Acute Kidney Injury and Renal Replacement Therapy

Acute Kidney Injury and Renal Replacement Therapy

Emilee Willhem-Leen and Glenn Chertow


Acute kidney injury (AKI) is common in critical illness. A recent, large, multinational prospective study reported that 5.7% of critically ill patients will develop AKI during their illness.1 AKI in the setting of critical illness also confers a poor prognosis. In-hospital or short-term (90-day) mortality rates for critically ill patients who develop AKI range from 45% to 60%.13 Fortunately, the majority of critically ill patients who develop AKI during their hospitalization and who survive to discharge do not require long-term dialysis.1 This chapter reviews common definitions and classifications of AKI, etiologies of the disease, and appropriate emergency department (ED) diagnostic and therapeutic interventions for patients with AKI.


Critically ill patients may have AKI at presentation or may develop it during the course of their illness. While there is no consensus definition for AKI, the diagnosis is commonly made based on the following:

  • Decreased urine output (<200 mL/12 hours) despite fluid resuscitation or diuresis
  • Uremia (elevated serum urea nitrogen [BUN > 80 mg/dL]) or clinical signs of uremia (e.g., pericardial effusion, pericarditis, altered mental status)
  • Serum creatinine (sCr) elevated above baseline. Of note, sCr may not rise for 12 to 24 hours following renal injury and may not be dramatically elevated at the time of presentation to the ED.

Classification of AKI

sCr concentration is not an optimal early marker of AKI because (1) it does not accurately reflect kidney function in patients whose glomerular filtration rate (GFR) is acutely changing and (2) it may be lowered by muscle wasting that accompanies critical illness. Given this limitation, several criteria have been proposed to classify the severity of AKI.

RIFLE Criteria

The RIFLE criteria (Risk, Injury, Failure, Loss, ESRD [end-stage renal disease]) consist of three levels of injury that are useful in ED assessment of kidney injury (R, I, and F) and two levels (L and E) that are more typically applied during inpatient evaluation:

  • RISK: 1.5 times increase in sCr, GFR decrease by 25%, or urine output <0.5 mL/kg/h for 6 hours
  • INJURY: 2 times increase in sCr, GFR decrease by 50%, or urine output <0.5 mL/kg/h for 12 hours
  • FAILURE: 3 times increase in sCr, GFR decrease by 75%, or urine output <0.3 mL/kg/h for 24 hours or anuria for 12 hours
  • LOSS: Complete loss of kidney function for more than 4 weeks
  • ESRD: Complete loss of kidney function for more than 3 months

Acute Kidney Injury Network Criteria

The Acute Kidney Injury Network (AKIN) criteria are based on the RIFLE criteria but simplify the system for ease of use and clarity:

  • AKIN criteria definition of AKI:

    • Stage 1: 1.5 times increase in sCr from baseline, ≥0.3 mg/dL increase in sCr, or urine output of <0.5 mL/kg/h for 6 hours
    • Stage 2: 2 times increase in sCr or urine output of <0.5 mL/kg/h for 12 hours
    • Stage 3: 3 times increase in sCr, sCr of ≥4 mg/dL (with an acute rise of ≥0.5 mg/dL), or urine output of <0.3 mL/kg/h for 24 hours or anuria for 12 hours

  • The AKIN and RIFLE criteria compare as follows:

    • Stage 1 equivalent to RIFLE RISK
    • Stage 2 equivalent to RIFLE INJURY
    • Stage 3 equivalent to RIFLE FAILURE

The Kidney Disease Improving Global Outcome Criteria

The Kidney Disease Improving Global Outcome (KDIGO) criteria consist of three levels of renal injury based on either sCr or urine output:

  • Stage 1: 1.5 to 1.9 times increase in sCr from baseline, ≥0.3 mg/dL increase in sCr, or urine output <0.5 mL/kg/h for 6 to 12 hours
  • Stage 2: 2.0 to 2.9 times increase in sCr from baseline and urine output <0.5 mL/kg/h for >12 hours
  • Stage 3: 3 times increase in sCr from baseline, increase in sCr to ≥4.0 mg/dL, or initiation of renal replacement and urine output <0.3 mL/kg/h for ≥24 hours or anuria for ≥12 hours

For simplicity, we recommend use of either the AKIN or KDIGO classification. Unfortunately, precise classification of AKI stage may not be possible in the ED setting; often, baseline sCr is not available, and observation of urine output takes 6 to 24 hours. However, providing critical care or nephrology colleagues with this information, as available, aids in rapid triage and prognosis. For example, if a patient with a known baseline sCr of 1.0 mg/dL presents to the ED with sepsis and an initial sCr of 2.5 mg/dL and makes <50 mL of urine during the first 2 hours of evaluation and management, he or she likely has sustained at least a stage 2 AKI (per AKIN and KDIGO criteria). No stage of AKI, alone, necessitates admission to the intensive care unit, but nephrology consultation in the ED should be considered for patients presenting with likely stage 2 or 3 AKI.


