Acute Kidney Injury (Renal Failure) in Emergency Medicine 

Updated: Nov 20, 2019
Author: Richard H Sinert, DO; Chief Editor: Gregory Sugalski, MD 

Practice Essentials

Acute kidney injury (AKI), formerly called acute renal failure (ARF), is commonly defined as an abrupt decline in renal function, clinically manifesting as a reversible acute increase in nitrogen waste products (measured by blood urea nitrogen [BUN] and serum creatinine levels) over the course of hours to weeks. Acute kidney injury is a common entity in the emergency department (ED). Emergency physicians play a critical role in recognizing early AKI,  preventing iatrogenic injury, and reversing the course.[1]  Imaging studies are important in the emergent workup of suspected postrenal azotemia. The distinction between community- and hospital-acquired AKI is important for the differential diagnoses, treatment, and eventual outcome of patients with AKI.[1, 2, 3, 4, 5]

RIFLE classification

The Acute Dialysis Quality Initiative (ADQI) group published the RIFLE classification, which is based on changes from the patient's baseline either in serum creatinine level, glomerular filtration rate (GFR), or urine output (UO).[6, 7, 8, 9, 10, 11, 12]

The RIFLE classification of AKI is as follows[2] :

  • Risk (R) - Increase in serum creatinine level X 1.5 or decrease in GFR by 25%, or UO < 0.5 mL/kg/hr 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/hr 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 with acute increase of >0.5 mg/dL; UO < 0.3 mL/kg/h for 24 hours, or anuria for 12 hours
  • Loss (L) - Persistent AKI, complete loss of kidney function >4 weeks
  • End-stage kidney disease (E) - Loss of kidney function >3 months

Since baseline serum creatinine level and GFRs may not be readily available, the consensus committee recommended the use of the Modification of Diet in Renal Disease (MDRD) equation to estimate the patient’s GFR/1.73 mm based on serum creatinine level, age, gender, and race. The proportional decrease in GFR should be calculated from 75 mL/min per 1.73 mm2, the agreed upon lower limit of normal.

Using the RIFLE classification, hospital-acquired AKI of the Risk, Injury, and Failure categories has been found in 9%, 5%, and 4% of hospital admissions,[6] respectively, and in approximately 17%, 12%, and 7% of critical care admissions.[7, 8]

Acute Kidney Injury Network classification system

The Acute Kidney Injury Network (AKIN) has developed specific criteria for the diagnosis of AKI. The AKIN defines AKI as abrupt (within 48 hours) reduction of kidney function, manifested by any one of the following[4, 13] :

  • An absolute increase in serum creatinine of 0.3 mg/dL or greater (≥26.4 µmol/L)
  • A percentage increase in serum creatinine of 50% or greater (1.5-fold from baseline)
  • A reduction in urine output, defined as less than 0.5 mL/kg/h for more than 6 hours

SOFA score

in critically ill patients, renal dysfunction severity can also be evaluated by combining renal function with functional parameters of other organs (eg, the Sequential Organ Failure Assessment [SOFA] score). In a study to assess the definition of renal dysfunction in multicenter, randomized, controlled trials involving critically ill patients, the renal SOFA score is the most commonly used system to quantify renal function at baseline or as a secondary outcome.[3] Changes have been assessed in critically ill patients over time or during treatment and have also been used to evaluate the degree of organ dysfunction in sepsis. In addition to assessing patient status, renal criteria can be used for prognosis. In patients with kidney injury, measuring changes in the SOFA score in the first 24 hours of renal replacement therapy (RRT) can identify patients at high risk for mortality. However, individual SOFA scores have been shown to be poor at predicting early (7 day) mortality in patients with septic AKI who require continuous RRT.[14]

Signs and symptoms

Skin

Skin examination may reveal the following in patients with AKI:

  • Livedo reticularis, digital ischemia, butterfly rash
  • Palpable purpura: systemic vasculitis
  • Maculopapular rash: Allergic interstitial nephritis
  • Track marks (ie, intravenous drug abuse): Endocarditis

Eyes

Eye examination may reveal the following:

  • 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 (ie, Hollenhorst plaque in cholesterol microembolism)

Ears

Examination of the patient’s ears may reveal the following signs:

