INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Until recently, a systematic definition of acute renal failure (ARF) was lacking, which led to significant confusion both clinically and in the medical literature. In 2004, the Acute Dialysis Quality Initiative (ADQI) group published the RIFLE classification of ARF, based on changes from the patient's baseline either in serum creatinine level or glomerular filtration rate (GFR), urine output (UO), or both.

The RIFLE classification of ARF is as follows:

• Risk (R) - Increase in serum creatinine level X 1.5 or decrease in GFR by 25%, or UO <0.5 mL/kg/h for 6 hours
• Injury (I) - Increase in serum creatinine level X 2.0 or decrease in GFR by 50%, or UO <0.5 mL/kg/h for 12 hours
• Failure (F) - Increase in serum creatinine level X 3.0, decrease in GFR by 75%, or serum creatinine level > 4 mg/dL; UO <0.3 mL/kg/h for 24 hours, or anuria for 12 hours
• Loss (L) - Persistent ARF, complete loss of kidney function > 4 wk
• End-stage kidney disease (E) - Loss of kidney function > 3 months

Since baseline serum creatinine level and GFRs are not readily available, the consensus committee recommends the use of the Modification of Diet in Renal Disease (MDRD) equation (see Lab Studies) to estimate the patients GFR/1.73 mm based upon: serum creatinine level, age, gender, and race. The proportional decrease in GFR should be calculated from 70 mL/min per 1.73 mm², the agreed upon lower limit of normal.

ARF is a common entity in the ED. Emergency physicians play a critical role in recognizing early ARF, preventing iatrogenic injury, and reversing the course of ARF.

Pathophysiology

The driving force for glomerular filtration is the pressure gradient from the glomerulus to the Bowman space. Glomerular pressure is primarily dependent on renal blood flow (RBF) and is controlled by combined resistances of renal afferent and efferent arterioles. Regardless of the cause of ARF, reductions in RBF represent a common pathologic pathway for decreasing GFR. The etiology of ARF comprises 3 main mechanisms.

• Prerenal failure is defined by conditions with normal tubular and glomerular function; GFR is depressed by compromised renal perfusion.
• Intrinsic renal failure includes diseases of the glomerulus or tubule, which are associated with release of renal afferent vasoconstrictors.
• Postobstructive renal failure initially causes an increase in tubular pressure, decreasing the filtration driving force. This pressure gradient soon equalizes, and maintenance of a depressed GFR is then dependent upon renal afferent vasoconstriction.

Patients with chronic renal failure also may present with superimposed ARF from any of the aforementioned etiologies.

Depressed RBF eventually leads to ischemia and cell death. This initial ischemic insult triggers production of oxygen free radicals and enzymes that continue to cause cell injury even after restoration of RBF. Tubular cellular damage results in disruption of tight junctions between cells, allowing back leak of glomerular filtrate and further depressing effective GFR. In addition, dying cells slough off into the tubules, forming obstructing casts, which further decrease GFR and lead to oliguria.

During this period of depressed RBF, the kidneys are particularly vulnerable to further insults. This is when iatrogenic renal injury is most common. The following are common iatrogenic combinations:

• Preexisting renal disease (elderly, diabetic patients, jaundiced patients) and radiocontrast agents, aminoglycosides, atheroembolism, or cardiovascular surgery
• Angiotensin-converting enzyme (ACE) inhibitors and diuretics, small- and large-vessel renal arterial disease
• Nonsteroidal anti-inflammatory drugs (NSAIDs) and congestive heart failure (CHF), hypertension (HTN), or renal artery stenosis
• Hypovolemia and aminoglycosides, amphotericin, heme pigments, or radiologic contrast agents

Recovery from ARF is first dependent upon restoration of RBF. Early RBF normalization predicts better prognosis for recovery of renal function. In prerenal failure, restoration of circulating blood volume is usually sufficient. Rapid relief of urinary obstruction in postrenal failure results in a prompt decrease of vasoconstriction. With intrinsic renal failure, removal of tubular toxins and initiation of therapy for glomerular diseases decreases renal afferent vasoconstriction.

Once RBF is restored, the remaining functional nephrons increase their filtration and eventually hypertrophy. GFR recovery is dependent upon the size of this remnant nephron pool. If the number of remaining nephrons is below some critical value, continued hyperfiltration results in progressive glomerular sclerosis, eventually leading to increased nephron loss. A vicious cycle ensues; continued nephron loss causes more hyperfiltration until complete renal failure results. This has been termed the hyperfiltration theory of renal failure and explains the scenario in which progressive renal failure is frequently observed after apparent recovery from ARF.

Frequency

United States

The distinction between community- and hospital-acquired ARF is important for the differential diagnoses, treatment, and eventual outcome of patients with ARF. The annual incidence of community-acquired ARF is approximately 100 case per 1 million population, and it is diagnosed in only 1% of hospital admissions at presentation. On the other hand, hospital-acquired ARF occurs in as many as 4% of hospital admissions and 20% of critical care admissions. This increased incidence of hospital-acquired ARF is multifactorial; it is related to an aging population with increased risks of ARF, the high prevalence of nephrotoxic exposures possible in a hospital setting, and increasing severity of illness.

