Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within seven days, as shown by an increase in serum creatinine or a decrease in urine output, or both.

Causes of AKI are classified as either prerenal (due to decreased blood flow to the kidney), intrinsic renal (due to damage to the kidney itself), or postrenal (due to blockage of urine flow). Prerenal causes of AKI include sepsis, dehydration, excessive blood loss, cardiogenic shock, heart failure, cirrhosis, and certain medications like ACE inhibitors or NSAIDs. Marked increases in the potassium level can lead to abnormal heart rhythms, which can be severe and life-threatening. Fluid balance is frequently affected, though blood pressure can be high, low, or normal.

Pain in the flanks may be encountered in some conditions (such as clotting of the kidneys' blood vessels or inflammation of the kidney). This is the result of stretching of the fibrous tissue capsule surrounding the kidney. If the kidney injury is the result of dehydration, there may be thirst as well as evidence of fluid depletion on physical examination. Certain medication classes such as antibiotics (e.g. amoxicillin/clavulanic acid) and calcineurin inhibitors (e.g., tacrolimus) can also directly damage the tubular cells of the kidney and result in a form of intrinsic AKI.

Postrenal

Postrenal AKI refers to acute kidney injury caused by disease states downstream of the kidney and most often occurs as a consequence of urinary tract obstruction. This may be related to:

  • Benign prostatic hyperplasia
  • Kidney stones
  • Obstructed urinary catheter
  • Bladder stones
  • Cancer of the bladder, ureters, or prostate
  • Damage to the nerves controlling urine flow and bladder function.

Diagnosis

Definition

Introduced by the KDIGO in 2012, specific criteria exist for the diagnosis of AKI.

AKI can be diagnosed if any one of the following is present:

  • Increase in SCr by ≥0.3 mg/dl (≥26.5 μmol/L) within 48 hours; or
  • Increase in SCr to ≥1.5 times baseline, which has occurred within the prior 7 days; or
  • Urine volume < 0.5 mL/kg/h for 6 hours.

Staging

The RIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in assessing the severity of a person's acute kidney injury. The acronym RIFLE is used to define the spectrum of progressive kidney injury seen in AKI:

thumb|Pathophysiology of acute kidney injury in the proximal renal tubule

  • Risk: 1.5-fold increase in serum creatinine, or a glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours.
  • Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine output <0.5 mL/kg per hour for 12 hours.
  • Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours.
  • Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than four weeks.
  • End-stage kidney disease: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than three months.

Evaluation

A measurable decrease in urine output may signal deterioration of kidney function. Often, it is diagnosed based on blood tests for substances normally eliminated by the kidneys: urea and creatinine. Additionally, the ratio of BUN to creatinine is used to evaluate kidney injury. Both tests have their disadvantages. For instance, it takes about 24 hours for the creatinine level to rise, even if both kidneys have ceased to function. Several alternative markers have been proposed (such as NGAL, HAVCR1, IL18, and cystatin C), but none are sufficiently established as of 2018 to replace creatinine as a marker of kidney function.

These may include urine sediment analysis, kidney ultrasound and/or kidney biopsy. Indications for kidney biopsy in the setting of AKI include the following:

  1. Unexplained AKI in a patient with two non-obstructed, normally sized kidneys.
  2. AKI in the presence of the nephritic syndrome.
  3. Systemic disease associated with AKI.
  4. Kidney transplant dysfunction.

In medical imaging, acute changes in the kidney are often examined with renal ultrasonography as the first-line modality, where CT scan and magnetic resonance imaging (MRI) are used for follow-up examinations and when US fails to demonstrate abnormalities. In the evaluation of the acute changes in the kidney, the echogenicity of the renal structures, the delineation of the kidney, the renal vascularity, the kidney size, and focal abnormalities are observed. CT is preferred in renal traumas, but US is used for follow-up, especially in the patients suspected for the formation of urinomas. A CT scan of the abdomen will also demonstrate bladder distension or hydronephrosis.

<gallery widths="200" heights="200">

File:Ultrasonography of acute pyelonephritis.jpg|Renal ultrasonograph of acute pyelonephritis with increased cortical echogenicity and blurred delineation of the upper pole

{| class="wikitable" style="float:right; text-align:center"

|+ Classic laboratory findings in AKI

! Type !! U<sub>Osm</sub> !! U<sub>Na</sub> !! Fe<sub>Na</sub> !! BUN/Cr

|-

| Prerenal || >500 || <10 || <1% ||>20

|-

| Intrinsic || <350 || >20 || >2% || <10-15 Mortality increases by 60-80% in post-cardiopulmonary bypass patients who go on to require renal replacement therapy. Preoperative creatinine greater than 1.2&nbsp;mg/dL, combined valve and bypass procedures, emergency surgery, and preoperative intra-aortic balloon pump are risk factors most strongly correlated with post-cardiopulmonary bypass acute kidney injury. Other well-known minor risk factors include female gender, congestive heart failure, chronic obstructive pulmonary disease, insulin-requiring diabetes, and depressed left ventricular ejection fraction.

Postoperative acute kidney injury is defined as an AKI based on the KDIGO criteria occurring within 7 days of an operative intervention.

Pediatric AKI is defined using the KDIGO definition and the modified neonatal KDIGO criteria for neonates.

