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Friday, April 20, 2012

Acute Renal Failure

Author: Dr Christopher Keller University of California, San Francisco2008-07-28
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). 

Table: Causes of Acute Renal Failure

Type of Injury
Description
Examples
Prerenal
 
Inadequate blood flow to the kidneys
Blood loss
Dehydration
Heart or liver failure
Severe systemic infections (sepsis)
Drugs (NSAIDs, ACE inhibitors)
Intrarenal
Direct damage to the kidneys
Tubular—acute tubular necrosis (drugs, progression of prerenal or postrenal acute renal failure)
Vascular—atherosclerotic renal artery stenosis, blood clots or cholesterol plaques in the kidney vessels after surgeries
Interstitial—drugs, infections
Glomerular—autoimmune diseases
Postrenal
Obstruction of urine leaving the kidneys
Anticholinergic medications
Enlarged prostate
Kidney stones blocking urine flow from both kidneys
Tumors of the kidney, prostate, bladder, or abdomen
NSAIDs = nonsteroidal anti-inflammatory drugs;
ACE inhibitors = angiotensin-converting enzyme inhibitors

               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)

References

1.      Van Biesen W, Vanholder R, Lameire N. Defining acute renal failure: RIFLE and beyond. Clin J Am Soc Nephrol 1: 1314-1319, 2006.
2.      Hilton R. Acute renal failure. BMJ 333: 786-790, 2006.
3.      Kellum J, Leblanc M, Venkataraman R. Acute renal failure. Clin Evid 16: 366-370, 2006.
4.      Needham E. Management of acute renal failure. Am Fam Physician 72: 1739-1746, 2005.
5.      Lameire N, Van Biesen WV. Acute renal failure. Lancet 2005;365:417-430.