Mortality/Morbidity

Because most cases of community-acquired ARF are secondary to volume depletion, as many as 90% of cases are estimated to have a potentially reversible cause. Hospital-acquired ARF often occurs in an ICU setting and is commonly the end result of multiorgan failure. This dichotomy in the etiology of ARF explains the increased mortality rate, dialysis requirements, and rates of progression to end-stage renal failure seen in hospital-acquired ARF compared with community-acquired ARF.

Mortality rates for ARF have changed little since the advent of dialysis at 50%. This curious statistic simply reflects the changing demographics of ARF from community- to hospital-acquired settings. Currently, the mortality rate for hospital-acquired ARF is reported to be as high as 70% and is directly correlated to the severity of the patient's other disease processes. The mortality rate among patients presenting to the ED with prerenal ARF may be as low as 7%. With the advent of dialysis, the most common causes of death associated with ARF are sepsis, cardiac failure, and pulmonary failure. Interestingly, patients who are older than 80 years with ARF have mortality rates similar to younger adult patients. Pediatric patients with ARF represent a different set of etiologies and have mortality rates averaging 25%.

• ARF is not a benign disease. In a recent study, a 31% mortality rate was noted in patients with ARF not requiring dialysis, compared with a mortality rate of only 8% in matched patients without ARF. Even after adjusting for comorbidity, the odds ratio for dying of ARF was 4.9 compared to patients without ARF.
• Mortality rates are generally lower for nonoliguric ARF (>400 mL/day) than for oliguric ( <400 mL/day) ARF, reflecting the fact that nonoliguric ARF is usually caused by drug-induced nephrotoxicity and interstitial nephritis, which have few other systemic complications.

Sex

Males and females are affected equally.

Age

The patient's age has significant implications for the differential diagnosis of ARF.

• Newborns and Infants
  
  • The most common cause of ARF is prerenal etiologies.
  • Prerenal ARF
    
    • Perinatal hemorrhage - Twin-twin transfusion, complications of amniocentesis, abruptio placenta, birth trauma
    • Neonatal hemorrhage - Severe intraventricular hemorrhage, adrenal hemorrhage
    • Perinatal asphyxia and hyaline membrane disease (newborn respiratory distress syndrome) both may result in preferential blood shunting away from kidneys (ie, prerenal) to central circulation.
  • Intrinsic ARF
    
    • Acute tubular necrosis (ATN) can occur in the setting of perinatal asphyxia. ATN also has been observed secondary to medications (aminoglycosides, NSAIDs) given to the mother perinatally.
    • ACE inhibitors can traverse placenta, resulting in a hemodynamically mediated form of ARF.
    • Acute glomerulonephritis is rare and most commonly the result of maternal-fetal transfer of antibodies against the neonate's glomeruli or transferofchronic infections (syphilis, cytomegalovirus) associated with acute glomerulonephritis.
  • Postrenal ARF: Congenital malformations of urinary collecting systems should be suspected.
• Children
• • The most common cause of ARF is prerenal etiologies.
  • Prerenal ARF
  • • The most common cause of hypovolemia in children is gastroenteritis.
    • Congenital and acquired heart diseases are also important causes of decreased renal perfusion in this age group.
  • Intrinsic ARF
  • • Hemolytic uremic syndrome (HUS) often is cited as the most common cause of ARF in children. The most common form of the disease is associated with a diarrheal prodrome caused by Escherichia coli 0157:H7.
    • These children usually present with microangiopathic anemia, thrombocytopenia, colitis, mental status changes, and renal failure.
  • Acute poststreptococcal glomerulonephritis should be considered in any child who presents with HTN, edema, hematuria, and renal failure.
• Adults
• • Please refer to History for a general discussion of ARF.
  • Please remember that postobstructive ARF in the elderly should never be overlooked in the ED.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Because ARF has such a long differential diagnosis, obtain a directed history along the lines of the pathophysiology of ARF (prerenal, intrinsic renal, postrenal failure).

