|
Evaluating and Managing
Acute Renal Failure
Acute renal failure in the emergency department is a different entity from what it is on an in-hospital unit. The authors explore the etiology, diagnosis, and treatment of this complex disease.
By Heidi A. Best, MD, and Francis L. Counselman, MD
Acute renal failure (ARF) is a nonspecific term describing a sudden or gradual deterioration in renal function resulting in the accumulation of nitrogenous waste in the kidneys. The term azotemia—an excess of urea and other nitrogenous bodies in the blood—is used interchangeably. Acute renal failure occurring in a community setting is distinct from ARF in an in-hospital setting. Patients who present to the emergency department with ARF frequently differ in etiology, treatment, and overall mortality. For example, community-acquired renal failure is usually reversible and caused by volume depletion, but hospital-acquired ARF usually occurs along with other organ disease processes that contribute to or complicate the patient’s treatment and outcome. Although overall mortality from ARF has not improved since the advent of dialysis, patients presenting to the emergency department with the disorder have significantly higher rates of recovery.
Even though ARF has no strict definition, a 50% or greater increase in serum creatinine above baseline is a widely accepted criterion. (A normal serum creatinine is considered less than 1 mg/dl.) Depending on the severity of ARF, a wide range of metabolic complications can occur, including electrolyte disturbances, metabolic acidosis, and fluid volume imbalance.
This article discusses the three types of ARF and their causes, signs and symptoms, and diagnostic tests, as well as management of the disorder.
TYPES OF ACUTE RENAL FAILURE
Acute renal failure can be divided into three types: prerenal, postrenal, and intrarenal (or intrinsic) (see box below).
Prerenal ARF. This is the most common type of ARF seen in the emergency department. Usually reversible, prerenal ARF is a physiologic response to renal hypoperfusion. A decrease in renal blood flow causes an increase in blood urea nitrogen (BUN) and creatinine, leading to a decrease in the glomerular filtration rate (GFR). Normal GFR is 70 +/- 14 ml/min/m² for men and 60 +/- 10 ml/min/m² for women.
Prerenal ARF occurs secondary to actual hypovolemia or to a relative decrease in renal blood flow—from volume redistribution, impaired cardiac output, or medications that cause intrarenal vasoconstriction, for example. The cause of hypovolemia may be obvious, such as vomiting or diarrhea revealed during a patient history, or it may be subtle, such as third-spacing secondary to pancreatitis. Possible etiologies of decreased cardiac output include cardiomyopathy, myocardial ischemia, or valvular heart disease. In patients with underlying renal disease, even a minimal decrease in renal perfusion can precipitate prerenal ARF. If these factors are treated in a timely manner, renal perfusion can often be restored and prerenal azotemia corrected.
Postrenal ARF. Also reversible, postrenal ARF is caused by an obstruction of urinary outflow. About 10% of patients with ARF have the postrenal type, in both community and hospital settings. Be aware that this condition is more common in elderly patients and men. Normal renal function can usually be recovered if the obstruction is relieved in a timely manner. Permanent loss of renal function can occur if the obstruction is not treated or if it is complicated by infection.
Obstruction can occur at any level of the urinary tract, and phimosis, benign prostatic hypertrophy, nephrolithiasis, and retroperitoneal disease are common causes. If the patient is able to urinate, a post-void residual can be measured easily with a bedside ultrasound examination, which may quickly lead to a diagnosis of postrenal obstruction.
Intrarenal ARF. Intrarenal or intrinsic ARF is caused by a parenchymal insult, where the structures of the nephron are affected. It can be subdivided into glomerulonephritis, interstitial nephritis, and, most commonly, acute tubular necrosis (ATN). While only 20% of patients with ARF in the community have the intrarenal type, nearly 70% of hospitalized patients with ARF have it, particularly in the intensive care unit (ICU).
When patients present to the emergency department with intrarenal ARF, the cause is usually medication or infection. In critically ill patients, more than 90% of episodes of ARF are thought to be due to ATN of ischemic etiology, toxic etiology, or a combination of both. While glomerular, vascular, and interstitial disease are more common etiologies in the community, they represent a minority of intrinsic ARF cases overall. For the emergency physician, the priority is not on diagnosing the specific type of intrinsic renal failure, but rather on excluding correctable prerenal or postrenal causes.
Glomerulonephritis can have a primary renal cause, such as post-streptococcal glomerulonephritis, or it can be caused by a systemic process, such as lupus, HIV, or Goodpasture syndrome. Acute interstitial nephritis is often drug-induced (for example, from nonsteroidal anti-inflammatory drugs or penicillin), but it may also have an infectious etiology.
Vascular causes of intrarenal disease can be divided into large-vessel disease and small- to medium-vessel disease. Diseases affecting large vessels, such as thrombosis, emboli, or renal artery stenosis, must affect both kidneys to cause ARF. Small-vessel disease is more common, as observed in scleroderma, hemolytic uremic syndrome, and malignant hypertension.
Acute tubular necrosis is a generic term encompassing ischemic or nephrotoxic injury. It is the most common type of intrinsic ARF and is generally reversible. Acute tubular necrosis is a histopathological entity in which the clinical diagnosis is made by exclusion after prerenal, postrenal, and other intrinsic causes have been ruled out. Prerenal ARF overlaps with ATN on a continuum, because hypoperfusion may begin as transient azotemia and subsequently develop into ischemia.
Common nephrotoxic causes of ATN include rhabdomyolysis and aminoglycoside or radiocontrast dye administration. Chronic renal insufficiency, diabetes mellitus, age over 60, and hypovolemia are all risk factors for contrast-induced nephropathy. A creatinine level greater than 1.5 mg/dl is also associated with an increased risk of contrast-induced nephropathy. Acute renal failure in this setting is defined as a rise in serum creatinine level greater than 25% of baseline within three days of exposure. Most of these patients return to baseline within 10 to 14 days; however, some patients progress to renal failure. In recent years, the use of low-osmolar radiocontrast dye and reduced dye load volume has decreased the risk of nephrotoxicity.
In some cases, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may cause ARF. These medications often cause a moderate increase in serum creatinine shortly after initiation because they cause an increase in renal blood flow and a decrease in GFR by dilating postglomerular capillaries. Rarely, a significant rise in serum creatinine is noted, which resolves after the drug is discontinued. An ultrasound examination of the renal vasculature is warranted because increased serum creatinine may be an indication the patient has bilateral renal artery stenosis.
Rhabdomyolysis-induced ATN is a direct result of the toxic effects of myoglobin on the renal tubules and of obstruction of the tubules. Creatine released from muscle results in serum creatinine levels approximately twice as high as seen in other causes of ARF. These patients are often oliguric—that is, their urine output has decreased to less than 500 ml in 24 hours.
CLINICAL PRESENTATION
Patients with ARF have a wide range of clinical presentations, ranging from nonspecific symptoms, such as weakness or nausea, to acute distress or profoundly altered mental status. Frequently, the presentation is overshadowed by the cause of the ARF. For example, patients may have urinary retention secondary to phimosis. Or those with volume overload secondary to ARF may present to the emergency department in respiratory distress with signs and symptoms that are clinically indistinguishable from acute congestive heart failure.
A thorough history may give clues to the cause of ARF. Inquire about potential sources of volume loss, such as vomiting or diarrhea, recently prescribed or over-the-counter medications, recent administration of radiocontrast dye, flank pain (from nephrolithiasis), or difficulty voiding. Suspect postrenal failure in patients who complain of an inability to void or difficulty voiding and in those with alternating oliguria and polyuria.
The physical examination should focus on prerenal and postrenal causes of ARF, which are correctable, before considering an intrinsic etiology. Volume-depleted patients may have dry mucous membranes, poor skin turgor, tachycardia, and orthostatic hypotension. On the other end of the spectrum, the physical examination may be notable for jugular venous distension, rales, an S3 gallop, or peripheral edema in volume-overloaded patients. Patients with urinary tract obstruction may have a percussible bladder if it contains 150 ml of urine or more. Rectal examination may demonstrate a mass or prostatic hypertrophy. In male patients, look for phimosis. Patients with myalgias and tender muscles may have rhabdomyolysis.
