Acute kidney injury (AKI), previously called acute renal failure (ARF),[1][2] is an abrupt loss

of kidney function that develops within 7 days.[3]

Its causes are numerous. Generally it occurs because of damage to the kidney tissue caused by
decreased kidney blood flow(kidney ischemia) from any cause (e.g., low blood pressure),
exposure to substances harmful to the kidney, an inflammatoryprocess in the kidney, or an
obstruction of the urinary tract that impedes the flow of urine. AKI is diagnosed on the basis of
characteristic laboratory findings, such as elevated blood urea nitrogen and creatinine, or inability
of the kidneys to produce sufficient amounts of urine.
AKI may lead to a number of complications, including metabolic acidosis, high potassium
levels, uremia, changes in body fluid balance, and effects on other organ systems, including
death. People who have experienced AKI may have an increased risk of chronic kidney
disease in the future. Management includes treatment of the underlying cause and supportive
care, such as renal replacement therapy.

Signs and symptoms[edit]

The clinical picture is often dominated by the underlying cause.The symptoms of acute kidney
injury result from the various disturbances of kidney function that are associated with the
disease. Accumulation of urea and other nitrogen-containing substances in the bloodstream lead
to a number of symptoms, such as fatigue, loss of
appetite, headache, nauseaand vomiting.[4] Marked increases in the potassium level can lead
to abnormal heart rhythms, which can be severe and life-threatening.[5] Fluid balance is frequently
affected, though blood pressure can be high, low or normal.[6]
Pain in the flanks may be encountered in some conditions (such as clotting of the kidneys' blood
vessels or inflammation of the kidney); this is the result of stretching of the fibrous tissue capsule
surrounding the kidney.[7] If the kidney injury is the result of dehydration, there may be thirst as
well as evidence of fluid depletion on physical examination.[7] Physical examination may also
provide other clues as to the underlying cause of the kidney problem, such as a rash in interstitial
nephritis (or vasculitis) and a palpable bladder in obstructive nephropathy.[7]

Causes[edit]
Classification[edit]
Acute kidney injury is diagnosed on the basis of clinical history and laboratory data. A diagnosis
is made when there is a rapid reduction in kidney function, as measured by serum creatinine, or
based on a rapid reduction in urine output, termed oliguria (less than 400 mLs of urine per 24
hours).

Classic laboratory findings in AKI

Type UOsm UNa FeNa BUN/Cr

Prerenal >500 <10 <1% >20[8]

Intrinsic <350 >20 >2% <10-15[8]

Postrenal <350 >40 >4% >20[8]

AKI can be caused by systemic disease (such as a manifestation of an autoimmune disease,

e.g. lupus nephritis), crush injury, contrast agents, some antibiotics, and more. AKI often occurs
due to multiple processes. The most common cause is dehydration and sepsis combined with
nephrotoxic drugs, especially following surgery or contrast agents.
The causes of acute kidney injury are commonly categorized into prerenal, intrinsic,
and postrenal.
Acute kidney injury occurs in up to 30% of patients following cardiac surgery.[9] Mortality
increases by 60-80% in post-cardiopulmonary bypass patients who go on to require renal
replacement therapy. Preoperative creatinine greater than 1.2 mg/dL, combined valve and
bypass procedures, emergency surgery, and preoperative intraaortic balloon pump are risk
factors most strongly correlated with post-cardiopulmonary bypass acute kidney injury. Other
well-known minor risk factors include: female gender, congestive heart failure, chronic
obstructive pulmonary disease, insulin-requiring diabetes, and depressed left ventricular ejection
fraction.[9]

Prerenal[edit]
Prerenal causes of AKI ("pre-renal azotemia") are those that decrease effective blood flow to the
kidney and cause a decrease in the glomerular filtration rate (GFR). Both kidneys need to be
affected as one kidney is still more than adequate for normal kidney function. Notable causes of
prerenal AKI include low blood volume (e.g., dehydration), low blood pressure, heart
failure (leading to cardiorenal syndrome), liver cirrhosis and local changes to the blood vessels
supplying the kidney. The latter include renal artery stenosis, or the narrowing of the renal
artery which supplies the kidney with blood, and renal vein thrombosis, which is the formation of
a blood clot in the renal vein that drains blood from the kidney.

Intrinsic[edit]
Intrinsic AKI refers to disease processes which directly damage the kidney itself. Intrinsic AKI can
be due to one or more of the kidney's structures including the glomeruli, kidney tubules, or
the interstitium. Common causes of each are glomerulonephritis, acute tubular necrosis (ATN),
and acute interstitial nephritis (AIN), respectively. Other causes of intrinsic AKI
are rhabdomyolysis and tumor lysis syndrome.[10] Certain medication classes such as calcineurin
inhibitors (e.g., tacrolimus) can also directly damage the tubular cells of the kidney and result in a
form of intrinsic AKI.

Postrenal[edit]
Postrenal AKI refers to acute kidney injury caused by disease states downstream of the kidney
and most often occurs as a consequence of urinary tract obstruction. This may be related
to benign prostatic hyperplasia, kidney stones, obstructed urinary catheter, bladder stones, or
cancer of the bladder, ureters, or prostate.

Diagnosis[edit]
Definition[edit]
Introduced by the KDIGO in 2012,[11] specific criteria exist for the diagnosis of AKI.
AKI can be diagnosed if any one of the following is present:

 Increase in SCr by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or

 Increase in SCr to ≥1.5 times baseline, which has occurred within the prior 7 days; or
 Urine volume < 0.5 ml/kg/h for 6 hours.
Staging[edit]
The RIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in
assessment of the severity of a person's acute kidney injury. The acronym RIFLE is used to
define the spectrum of progressive kidney injury seen in AKI:[12][13]

Pathophysiology of acute kidney injury in the proximal renal tubule

 Risk: 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease
by 25 percent, or urine output <0.5 mL/kg per hour for six hours.
 Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine
output <0.5 mL/kg per hour for 12 hours
 Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine
output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours
 Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more
than four weeks
 End-stage kidney disease: Complete loss of kidney function (e.g., need for renal
replacement therapy) for more than three months
Evaluation[edit]
The deterioration of kidney function may be signaled by a measurable decrease in urine output.
Often, it is diagnosed on the basis of blood tests for substances normally eliminated by the
kidney: urea and creatinine. Additionally, the ratio of BUN to creatinine is used to evaluate kidney
injury. Both tests have their disadvantages. For instance, it takes about 24 hours for the
creatinine level to rise, even if both kidneys have ceased to function. A number of alternative
markers has been proposed (such as NGAL, KIM-1, IL18 and cystatin C), but none of them is
currently established enough to replace creatinine as a marker of kidney function.[14]
Once the diagnosis of AKI is made, further testing is often required to determine the underlying
cause. It is useful to perform a bladder scan or a post void residual to rule out urinary retention.
In post void residual, a catheter is inserted into the urinary tract immediately after urinating to
measure fluid still in the bladder. 50–100 ml suggests neurogenic bladder dysfunction.
These may include urine sediment analysis, renal ultrasound and/or kidney biopsy. Indications
for kidney biopsy in the setting of AKI include the following:[15]

1. Unexplained AKI, in a patient with two non-obstructed normal sized kidneys

2. AKI in the presence of the nephritic syndrome
3. Systemic disease associated with AKI
4. Kidney transplant dysfunction
In medical imaging, the acute changes in the kidney are often examined with renal
ultrasonography as the first-line modality, where CT scan and magnetic resonance imaging
(MRI) are used for the follow-up examinations and when US fails to demonstrate abnormalities.
In evaluation of the acute changes in the kidney, the echogenicity of the renal structures, the
delineation of the kidney, the renal vascularity, kidney size and focal abnormalities are
observed.[16] CT is preferred in renal traumas, but US is used for follow-up, especially in the
patients suspected for the formation of urinomas. A CT scan of the abdomen will also
demonstrate bladder distension or hydronephrosis. However, in AKI, the use of IV contrast is
contraindicated as the contrast agent used is nephrotoxic.

Renal ultrasonograph of acute pyelonephritis with increased cortical echogenicity and blurred
delineation of the upper pole.[16]

Renal ultrasonograph in renal failure after surgery with increased cortical echogenicity and kidney
size. Biopsy showed acute tubular necrosis.[16]

Renal ultrasonograph in renal traumawith laceration of the lower pole and subcapsular fluid collection
below the kidney.[16]

Treatment[edit]
The management of AKI hinges on identification and treatment of the underlying cause. The
main objectives of initial management are to prevent cardiovascular collapse and death and to
call for specialist advice from a nephrologist. In addition to treatment of the underlying disorder,
management of AKI routinely includes the avoidance of substances that are toxic to the kidneys,
called nephrotoxins. These include NSAIDs such as ibuprofen or naproxen, iodinated
contrasts such as those used for CT scans, many antibiotics such as gentamicin, and a range of
other substances.[17]
Monitoring of kidney function, by serial serum creatinine measurements and monitoring of urine
output, is routinely performed. In the hospital, insertion of a urinary catheter helps monitor urine
output and relieves possible bladder outlet obstruction, such as with an enlarged prostate.