• Prerenal failure
• • Patients commonly present with symptoms related to hypovolemia, including thirst, decreased urine output, dizziness, and orthostatic hypotension.
  • Look for a history of excessive fluid loss via hemorrhage, GI losses, sweating, or renal sources.
  • Patients with advanced cardiac failure leading to depressed renal perfusion may present with orthopnea and paroxysmal nocturnal dyspnea.
  • Insensible fluid losses can result in severe hypovolemia in patients with restricted fluid access and should be suspected in the elderly and in comatose or sedated patients.
• Intrinsic renal failure
• • Patients can be divided into those with glomerular and those with tubular etiologies of ARF.
  • Glomerular diseases: Nephritic syndrome of hematuria, edema, and HTN is synonymous with a glomerular etiology of ARF. Query about prior throat or skin infections. A history of an earlier episode resembling this symptom complex is often helpful in establishing a differential diagnosis.
  • Tubular diseases: ATN should be suspected in any patient presenting after a period of hypotension secondary to cardiac arrest, hemorrhage, sepsis, drug overdose, or surgery.
  • A careful search for exposure to nephrotoxins should include a detailed list of all current medications and any recent radiologic examinations (ie, exposure to radiologic contrast agents).
  • Pigment-induced ARF should be suspected in patients with possible rhabdomyolysis (muscle tenderness, recent coma, seizures, drug abuse, alcohol, excessive exercise, limb ischemia) or hemolysis (recent blood transfusion).
  • Allergic interstitial nephritis should be suspected with recent drug ingestion, fevers, rash, and arthralgias.
• Postrenal failure
• • Postrenal failure usually occurs in older men with prostatic obstruction and symptoms of urgency, frequency, and hesitancy. Patients may present with asymptomatic high-grade urinary obstruction because of chronicity of their symptoms.
  • History of prior gynecologic surgery or carcinoma often can be helpful in providing clues to the level of obstruction.
  • Flank pain and hematuria should raise a concern about renal calculi or papillary necrosis as the source of urinary obstruction.
  • Use of acyclovir, methotrexate, triamterene, indinavir, or sulfonamides implies the possibility of tubular obstruction by crystals of these medications.

Physical

• Hypotension and tachycardia are obvious clues to decreased renal perfusion. Evaluation for hypovolemia should include evaluations for orthostatic hypotension, mucosal membrane moisture, and tissue turgor.
• Acute fluid overload may lead to compromise of a patient's ability to oxygenate and ventilate.
• Patients also may present hypovolemic, with increased risk for iatrogenic complications of their renal failure. Physical examination should include a search for the following signs:
• Skin
• • Livido reticularis, digital ischemia, butterfly rash, palpable purpura - Systemic vasculitis
    
  • Maculopapular rash - Allergic interstitial nephritis
    
  • Track marks (ie, intravenous drug abuse) - Endocarditis
• Eyes
• • Keratitis, iritis, uveitis, dry conjunctivae - Autoimmune vasculitis
  • Jaundice - Liver diseases
    
  • Band keratopathy (ie, hypercalcemia) - Multiple myeloma
    
  • Signs of diabetes mellitus
    
  • Signs of hypertension
    
  • Atheroemboli (retinopathy)
• Ears
• • Hearing loss - Alport disease and aminoglycoside toxicity
    
  • Mucosal or cartilage ulcerations - Wegener granulomatosis
• Cardiac
• • Irregular rhythms (ie, atrial fibrillation) - Atheroemboli
    
  • Murmurs - Endocarditis
    
  • Increased jugulovenous distention, rales, S3 - CHF
• Pulmonary
• • Rales - Goodpasture syndrome, Wegener granulomatosis
    
  • Hemoptysis - Wegener granulomatosis
• Abdomen
• • Pulsatile mass (ie, aneurysm) - Atheroemboli
    
  • Costovertebral angle tenderness - Nephrolithiasis, papillary necrosis
  • Pelvic, rectal masses; prostatic hypertrophy; distended bladder - Urinary obstruction
  • Limb ischemia, edema - Rhabdomyolysis

Causes

• Prerenal failure - Diseases that compromise renal perfusion
• • Decreased effective arterial blood volume - Hypovolemia, CHF, liver failure, sepsis
  • Renal arterial disease - Renal arterial stenosis (atherosclerotic, fibromuscular dysplasia), embolic disease (septic, cholesterol)
• Intrinsic renal failure - Diseases of the renal parenchyma, specifically involving the renal tubules, glomeruli, interstitium
• • ATN, ischemia, toxins (eg, aminoglycosides, radiocontrast, heme pigments, cisplatin, myeloma light chains, ethylene glycol)
  • Interstitial diseases - Acute interstitial nephritis, drug reactions, autoimmune diseases (eg, systemic lupus erythematosus [SLE]), infiltrative disease (sarcoidosis, lymphoma), infectious agents (Legionnaire disease, hantavirus)
  • Acute glomerulonephritis
  • Vascular diseases - Hypertensive crisis, polyarteritis nodosa, vasculitis
• Postrenal failure - Diseases causing urinary obstruction from the level of the renal tubules to the urethra
• • Tubular obstruction from crystals (eg, uric acid, calcium oxalate, acyclovir, sulfonamide, methotrexate, myeloma light chains)
  • Ureteral obstruction - Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol, hydralazine), urolithiasis, papillary necrosis
  • Urethral obstruction - Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder; stricture

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urine output: Changes in urine output generally are poorly correlated with changes in GFR. Approximately 50-60% of all causes of ARF are nonoliguric. However, categories of anuria, oliguria, and nonoliguria may be useful in differential diagnosis of ARF.
• • Anuria ( <100 mL/d) - Urinary tract obstruction, renal artery obstruction, rapidly progressive glomerulonephritis, bilateral diffuse renal cortical necrosis
    
  • Oliguria (100-400 mL/d) - Prerenal failure, hepatorenal syndrome
    
  • Nonoliguria (>400 mL/d) - Acute interstitial nephritis, acute glomerulonephritis, partial obstructive nephropathy, nephrotoxic and ischemic ATN, radiocontrast-induced ARF, and rhabdomyolysis
    
• Urinalysis: Microscopic examination of urine is essential in establishing differential diagnosis.
  
  • Normal urinary sediment without hemoglobin, protein, cells, or casts generally consistent with prerenal and postrenal failure, HUS/thrombotic thrombocytopenic purpura (TTP), preglomerular vasculitis, or atheroembolism
    
  • Granular casts - ATN, glomerulonephritis, interstitial nephritis
    
  • RBC casts - Glomerulonephritis, malignant HTN
    
  • WBC casts - Acute interstitial nephritis, pyelonephritis
    
  • Eosinophiluria - Acute allergic interstitial nephritis, atheroembolism
    
  • Crystalluria - Acyclovir, sulfonamides, methotrexate, ethylene glycol toxicity, radiocontrast agents
• BUN: The urea concentration correlates poorly with the GFR. Because urea is highly permeable to renal tubules, urea clearance varies with urine flow rate.
• • Urea is filtered freely, but reabsorption along the tubule is a function of urine flow rate. During antidiuresis with urine flow rates less than 30 mL/h, urea clearance is as low as an estimated 30% of GFR. Under conditions of diuresis, with urine outputs greater than 100 mL/h, urea clearance can increase to 70-100% of GFR.
    
    • This information can be used clinically to help differentiate prerenal failure from other etiologies of ARF.
      
    • In prerenal conditions, low urine flow rates favor BUN reabsorption out of proportion to decreases in GFR, resulting in a disproportionate rise of BUN relative to creatinine, creating a serum BUN-creatinine ratio >20 in prerenal failure.
    
    
  • BUN concentration is dependent on nitrogen balance and renal function.
    
    • BUN concentration can rise significantly with no decrement in GFR by increases in urea production with steroids, trauma, or GI bleeding.
      
    • Tetracycline increases BUN by decreasing tissue anabolic rates.
      
    • Basal BUN concentration can be depressed severely by malnutrition or advanced liver disease.
      
    • Always first estimate basal BUN concentration when attempting to correlate changes in BUN with GFR. For example, in a patient with cirrhosis and a BUN of 12 mg/dL, a GFR in the normal range may be assumed. Only with the knowledge of a baseline BUN of 4 mg/dL does the real decrease in GFR become apparent.
    
    
• Creatinine: Serum creatinine provides the ED physician with the most accurate and consistent estimation of GFR. Correct interpretation of serum creatinine extends beyond just knowing normal values for the specific laboratory.
• • Creatinine measuring methods
    
    • Serum creatinine level varies by method of measurement, either Jaffe or iminohydrolase. Upper limit of normal creatinine can be 1.6-1.9 mg/dL or 1.2-1.4 mg/dL, respectively. This becomes important when patients present with changes in creatinine measured in different labs.
      
    • Differing methods report markedly different results when interfacing with certain chemicals.
      
    • Jaffe method of measuring creatinine reports falsely elevated serum creatinine in the presence of the following noncreatinine chromogens: glucose, fructose, uric acid, acetone, acetoacetate, protein, ascorbic acid, pyruvate, cephalosporin antibiotics. High levels of bilirubin cause reports of falsely low creatinine by the Jaffe method.
      
    • Extremely high glucose levels and the antifungal agent flucytosine interfere with the iminohydrolase method.
    
    
  • Serum creatinine is a reflection of creatinine clearance.
    
    • Serum creatinine is a function of its production and excretion rates.
      
    • Creatinine production is determined by muscle mass. Serum creatinine must always be interpreted with respect to patient's weight, age, and sex. The GFR can be estimated by the following formulas: The ADQI consensus committee on ARF favors the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR (70 mL/min per 1.73 mm² is considered the lower limit of normal).

      Cockcroft-Gault equation: GFR mL/min = (140 - age y)(weight kg)(0.85 if female)/(72 X serum creatinine mol/L)

      MDRD equation: GFR, in mL/min per 1.73 mm² =   186.3 X ((serum creatinine) exp[-1.154]) X (Age exp[-0.203]) X (0.742 if female) X (1.21 if African American)

    • For example, GFR decreases by 1% per year after age 40, yet serum creatinine generally remains stable. Balance is achieved via a decrease in muscle mass with age, which matches the fall in GFR.
      
    • Men generally have a higher muscle mass per kilogram of body weight and thus a higher serum creatinine than women.
    
