and for the prevention of contrast medium nephropathy is shown in Table 3.

Table 3 - Click to enlarge in new window   TABLE 3 A Summary of Studies Investigating the Use of Goal-Directed Hemodynamic Therapy in Support of Cardiac Output


Despite the absence of randomized controlled trials, experience suggests that the depletion of intravascular volume without adequate fluid resuscitation places the patient at risk of developing AKI.

There are no recommendations in regard to a specific intravascular volume that is more protective in safeguarding the kidney against the effects of hypovolemia.

Intravascular fluid expansion is recommended in the management of rhabdomyolysis (grade C) and for diagnostic procedures that require the administration of radiocontrast agents (grade B).

Cardiac Output

The maintenance of CO is important in order to sustain adequate blood flow and perfusion of body tissues. At what point diminished CO results in renal dysfunction is nevertheless unclear from the literature. A number of studies have investigated the use of various measures that support CO in patients at risk of AKI and the failure of other organs.49-51 The array of interventions can range from the administration of intravenous fluids and the use of vasopressor/inotropic agents to a more invasive approach of surgery and the insertion of mechanical assist devices.

In a prospective multicenter study, no effect on reducing mortality or in the development of specific organ dysfunction was observed in critically ill patients who were randomized to receive goal-directed hemodynamic therapy when compared with those who were managed without following a predetermined range of hemodynamic parameters.52 This result contrasts with the findings of another prospective single-center study involving patients with a diagnosis of early stages of severe sepsis and septic shock before admission to the intensive care unit.53 Patients who were randomized to receive standard hemodynamic therapy that did not specifically target Svo2 levels had a significantly higher mortality when compared with those who were assigned to receive goal-directed hemodynamic therapy that achieved Svo2 levels of 70% or greater. Although this study was not designed to specifically investigate the incidence of renal insufficiency, the strategy of reducing tissue hypoxia would nevertheless have had a possible beneficial effect on preserving kidney function. A summary of studies investigating the use of goal-directed hemodynamic therapy in support of CO is shown in Table 4.

Table 4 - Click to enlarge in new window   TABLE 4 A Summary of Studies Investigating the Use of Intravenous Fluid Expansion for the Prevention of Contrast Medium Nephropathy and in the Management of Patients With Rhabdomyolysis
Table 4 - Click to enlarge in new window   TABLE 4 A Summary of Studies Investigating the Use of Intravenous Fluid Expansion for the Prevention of Contrast Medium Nephropathy and in the Management of Patients With Rhabdomyolysis, continued


Unless efforts are made to successfully maintain adequate CO, the loss of blood supply will result in renal insufficiency and the dysfunction of other organs.

Goal-directed hemodynamic therapy guided by Svo2 monitoring may assist with reducing oxygen mismatch between demand and supply during the early stages of sepsis (grade B).

Renal Perfusion Pressure

A decrease in urinary output when combined with a fall in blood pressure can suggest a reduction has occurred in renal perfusion pressure. In adult humans, the lowest threshold of renal autoregulation is estimated to be around 80 mm Hg before the mechanism is unable to compensate for a drop in systemic blood pressure, and the GFR can no longer be maintained at normal levels.54 Once the autoregulatory mechanism is below this threshold, any further drop in systemic blood pressure stimulates the release of endogenous vasoconstrictors, but the effects of prolonged hypotension will eventually cause a reduction in renal blood flow to the glomeruli and in the perfusion of other tubular structures.23

The management of hypotension is directed at targeting a mean arterial blood pressure that is sufficient to perfuse the kidneys and in the perfusion of blood to other organs. International guidelines put forward by members of the Surviving Sepsis Campaign recommend a mean arterial blood pressure of 65 mm Hg or greater as the minimum pressure required to reduce the incidence of organ dysfunction as the result of tissue hypoperfusion.55 When this is not able to be achieved with the administration of intravenous fluids, the use of vasopressor and inotropic agents should be considered. A number of measures suggested to maintain renal perfusion pressure are hindered by the lack of evidence from clinical investigation. Under situations of pronounced vasodilation as seen in patients with septic shock, the use of noradrenaline may assist in the return of normal vascular tone and as a result improve renal perfusion pressure. The findings of a prospective study investigating the management of septic shock are summarized in Table 5. Noradrenaline was associated with a significant improvement in the reversal of hypotension and in the restoration of urinary output.56

Table 5 - Click to enlarge in new window   TABLE 5 A Study Summary of Noradrenaline in the Management of Septic Shock for the Improvement of Renal Perfusion Pressure


The replacement of intravascular fluid to correct hypovolemia and maintain sufficient circulatory volume to achieve a mean arterial pressure of 65 mm Hg or greater should be considered before the administration of vasopressor and inotropic agents.