Cardiovascular system

Cardiovascular examination may reveal the following:

  • Irregular rhythms (ie, atrial fibrillation): Thromboemboli
  • Murmurs: Endocarditis
  • Pericardial friction rub: Uremic pericarditis
  • Increased jugulovenous distention, rales, S 3: Heart failure

Abdomen

The following signs of acute kidney injury may be discovered during an abdominal examination:

  • Pulsatile mass or bruit: Atheroemboli
  • Abdominal or costovertebral angle tenderness: Nephrolithiasis, papillary necrosis, renal artery thrombosis, renal vein thrombosis
  • Pelvic, rectal masses; prostatic hypertrophy; distended bladder: Urinary obstruction
  • Limb ischemia, edema: Rhabdomyolysis

Pulmonary system

Pulmonary examination may reveal the following:

  • Rales: Pulmonary edema, infectious pulmonary process 
  • Hemoptysis: ANCA (antineutrophilic cytoplasmic antibodies) vasculitis, anti–glomerular basement membrane (anti-GBM, Goodpasture) syndrome

Diagnostic testing

The following tests can aid in the diagnosis and assessment of AKI[2, 15, 16, 17] :

  • Kidney function studies: Increased levels of blood urea nitrogen (BUN) and creatinine are the hallmarks of renal failure; the ratio of BUN to creatinine can exceed 20:1 in conditions that favor the enhanced reabsorption of urea, such as volume contraction (this suggests prerenal AKI).
  • Complete blood count (can indicate infection; acute blood loss or chronic anemia; thrombotic microangiopathy).
  • Peripheral smear (eg, schistocytes such as hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura).
  • Serologic tests: These may show evidence of conditions associated with AKI, such as in lupus nephritis, ANCA vasculitis or anti-GBM disease or syndrome.
  • Complement testing: Pattern may indicate AKI related to endocartis or various glomerulonephritidites.
  • Fractional excretion of sodium and urea in the setting of oliguria.
  • Bladder pressure: Patients with a bladder pressure above 25 mm Hg should be suspected of having AKI caused by abdominal compartment syndrome.
  • Ultrasonography: Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the urinary collecting system.
  • Aortorenal angiography: Can be helpful in establishing the diagnosis of renal vascular diseases, such as renal artery stenosis, renal atheroembolic disease, atherosclerosis with aortorenal occlusion, and certain cases of necrotizing vasculitis (eg, polyarteritis nodosa).
  • Renal biopsy: Can be useful in identifying intrarenal causes of AKI and directing targeted therapy.

Management

The current treatment for acute kidney injury is mainly supportive. Therapeutic agents (eg, dopamine, nesiritide, fenoldopam, mannitol) are not indicated in the management of AKI and may be harmful.[1, 2, 18, 19, 20, 21]

Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary goals of treatment and may include the following measures:

  • Correction of fluid overload with furosemide.
  • Correction of severe acidosis with bicarbonate administration, which can be important as a bridge to dialysis.
  • Correction of hyperkalemia.
  • Correction of hematologic abnormalities (eg, anemia, uremic platelet dysfunction) with measures such as transfusions and administration of desmopressin or estrogens.
  • Treatment of AKI ideally should begin before the diagnosis is firmly established. A high index of suspicion is often necessary to diagnose early AKI. 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 AKI included early in their differential diagnosis.

Stabilize acute life-threatening conditions and initiate supportive therapy. Watch for electrocardiographic evidence of hyperkalemia.  Treatment of AKI ideally should begin before the diagnosis is firmly established. A high index of suspicion often is necessary to diagnose early AKI. 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 AKI included early in their differential diagnosis. After providing an adequate airway and ventilation, focus on fluid management of the patient with AKI.

Reversal of hypovolemia by rapid fluid infusion often is sufficient to treat many forms of AKI. However, rapid fluid infusion can result in life-threatening fluid overload.

Placement of a urinary catheter early in the workup of a patient with KI not only allows diagnosis and treatment of urethral and bladder outlet urinary obstruction but also allows for accurate measurement of urine output. Routine use of urinary catheters should be tempered by consideration of the inherent risks of catheter-associated infections.