DIAGNOSTIC CONSIDERATIONS
Although the history and physical examination may suggest ARF, the diagnosis may come as a surprise to clinicians when they read the laboratory studies. Although they are not perfect indicators, BUN and serum creatinine levels are the best gauges of renal function in the emergency department. The normal BUN to creatinine ratio is 10:1. In prerenal ARF, the ratio is usually greater than 20:1. However, be aware that processes other than ARF, such as upper gastrointestinal bleeding, and medications, such as tetracycline or a corticosteroid like prednisone, can increase this ratio and create a similar clinical scenario. For intrinsic renal failure, the BUN-creatinine ratio is frequently normal.
A urinalysis can provide valuable information that suggests the presence and even the type of ARF. The presence of proteinuria and casts can indicate intrinsic renal failure. Red cell casts suggest glomerulonephritis or vasculitis. A urine that is dip-positive for blood but without red blood cells suggests myoglobinuria and rhabdomyolysis. For prerenal causes, the urinalysis is often normal, except for a high specific gravity.
Other laboratory studies that can be helpful in evaluating ARF include the fractional excretion of sodium (FENa), creatinine clearance, and the estimated GFR. The box below shows how to calculate these three values. In clinical practice, the creatinine clearance is used as a close approximation of GFR. For actual calculation of GFR, the easiest method is to use one of the online calculators available at www.medcalc.com and nkdep.nih.gov. The Modification of Diet in Renal Disease (MDRD) formula is the one most commonly used for estimating GFR as opposed to actual measurement. In general, the GFR must fall below 15 ml/min before symptomatic uremia is evident.
In order for the calculation for FENa to be used, the urine and plasma creatinine and sodium measurements must be drawn at the same time. In prerenal ARF, urinary sodium (UNa) is typically less than 20 mEq/L and FENa is less than 1%. In most cases of ATN, UNa is greater than 40 mEq/L and FENa is greater than 1%.
Whenever ARF is suspected or diagnosed, a basic metabolic profile should be obtained to check for hyperkalemia and metabolic acidosis, two common complications of ARF. If moderate or severe hyperkalemia is present (evidenced by ECG changes with peaked T waves or a potassium level greater than 6.5 mEq/L, or both), treatment should be started immediately. Treatment consists of inhaled beta-2 agonists and intravenous calcium, dextrose, insulin, sodium bicarbonate, and sodium polystyrene (Kayexelate); dialysis is also frequently necessary. All patients with diagnosed or suspected ARF should be placed on a cardiac and pulse oximetry monitor and have an ECG and portable chest films. Nasal cannula oxygen should also be provided for any patient with dyspnea or hypoxia.
Although imaging plays a role in the evaluation of ARF, emergency physicians mainly use it to evaluate for obstructive (postrenal) causes. Currently, noncontrast CT scanning and ultrasound examination are the modalities most frequently used for this purpose. Findings indicating obstruction of urinary outflow include hydronephrosis, hydroureter, and the presence of stones.
MANAGEMENT GOALS
The goals in managing ARF are restoring renal perfusion, minimizing toxic effects, and correcting metabolic derangements. The most immediate life-threatening complications should be addressed first. These include airway management for the patient in severe fluid overload and treatment of severe hyperkalemia. For the patient with pulmonary edema, treatment ranges from simple nasal cannula oxygen, nitrates, and intravenous furosemide, to bilevel positive airway pressure with positive pressure ventilation, and ultimately to orotracheal intubation with mechanical ventilation and emergent dialysis.
