Author: Dr Christopher Keller University of California, San Francisco2008-07-28
Acute Renal Failure: Causes, Prognosis, and Treatment
Acute Renal Failure: Causes, Prognosis, and Treatment
What is acute renal failure?
Acute
renal failure (also known as acute kidney injury) is a decline in
kidney function that occurs over hours to weeks.
Acute renal failure can
be detected in two ways: 1) a rise in blood creatinine levels, and/or
2) a decline in urine output. A waste product of muscle cells,
creatinine is a small molecule that is filtered from the bloodstream by
the kidney and removed in the urine. When kidney function declines, the
creatinine concentration rises in the blood, and this rise can be
detected by a simple blood test. Doctors debate the change in serum
creatinine needed to define acute renal failure, but most would agree
that a rise in serum creatinine correlating to a 25%-50% drop in kidney
function is a reasonable definition.
A drop in
urine output also may be seen with acute renal failure. Changes in urine
output give doctors and patients a sense of kidney function in real
time (as opposed to blood tests for serum creatinine, which may be
monitored infrequently). In adults, oliguria (low urine output) is
defined as less than 500 mL (17 ounces) of urine output per day, the
minimum amount of urine needed to excrete the body’s waste products.
Anuria (no urine output) is defined as less than 50 mL (1.7 ounces) per
day of urine output. By definition, patients with oliguria or anuria are
in renal failure. Unfortunately, many patients with ARF have normal
urine output. Thus, abnormally low urine output is a sign of kidney
failure, but normal urine output does not necessarily mean normal kidney
function.
Risk factors for acute renal failure
Acute
renal failure can occur in any setting, including the outpatient
clinic, the emergency department, the hospital, or the intensive care
unit (ICU). ARF is a common complication that occurs in patients who are
hospitalized for other conditions. In fact, acute renal failure may
occur in up to 5% of all patients during their hospital stays. It tends
to occur in people who are older (age > 65 years) and people with
preexisting chronic kidney disease (e.g., baseline serum creatinine >
2.0 mg/dL). People who require a stay in the intensive care unit (ICU)
during their hospitalization are more likely to get acute renal failure
(up to 15% of patients in the ICU). ARF may occur in the setting of
multi-organ failure, when a patient has several organ systems (such as
brain, heart, lungs, blood, kidneys, and liver) failing simultaneously.
Additionally, people with pre-existing conditions of the heart or liver,
and people with diabetes mellitus all have an increased risk for
developing acute renal failure.
What causes acute renal failure?
In
considering causes of acute renal failure, physicians think about 1)
conditions that decrease the blood flow to the kidney (“prerenal” acute
renal failure), 2) conditions that directly damage the kidney itself
(intrinsic or “intrarenal” acute renal failure), and 3) and conditions
that block urine output from the kidney (“postrenal” acute renal
failure) (Table). Prerenal acute renal failure occurs when inadequate
blood flow reaches the kidney; conditions such as severe dehydration or
hemorrhage can result in volume depletion (loss of body water to the
point of low blood flow) and kidney injury. Adequate blood pressure is
also important for delivering blood to the kidney. Severe infections and
severe allergic reactions (e.g., to medicines or after a bee sting in
people susceptible to those allergies) can cause lower blood pressures
and bring about acute renal failure. Severe heart failure or liver
failure can also decrease blood flow to the kidneys. Low blood pressures
from excessive blood pressure medications can also cause acute renal
failure.
Even if blood pressure is normal overall
in the body, local drops in blood pressure to the kidney caused by
certain medications, such as high doses of a nonsteroidal
anti-inflammatory drug (NSAID; e.g., naproxen or ibuprofen), or by the
initiation of an angiotensin-converting enzyme (ACE) inhibitor or an
angiotensin-receptor blocker in certain people, can lead to acute renal
failure. With prerenal ARF, there is no damage to the kidney itself,
simply decreased kidney function from poor kidney blood flow
(perfusion).