The principal methods of renal replacement therapy (RRT) are intermittent hemodialysis (IHD), continuous venovenous hemodiafiltration (CVVHD), and peritoneal dialysis (PD). Each has advantages and limitations.

 

Prognosis

Because most cases of community-acquired acute kidney injury are secondary to volume depletion, as many as 90% of cases are estimated to have a potentially reversible cause. Hospital-acquired AKI often occurs in an ICU setting and is commonly part of multiorgan failure.

This dichotomy in the etiology of AKI explains the increased mortality rate, dialysis requirements, and rates of progression to end-stage renal failure seen in hospital-acquired AKI compared to community-acquired AKI.

Mortality

Mortality rates for AKI have changed little since the advent of dialysis at 50%.[22] This curious statistic simply reflects the changing demographics of AKI from community- to hospital-acquired settings. The mortality for hospital-acquired AKI is reported to be as high as 70% and is directly correlated to the severity of the patient's other disease processes. The mortality among patients presenting to the ED with prerenal AKI may be as low as 7%.

The inhospital mortality rate for AKI is 40-50%. The mortality for ICU patients with AKI is higher (>50% in most studies), particularly when AKI is severe enough to require dialysis treatment. ICU patients with sepsis-associated AKI have significantly higher mortality rates than do nonseptic AKI patients. In addition, the pooled estimate for general ICU patients with AKI shows a stepwise increase in relative risk for death through the risk, injury, and failure classifications of the RIFLE criteria in AKI patients versus non-AKI patients. The survival rate is nearly 0% among patients with AKI who have an Acute Physiology and Chronic Health Evaluation II (APACHE II) score higher than 40. In patients with APACHE II scores of 10-19, the survival rate is 40%.[9, 11, 13, 14, 22, 23, 24, 25, 26]

AKI is not a benign disease. One study noted a 31% mortality rate in patients with AKI not requiring dialysis, compared to a mortality rate of only 8% in matched patients without AKI. Even after adjusting for comorbidity, the odds ratio for dying of AKI was 4.9, as compared to patients without AKI.

With the advent of dialysis, the most common causes of death associated with AKI are sepsis, cardiac failure, and pulmonary failure. Interestingly, patients who are older than 80 years with AKI have mortality rates similar to those of younger adult patients. Pediatric patients with AKI represent a different set of etiologies and have mortality rates averaging 25%.

Mortality rates are generally lower for nonoliguric AKI (>400 mL/day) than for oliguric (< 400 mL/day) AKI, reflecting the fact that nonoliguric AKI is usually caused by drug-induced nephrotoxicity and interstitial nephritis, which have few other systemic complications.

 

Differential Diagnosis

The following conditions should be considered in the differential diagnosis of acute kidney injury (AKI):

  • Alcoholic Ketoacidosis

  • Anemia, Sickle Cell

  • Aneurysm, Abdominal

  • Congestive Heart Failure and Pulmonary Edema

  • Diabetic Ketoacidosis

  • Acute Glomerulonephritis

  • Hemolytic Uremic Syndrome

  • Henoch-Schönlein Purpura

  • Hyperkalemia

  • Hypermagnesemia

  • Hypernatremia

  • Hypertensive Emergencies

  • Metabolic Acidosis

  • Pediatrics, Dehydration

  • Pediatrics, Diabetic Ketoacidosis

  • Pediatrics, Inborn Errors of Metabolism

  • Pediatrics, Sickle Cell Disease

  • Pediatrics, Urinary Tract Infections and Pyelonephritis

  • Renal Calculi

  • Renal Failure, Chronic and Dialysis Complications

  • Toxicity, Alcohols

  • Urinary Obstruction

  • Urinary Tract Infection in Females

  • Urinary Tract Infection in Males

Normal-range blood urea nitrogen (BUN) and creatinine levels do not reliably rule out the diagnosis of AKI. 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 are absolute numerical values.

 

Urinalysis

Microscopic examination of urine is essential in establishing a differential diagnosis for acute kidney injury. Often, oxalate crystals are observed in cases of acute tubular necrosis (ATN). Reddish-brown or cola-colored urine suggests the presence of myoglobin or hemoglobin, especially in the setting of a positive dipstick for heme and no red blood cells (RBCs) on microscopic examination. The dipstick assay may reveal significant proteinuria as a result of tubular injury.