A variety of pharmacological strategies have been used to protect the critically ill patient from AKI. The possibility of avoiding undesirable consequences of renal insufficiency has seen a number of drugs undergo considerable investigation.57 Despite the abundance of statistically well-powered studies, the observations made have proven disappointing in the detection of a protective effect on kidney function. Although some of the interventions have been shown to be useful in the immediate management of the critically ill patient, there is the potential to cause harm when caution is not exercised in the application of these drugs and only limited evidence to suggest improvement in renal recovery. The use of pharmacological strategies to prevent AKI can be classified according to whether they increase urinary output, improve intrarenal blood flow, or offer protection against radiocontrast-induced nephropathy. A description is given on evidence surrounding the use of 3 drugs commonly used in clinical practice as pharmacological strategies for the protection against AKI.

Furosemide (Loop Diuretic)

Furosemide is a loop diuretic frequently used in clinical practice to induce diuresis in the critically ill patient who has low urinary output and requires the regulation of excess fluid volume.58 Under experimental conditions, furosemide has been shown to increase medullary oxygenation, suggesting a protective effect on kidney function due to a reduction in oxygen consumption required for active transport by the tubular system.59 Although the use of loop diuretics may assist with the management of fluid volume (if a diuresis is achieved), there is no evidence to suggest that the outcome of patients who have sustained AKI is improved. In addition, caution should be exercised when using high doses of furosemide, with reports of ototoxicity and deafness following administration.60 Many of the limited number of randomized controlled trials undertaken and evaluated by meta-analyses are of poor quality in the methods used to detect the effect of furosemide and other loop diuretics on patient survival and renal recovery.61,62

In addition, caution should be exercised when using high doses of furosemide, with reports of ototoxicity and deafness following administration.


There is no evidence that furosemide improves patient survival or promotes the return of kidney function (grade A).

The use of furosemide may be useful in patients with excess fluid volume to achieve symptomatic relief and achieve greater fluid balance control.

Furosemide should not be used solely to achieve diuresis and worsen the deterioration of renal insufficiency by causing a delay in the commencement of renal replacement therapy.

Dopamine (Renal Vasodilator)

Low-dose dopamine (1-3 [micro]g/kg per minute intravenously) is a renal vasodilator that acts on dopaminergic receptors in the kidney.63 At this dose, dopamine has been shown to augment renal blood flow in healthy individuals, causing an increase in urinary output independent of changes in renal perfusion pressure. The use of low-dose dopamine as a continuous infusion has been used with some success,64 but overtime has failed to produce convincing evidence of its protective effect on renal function. In the presence of AKI, the use of dopamine has been shown to worsen ischemia by increasing renal vascular resistance.65 A meta-analysis of more than 50 published studies investigating the effect of dopamine showed no evidence of a reduction in the incidence of AKI, the requirement for renal replacement therapy, or patient survival to support its continued use for the prevention or management of acute renal failure.66


The use of low-dose dopamine is no longer recommended as a protective pharmacological agent for patients at risk of developing AKI (grade A).

-Acetylcysteine (Antioxidant)

N-acetylcysteine contains antioxidant properties that scavenge oxygen-free radicals and reduce ischemia by causing endothelial vasodilation.67 The use of N-acetylcysteine for renal protection against radiographic contrast dyes has been evaluated in several randomized controlled trials but with conflicting results on the responses observed.68-70 Many of the studies undertaken made omissions in regard to describing the dose of N-acetylcysteine required and when the agent should be administered. To clarify the degree of benefit observed, several meta-analyses have examined these studies collectively.71-73 Although some studies had shown no benefit, the overall recommendations from each of the systematic reviews support the use of N-acetylcysteine as a strategy to decrease radiographic contrast nephropathy. The use of N-acetylcysteine for nonradiographic contrast injury has also been collectively reviewed in several other meta-analyses.74,75 The meta-analyses of predominantly randomized controlled studies have not shown a beneficial effect of N-acetylcysteine in the prevention of renal dysfunction after major cardiovascular surgery.


N-acetylcysteine offers protection against injury and loss of renal function from radiographic contrast dyes. The effect is more noticeable in patients who have chronic renal insufficiency and should be combined with hydration before the diagnostic procedure (grade A).