Intrarenal (within the kidney) acute renal failure is the most broad
and complicated category of acute renal failure. Within the kidney, four
key structures can be primarily affected in intrarenal ARF: 1) the
glomeruli (the filtration units of the kidney), 2) the tubules (the
tubes that collect the filtered fluid to form urine), 3) the
interstitium (the soft tissue surrounding the glomeruli and tubules),
and 4) the blood vessels that supply blood to the kidney. One of the
most common forms of intrarenal ARF is acute tubular necrosis (ATN; the
death of tubular cells). ATN is characterized by damage to the tubular
cells of the kidney due to poor blood flow (ischemia) or toxic injury to
the kidney. Ischemic ATN results from overwhelming infections (sepsis),
massive hemorrhage, poor cardiac function, and extremely low blood
pressures. Toxic ATN can result from certain medications
(aminoglycosides, platinum-based chemotherapy), medical therapies
(iodinated contrast material for CT scans and angiography), and the
release of harmful chemicals from the body’s cells (such as muscle cells
and tumor cells). ATN is usually reversible after days to weeks of
recovery, but may lead to permanent chronic kidney disease.
In addition to the tubules of the kidney, other causes of intrarenal
acute renal failure can damage the larger blood vessels that supply the
kidney (vascular disease), the tissue and cells surrounding the tubules
(interstitial disease) and the small tufts of capillary blood vessels in
the kidney that filter the blood (glomerular disease). Vascular causes
of intrarenal acute renal failure are often caused by blockage of the
renal arteries by cholesterol plaques (atherosclerosis), but can also
occur after surgeries or major procedures that cause blood clots or
cholesterol to lodge in the renal arteries. Interstitial causes
of acute renal failure can be related to medications (e.g.,
antibiotics, NSAIDs), or potentially related to certain viral or
bacterial infections. Glomerular acute renal failure is rare, but
includes systemic autoimmune diseases (e.g. systemic lupus
erythematosus, Wegener’s granulomatosis, or Churg-Strauss disease) or
diseases characterized by an antibody attacking the kidney (e.g.,
post-infectious glomerulonephritis after an acute infection,
anti-glomerular basement membrane disease).
If
severe and/or prolonged, prerenal and postrenal ARF can progress to
intrinsic or intrarenal ARF. For example, prolonged obstruction of the
urinary tract can lead to permanent swelling and dilation of the kidneys
(hydronephrosis), causing acute renal failure and chronic kidney
disease. Prolonged prerenal conditions will lead to intrinsic kidney
damage due to inadequate blood flow.
Finally,
postrenal acute renal failure is caused by any severe obstruction of the
urinary tract that blocks urine flow leaving both kidneys. A common
cause in men is an enlarged prostate (benign prostatic hypertrophy),
which can occur during an infection, from prostate cancer, or just
simply from aging. Anticholinergic medications (those that block the
effects of the neurotransmitter acetylcholine, including diphenhydramine
and hydroxyzine), often used to treat itching, anxiety, or nasal
congestion, can precipitate urine obstruction at the bladder, leading to
postrenal acute renal failure. Kidney stones themselves can block the
urine from one kidney during an acute attack, but generally do not cause
acute renal failure, as the stones would usually need to be bilateral,
blocking urine flow from both kidneys. Cancers of the kidney, urinary
tract, pelvis, or abdomen can obstruct urine flow and cause postrenal
acute renal failure. Enlarged lymph nodes from infections, cancer,
autoimmune disease, and other conditions can block urine flow if located
near the kidneys, ureters, and bladder.
What are some signs and symptoms of acute renal failure?
As
mentioned above, the two hallmark signs of acute renal failure are 1) a
rise in serum creatinine levels and 2) oliguria (low urine output, less
than 500 mL (17 ounces) per day for adults), both of which can occur
early in the disease. Some cases of acute renal failure will have normal
urine output; oliguria and anuria will not be present. Symptoms of
acute renal failure do not usually occur until late in the disease
course and can indicate the need for urgent treatment. They include
generalized malaise and fatigue, nausea and vomiting, confusion,
shortness of breath, and an inability to stay attentive during
conversation. Patients may also report trouble sleeping, loss of
appetite, and may note that food seems to taste bland and unappealing.