Findings may include the following:

  • 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 - Acute tubular necrosis (ATN), glomerulonephritis, interstitial nephritis. Findings of granular, muddy-brown casts in urine sediment are highly suggestive of tubular necrosis. The presence of tubular cells or tubular cell casts also supports the diagnosis of ATN.

  • Red blood cell (RBC) casts - Glomerulonephritis, malignant hypertension. The presence of RBCs in the urine is always pathologic. Eumorphic RBCs suggest bleeding along the collecting system. Dysmorphic RBCs or RBC casts indicate glomerular inflammation, suggesting glomerulonephritis is present.

  • White blood cell (WBC) casts - Pyelonephritis. The presence of white blood cells (WBCs) or WBC casts suggests pyelonephritis or acute interstitial nephritis. The presence of urine eosinophils is helpful in establishing a diagnosis but is not necessary for allergic interstitial nephritis to be present.

  • Eosinophiluria - Acute allergic interstitial nephritis, atheroembolism. The presence of eosinophils, as visualized with Wright stain or Hansel stain, suggests interstitial nephritis. However, this finding can also be seen in urinary tract infections, glomerulonephritis, and atheroembolic disease.

  • Crystalluria - Acyclovir, sulfonamides, methotrexate, ethylene glycol toxicity, radiocontrast agents (mild crystalluria can be a normal finding). The presence of uric acid crystals may represent ATN associated with uric acid nephropathy. Calcium oxalate crystals are usually present in cases of ethylene glycol poisoning.

 

Blood Urea Nitrogen

Although increased levels of blood urea nitrogen (BUN) and creatinine are the hallmarks of renal failure, the rate of rise depends on the degree of renal insult and, with respect to BUN, on protein intake. BUN may be elevated in patients with gastrointestinal (GI) or mucosal bleeding, steroid treatment, or protein loading.[2]

The ratio of BUN to creatinine is an important finding. The ratio can exceed 20:1 in conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction); this suggests prerenal AKI.

Assuming that the patient has no renal function, the rise in BUN over 24 hours can be roughly predicted using the following formula:

  • (24-hour protein intake in milligrams × 0.16) ÷ total body water

The result is expressed in mg/dL and added to the baseline BUN value to yield the predicted BUN.

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 the 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.

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 of less than 30 mL/hr, urea clearance is as low as an estimated 30% of GFR. Under conditions of diuresis, with urine outputs greater than 100 mL/hr, urea clearance can increase to 70-100% of GFR.

This information can be used clinically to help differentiate prerenal failure from other etiologies of AKI. 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-to-creatinine ratio of more than 20 in prerenal failure.

 

Creatinine

Assuming no renal function, the rise in creatinine can be predicted using the following formulas[2, 16] :

  • For males: Weight in kilograms × [28 - 0.2(age)] ÷ total body water, with the result in mg/dL added to the creatinine value.
  • For females: Weight in kilograms × [23.8 - 0.17(age)] ÷ total body water, with the result in mg/dL added to the creatinine value.

Serum creatinine measurement provides the ED physician with an accurate and consistent estimation of GFR. Correct interpretation of serum creatinine measurement extends beyond just knowing normal values for the specific laboratory.

The serum creatinine level varies by method of measurement, either Jaffe or iminohydrolase. The upper limit of the normal creatinine level 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 laboratories.

The 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.

The serum creatinine level, a reflection of creatinine clearance, is a function of creatinine production and excretion rates. Creatinine production is determined by muscle mass. The serum creatinine level must always be interpreted with respect to patient's weight, age, and sex. For example, GFR decreases by 1% per year after age 40 years, yet serum creatinine level generally remains stable. Balance is achieved via a decrease in muscle mass with age, which matches the fall in GF.

Men generally have a higher muscle mass per kilogram of body weight and thus a higher serum creatinine level than women.

The GFR can be estimated by the following formulas:

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

  • Modification of Diet in Renal Disease (MDRD) equation: GFR, in mL/min per 1.73 mm2 = 186.3 × ([serum creatinine] exp[-1.154]) × (age exp[-0.203]) × (0.742 if female) × (1.21 if African American)

The Acute Dialysis Quality Initiative ADQI consensus committee on AKI favors the (MDRD) equation to estimate GFR.[2]

An important consideration and limitation is that significant decrements in GFR can occur while creatinine levels remain in the normal range.