Treatment

The management of AKI hinges on identifying the underlying cause and treating it. The main objectives of initial management are to prevent cardiovascular collapse and death and to call for specialist advice from a nephrologist. In addition to treatment of the underlying disorder, management of AKI routinely includes the avoidance of substances that are toxic to the kidneys, called nephrotoxins. These include NSAIDs such as ibuprofen or naproxen, iodinated contrasts such as those used for CT scans, many antibiotics such as gentamicin, and a range of other substances.

Intrinsic

The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to vasculitis or glomerulonephritis may respond to steroid medication, cyclophosphamide, and (in some cases) plasma exchange. Toxin-induced prerenal AKI often responds to discontinuation of the offending agent, such as ACE inhibitors, ARB antagonists, aminoglycosides, penicillins, NSAIDs, or paracetamol. nor with any reduced mortality or length of intensive care unit or hospital stay.

Postrenal

If the cause is obstruction of the urinary tract, relief of the obstruction (with a nephrostomy or urinary catheter) may be necessary.

Renal replacement therapy

Renal replacement therapy, such as with hemodialysis, may be instituted in some cases of AKI. Renal replacement therapy can be applied intermittently (IRRT) and continuously (CRRT). Study results regarding differences in outcomes between IRRT and CRRT are inconsistent. A systematic review of the literature in 2008 demonstrated no difference in outcomes between the use of intermittent hemodialysis and continuous venovenous hemofiltration (CVVH) (a type of continuous hemodialysis). Among critically ill patients, intensive renal replacement therapy with CVVH does not appear to improve outcomes compared to less intensive intermittent hemodialysis. However, other clinical and health economic studies demonstrated that, initiation of CRRT is associated with a lower likelihood of chronic dialysis and was cost-effective compared with IRRT in patients with acute kidney injury.

Complications

Metabolic acidosis, hyperkalemia, and pulmonary edema may require medical treatment with sodium bicarbonate, antihyperkalemic measures, and diuretics.

Lack of improvement with fluid resuscitation, therapy-resistant hyperkalemia, metabolic acidosis, or fluid overload may necessitate artificial support in the form of dialysis or hemofiltration. but the effect of a fluid load is highly variable. Striving toward a predefined urine output target to prevent AKI is futile.

Early recovery of AKI

AKI recovery can be classified into three stages 1–3 based on the inverse of the AKI KDIGO serum creatinine criteria.

Prognosis

Mortality

Mortality after AKI remains high. AKI has a death rate as high as 20%, which may reach up to 50% in the intensive care unit (ICU). Each year, around two million people die of AKI worldwide.

AKI develops in 5% to 30% of patients who undergo cardiothoracic surgery, depending on the definition used for AKI. If AKI develops after major abdominal surgery (13.4% of all people who have undergone major abdominal surgery) the risk of death is markedly increased (over 12-fold).

Kidney function

Depending on the cause, a proportion of patients (5–10%) will never regain full kidney function, thus entering end-stage kidney failure and requiring lifelong dialysis or a kidney transplant. Patients with AKI are more likely to die prematurely after being discharged from the hospital, even if their kidney function has recovered.

Epidemiology

New cases of AKI are unusual but not rare, affecting approximately 0.1% of the UK population per year (2000 ppm/year), 20x incidence of new ESKD (end-stage kidney disease). AKI requiring dialysis (10% of these) is rare (200 ppm/year), 2x incidence of new ESKD.

Hot weather can increase the risk of AKI. For example, there is an increased incidence of AKI in agricultural workers because of occupational hazards such as dehydration and heat illness. No other traditional risk factors, including age, BMI, diabetes, or hypertension, were associated with incident AKI.

Acute kidney injury is common among hospitalized patients. It affects some 3–7% of patients admitted to the hospital and approximately 25–30% of patients in the intensive care unit.

Acute kidney injury was one of the most expensive conditions seen in U.S. hospitals in 2011, with an aggregated cost of nearly $4.7 billion for approximately 498,000 hospital stays. This was a 346% increase in hospitalizations from 1997, when there were 98,000 acute kidney injury stays. According to a review article of 2015, there has been an increase in cases of acute kidney injury in the last 20 years which cannot be explained solely by changes to the manner of reporting.

Clinical investigations have revealed a higher incidence of AKI and associated mortality in males compared to premenopausal women.

History

Before the advancement of modern medicine, acute kidney injury was referred to as uremic poisoning while uremia was contamination of the blood with urine. Starting around 1847, uremia came to be used for reduced urine output, a condition now called oliguria, which was thought to be caused by the urine's mixing with the blood instead of being voided through the urethra.

Acute kidney injury due to acute tubular necrosis (ATN) was recognized in the 1940s in the United Kingdom, where crush injury victims during the London Blitz developed patchy necrosis of kidney tubules, leading to a sudden decrease in kidney function. During the Korean and Vietnam wars, the incidence of AKI decreased due to better acute management and administration of intravenous fluids.

See also

  • BUN-to-creatinine ratio
  • Chronic kidney disease
  • Dialysis
  • Genitourinary tract injury
  • Kidney failure
  • Rhabdomyolysis
  • Contrast-induced nephropathy
  • Ischemia-reperfusion injury of the appendicular musculoskeletal system
  • Kidney Ischemia

References