Some report that food has metallic or rusty aftertaste. Patients may
report difficulty urinating, pain with urination, decreased urine
output, or even increased urine output. Unfortunately, urinary
obstruction may produce few or no urinary symptoms such as difficulty
voiding, incomplete voiding, or pain with urination; decreased urine
output may or may not be present. The urine may have different
characteristics, such as blood in the urine (hematuria), tea-colored
urine, foamy urine, and foul smelling urine.
On
physical exam, there may be progressive swelling of the legs. Late in
the course, the patient may develop twitching (called fasciculations) of
the tongue, myoclonus (jerking intermittent contractions of the
muscles) or asterixis (involuntary flapping of the hands when the arms
are raised and the wrists bent as if pushing against a wall). Laboratory
test abnormalities that can occur with acute renal failure include
elevations in serum potassium and phosphorous, decreased serum calcium
levels, and a worsening metabolic acidosis (increasing acidity of the
blood).
Can acute renal failure be prevented?
Acute
renal failure is more likely to occur in patients who already have
kidney disease, diabetes mellitus, or who are elderly. For these
patients, we recommend avoiding or minimizing exposure to tests and
treatments known to put people at increased risk for acute renal
failure. For example, patients with chronic kidney disease should
minimize or avoid NSAID use (e.g. ibuprofen, naproxen), and should be
monitored closely by a physician when starting or increasing
ACE-inhibitor medications (e.g. lisinopril, benazepril) or angiotensin
receptor blocker medications (e.g., losartan, irbesartan, candesartan).
One
important precipitant of acute renal failure in at-risk patients is
iodinated contrast, an intravenous medication given to certain patients
who are to receive computed tomography (CT) scans or angiograms of the
heart or blood vessels. Often, use of iodinated contrast cannot be
avoided because the tests are essential to diagnosis or treatment of
medical conditions. In these situations, we recommend 1) reducing the
amount of contrast given to the minimum possible to perform the
procedure, and 2) ensuring that the patient has been adequately hydrated
prior to the procedure, since dehydration can increase the risk.
Administration of certain medications prior to the study, including
N-acetylcysteine (also called Mucomyst®) or intravenous fluid
containing sodium bicarbonate, may reduce the risk of contrast-induced
acute renal failure in people at risk for kidney injury. Of note,
hemodialysis (a machine used to clean the blood in place of the kidney)
has not been shown to prevent acute renal failure from an iodinated
contrast study.
How is acute renal failure evaluated?
Doctors
start the evaluation of acute renal failure with a careful history and
physical examination. Any changes in fluid intake or fluid output
(vomit, stool, and urine) may give clues about volume depletion (loss of
body water to the point of low blood flow)and decreased kidney blood
flow. Medications can cause allergic reactions and kidney failure,
sometimes with an accompanying rash or fever. An abdominal ultrasound is
a safe, fast, and easy radiology study to look for possible urinary
obstruction; the kidneys, ureters, or bladder may appear distended
(swollen) with excess urine. Occasionally, additional radiology studies
such as MRI (magnetic resonance imaging) or CT (computed tomography)
scans are needed.
Previous blood
tests for creatinine and urine tests will give doctors a sense of
underlying chronic kidney disease, the onset of acute renal failure, and
its progression. The urine can be evaluated under the microscope for
possible clues to the cause of the acute renal failure. Occasionally,
specialized blood tests (serologies) or a kidney biopsy (please see the
Google knol on kidney biopsy) is necessary to diagnose the exact cause
of ARF. A nephrologist (kidney doctor) should be contacted for
assistance in certain cases of ARF: 1) unknown cause of the renal
failure, 2) rare causes of renal failure requiring specialized care, 3)
severe and symptomatic ARF, 4) ARF requiring hemodialysis.