Changes in serum creatinine level reflect changes in GFR. Rate of change in serum creatinine level is an important variable in estimating GFR. Stable changes in serum creatinine level correlate with changes in GFR by the following relationships:

  • If creatinine 1 mg/dL is baseline for a given patient with normal GFR

  • Creatinine 2 mg/dL - 50% reduction in GFR

  • Creatinine 4 mg/dL - 70–85% reduction in GFR

  • Creatinine 8 mg/dL - 90–95% reduction in GFR

As suggested by these data, knowledge of a patient's baseline creatinine level becomes very important. Small changes with low baseline levels of creatinine may be much more important clinically than large changes with high basal 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 level when AKI occurs in acute glomerulonephritis. Trimethoprim and cimetidine cause decreased creatinine secretion and a falsely elevated creatinine with no change in GFR.

 

Cystatin C

Cystatin C is emerging as a superior biomarker for early kidney injury. In a study of 198 patients presenting to an emergency department, serum cystatin C  greater than 1.44 mg/L alone or along with serum creatinine and estimated glomerular filtration rate has been found to be a strong predictor for the risk of acute kidney injury.[15]  It is generated at a constant rate by all nucleated cells and is not secreted by the tubules or eliminated by other routes than renal excretion. It does not appear to be affected by body habitus, nutritional state, or comorbid illness. One of its principal advantages is that it identifies kidney injury while creatinine levels remain in the normal range.

A prospective study of serum cystatin C as a biomarker for acute kidney injury after cardiac surgery found that the cystatin C level was less sensitive than the creatinine level for detecting AKI. However, confirmation by cystatin C level appeared to identify a subset of patients with AKI with a substantially higher risk for adverse outcomes.[16]

 

Complete Blood Count

The following points should be kept in mind concerning complete blood count (CBC) results:

  • Leukocytosis - Common in AKI

  • Leukopenia and thrombocytopenia - Suggest systemic lupus erythematosus (SLE) or TTP

  • Anemia and rouleaux formation - Suggest multiple myeloma

  • Microangiopathic anemia - Suggests disseminated intravascular coagulation (DIC), TTP, or atheroemboli

  • Eosinophilia - Suggests allergic interstitial nephritis, polyarteritis nodosa, or atheroemboli

  • Coagulation disturbances - Indicate liver disease, DIC, TTP, or hepatorenal syndrome

 

Blood Chemistry

Creatine phosphokinase (CPK) elevations are seen in rhabdomyolysis and myocardial infarction.

Elevations in liver transaminase levels are seen in rapidly progressive liver failure and hepatorenal syndrome.

Hypocalcemia (moderate) is common in AKI; marked hypocalcemia is more typical of chronic renal failure.

Hyperkalemia is a common and important complication of AKI.

 

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 AKI. However, overly aggressive volume resuscitation in a patient with ATN who is unable to excrete the extra fluid can result in volume overload and respiratory embarrassment.

To help with the differentiation of prerenal azotemia, analysis of urine may provide important clues. Diuretics interfere with some of these indices, so collect urine prior to any considered administration of diuretics.

Urine indices that suggest prerenal AKI include the following:

  • Urine specific gravity >1.018

  • Urine osmolality (mOsm/kg water) >500

  • Urine sodium (mEq/L) < 15-20

  • Plasma BUN-to-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 water) < 500

  • Urine sodium (mEq/L) >40

  • Plasma BUN-to-creatinine ratio < 10-15

  • Urine-plasma creatinine ratio < 20

 

Calculation of Fractional Excretion of Sodium

Urine electrolyte findings also can serve as valuable indicators of functioning renal tubules. The fractional excretion of sodium (FeNa) is the commonly used indicator. However, the interpretation of results from patients in nonoliguric states, those with glomerulonephritis, and those receiving or ingesting diuretics can lead to an erroneous diagnosis.

FeNa can be a valuable test for helping to detect extreme renal avidity for sodium in conditions such as hepatorenal syndrome.