    
  • Changes in serum creatinine reflect changes in GFR. Rate of change in serum creatinine is an important variable in estimating GFR. Stable changes in serum creatinine correlate with changes in GFR by the following relationships:
    
    • Creatinine 1.0 mg/dL - Normal GFR
      
    • Creatinine 2.0 mg/dL - 50% reduction in GFR
      
    • Creatinine 4.0 mg/dL - 70–85% reduction in GFR
      
    • Creatinine 8.0 mg/dL - 90–95% reduction in GFR
      
    • As suggested by these data, knowledge of a patient's baseline creatinine becomes very important. Small changes with low baseline levels of creatinine are important clinically much more than large changes with high basal creatinine. Significant decrements in GFR can occur in the normal range of creatinine.
      
    • Certain diseases and medications can interfere with the correlation of serum creatinine with GFR. Acute glomerulonephritis causes increased tubular secretion of creatinine, falsely depressing the rise in serum creatinine when ARF occurs in acute glomerulonephritis. Trimethoprim and cimetidine cause decreased creatinine secretion and a falsely elevated creatinine with no change in GFR.
• Complete blood count
• • Leukocytosis is common in ARF.
    
  • Leukopenia and thrombocytopenia suggest SLE or TTP.
    
  • Anemia and rouleaux formation suggest multiple myeloma.
    
  • Microangiopathic anemia suggests TTP or atheroemboli.
    
  • Eosinophilia suggests allergic interstitial nephritis, polyarteritis nodosa, or atheroemboli.
    
  • Coagulation disturbances indicate liver disease or hepatorenal syndrome.
    
• Blood chemistry
• • Creatine phosphokinase (CPK) elevations are seen in rhabdomyolysis and myocardial infarction.
    
  • Elevations in liver transaminases are seen in rapidly progressive liver failure and hepatorenal syndrome.
    
  • Hypocalcemia (moderate) is common in ARF.
    
  • Hyperkalemia is a common complication of ARF.
    
• Urine chemical indices
• • Differentiation of prerenal azotemia from ATN takes on a special importance in early management of these patients.
    
  • Aggressive fluid resuscitation is appropriate in prerenal ARF. However, rapid fluid infusion in a patient with ATN who is unable to excrete the extra fluid could result in life-threatening volume overload.
    
  • To help with the differentiation of prerenal azotemia, analysis of urine may provide important clues. If possible, collect urine prior to any administration of diuretics.
    
  • Urine indices that suggest prerenal ARF include the following:
    
    • Urine specific gravity >1.018
      
    • Urine osmolality (mOsm/kg H₂O) >500
      
    • Urine sodium (mEq/L) <15-20
      
    • Plasma BUN/creatinine ratio >20
      
    • Urine/plasma creatinine ratio >40
    
    
  • Urine indices that suggest ATN include the following:
    
    • Urine specific gravity <1.012
      
    • Urine osmolality (mOsm/kg H₂O) <500
      
    • Urine sodium (mEq/L) >40
      
    • Plasma BUN/creatinine ratio <10-15
      
    • Urine/plasma creatinine ratio <20
• Calculation of fractional excretion of sodium (FeNa)
  
  • FeNa = (urine Na/plasma Na)/(urine creatinine/plasma creatinine)
    
  • FeNa <1 % = prerenal ARF
    
  • FeNa >1% = ATN
  
  
• Advantages of FeNa compared to other indices
• • Physiologic measure of sodium reabsorption
    
  • Measured creatinine and sodium clearances, accounting for filtration and reabsorption of sodium
    
  • FeNa increased before oliguric phase established and predictive of incipient ARF
• Exceptions (intrinsic renal failure with FeNa <1%)
• • Urinary tract obstruction
    
  • Acute glomerulonephritis
    
  • Hepatorenal syndrome
    
  • Radiologic contrast–induced ATN
    
  • Myoglobinuric and hemoglobinuric ARF
    
  • Renal allograft rejection
    
  • Drug-related alterations in renal hemodynamics (eg, captopril, NSAIDs)

Imaging Studies

• Imaging studies in ARF are most important in the emergent workup of suspected postrenal azotemia. Please refer to Urinary Obstruction for a complete discussion of available imaging studies for this cause of ARF.
• Chest radiography
• • Obtain chest radiographs on a routine basis to look for evidence of volume overload.
  • Findings of lung infiltration can lead to pulmonary/renal syndromes, such as Wegener granulomatosis and Goodpasture syndrome, or evidence of pulmonary emboli from endocarditis or atheroembolic disease.

Other Tests

• Electrocardiography: Obtain routine ECGs to look for manifestations of hyperkalemia and arrhythmias, such as atrial fibrillation, related to atheroemboli.

Procedures

• Renal biopsy
• • Often helpful in finding specific cause of renal failure; however, not an ED procedure
  • Reserved for evaluation of ARF when cause cannot be determined
  • Especially important when glomerular causes of ARF are suspected
  • Often helpful in finding specific cause of renal failure

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Stabilize acute life-threatening conditions and initiate supportive therapy.