The protective effect of N-acetylcysteine on renal function has not been shown to occur in patients undergoing major surgery or other nonradiographic procedures (grade A).


The development of AKI is a serious complication for the critically ill patient when damage to the kidneys causes a decline in renal function. Efforts to prevent injury reduce the degree of intrarenal damage that occurs as a result of ischemia and nephrotoxicity. Observations undertaken by the critical care nurse for signs of peripheral edema and changes in body weight, accurate recording of daily fluid balance, and the recording of reduced urinary output can identify patients who are in a positive fluid balance. The sampling of blood in at-risk patients also allows for the monitoring of kidney function by the detection of electrolyte disorders, early recognition of elevated SCr and BUN levels, and the presence of a widening anion-gap in response to a worsening metabolic acidosis.

The implementation of protection strategies often administered and monitored by the critical care nurse includes measures that restore intravascular volume, preserve CO, and maintain renal perfusion pressure. The maintenance of adequate perfusion pressure requires assessment of circulatory volume and the correction of hypovolemia. This may demand the instigation of intravenous fluid expansion and the commencement of vasopressors and inotropic therapy. Once CO has been stabilized, only then should pharmacological interventions be considered as strategies for the prevention of AKI. The use of N-acetylcysteine against radiocontrast-induced nephropathy is the only drug shown to be effective in the prevention of AKI. Loop diuretics such as furosemide allow the removal of excess fluid where a urinary output is sustained but are not associated with increased patient survival or improved recovery of renal function. The use of low-dose dopamine as a renal vasodilator is no longer justified with the absence of any evidence to support the continued use of the drug in clinical practice.


1. Kellum JA, Bellomo R, Ronco C. The concept of acute kidney injury and the RIFLE criteria. Contrib Nephrol. 2007; 156: 10-16. [Context Link]

2. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. JAMA. 1996; 275 (19): 1489-1494. [Context Link]

3. Hoste EAJ, de Waele JJ. Physiologic consequences of acute renal failure on the critically ill. Crit Care Clin. 2005; 21: 251-260. [Context Link]

4. Bagshaw SM, Laupland KB, Doig CJ, et al.. Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study. Crit Care. 2005; 9 (6): R700-R7009. [Context Link]

5. de Mendonca A, Vincent JL, Suter P, et al.. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med. 2000; 26: 915-921. [Context Link]

6. Mehta RL, Pascual M, Soroko S, et al.. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004; 66: 1613-1621. [Context Link]

7. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005; 16: 3365-3370. [Context Link]

8. National Health and Medical Research Council. National Health and Medical Research Council (NHMRC) additional levels of evidence and grades for recommendations for developers of guidelines: pilot program 2005-2007. Canberra: Commonwealth of Australia; 2005. [Context Link]

9. Hilton R. Acute renal failure. Br Med J. 2006; 333: 786-790. [Context Link]

10. Lameire N, Biesen WV, Vanholder R. Acute renal failure. Lancet. 2005; 365 (9457): 417-430. [Context Link]

11. Singri N, Ahya SN, Levin ML. Acute renal failure. JAMA. 2003; 289 (6): 747-751. [Context Link]

12. Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med. 2008; 36 (4 suppl): S159-S165. [Context Link]

13. Bellomo R, Champman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet. 2000; 356: 2139-2143. [Context Link]

14. Bernard GR, Vincent JL, Laterre PF, et al.. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001; 344 (10): 699-709. [Context Link]

15. Manns B, Doig CJ, Lee H, et al.. Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery. Crit Care Med. 2003; 31 (2): 449-455. [Context Link]

16. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA. 1995; 273 (2): 117-123. [Context Link]

17. Bellomo R, Ronco C, Kellum JA, et al.. Acute renal failure-definition, outcomes measures, animal models, fluid therapy and information technology needs. The second international concensus conference of the Acute Dialysis Quality Initiative (ADQI) group. Crit Care. 2004; 8 (4): R204-R212. [Context Link]

18. Mehta RL, Kellum JA, Shah SV, et al.. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007; 11 (2): R31-R38. [Context Link]

19. Bell M, Liljestam E, Granath F, Fryckstedt J, Ekbom A, Martling C-R. Optimal follow-up time after continuous renal replacement therapy in actual renal failure patients stratified with the RIFLE criteria. Nephrol Dial Transpl. 2005; 20: 354-360. [Context Link]

20. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V. Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann Thorac Surg. 2006; 81: 542-546. [Context Link]

21. Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med. 2006; 34 (7): 1913-1917. [Context Link]

22. Lameire N. The pathophysiology of acute renal failure. Crit Care Clin. 2005; 21: 197-210. [Context Link]

23. Abuelo JG. Normotensive ischemic acute renal failure current concepts. N Engl J Med. 2007; 357 (8): 797-805. [Context Link]

24. Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischaemic acute renal failure. J Am Soc Nephrol. 2003; 14: 2199-2210. [Context Link]

25. Lameire N, Vanholder R. Pathophysiology of ischaemic acute renal failure. Best Pract Res Clin Anaesthesiol. 2004; 18 (1): 21-36. [Context Link]

26. Evenepoel P. Acute toxic renal failure. Best Pract Res Clin Anaesthesiol. 2004; 18 (1): 37-52. [Context Link]

27. Wan L, Bellomo R, Giantomasso DD, Ronco C. The pathogenesis of septic acute renal failure. Curr Opin Crit Care. 2003; 9: 496-502. [Context Link]

28. Uchino S, Kellum JA, Bellomo R, et al.. Beginning and Ending Supportive Therapy for the Kidney (B.E.S.T. Kidney) investigators. Acute renal failure in critically ill patients. A multinational, multicenter study. JAMA. 2005; 294 (7): 813-818. [Context Link]

29. Brivet G, Kleinknecht D, Loirat P, Landais P. Acute renal failure in intensive care units: causes, outcome, and prognostic features of hospital mortality: a prospective, multicentre study. French study group on acute renal failure. Crit Care Med. 1996; 24 (2): 192-198. [Context Link]

30. Sakr Y, Vincent J-L, Reinhart K, et al.. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005; 128 (5): 3098-3108. [Context Link]

31. Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R. Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010; 6: 107-115. [Context Link]

32. Cerda J, Sheinfeld G, Ronco C. Fluid overload in critically ill patients with acute kidney injury. Blood Purif. 2010; 29: 331-338. [Context Link]

33. Ahern-Gould K, Stark J. Quick resource for electrolyte imbalance. Crit Care Nurs Clin North Am. 1998; 10 (4): 477-490. [Context Link]

34. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000; 342 (21): 1581-1589. [Context Link]

35. Mattu A, Brady WJ, Robinson DA. Electrocardiographic manifestations of hyperkalemia. Am J Emerg Med. 2000; 18 (6): 721-729. [Context Link]

36. Nyirenda MJ, Tang JI, Padfield PL, Seckl JR. Hyperkalaemia. Br Med J. 2009; 339: 1019-1024. [Context Link]

37. Thomson H, Macnab R. Fluid and electrolyte problems in renal dysfunction. Anaesth Intensive Care Med. 2009; 10 (6): 289-292. [Context Link]

38. van Holder R, de Smet R. Pathophysiologic effects of uremic retention solutes. J Am Soc Nephrol. 1999; 10: 1815-1823. [Context Link]

39. Alper AB Jr, Shenava RG, Young BA. 2010. Accessed March 23, 2010. [Context Link]

40. Gauthier PM, Szerlip HM. Metabolic acidosis in the intensive care unit. Crit Care Clin. 2002; 18: 289-308. [Context Link]

41. Ronco C, Bellomo R. Prevention of acute renal failure in the critically ill. Nephron Clin Pract. 2003; 93: c13-c20. [Context Link]

42. Ragaller M, Theilen H, Koch T. Volume replacement in critically ill patients with acute renal failure. J Am Soc Nephrol. 2001; 12 (suppl 17): S33-S39. [Context Link]

43. The National Heart, Lung and Blood Institute Acute Respiratory Disease Syndrome Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354 (24): 2564-2575. [Context Link]

44. Murch P. Optimizing the fluid management of ventilated patients with suspected hypovolaemia. Nurs Crit Care. 2005; 10 (6): 279-288. [Context Link]

45. Gunal AI, Celiker H, Dogukan A, et al.. Early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes. J Am Soc Nephrol. 2004; 15: 1862-1867. [Context Link]

46. Ron D, Taitelman U, Michaelson M, Bar-Joseph G, Bursztein S, Better OS. Prevention of acute renal failure in traumatic rhabdomyolysis. Arch Intern Med. 1984; 144: 277-280. [Context Link]

47. Bader BD, Berger ED, Heede MB. What is the best hydration regimen to prevent contrast media-induced nephrotoxicity? Clin Nephrol. 2004; 62 (1): 1-7. [Context Link]