AKI is a heterogeneous disease that can be caused by many factors. Typically, these factors are grouped into prerenal, intrarenal, and postrenal etiologies.


Prerenal AKI is caused by a reduction in renal perfusion. Precipitating conditions include hypovolemic shock (usually from gastrointestinal losses or severe burns), cardiogenic shock (usually from left-sided or biventricular failure), cirrhosis (including hepatorenal syndrome), and sepsis/systemic inflammatory response syndrome. Diuretic therapy and other drugs like ACE inhibitors and NSAIDs can exacerbate a prerenal state, especially in patients with additional risk factors. Typically, the urine sodium is low (<20 mmol/L), with a fractional excretion of sodium (FENa) <1% indicating a sodium-avid state in which the body is attempting to retain or replace lost volume.


Etiologies of intrarenal AKI include vascular, glomerular, and tubular/interstitial disease. Common vascular diseases associated with AKI include atheroemboli (typically associated with angiographic or surgical/endovascular procedures), vasculitis, thromboembolic disease including hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) malignant hypertension, and scleroderma renal crisis. Glomerular diseases that result in AKI include the nephritic (generally accompanied by active sediment on urinalysis [UA], i.e., red cells, white cells, and/or cellular casts) and nephrotic (generally accompanied by heavy proteinuria) syndromes (Table 40.1). Tubular and interstitial diseases are the most common causes of AKI in hospitalized patients; they include acute tubular necrosis (ATN), acute interstitial nephritis (AIN), and, less commonly, multiple myeloma cast nephropathy and tumor lysis syndrome.

TABLE 40.1 Clinical Significance of Findings on UA or Urine Microscopy


ATN is the most common cause of AKI in hospitalized patients and accounts for nearly 45% of in-hospital AKI.2 Renal ischemia, sepsis, and nephrotoxins, including radiocontrast media, heme pigment (e.g., in patients with rhabdomyolysis or hemolysis), selected cancer chemotherapeutic agents (e.g., platinum-based agents), and antibiotics (e.g., amphotericin B, aminoglycosides), are all common causes of ATN. Because ATN can occur after prolonged or severe prerenal physiology, it can at times be difficult to distinguish the two processes. In general, prerenal disease, unless it is due to hemodynamic derangements associated with heart failure, cirrhosis, or sepsis, will resolve with the correction of hypovolemia or hypotension. When the cause of injury is uncertain, urine studies can help distinguish the two etiologies; ATN will demonstrate an FENa >1% (as opposed to <1% seen in prerenal conditions) and the presence of muddy brown casts. In the future, ATN may be more rapidly identified by the detection of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other renal tubular injury markers, discussed below.

AIN is another cause of tubular/interstitial AKI, but it is significantly less common than ATN. AIN is typically the result of exposure to drugs; common offenders include NSAIDs and antibiotics, including penicillins and cephalosporins. Less commonly, AIN can result from infection or systemic illness (e.g., sarcoidosis, Sjogren’s, systemic lupus erythematosus [SLE]). A diagnosis of AIN requires the presence of pyuria and white cell casts on UA or urine microscopy.


Postrenal AKI is caused by obstruction to the flow of urine, typically from ureteral compression and occasionally from other causes (e.g., stones, papillary necrosis). Pelvic malignancies (e.g., colorectal carcinoma, ovarian or cervical carcinoma, retroperitoneal lymphadenopathy) are relatively common culprits. Generally, unless the patient has preexisting chronic kidney disease (CKD), the obstruction must affect both kidneys in order for changes in sCr to be detected.


Because renal disease can impact all organ systems, a comprehensive history and physical exam should be taken. Special priority should be given to the assessment of urgent or emergent indications for dialysis, such as volume overload (shortness of breath, edema) and clinical uremia (myoclonus or asterixis, pericardial rub) (Table 40.2).

TABLE 40.2 Targeted Medical History and Physical Exam


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Dec 22, 2016 | Posted by in CRITICAL CARE | Comments Off on Acute Kidney Injury and Renal Replacement Therapy
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