The calculation of fractional excretion of sodium (FeNa) is as follows:

  • FeNa = (urine Na/plasma Na)/(urine creatinine/plasma creatinine)

If FeNa is less than 1%, this suggests prerenal AKI.

If FeNa is greater than 1%, this suggests ATN.

The advantages of FeNa compared with other indices include the following:

  • 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 AKI

Exceptions (intrinsic renal failure with FeNa < 1%) include the following:

  • Acute glomerulonephritis

  • Hepatorenal syndrome

  • Radiologic contrast–induced ATN

  • Myoglobinuric and hemoglobinuric AKI

  • Renal allograft rejection

  • Drug-related alterations in renal hemodynamics (eg, captopril, nonsteroidal anti-inflammatory drugs [NSAIDs])

 

Imaging Studies

Renal ultrasonography is the test of choice for urologic imaging in the setting of acute renal failure.[27] It has excellent sensitivity and specificity for detecting hydronephrosis due to obstruction, and it can also give valuable information other than ruling obstruction in or out.

In critically ill patients, bedside ultrasonography warrants special consideration, because it can quickly diagnose treatable etiologies of the patient’s condition and give guidance for fluid resuscitation. Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the urinary collecting system. However, obtaining images of the kidneys can be technically difficult in patients who are obese, as well as in those with abdominal distention from ascites, gas, or retroperitoneal fluid collection. The degree of hydronephrosis found on ultrasonograms does not necessarily correlate with the degree of obstruction. Mild hydronephrosis may be observed with complete obstruction if found early. Small kidneys suggest chronic renal failure.

Bipolar renal length is easy to assess, and kidneys smaller than 9 cm suggest chronic renal failure. Renal parenchyma should be isoechogenic or hypoechogenic when compared with that of the liver and spleen; hyperechogenicity indicates diffuse parenchymal disease.

Color Doppler ultrasound allows assessment of renal perfusion and can allow diagnosis of large-vessel etiologies of AKI. Doppler scans can be quite useful in the diagnosis of thromboembolic or renovascular disease. Increased resistive indices can be observed in patients with hepatorenal syndrome.

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.

Obtain routine electrocardiograms to look for manifestations of hyperkalemia and arrhythmias, ischemia, and infarction.

Radionuclide imaging with technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3),99mTc-diethylenetriamine penta-acetic acid (99mTc-DTPA), or iodine-131 (131I)-hippurate can be used to assess renal blood flow, as well as tubular function. There is, however, a marked delay in the tubular excretion of radionuclide in prerenal and intrarenal AKI, limiting the value of nuclear scans.

Aortorenal angiography can be helpful in establishing the diagnosis of renal vascular diseases, including the following:

  • Renal artery stenosis
  • Renal atheroembolic disease
  • Atherosclerosis with aortorenal occlusion
  • Certain cases of necrotizing vasculitis (eg, polyarteritis nodosa)
 

Renal Biopsy

A renal biopsy can be useful in identifying intrarenal causes of AKI and can be justified if the results may change management (eg, initiation of immunosuppressive medications).

A renal biopsy may also be indicated when renal function does not return for a prolonged period and a prognosis is required to develop long-term management. In as many as 40% of cases, renal biopsy results reveal an unexpected diagnosis.

Acute cellular or humoral rejection in a transplanted kidney can be definitively diagnosed only by performing a renal biopsy.

 

Management

The current treatment for acute kidney injury (AKI) is mainly supportive. ED physicians can play a pivotal role in reversing many of the underlying causes and preventing further iatrogenic renal injury if AKI is recognized early. After providing an adequate airway and ventilation, focus on fluid management of the patient with AKI. Most cases of AKI in inpatients are secondary to iatrogenic causes. Be especially careful in prescribing potential nephrotoxins (eg, radiocontrast agents, aminoglycosides, NSAIDs) to patients predisposed to AKI (eg, dehydration, CHF, diabetes mellitus, chronic renal failure, elderly patients).[1, 2, 18, 19, 20, 21]

Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary goals of treatment and may include the following measures:

  • Correction of fluid overload with furosemide
  • Correction of severe acidosis with bicarbonate administration, which can be important as a bridge to dialysis
  • Correction of hyperkalemia
  • Correction of hematologic abnormalities (eg, anemia, uremic platelet dysfunction) with measures such as transfusions and administration of desmopressin or estrogens
  • Treatment of AKI ideally should begin before the diagnosis is firmly established. A high index of suspicion often is necessary to diagnose early AKI. 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 AKI included early in their differential diagnosis.

Diuretics and vasodilators are used commonly to treat AKI but have failed to prove effective. Atrial natriuretic factor hast also failed to improve the course of the disease.

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

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

Prerenal azotemia from volume contraction is treated with volume expansion; if left untreated for a prolonged period, tubular necrosis may result and may not be reversible. Postrenal AKI, if left untreated for a long time, also may result in irreversible renal damage. Procedures such as catheter placement, lithotripsy, prostatectomy, stent placement, and percutaneous nephrostomy can help prevent permanent renal damage.

Fluid management

Patients with AKI represent challenging fluid management problems.[18]  Hypovolemia potentiates and exacerbates all forms of AKI. Reversal of hypovolemia by rapid fluid infusion is often sufficient to treat many forms of AKI. However, rapid fluid infusion can result in life-threatening fluid overload in patients with AKI. 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. Bedside ultrasonographic evaluation, including IVC measurement, may give additional useful information. 

Urinary catheter placement

Urinary obstruction is often an easily reversible cause of AKI. Placement of a urinary catheter early in the workup of a patient with AKI not only allows diagnosis and treatment of urethral and bladder outlet urinary obstruction but also 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 the inherent risks of catheter-associated infections.

Renal replacement therapy

The principal methods of renal replacement therapy (RRT) are intermittent hemodialysis (IHD), continuous venovenous hemodiafiltration (CVVHD), 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 hemodynamically unstable. This is one reason CVVHD is widely recommended in this setting.

Continuous RRT techniques are more expensive, associated with increased bleeding risk, 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. CVVHD may also preserve cerebral perfusion pressure more effectively. Although several studies have sought to directly compare CVVHD with IHD, no study has shown a convincing advantage of one therapy over the other.

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 and in developing countries.[19]

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 single indication for emergent dialysis, because other effective therapeutic interventions are available for most of the other complications of AKI. Volume overload can be treated with nitrates and phlebotomy; hyperkalemia can be treated with calcium, insulin, glucose, bicarbonate, binding resins, and beta-agonists.

In managing severe AKI in patients with septic shock, when to initiate RRT is unclear. A multicenter, randomized, controlled trial among patients with septic shock who had severe acute kidney injury found there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy (within 12 hours) for the initiation of renal replacement therapy and those who were assigned to a delayed strategy of RRT after 48 hours.[20]

Note that, in light of little evidence of effectiveness, the possible adverse effects of the ion-exchange resin, sodium polystyrene sulfonate, in sorbitol should be considered. There is emerging concern about use of this time-honored, but scientifically unproven, management of hyperkalemia.[21]

The timing of initiation of RRT in the absence of the aforementioned indications is controversial, although the consensus that RRT itself contributes to the resolution of AKI may be growing. 

Intensity of RRT is another area of active controversy and research; some studies suggest that more is better. In a study of CVVH intensity in which patients with AKI 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 AKI and found that the mortality rate (28% vs 46%) and speed of renal recovery (9 days vs 16 days) were significantly improved. However, before these studies, no significant evidence indicated that increased dialysis dosage improved outcomes.

Dopamine agonists

Low-dose dopamine is a potent vasodilator, increasing renal blood flow in AKI, and acts as a dopamine agonist. Unfortunately, most clinical studies fail to show that it improves recovery or mortality rates. In the majority of AKI studies, dopamine was associated only with an increase in urine output. Current recommendations for dopamine favor its use in patients with AKI and concomitant hypodynamic heart failure. Benefits of diuretic action should be balanced with proarrhythmic side effects.

Fenoldopam is a potent dopamine A-1 receptor agonist that increases blood flow to the renal cortex and outer medulla, and evidence to date suggests that it reduces mortality and provides renal protection in critically ill patients with, or at risk of, renal failure. Because it is titratable and reliably controls severe hypertension, fenoldopam may be ideal for treating hypertensive emergencies where the affected end organ is the kidneys.

Diuretics

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