Prerenal[edit]
In prerenal AKI without fluid overload, administration of intravenous fluids is typically the first step
to improving kidney function. Volume status may be monitored with the use of a central venous
catheter to avoid over- or under-replacement of fluid.
If low blood pressure persists despite providing a person with adequate amounts of intravenous
fluid, medications that increase blood pressure (vasopressors) such as norepinephrine and in
certain circumstances medications that improve the heart's ability to pump (known as inotropes)
such as dobutamine may be given to improve blood flow to the kidney. While a useful
vasopressor, there is no evidence to suggest that dopamine is of any specific benefit and may be
harmful.[18]

Intrinsic[edit]
The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to
vasculitis or glomerulonephritis may respond to steroid medication, cyclophosphamide, and (in
some cases) plasma exchange. Toxin-induced prerenal AKI often responds to discontinuation of
the offending agent, such as ACE inhibitors, ARB antagonists, aminoglycosides, penicillins,
NSAIDs, or paracetamol.[7]
The use of diuretics such as furosemide, is widespread and sometimes convenient in improving
fluid overload. It is not associated with higher mortality (risk of death),[19] nor with any reduced
mortality or length of intensive care unit or hospital stay.[20]

Postrenal[edit]
If the cause is obstruction of the urinary tract, relief of the obstruction (with
a nephrostomy or urinary catheter) may be necessary.

Renal replacement therapy[edit]

Renal replacement therapy, such as with hemodialysis, may be instituted in some cases of AKI.
Renal replacement therapy can be applied intermittently (IRRT) and continuously (CRRT). Study
results regarding differences in outcomes between IRRT and CRRT are inconsistent. A
systematic review of the literature in 2008 demonstrated no difference in outcomes between the
use of intermittent hemodialysis and continuous venovenous hemofiltration (CVVH) (a type of
continuous hemodialysis).[21] Among critically ill patients, intensive renal replacement therapy with
CVVH does not appear to improve outcomes compared to less intensive intermittent
hemodialysis.[17][22] However, other studies demonstrated that compared with IRRT, initiation of
CRRT is associated with a lower likelihood of chronic dialysis.[23][24]

Complications[edit]
Metabolic acidosis, hyperkalemia, and pulmonary edema may require medical treatment
with sodium bicarbonate, antihyperkalemic measures, and diuretics.
Lack of improvement with fluid resuscitation, therapy-resistant hyperkalemia, metabolic acidosis,
or fluid overload may necessitate artificial support in the form of dialysis or hemofiltration.[5]

Prognosis[edit]
Mortality[edit]
Mortality after AKI remains high. Overall it is 20%, 30% if the patient is referred to nephrology,
50% if dialyzed, and 70% if on ICU.[citation needed]
If AKI develops after major abdominal surgery (13.4% of all people who have undergone major
abdominal surgery) the risk of death is markedly increased (over 12-fold).[25]
Kidney function[edit]
Depending on the cause, a proportion of patients (5–10%) will never regain full kidney function,
thus entering end-stage kidney failure and requiring lifelong dialysis or a kidney transplant.
Patients with AKI are more likely to die prematurely after being discharged from hospital, even if
their kidney function has recovered.[2]
The risk of developing chronic kidney disease is increased (8.8-fold).[26]

Epidemiology[edit]
New cases of AKI are unusual but not rare, affecting approximately 0.1% of the UK population
per year (2000 ppm/year), 20x incidence of new ESKD. AKI requiring dialysis (10% of these) is
rare (200 ppm/year), 2x incidence of new ESKD.[27]
There is an increased incidence of AKI in agricultural workers, particularly those paid by the
piece. No other traditional risk factors, including age, BMI, diabetes, or hypertension, were
associated with incident AKI. Agricultural workers are at increased risk for AKI because of
occupational hazards such as dehydration and heat illness.[28]
Acute kidney injury is common among hospitalized patients. It affects some 3–7% of patients
admitted to the hospital and approximately 25–30% of patients in the intensive care unit.[29]
Acute kidney injury was one of the most expensive conditions seen in U.S. hospitals in 2011,
with an aggregated cost of nearly $4.7 billion for approximately 498,000 hospital stays.[30] This
was a 346% increase in hospitalizations from 1997, when there were 98,000 acute kidney injury
stays.[31] According to a review article of 2015, there has been an increase in cases of acute
kidney injury in the last 20 years which cannot be explained solely by changes to the manner of
reporting.[32]

History[edit]
Before the advancement of modern medicine, acute kidney injury was referred to as uremic
poisoning while uremia was contamination of the blood with urine. Starting around
1847, uremia came to be used for reduced urine output, a condition now called oliguria, which
was thought to be caused by the urine's mixing with the blood instead of being voided through
the urethra.[citation needed]
Acute kidney injury due to acute tubular necrosis (ATN) was recognized in the 1940s in the
United Kingdom, where crush injury victims during the London Blitz developed patchy necrosis of
kidney tubules, leading to a sudden decrease in kidney function.[33] During
the Korean and Vietnam wars, the incidence of AKI decreased due to better acute management
and administration of intravenous fluids.[34]

See also[edit]
 BUN-to-creatinine ratio
 Chronic kidney disease
 Dialysis
 Kidney failure
 Rhabdomyolysis
 Contrast-induced nephropathy
 Ischemia-reperfusion injury of the appendicular musculoskeletal system

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