Emergency Department Care

Treatment of ARF ideally should begin before the diagnosis of ARF is firmly established. A high index of suspicion often is necessary to diagnose early ARF. Significant decreases in GFR frequently occur before indirect measures of GFR reveal a problem. All seriously ill medical patients (eg, elderly patients, diabetic patients, hypovolemic patients) should have ARF included early in their differential diagnosis.

• Physicians can play a pivotal role in reversing many of the underlying causes and preventing further iatrogenic renal injury if ARF is recognized early. After providing an adequate airway and ventilation, focus on fluid management of the ARF patient.
• Fluid management
• • Patients with ARF represent challenging fluid management problems.
  • Hypovolemia potentiates and exacerbates all forms of ARF.
  • Reversal of hypovolemia by rapid fluid infusion often is sufficient to treat many forms of ARF. However, rapid fluid infusion can result in life-threatening fluid overload in patients with ARF.
  • Accurate determination of a patient's volume status is essential and may require invasive hemodynamic monitoring if physical examination and laboratory results do not lead to a definite conclusion.
• Urinary catheter placement
• • Urinary obstruction often is an easily reversible cause of ARF.
  • Placement of a urinary catheter early in the workup of a patient with ARF not only allows diagnosis and treatment of urethral and bladder outlet urinary obstruction, and allows for accurate measurement of urine output.
  • If available, bedside ultrasonography can quickly identify a large and distended bladder.
  • Routine use of urinary catheters should be tempered by consideration of their inherent risks of introducing infections.
• Renal replacement therapy
• • The principal methods of renal replacement therapy (RRT) are intermittent hemodialysis (IHD), continuous venovenous hemofiltration (CVVH), and peritoneal dialysis (PD). Each has advantages and limitations.
  • IHD is widely available, has only moderate technical difficulty, and is the most efficient way of removing a volume or solute from the vascular compartment quickly. Unfortunately, dialysis-associated hypotension may adversely affect remaining renal function, particularly in patients who are critically ill. This is one reason CVVH is widely recommended in this setting.
  • Continuous RRT techniques are more expensive and not universally available; however, in addition to avoiding hypotension, they are believed to achieve better control of uremia and clearance of solute from the extravascular compartment. Because it continues around the clock, CVVH is able to remove larger fluid volumes, which is a significant advantage with critical care patients on parenteral nutrition and multiple infusions. CVVH may also preserve cerebral perfusion pressure more effectively. A theoretical though contested advantage of CVVH is the clearance of mediators of the inflammatory cascade. Although several studies have sought to directly compare CVVH to IHD, no study has shown a convincing advantage for one therapy over the other; in spite of this, many authorities assert that the choice of IHD over CVVH in the setting of shock would be inappropriate and unethical.
  • Peritoneal dialysis is inexpensive, widely available, and does not result in hypotension. However, it is not capable of removing large volumes of fluid or solute. Its use may be most common in children.
  • Indications for and timing of initiation of RRT are also important and somewhat controversial subjects. Widely accepted indications for initiation of RRT include the following:
    • Volume overload
    • Hyperkalemia (K⁺ >6.5 or rising)
    • Acid-base imbalance
    • Symptomatic uremia (pericarditis, encephalopathy, bleeding dyscrasia, nausea, vomiting, pruritus)
    • Uremia (BUN>100)
    • Dialyzable intoxications
  • Severe dysnatremia ( <115 or >165), and dysthermia may also be appropriate indications for RRT. Significant intoxications with a dialyzable agent (eg, methanol, ethylene glycol, theophylline, aspirin, lithium) may be the strongest indication for emergent dialysis because other effective therapeutic interventions are available for most of other complications of ARF. Volume overload can be treated with nitrates and phlebotomy; hyperkalemia can be treated with calcium, insulin, glucose, bicarbonate, binding resins, and beta agonists.
  • The timing of initiation of RRT in the absence of the aforementioned indications is more controversial, although the consensus that RRT itself contributes to the resolution of ARF may be growing. Intensity of RRT is another area of active controversy and research; 2 recent studies suggest that more is better. In a study of CVVH intensity in which patients with ARF were randomly given standard or supernormal levels of ultrafiltration, the patients with more intense RRT had significantly lower mortality rates. A second randomized trial compared daily IHD with traditional every-other-day IHD in patients with ARF and found that the mortality rate (28% vs 46%) and speed of renal recovery (9 d vs 16 d) were significantly improved. However, before these studies, no significant evidence indicated that increased dialysis dosage improved outcomes.

Consultations

Refer all patients with suspected ARF to a nephrologist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Diuretics and vasodilators are used commonly to treat ARF. Unfortunately, in large randomized studies these agents have failed to prove effective.

Atrial natriuretic factor also has been tested in a randomized double-blind study in ARF but failed to improve the course of ARF.

