Angela M. Love1, Adam Rothman2, and Alfredo Astua2
1 Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
2 Icahn School of Medicine at Mount Sinai, New York, NY, USA
Background
Definition of disease
AKI is defined as an abrupt decline in kidney function, either reversible or irreversible, associated with retention of metabolic waste products.
AKI is defined as:
Increase in serum creatinine over 48 hours of ≥0.3 mg/dL from baseline, or
Increase in serum creatinine of >50%, or
Urine output <0.5 mL/kg/h for more than 6 hours.
There are two further refined definitions for AKI. The RIFLE and Acute Kidney Injury Network (AKIN) criteria are supported by the Kidney Disease Improving Global Outcomes clinical practice guidelines.
Disease classification
The RIFLE criteria consist of three grading levels defined as risk, injury, or failure, and two clinical outcomes defined as loss of kidney function and end‐stage kidney disease.
The AKIN criteria are a modification of the RIFLE criteria and include a staging system (Table 50.1).
Incidence/prevalence
The exact prevalence of AKI in the ICU is limited by varying definitions of AKI and under‐reporting based on this limitation. Studies have reported an overall incidence of 20–50%.
Patients with sepsis have been reported to have a higher incidence of AKI.
Table 50.1AKIN and RIFLE criteria for acute kidney injury.
AKIN
RIFLE
Both
Stage
Serum creatinine or GFR
Class
Serum creatinine or GFR
Urine output
1
Increase of ≥0.3 mg/dL or 1.5–2× baseline
Risk
Creatinine >1.5× baseline or GFR decrease >25%
<0.5 mL/kg/h for at least 6 hours
2
Increase of 2–3× baseline
Injury
Creatinine >2× baseline or GFR decrease >50%
<0.5 mL/kg/h for at least 12 hours
3
Increase >3× baseline or ≥4 mg/dL with an acute increase of at least 0.5 mg/dL or newly required renal replacement therapy
Failure
Creatinine >3× baseline or >4 mg/dL with an acute increase of at least 0.5 mg/dL or GFR decrease >75%
<0.3 mL/kg/h for at least 24 hours or anuria for at least 12 hours
Loss
Persistent loss of kidney function for >4 weeks
End‐stage renal disease (ESRD)
ESRD >3 months
Etiology
AKI has multiple etiologies, further defined based on location of injury as pre‐renal, intrinsic, or post‐renal.
Pre‐renal: due to transient renal hypoperfusion
Hypotension
Hypovolemia
Congestive heart failure with reduced ejection fraction
Urinary tract obstruction: urethral (such as benign prostatic hyperplasia), ureteral
Pathology/pathogenesis
Pre‐renal injury occurs secondary to underperfusion of an otherwise healthy kidney.
Intrinsic renal injury is caused by disease of the renal parenchyma:
Acute tubular necrosis (ATN) is the most common intrinsic cause, and can develop from renal ischemia or injury from endogenous and exogenous substances.
Acute interstitial nephritis (AIN) is frequently secondary to one of five etiologies: drug hypersensitivity reaction (most common), infection, immune‐mediated, glomerular disease, or idiopathic.
Post‐renal injury occurs in the setting of urinary tract obstruction. Causes of the obstruction can be within the urinary tract itself (clots, stones) or outside the tract (enlarged prostate, tumors, increased surrounding pressures). The increased pressure in the urinary tract alters the pressure gradient at the glomerular capillaries with a resultant decrease in glomerular filtration rate (GFR) and signs and symptoms of AKI.
Prevention
Recognition of high risk patients is key to prevention of AKI. Hospitalized patients, in particular, should have their renal function assessed before any surgical procedures, imaging studies requiring contrast, or administration of any nephrotoxic agents. These patients should also be monitored for any change in urine output from baseline.
Risk factors for acute kidney injury
Acute on chronic kidney disease (CKD).
Heart failure.
Liver disease.
Diabetes.
Prior history of AKI.
Oliguria (<0.5 mL/kg/h).
Neurologic impairment.
Hypovolemia.
Nephrotoxic agent exposure.
Use of iodinated contrast.
Symptoms or history of obstruction.
Age over 65 years.
Recent chemotherapy.
Primary prevention
Primary prevention is focused on understanding and responding to the associated risk factor.
Key components include:
Maintaining renal perfusion by correcting for hypovolemia, decreased cardiac output, and sepsis‐related vasodilation.
Avoiding nephrotoxic agents.
Limiting iodinated contrast (especially in diabetic and CKD patients).
Ensuring adequate urine output in rhabdomyolysis (>0.5 mL/kg/h).
Alkalinizing urine in hyperuricemia.
Causes of intrinsic renal disease
Common causes of ATN
Common causes of AIN
Ischemia (shock state)
Beta‐lactam antibiotics
Rhabdomyolysis
Rifampin
Cast nephropathy (myeloma light chains)
Sulfonamides
Aminoglycosides
Fluoroquinolones
Amphotericin B
NSAIDs
Acyclovir IV
Allopurinol
Cisplatin
Proton pump inhibitors
Ethylene glycol
Sarcoidosis
Methanol
Diuretics
Tumor lysis
Aspirin
IV iodinated contrast
Bacterial pyelonephritis
Viruses (CMV, EBV, HIV, rubeola)
Diagnosis
Typical presentation
AKI generally presents as an increase in serum creatinine on surveillance blood work. This can be associated with a decrease in urine output. Many times, however, patients are asymptomatic, and may be diagnosed incidentally on routine blood work testing.
Clinical diagnosis
History
Key questions include pertinent prior history and details of the current illness.
Important past medical history includes prior history of renal dysfunction (acute or chronic), diabetes mellitus, and congestive heart failure.
Important current information includes NSAID use, decreased oral intake or decreased urine output, difficulty with urination, recent iodinated contrast, and severe volume loss.
Physical examination
The physician should conduct a physical exam directed at possible causes and consequences of AKI.
Physical exam findings for patients with AKI may include tachycardia, loss of skin turgor, or dry mucous membranes. One can also evaluate for bladder distension by checking for suprapubic tenderness. Flank tenderness could be suggestive of possible pyelonephritis.
Physical exam findings for sequelae of AKI include assessing volume overload manifested as peripheral edema, pulmonary crackles, and jugular venous distension. Also assess for uremia manifesting as altered mental status, pericardial rub in pericarditis, or distant cardiac sounds in uremic pericardial effusions.
More invasive exam techniques include measuring bladder pressure through an indwelling urinary catheter in order to assess for abdominal compartment syndrome. Ultrasound can also be used to evaluate for bladder distention.
Laboratory diagnosis
List of diagnostic tests
Initial blood work should include blood urea nitrogen (BUN) and serum creatinine.
Urine osmolality, urine sodium, urine creatinine, and urine urea are useful to calculate FeNa and FeUrea to help differentiate the location of the injury (pre‐renal, intrinsic/ATN) (see Algorithm 50.1).
FeNa is <1% in pre‐renal injury, reflecting increased reuptake of sodium at the renal tubules. FeNa utility is limited in patients with CKD, early intrinsic injury, and in the elderly.
FeUrea has improved sensitivity and specificity in patients taking loop diuretics. A value of <35% suggests pre‐renal injury due to renal hypoperfusion.
Urinalysis is also essential for differentiating between different intrinsic diagnoses and pre‐renal AKI.
Pre‐renal and post‐renal AKI: urine sediment is usually bland.
Glomerular injury: RBC casts, dysmorphic RBCs.
Vascular injury: RBC casts.
Tubular injury: muddy brown granular casts, tubular epithelial cells.
