Acute Kidney Injury (AKI): Practice Essentials, Background, Pathophysiology

Acute kidney injury (AKI) 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 azotemia (a rise in blood urea nitrogen [BUN] concentration).
[2] However, immediately after a kidney insult, BUN or serum creatinine levels may be normal. In the early phase, the only sign of a kidney injury may be decreased urine production. (See History.)

Furthermore, a rise in serum creatinine might not always be related to a decrease in kidney function; certain medications (eg, cimetidine, trimethoprim, Poly ADP-ribose polymerase [PARP] inhibitors, and cyclin-dependent kinase 4 and 6 [CDK4/6] inhibitors) can inhibit the kidney’s tubular secretion of creatinine independent of glomerular filtration rate (GFR). A rise in the BUN level can also occur without renal injury, as a result of gastrointestinal (GI) or mucosal bleeding, steroid use, or protein loading. Therefore, a careful inventory must be taken before concluding that a kidney injury is present. (See Etiology and History.)

See Chronic Kidney Disease and Acute Tubular Necrosis for complete information on these topics. For information on pediatric cases, see Chronic Kidney Disease in Children.

Mục Lục

Categories of AKI

Traditionally, 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 helps guide the development of 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 on the basis of daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume of less than 400-500 mL, which is the minimum amount of urine required to eliminate the average daily solute load and has a worse prognosis.

Anuria is defined as a urine output of less than 50-100 mL/day and, if abrupt in onset, suggests bilateral obstruction or catastrophic injury to both kidneys.

Stratification of kidney injury along these lines helps in diagnosis and decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.

RIFLE classification system

In 2004, the Acute Dialysis Quality Initiative workgroup 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).
[3] 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. See Table 1 below.

Table 1. RIFLE Classification System for Acute Kidney Injury (Open Table in a new window)

Stage

GFR Criteria

Urine Output Criteria

Probability

Risk

SCreat increased × 1.5

GFR decreased >25%

UO < 0.5 mL/kg/h × 6 h

High sensitivity (Risk >Injury >Failure)

Injury

SCreat increased × 2

GFR decreased >50%

UO < 0.5 mL/kg/h × 12 h

Failure

SCreat increased × 3

GFR decreased 75%

SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL

UO < 0.3 mL/kg/h × 24 h

(oliguria)

anuria × 12 h

Loss

Persistent acute renal failure: complete loss of kidney function >4 wk

High specificity

ESKD

Complete loss of kidney function >3 mo

ESKD—end-stage kidney disease; GFR—glomerular filtration rate; SCreat—serum creatinine; UO—urine output

Note: Patients can be classified by GFR criteria and/or UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCreat is less than 3-fold, provided that the new SCreat is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L).

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 kidney failure. Progression through the increasingly severe stages of RIFLE is marked by decreasing sensitivity and increasing specificity.

Acute Kidney Injury Network classification system

The Acute Kidney Injury Network (AKIN) has developed specific criteria for the diagnosis of AKI. The AKIN defines AKI as abrupt (within 48 hours) reduction of kidney function, after excluding urinary obstruction and achieving adequate hydration, manifested by any 1 of the following
[4]

An absolute increase in serum creatinine of 0.3 mg/dL or greater (≥26.4 µmol/L)
A percentage increase in serum creatinine of 50% or greater (1.5-fold from baseline)
A reduction in urine output, defined as less than 0.5 mL/kg/h for more than 6 hours

AKIN has proposed a staging system for AKI that is modified from RIFLE. In this system, either serum creatinine or urine output criteria can be used to determine the stage. See Table 2 below.

Table 2. Acute Kidney Injury Network Classification/Staging System for AKI (Open Table in a new window)

Stage

Serum Creatinine Criteria

Urine Output Criteria

Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline

< 0.5 mL/kg/h for >6 h

> 2-fold to 3-fold increase from baseline

< 0.5 mL/kg/h for >12 h

> 3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)

< 0.3 mL/kg/h for 24 h or anuria for 12 h

*Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.

KDIGO classification system

The KDIGO system, which is the most recent and widely accepted classification, was developed by merging the RIFLE and AKIN classifications into a single simplified one. It offers equivalent or superior sensitivity for AKI detection and prognostic performance compared with RIFLE and AKIN.
[1]

AKI is defined by any of the following:

Rise in serum creatinine ≥0.3 mg/dL within 48 hours
Rise in serum creatinine ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days
Urine output < 0.5 ml/kg/hour for six hours

The criteria for AKI stages are similar to AKIN, except for stage 3 AKI, which comprises an increase in serum creatinine of ≥0.3 mg/dL (rather than ≥ 0.5 mg/dL) to ≥4 mg/dL.

Cardiovascular complications

Cardiovascular complications (eg, heart failure, 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 limited cardiac reserve. Additionally, AKI is associated with electrolyte and acid-base imbalance that can increase the risk of developing arrhythmia and decrease myocardial contractility. In cardiac patients who experience AKI either in the setting of acute decompensated heart failure or cardiac surgery, AKI is associated with worse morbidity and mortality.
[5]

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, decompensated heart failure, or atrial fibrillation with emboli. Cardiac arrest in a patient with AKI should always arouse suspicion of hyperkalemia. Many authors recommend that in addition to ACLS measures in patients with PEA arrest, a trial of intravenous calcium chloride (or gluconate) should be considered in patients with AKI with known or suspected hyperkalemia.

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. Proposed mechanisms for acute lung injury during AKI include hypervolemia, increased proinflammatory cytokine levels, leukocyte infiltration, and increased pulmonary vascular permeability. In addition, diseases exist that commonly present with simultaneous pulmonary and renal involvement, including the following:

Goodpasture syndrome
Granulomatosis with polyangiitis (Wegener granulomatosis)
Polyarteritis nodosa
Cryoglobulinemia
Sarcoidosis

Hypoxia commonly occurs during hemodialysis and can be particularly significant in patients with pulmonary disease. This dialysis-related hypoxia is thought to occur secondary to white blood cell (WBC) lung sequestration and alveolar hypoventilation.

Gastrointestinal complications

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.

Pancreatitis

Mild hyperamylasemia is commonly seen in AKI. Elevation of baseline amylase concentrations can complicate the diagnosis of pancreatitis in patients with AKI. Lipase measurement, frequently suppressed in AKI, should be considered in this light when there is suspicion of pancreatitis. Pancreatitis has been reported as a concurrent illness with AKI in patients with atheroemboli, vasculitis, and sepsis from ascending cholangitis.

Jaundice

Jaundice frequently complicates AKI. Etiologies of jaundice with AKI include hepatic congestion, blood transfusions, and sepsis.

Hepatitis

Hepatitis occurring concurrently with AKI should prompt consideration of the following disorders in the differential diagnosis:

Common bile duct obstruction
Fulminant hepatitis
HBV- and HCV-associated glomerulonephritis
Leptospirosis
Medication toxicity (eg, acetaminophen toxicity)
Amanita phalloides poisoning

Infectious complications

Infections commonly complicate the course of AKI and have been reported to occur in as many as 33% of patients with AKI. It is attributed to possible altered cytokine homeostasis and immune cell dysfunction associated with AKI. The most common sites of infection are the 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 symptoms of uremia 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 are rarely caused solely by uremia.

The pathophysiology of neurologic symptoms is still unknown but is partially attributed to the possible accumulation of neurotoxic metabolites in patients with severe AKI that can lead to an imbalance in cellular water transportation and disturbance of the blood-brain barrier. However, these symptoms do not correlate well with levels of BUN or creatinine.

A number of diseases can present with concurrent neurologic and renal manifestations, including the following: