Acute kidney injury (AKI), previously known as acute kidney

failure, is the term used to encompass the entire range of the

syndrome, ranging from a slight deterioration in kidney function
to severe impairment. AKI is characterized by a rapid loss
of kidney function. This loss is accompanied by a rise in serum creatinine and/or a reduction
in urine output. The severity of
dysfunction can range from a small increase in serum creatinine
or reduction in urine output to the development of azotemia
(an accumulation of nitrogenous waste products [urea nitrogen,
creatinine] in the blood).
Although AKI is potentially reversible, it has a high mortality
rate.1 AKI usually affects people with other life-threatening
conditions2 (Table 47-2). Most commonly, AKI follows severe,
prolonged hypotension or hypovolemia or exposure to a nephrotoxic
agent.
AKI can develop over hours or days with progressive elevations
of blood urea nitrogen (BUN), creatinine, and potassium
with or without a reduction in urine output. Hospitalized
patients develop AKI at a high rate (1 in 5) and have a high
mortality rate. When AKI develops in patients in intensive
care units (ICUs), the mortality rate can be as high as 70%
to 80%.3-5
Etiology and Pathophysiology
The causes of AKI, which are multiple and complex, are categorized
as prerenal, intrarenal (or intrinsic), and postrenal causes
(see Table 47-2).
Prerenal. Prerenal causes of AKI are factors external to the
kidneys. These factors reduce systemic circulation, causing a
reduction in renal blood flow. The decrease in blood flow
leads to decreased glomerular perfusion and filtration of the
kidneys. Although kidney tubular and glomerular function is
preserved, glomerular filtration is reduced as a result of
decreased perfusion.
It is important to distinguish prerenal oliguria from the oliguria
of intrarenal AKI. In prerenal oliguria there is no damage
to the kidney tissue (parenchyma). The oliguria is caused by a
decrease in circulating blood volume (e.g., severe dehydration,
heart failure [HF], decreased cardiac output) and is readily
reversible with appropriate treatment. With a decrease in circulating
blood volume, autoregulatory mechanisms that increase
angiotensin II, aldosterone, norepinephrine, and antidiuretic
hormone attempt to preserve blood flow to essential organs.
Prerenal azotemia results in a reduction in the excretion of
sodium (less than 20 mEq/L), increased sodium and water
retention, and decreased urine output.
Prerenal conditions can lead to intrarenal disease if renal
ischemia is prolonged. Prerenal conditions account for many
cases of intrarenal AKI. If decreased perfusion persists for an
extended time, the kidneys lose their ability to compensate and
damage to kidney parenchyma occurs (intrarenal damage).
Intrarenal. Intrarenal causes of AKI (see Table 47-2) include
conditions that cause direct damage to the kidney tissue, resulting
in impaired nephron function. The damage from intrarenal
causes usually results from prolonged ischemia, nephrotoxins (e.g., aminoglycoside
antibiotics, contrast media), hemoglobin
released from hemolyzed red blood cells (RBCs), or myoglobin
released from necrotic muscle cells.
Nephrotoxins can cause obstruction of intrarenal structures
by crystallizing or by causing damage to the epithelial cells of
the tubules. Hemoglobin and myoglobin can block the tubules
and cause renal vasoconstriction. Diseases of the kidney such
as acute glomerulonephritis and systemic lupus erythematosus
may also cause AKI.
Acute tubular necrosis (ATN) is the most common intrarenal
cause of AKI and is primarily the result of ischemia, nephrotoxins,
or sepsis (Fig. 47-1). Ischemic and nephrotoxic ATN
is responsible for 90% of intrarenal AKI cases.6,7 Severe kidney
ischemia causes a disruption in the basement membrane and
patchy destruction of the tubular epithelium. Nephrotoxic
agents cause necrosis of tubular epithelial cells, which slough
off and plug the tubules. ATN is potentially reversible if the
basement membrane is not destroyed and the tubular epithelium
regenerates.
ATN is the most common cause of AKI for hospitalized
patients. Risks associated with development of ATN while in
the hospital include major surgery, shock, sepsis, blood transfusion
reaction, muscle injury from trauma, prolonged hypotension,
and nephrotoxic agents (see Table 47-2).
Postrenal. Postrenal causes of AKI involve mechanical
obstruction in the outflow of urine. As the flow of urine is
obstructed, urine refluxes into the renal pelvis, impairing kidney
function. The most common causes are benign prostatic hyperplasia,
prostate cancer, calculi, trauma, and extrarenal tumors.
Bilateral ureteral obstruction leads to hydronephrosis (kidney
dilation), increase in hydrostatic pressure, and tubular blockage,
resulting in a progressive decline in kidney function. If bilateral
obstruction is relieved within 48 hours of onset, complete
recovery is likely. After 12 weeks, recovery is unlikely. Prolonged
obstruction can lead to tubular atrophy and irreversible
kidney fibrosis. Postrenal causes of AKI account for less than
10% of AKI cases