Acute renal failure (ARF), or acute kidney injury (AKI), as it is now referred to in the literature, is defined as an abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum creatinine concentration or by azotemia (a rise in blood urea nitrogen [BUN] concentration).[1] (See Etiology and Prognosis.)
However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production. (See History.)
A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim) that inhibit the kidney’s tubular secretion. A rise in the BUN level can occur without renal injury, resulting instead from such sources as GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be taken before determining if a kidney injury is present. (See Etiology and History.)
See Chronic Kidney Disease and Acute Tubular Necrosis for complete information on these topics.
An example of AKI, apparently the result of acute tubular necrosis (ATN), is seen in the image below.
Categories of AKI
AKI may be classified into 3 general categories, as follows:
Prerenal - as an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons
Intrinsic - in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage
Postrenal - from obstruction to the passage of urine
While this classification is useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories. (See Etiology.)
Oliguric and nonoliguric patients with AKI
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in creatinine levels, and may have qualitative differences in urine solute concentrations and cellular content. (Approximately 50-60% of all causes of AKI are nonoliguric.)
This lack of a uniform clinical presentation reflects the variable nature of the injury.
Classifying AKI as oliguric or nonoliguric based on daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure.
Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, suggests bilateral obstruction or catastrophic injury to both kidneys. Stratification of renal failure along these lines helps in decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.
The RIFLE system
In 2004, the Acute Dialysis Quality Initiative work group set forth a definition and classification system for acute renal failure, described by the acronym RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease; see the table, below).[2] Investigators have since applied the RIFLE system to the clinical evaluation of AKI, although it was not originally intended for that purpose. AKI research increasingly uses RIFLE.
When the failure classification is achieved by UO criteria, the designation of RIFLE-FO is used to denote oliguria. The initial stage, risk, has high sensitivity; more patients will be classified in this mild category, including some who do not actually have renal failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity.
A vast array of fluid and electrolyte abnormalities can be seen with acute kidney injury (AKI).
Cardiovascular complications
Cardiovascular complications (eg, congestive heart failure [CHF], myocardial infarction, arrhythmias, cardiac arrest) have been observed in as many as 35% of patients with AKI. Fluid overload secondary to oliguric AKI is a particular risk for elderly patients with little cardiac reserve.
Pericarditis is a relatively rare complication of AKI. When pericarditis complicates AKI, consider additional diagnoses, such as systemic lupus erythematosus (SLE) and hepatorenal syndrome.
AKI also can be a complication of cardiac diseases, such as endocarditis, worsening CHF, or atrial fibrillation with emboli. Cardiac arrest in a patient with AKI always should arouse suspicion of hyperkalemia. Many authors recommend a trial of intravenous calcium chloride (or gluconate) in all patients with AKI who experience cardiac arrest.
Pulmonary complications
Pulmonary complications have been reported in approximately 54% of patients with AKI and are the single most significant risk factor for death in patients with AKI. Several diseases exist that commonly present with simultaneous pulmonary and renal involvement, including pulmonary/renal syndromes (eg, Goodpasture syndrome, Wegener granulomatosis, polyarteritis nodosa, cryoglobulinemia, sarcoidosis). Hypoxia commonly occurs during hemodialysis and can be particularly significant in the patient with pulmonary disease. This dialysis-related hypoxia is thought to occur secondary to white blood cell (WBC) lung sequestration and alveolar hypoventilation.
GI complications
GI symptoms of nausea, vomiting, and anorexia are frequent complications of AKI and represent one of the cardinal signs of uremia. GI bleeding occurs in approximately one third of patients with AKI. Most episodes are mild, but GI bleeding accounts for 3-8% of deaths in patients with AKI.
Mild hyperamylasemia commonly is seen in AKI (2-3 times controls). Elevation of baseline amylase can complicate diagnosis of pancreatitis in patients with AKI. Lipase, which commonly is not elevated in AKI, often is necessary to make the diagnosis of pancreatitis. Pancreatitis has been reported as a concurrent illness with AKI in patients with atheroemboli, vasculitis, and sepsis from ascending cholangitis.
Jaundice has been reported to complicate AKI in approximately 43% of cases. Etiologies of jaundice with AKI include hepatic congestion, blood transfusions, and sepsis.
Hepatitis occurring concurrently with AKI should prompt the differential diagnosis of common bile duct obstruction, fulminant hepatitis B, leptospirosis, acetaminophen toxicity, and Amanita phalloides toxin.
Infectious complications
Infections commonly complicate the course of AKI and have been reported to occur in as many as 33% of patients with AKI. Most common sites are pulmonary and urinary tracts. Infections are the leading cause of morbidity and death in patients with AKI. Various studies have reported mortality rates of 11-72% in infections complicating AKI.
Neurologic complications
Neurologic signs of uremia are a common complication of AKI and have been reported in approximately 38% of patients with AKI. Neurologic sequelae include lethargy, somnolence, reversal of the sleep-wake cycle, and cognitive or memory deficits. Focal neurologic deficits rarely are due solely to uremia and should remain a diagnosis of exclusion in patients with AKI.
The pathophysiology of neurologic symptoms is still unknown, but they do not correlate well to levels of BUN or creatinine.