48. Mueller C, Buerkle G, Buettner HJ, et al.. Prevention of contrast media-associated nephropathy. Arch Intern Med. 2002; 162: 329-336. [Context Link]

49. Annane D, Vignon P, Renault A, et al.. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007; 370: 676-684. [Context Link]

50. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004; 350 (22): 2247-2256. [Context Link]

51. Waksman R, Weiss AT, Gotsman MS, Hasin Y. Intra-aortic balloon counterpulsation improves survival in cardiogenic shock complicating acute myocardial infarction. Eur Heart J. 1993; 14: 71-74. [Context Link]

52. Gattinoni L, Brazzi L, Pelosi P, et al.. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med. 1995; 333 (16): 1025-1032. [Context Link]

53. Rivers E, Nguyen B, Havstad S, et al.. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345 (19): 1368-1377. [Context Link]

54. Bersten AD, Holt AW. Vasoactive drugs and the importance of renal perfusion pressure. New Horiz. 1995; 3 (4): 650-661. [Context Link]

55. Dellinger RP, Levy MM, Carlet J, et al.. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008; 36 (1). [Context Link]

56. Martin C, Papazian L, Perrin G, Saux P, Gouin F. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock ? Chest. 1993; 103: 1826-1831. [Context Link]

57. Lameire N, Biesen WV, Hoste EAJ, van Holder R. The prevention of acute kidney injury an in-depth narrative review. Part 2: drugs in the prevention of acute kidney injury. NDT Plus. 2009; 2: 1-10. [Context Link]

58. Uchino S, Doig GS, Bellomo R, et al.. Diuretics and mortality in acute renal failure. Crit Care Med. 2004; 32 (8): 1669-1677. [Context Link]

59. Brezis M, Rosen S. Hypoxia of the renal medulla: its implications for disease. N Engl J Med. 1995; 332 (10): 647-655. [Context Link]

60. Wigand ME, Heidland A. Ototoxic side-effects of high doses of furosemide in patients with uraemia. Postgrad Med J. 1971; 47 (suppl): 54-56. [Context Link]

61. Bagshaw SM, Delaney A, Haase M, Ghali WA, Bellomo R. Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resuscitation. 2007; 9 (1): 60-68. [Context Link]

62. Ho KM, Sheridan DJ. Meta-analysis of furosemide to prevent or treat acute renal failure. Br Med J. 2006; 333 (7565): 420-425. [Context Link]

63. Hollenberg N, Adams D, Mendall P, Abrams H, Merril J. Renal vascular responses to dopamine: haemodynamic and angiographic observations in normal man. Clin Sci. 1973; 45: (733-742). [Context Link]

64. Polson RJ, Park GR, Lindop MJ, Farman JV, Calne RY, Williams R. The prevention of renal impairment in patients undergoing orthotopic liver grafting by infusion of low dose dopamine. Anaesthesia. 1987; 42: 15-19. [Context Link]

65. Lauschke A, Teichgraber UKM, Frei U, Eckardt K-U. "Low-dose" dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006; 69 (9): 1669-1674. [Context Link]

66. Kellum JA, Decker JM. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med. 2001; 29 (8): 1526-1531. [Context Link]

67. DiMari J, Megyesi J, Udvarhelyi N, Price P, Davis R, Safirstein R. N-acetyl cysteine ameliorates ischemic renal failure. American Journal of Physiology. 1997; 272 (3): F292-F298. [Context Link]

68. Durham JD, Caputo C, Dokko J, et al.. A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney Int. 2002; 62: 2202-2207. [Context Link]

69. Kay J, Chow WH, Chan TM, et al.. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention. J Am Med Assoc. 2003; 289 (5): 553-558. [Context Link]

70. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000; 343 (3): 180-184. [Context Link]

71. Alonso A, Lau J, Jaber BL, Weintraub A, Sarnak MJ. Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomised, controlled trials. Am J Kidney Dis. 2004; 43 (1): 1-9. [Context Link]

72. Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet. 2003; 362: 598-603. [Context Link]

73. Isenbarger DW, Kent SM, O'Malley P. Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine for prevention of contrast nephropathy. Am J Cardiol. 2003; 92: 1454-1458. [Context Link]

74. Ho KM, Morgan D. Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis. 2009; 53 (1): 33-40. [Context Link]

75. Nigwekar SU, Kandula P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac Surg. 2009; 87: 139-147. [Context Link]