Calcium channel blockers have been shown in animal models to be protective in ARF if given before renal insult. Their only benefit in humans is preventing ARF in renal transplant patients receiving cyclosporine.

Infusion of mannitol is reported to be protective of myoglobinuric ARF if given within 6 hours of rhabdomyolysis. In addition, mannitol infusion has been shown to decrease the rate of ARF if given before cardiothoracic surgery and radiocontrast agents. No controlled studies have shown any benefit to mannitol infusion in patients with established ARF. In fact, mannitol given in high doses has been associated with ARF. Significant risks of prescribing large doses of mannitol to patients with ARF include fluid overload and hyperkalemia.

Drug Category: Diuretics

Patients with nonoliguric (rather than oliguric) ARF have better mortality and renal recovery rates, prompting many to recommend diuretics in oliguric ARF. Unfortunately, randomized double-blind controlled trials fail to show benefit. Studies conclude that diuretics are useful only in management of fluid-overloaded patients.

Drug Category: Vasodilators

Renal vascular vasodilators in ARF make a great deal of sense from theoretical and experimental viewpoints. However, effective blood-volume restoration is the best physiologic vasodilator.

Low-dose dopamine is a potent vasodilator, increasing RBF in ARF. Unfortunately, most clinical studies fail to show that it improves recovery or mortality rates. In the majority of ARF studies, dopamine was associated only with an increase in urine output. Current recommendations for dopamine favor its use in patients with ARF patients and CHF. Balance benefits of diuretic action with proarrhythmic side effects.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Transfer

• Transfer patients with significant ARF to a facility with capability for hemodialysis on a 24-hour basis.

Complications

• A vast array of fluid and electrolyte abnormalities can be seen with ARF. Please refer to the appropriate chapters for a more complete discussion of these disorders.
• Cardiovascular complications (eg, CHF, myocardial infarction, arrhythmias, cardiac arrest) have been observed in as many as 35% of patients with ARF. Fluid overload secondary to oliguric ARF is a particular risk for the elderly with little cardiac reserve.
• • Pericarditis is a relatively rare complication of ARF. When pericarditis complicates ARF, consider additional diagnoses, such as SLE and hepatorenal syndrome.
  • ARF also can be a complication of cardiac diseases, such as endocarditis or atrial fibrillation with emboli.
  • Cardiac arrest in a patient with ARF always should arouse suspicion of hyperkalemia. Many authors recommend a trial of intravenous calcium chloride (or gluconate) in all patients with ARF who suffer cardiac arrest.
• Pulmonary complications have been reported in approximately 54% of patients with ARF. Pulmonary complications are the single most significant risk factor for death in patients with ARF.
• • Several diseases exist that commonly present with simultaneous pulmonary and renal involvement, including pulmonary/renal syndromes (eg, Goodpasture syndrome, Wegener granulomatosis, polyarteritis nodosa, cryoglobulinemia, sarcoidosis).
  • Hypoxia commonly occurs during hemodialysis and can be particularly significant in the patient with pulmonary disease. This dialysis-related hypoxia is thought to occur secondary to WBC lung sequestration and alveolar hypoventilation.
• GI symptoms of nausea, vomiting, and anorexia are frequent complications of ARF and represent one of the cardinal signs of uremia.
• • GI bleeding occurs in approximately one third of patients with ARF. Most episodes are mild, but GI bleeding accounts for 3-8% of deaths in patients with ARF.
  • Mild hyperamylasemia (2-3 times controls) commonly is seen in ARF. Elevation of baseline amylase can complicate diagnosis of pancreatitis in patients with ARF.
  • Lipase, which commonly is not elevated in ARF, often is necessary to make the diagnosis of pancreatitis. Pancreatitis has been reported as a concurrent illness with ARF in patients with atheroemboli, vasculitis, and sepsis from ascending cholangitis.
  • Jaundice has been reported to complicate ARF in approximately 43% of cases. Etiologies of jaundice with ARF include hepatic congestion, blood transfusions, and sepsis.
  • Hepatitis occurring concurrently with ARF should prompt the differential diagnosis of common bile duct obstruction, fulminant hepatitis B, leptospirosis, acetaminophen toxicity, and Amanita phalloides toxin.
• Infections commonly complicate the course of ARF and have been reported to occur in as many as 33% of patients with ARF. Most common sites are pulmonary and urinary tracts. Infections are the leading cause of morbidity and death in patients with ARF. Various studies have reported mortality rates of 11-72% in infections complicating ARF.
• Neurologic signs of uremia are a common complication of ARF and have been reported in approximately 38% of patients with ARF.
• • Neurologic sequelae include lethargy, somnolence, reversal of the sleep-wake cycle, and cognitive or memory deficits.
  • Focal neurologic deficits rarely are due solely to uremia and should remain a diagnosis of exclusion in patients with ARF.
  • Pathophysiology of neurologic symptoms is still unknown but clearly is not correlated to levels of BUN or creatinine. A number of diseases express themselves with concurrent neurologic and renal manifestations (eg, SLE, TTP, HUS, endocarditis, malignant hypertension).