After the patient is stabilized, the focus should be on identifying and treating prerenal and postrenal causes of ARF. The clinician must determine if the patient is hypovolemic, euvolemic, or fluid overloaded. If the patient is hypovolemic, an intravenous crystalloid such as normal saline solution should be used for fluid resuscitation. Avoid crystalloids containing potassium, such as Ringer’s lactate solution, in the patient with ARF. Vasopressors for hypotension should be reserved for patients who already have been adequately fluid resuscitated and who continue to have low mean arterial pressures. As mentioned above, normal urinary outflow should be restored in patients with postrenal obstruction. Frequently, this involves simply placing a Foley catheter, but patients with obstruction at the level of the ureters or above may require percutaneous nephrostomy.
Drugs that are possible causative agents of intrinsic ARF should be discontinued immediately. Furthermore, use caution when administering any medications to these patients, because poor renal function can prolong the metabolism of many drugs.
While urine output is a poor predictor of GFR, especially in the acute setting, it is helpful to determine if the patient has anuria or oliguria. The treatment strategy for oliguric ATN is to convert the patient to nonoliguric ARF, since oliguria has a higher rate of mortality and complications. However, many of the current treatments have not been shown to improve overall patient mortality.
For example, loop diuretics such as furosemide should be used in patients with volume overload. For some of these patients, emergent dialysis will also be required. For the euvolemic patient, reduction in oliguria with furosemide has not improved survival outcome. Low-dose or “renal-dose” intravenous dopamine at 0.5 to 2 µg/kg/min has been used to increase urinary output in this setting. While urinary output does improve, no improvement has been shown in peak serum creatinine concentration, need for dialysis, length of hospital stay, or mortality rate when compared to placebo groups.
Traditionally, the treatment for ARF secondary to rhabdomyolysis includes fluid resuscitation, alkalinization of the urine, and mannitol infusion. Sodium bicarbonate administration attempts to counteract the tubular acidosis created by the direct toxic effects of myoglobinuria. Mannitol provides a theoretical dilutional benefit by flushing out tubular casts and restoring flow. It also acts as a free-radical scavenger. Unfortunately, studies have failed to show any benefit in using intravenous mannitol or sodium bicarbonate instead of fluid resuscitation with normal saline alone in these patients.
Management of contrast-induced ARF in the emergency department focuses primarily on prevention. The role of N-acetylcysteine in the prevention of contrast-induced renal insufficiency is unclear. Several studies have suggested a benefit of administering intravenous N-acetylcysteine before and after a contrast study in patients with underlying renal insufficiency. The most recent studies, however, show that N-acetylcysteine offers no benefits compared to intravenous hydration with crystalloids alone, suggesting the benefit in previous studies was secondary to superior hydration in the N-acetylcysteine group. Finally, a few recent studies have demonstrated a consistent benefit in using sodium bicarbonate for contrast-induced renal insufficiency prevention but more studies are required.
NEPHROLOGY CONSULTATION
Regardless of the etiology, patients with ARF require admission to the hospital, cardiac monitoring, and usually admission to the ICU. A nephrology consultation is essential before physicians can decide whether to dialyze the patient. If dialysis is indicated but not available at a particular institution, patients should be transferred to a facility that has dialysis as soon as they are hemodynamically stable.
Suggested Reading
Bellomo R: Defining, quantifying, and classifying acute renal failure. Crit Care Clin 21(2):223, 2005.
Bellomo R, et al.: Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 356(9248):2139, 2000.
Brigouri C, et al.: Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL), a randomized comparison of 3 preventive strategies. Circulation 115(10):1211, 2007.
Dursun B and Edelstein CL: Acute renal failure. Am J Kidney Dis 45(3):614, 2005.
Lameire N: The pathophysiology of acute renal failure. Crit Care Clin 21(2):197, 2005.
Palevsky PM: Renal replacement therapy I: indications and timing. Crit Care Clin 21(2):347, 2005.
Sinert R and Peacock PR: Acute renal failure. In Tintinalli JE, et al. (eds): Emergency Medicine: A Comprehensive Study Guide, 6th ed, McGraw-Hill, 2004, pp. 593-598.
Venkataraman R and Kellum JA: Prevention of acute renal failure. Chest 131(1):300, 2007
Wolfson AB: Renal failure. In Marx JA, et al. (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6th ed, Mosby Elsevier, 2006, pp. 1524-1556. |
|