Available treatments for acute renal failure
Treatment
is directed at 1) reversing the cause of the renal failure, and 2)
providing supportive care until recovery of kidney function occurs. In
terms of reversing the cause, a thorough medication history should be
obtained, with all potential offending medications stopped or
dose-reduced. In addition, evaluation for dehydration or volume overload
(an increase in body water to the point of symptoms such as leg
swelling and shortness of breath) is critical, with correction
administered as needed to reestablish the appropriate volume balance.
Cardiologists may be needed to optimize cardiac function and blood flow
to the kidney. Finally, any obstruction of urine output should be
corrected promptly with a bladder catheter or via surgery, as
appropriate. Urologists (physicians with specialized knowledge of the
urinary tract) may be needed to correct any urinary obstruction problems
with the kidneys, ureters, bladder, and urethra.
One
of the key functions of the kidney is to keep tight control of blood
levels of electrolytes (e.g. sodium, potassium, and phosphorous), since
abnormal levels of electrolytes can quickly lead to muscle weakness,
confusion, abnormal heart rhythms, and even death. Therefore,
in acute renal failure it is essential for physicians to assist the
patient in maintaining electrolyte balance by providing medications for
lowering serum potassium, lowering phosphorous levels, and raising
bicarbonate levels to correct acidic blood. However, patients making
little urine with high potassium and creatinine levels should receive
prompt hemodialysis to correct these blood abnormalities. Hemodialysis
involves a machine that cleans the patient’s blood, removing waste
products, normalizing electrolyte levels, and correcting blood acid
imbalances. Excess fluid in the patient can be removed with a dialysis
machine. Most patients with acute renal failure who require hemodialysis
will eventually regain enough function to no longer require the
machine. However, hemodialysis should continue until urine output and
kidney function improve to the point where potassium, phosphorous, and
bicarbonate levels are stable.
Unfortunately,
there are no known effective medications for one of the most common
forms of acute renal failure called acute tubular necrosis (ATN). ATN
often occurs in hospitalized patients with acute conditions such recent
surgery, major infections, and critical illness such as multi-organ
failure patients in intensive care units. Dozens of medications have
been tried over many years, but no therapies have been conclusively
proven to be effective for ATN. Therapy for ATN and ARF is an area of
active medical research.
What is the prognosis for patients who have acute renal failure?
Patients
who develop acute renal failure for any reason during a hospitalization
have a higher complication and death rate than those who do not. This
worse prognosis holds even if the patient is optimally managed and the
appropriate supportive care is provided. The reasons why patients with
acute renal failure tend to do worse in the hospital are unclear.
Despite the higher complication rate overall, more than 80% of patients
who develop acute renal failure will recover enough kidney function to
avoid long-term hemodialysis. Although acute renal failure is a serious
condition that needs prompt medical management, appropriate supportive
care can often result in a successful recovery of kidney function.
Patients who have not fully recovered from acute renal failure may need
to see a nephrologist for follow-up and close monitoring for the
possible complications of chronic kidney disease.
Summary
Acute renal failure (ARF) is a rapid decline in kidney function that
occurs over hours to weeks. ARF may occur in the outpatient setting or
in the hospital. The therapy for ARF is directed at reversing the
underlying cause and providing supportive care with medications and
hemodialysis (kidney dialysis) if necessary. While most patients with
acute renal failure will eventually regain kidney function, they
generally require hospitalization for safe management and monitoring.
Patients who develop ARF while hospitalized for another condition are at
higher risk for complications during their hospitalization than
patients without acute renal failure. ARF may prolong length of stay in
the hospital and decrease survival of hospitalized patients. Patients
with ARF should usually be managed with the assistance of a kidney
specialist called a nephrologist.
More information
Web resources for patients with chronic conditions of the kidney
National Kidney Foundation (www.kidney.org/patients)
American Association of Kidney Patients (www.aakp.org)
The National Institute of Health (www.niddk.nih.gov and http://www2.niddk.nih.gov/Research/ScientificAreas/Kidney/KARF.htm)
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