Prognosis

• Mortality rates from ARF remain 50%, despite the institution of effective renal replacement therapies.
• • Deaths from ARF are related directly to the patient's underlying disease process (eg, sepsis, CHF).
  • Mortality rates in patients older than 80 years are approximately 40%, very similar to those in younger patients. Age should not be a determining factor in instituting renal replacement therapy.
• Approximately 20–60% of patients experiencing ARF require dialysis during their hospital stay. The majority of these patients recover, with only 25% requiring long-term renal replacement therapy.

Patient Education

• Stress to patients that progressive renal failure is a silent disease. Symptoms of uremia occur only with advanced, generally irreversible renal failure. The only way for patients to reliably follow the course of their disease is by regular checkups with their physicians.
• For excellent patient education resources, see eMedicine's Diabetes Center. Also, visit eMedicine's patient education article, Acute Kidney Failure.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failing to consider ARF: Normal-range BUN and creatinine do not reliably rule out the diagnosis of ARF. Patients with low muscle mass and/or vegetarians may have significant decreases in GFR and still remain in normal ranges for BUN and creatinine. Comparison with baseline values and trends are more important than absolute numerical values.
• Most cases of ARF in inpatients are secondary to iatrogenic causes. Be especially careful in prescribing potential nephrotoxins (eg, radiocontrast agents, aminoglycosides, NSAIDs) to patients predisposed to ARF (eg, dehydration, CHF, diabetes mellitus, chronic renal failure, elderly).

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Akposso K, Hertig A, Couprie R, et al. Acute renal failure in patients over 80 years old: 25-years'' experience. Intensive Care Med. Apr 2000;26(4):400-6. [Medline].
• Bellomo R, Ronco C, Kellum JA. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. Aug 2004;8(4):R204-12. [Medline].
• Bonventre JV. Mechanisms of ischemic acute renal failure. Kidney Int. May 1993;43(5):1160-78. [Medline].
• Druml W. Prognosis of acute renal failure 1975-1995. Nephron. 1996;73(1):8-15. [Medline].
• Kaufman J, Dhakal M, Patel B, Hamburger R. Community-acquired acute renal failure. Am J Kidney Dis. Feb 1991;17(2):191-8. [Medline].
• Kellum JA, M Decker J. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med. Aug 2001;29(8):1526-31. [Medline].
• Klahr S, Miller SB. Acute oliguria. N Engl J Med. Mar 5 1998;338(10):671-5. [Medline].
• Korevaar JC, Jansen MA, Dekker FW. Evaluation of DOQI guidelines: early start of dialysis treatment is not associated with better health-related quality of life. National Kidney Foundation-Dialysis Outcomes Quality Initiative. Am J Kidney Dis. Jan 2002;39(1):108-15. [Medline].
• Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA. May 15 1996;275(19):1489-94. [Medline].
• Lewis J, Salem MM, Chertow GM, et al. Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group. Am J Kidney Dis. Oct 2000;36(4):767-74. [Medline].
• Liano F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int. Sep 1996;50(3):811-8. [Medline].
• Moghal NE, Brocklebank JT, Meadow SR. A review of acute renal failure in children: incidence, etiology and outcome. Clin Nephrol. Feb 1998;49(2):91-5. [Medline].
• Molitoris BA, Sandoval R, Sutton TA. Endothelial injury and dysfunction in ischemic acute renal failure. Crit Care Med. May 2002;30(5 Suppl):S235-40. [Medline].
• Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. May 2002;39(5):930-6. [Medline].
• Ragaller MJ, Theilen H, Koch T. Volume replacement in critically ill patients with acute renal failure. J Am Soc Nephrol. Feb 2001;12 Suppl 17:S33-9. [Medline].
• San A, Selcuk Y, Tonbul Z, Soypacaci Z. Etiology and prognosis in 438 patients with acute renal failure. Ren Fail. Jul 1996;18(4):593-9. [Medline].
• Schiffl H, Lang SM, Fischer R. Daily hemodialysis and the outcome of acute renal failure. N Engl J Med. Jan 31 2002;346(5):305-10. [Medline].
• Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. Oct 16 2001;104(16):1985-91. [Medline].
• Shilliday IR, Quinn KJ, Allison ME. Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study. Nephrol Dial Transplant. Dec 1997;12(12):2592-6. [Medline].
• Stapleton FB, Jones DP, Green RS. Acute renal failure in neonates: incidence, etiology and outcome. Pediatr Nephrol. Jul 1987;1(3):314-20. [Medline].
• Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. May 30 1996;334(22):1448-60. [Medline].
• Thurau K, Boylan JW. Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med. Sep 1976;61(3):308-15. [Medline].

Article Last Updated: May 10, 2006