A number of diseases express themselves with concurrent neurologic and renal manifestations (eg, SLE, thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], endocarditis, malignant hypertension).
However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production. (See History.)
A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim) that inhibit the kidney’s tubular secretion. A rise in the BUN level can occur without renal injury, resulting instead from such sources as GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be taken before determining if a kidney injury is present. (See Etiology and History.)
See Chronic Kidney Disease and Acute Tubular Necrosis for complete information on these topics.
An example of AKI, apparently the result of acute tubular necrosis (ATN), is seen in the image below.
Categories of AKI
AKI may be classified into 3 general categories, as follows:
Prerenal - as an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons
Intrinsic - in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage
Postrenal - from obstruction to the passage of urine
While this classification is useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories. (See Etiology.)
Oliguric and nonoliguric patients with AKI
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in creatinine levels, and may have qualitative differences in urine solute concentrations and cellular content. (Approximately 50-60% of all causes of AKI are nonoliguric.)
This lack of a uniform clinical presentation reflects the variable nature of the injury.
Classifying AKI as oliguric or nonoliguric based on daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure.
Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, suggests bilateral obstruction or catastrophic injury to both kidneys. Stratification of renal failure along these lines helps in decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.
The RIFLE system
In 2004, the Acute Dialysis Quality Initiative work group set forth a definition and classification system for acute renal failure, described by the acronym RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease; see the table, below).[2] Investigators have since applied the RIFLE system to the clinical evaluation of AKI, although it was not originally intended for that purpose. AKI research increasingly uses RIFLE.
When the failure classification is achieved by UO criteria, the designation of RIFLE-FO is used to denote oliguria. The initial stage, risk, has high sensitivity; more patients will be classified in this mild category, including some who do not actually have renal failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity.
A vast array of fluid and electrolyte abnormalities can be seen with acute kidney injury (AKI).
Cardiovascular complications
Cardiovascular complications (eg, congestive heart failure [CHF], myocardial infarction, arrhythmias, cardiac arrest) have been observed in as many as 35% of patients with AKI. Fluid overload secondary to oliguric AKI is a particular risk for elderly patients with little cardiac reserve.
Pericarditis is a relatively rare complication of AKI. When pericarditis complicates AKI, consider additional diagnoses, such as systemic lupus erythematosus (SLE) and hepatorenal syndrome.
AKI also can be a complication of cardiac diseases, such as endocarditis, worsening CHF, or atrial fibrillation with emboli. Cardiac arrest in a patient with AKI always should arouse suspicion of hyperkalemia. Many authors recommend a trial of intravenous calcium chloride (or gluconate) in all patients with AKI who experience cardiac arrest.
Pulmonary complications
Pulmonary complications have been reported in approximately 54% of patients with AKI and are the single most significant risk factor for death in patients with AKI. Several diseases exist that commonly present with simultaneous pulmonary and renal involvement, including pulmonary/renal syndromes (eg, Goodpasture syndrome, Wegener granulomatosis, polyarteritis nodosa, cryoglobulinemia, sarcoidosis). Hypoxia commonly occurs during hemodialysis and can be particularly significant in the patient with pulmonary disease. This dialysis-related hypoxia is thought to occur secondary to white blood cell (WBC) lung sequestration and alveolar hypoventilation.
GI complications
GI symptoms of nausea, vomiting, and anorexia are frequent complications of AKI and represent one of the cardinal signs of uremia. GI bleeding occurs in approximately one third of patients with AKI. Most episodes are mild, but GI bleeding accounts for 3-8% of deaths in patients with AKI.
Mild hyperamylasemia commonly is seen in AKI (2-3 times controls). Elevation of baseline amylase can complicate diagnosis of pancreatitis in patients with AKI. Lipase, which commonly is not elevated in AKI, often is necessary to make the diagnosis of pancreatitis. Pancreatitis has been reported as a concurrent illness with AKI in patients with atheroemboli, vasculitis, and sepsis from ascending cholangitis.
Jaundice has been reported to complicate AKI in approximately 43% of cases. Etiologies of jaundice with AKI include hepatic congestion, blood transfusions, and sepsis.
Hepatitis occurring concurrently with AKI should prompt the differential diagnosis of common bile duct obstruction, fulminant hepatitis B, leptospirosis, acetaminophen toxicity, and Amanita phalloides toxin.
Infectious complications
Infections commonly complicate the course of AKI and have been reported to occur in as many as 33% of patients with AKI. Most common sites are pulmonary and urinary tracts. Infections are the leading cause of morbidity and death in patients with AKI. Various studies have reported mortality rates of 11-72% in infections complicating AKI.
Neurologic complications
Neurologic signs of uremia are a common complication of AKI and have been reported in approximately 38% of patients with AKI. Neurologic sequelae include lethargy, somnolence, reversal of the sleep-wake cycle, and cognitive or memory deficits. Focal neurologic deficits rarely are due solely to uremia and should remain a diagnosis of exclusion in patients with AKI.
The pathophysiology of neurologic symptoms is still unknown, but they do not correlate well to levels of BUN or creatinine.
A number of diseases express themselves with concurrent neurologic and renal manifestations (eg, SLE, thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], endocarditis, malignant hypertension).
