What is acute kidney injury

Acute kidney injury formerly known as acute renal failure, is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days ¹. Acute kidney injury denotes a sudden and often reversible reduction in the kidney function, as measured by glomerular filtration rate (GFR) ². Acute kidney injury causes a build-up of waste products in your blood and makes it hard for your kidneys to keep the right balance of fluid in your body. Acute kidney injury can also affect other organs such as the brain, heart, and lungs. Acute kidney injury is common in patients who are in the hospital, in intensive care units (ICUs) and especially in older adults.

There is no clear definition of acute kidney injury ¹. Several different criteria have been used in research studies such as RIFLE ³, Acute Kidney Injury Network ⁴ or Kidney Disease: Improving Global Outcomes (KDIGO) criteria ⁵. All these criteria sets enable the diagnosis and staging of acute kidney injury based on changes in the serum creatinine or the urine output ⁶. However, Kidney Disease: Improving Global Outcomes (KDIGO) is the most recent and most commonly used. According to KDIGO, acute kidney injury is the presence of any of the following:

1. Increase in serum creatinine by 0.3 mg/dL or more (26.5 micromoles/L or more) within 48 hours
2. Increase in serum creatinine to 1.5 times or more baseline, within the prior 7 days
3. Urine volume less than 0.5 mL/kg/h for at least 6 hours

Acute kidney injury stages

1. Stage 1 Increased in serum creatinine of ≥ 0.3 mg/dl or increase to 1.5–1.9 × baseline. Urine volume < 0.5 ml/kg/h × 6 h
2. Stage 2 Increase in serum creatinine to 2.0–2.9 × baseline. Urine volume < 0.5 ml/kg/h × 12 h
3. Stage 3 Increase in serum creatinine > 3.0 × baseline or serum creatinine ≥ 4.0 mg/dl or Initiation of renal replacement therapy. Urine volume < 0.3 ml/kg/h × 24 h or anuria x 12 h

The common endpoint in all acute tubular necrosis is a cellular insult either secondary to ischemia or direct toxins which result in effacement of the brush border and eventually cell death thus shutting down the function of tubular cells.

Acute kidney injury is one of the most clinically impactful diseases since it affects patient management to a great extent regarding the treatment options for their primary disease. Most drugs or procedures that use contrast media may need to delay due to co-existent acute kidney injury. Most of the drugs are renally excreted, and dosages might need to be adjusted to account for the reduced renal function. Sometimes, it may even necessitate frequent monitoring of drug levels, for example, Vancomycin. acute kidney injury is thus an important contributor to longer hospital stays and patient morbidity ⁷.

Difference between acute renal failure and chronic renal failure

If you have an acute kidney injury (AKI), you must seek proper treatment and ongoing medical advice. This is because acute kidney injury increases your risk of developing chronic kidney disease (CKD) in the future. It is recommended you have a Kidney Health Check performed by your doctor every year for the first three years following an acute kidney injury.

In common usage, chronic renal failure (chronic renal disease) and chronic kidney disease (CKD) generally mean the same thing. The proper term experts advocate for now is “chronic kidney disease” (CKD). “Failure” is generally reserved for Stage 5 chronic kidney disease (CKD), but the terms are interchangeable.

If you have chronic kidney disease (CKD), you are at an increased risk of acute kidney injury (for example, if you become unwell with a viral infection or become dehydrated). In such cases, damage to your kidneys can happen quickly – in a matter of days. Speak to your doctor immediately if you start to feel unwell or experience any symptoms.

Acute kidney injury stages

There are 4 well-defined stages of acute kidney injury (acute kidney failure): onset, oliguric-anuric, diuretic, and convalescent ⁸. Whether patients go through all 4 and how long each stage lasts depends on the cause of acute renal failure and its severity.

1. Onset phase: Kidney injury occurs.
   1. Features:
      • Common triggering events such as significant blood loss, burns, fluid loss, diabetes insipidus
      • Renal blood flow 25% of normal
      • Tissue oxygenation 25% of normal
      • Urine output below 0.5 ml/kg/hour
   2. Duration:
      • Hours to days
2. Oliguric (anuric) phase: Urine output decreases from renal tubule damage.
   1. Features:
      • Urine output below 400 ml/day, possibly as low as 100 ml/day
      • Increases in blood urea nitrogen (BUN) and creatinine levels
      • Electrolyte disturbances, acidosis and fluid overload (from kidneys inability to excrete water)
   2. Duration:
      • 8 to 14 days or longer, depending on the nature of the acute kidney injury and dialysis initiation
3. Diuretic phase: The kidneys try to heal and urine output increases, but tubule scarring and damage occur.
   1. Features:
      • Occurs when the cause of acute kidney injury is corrected
      • Renal tubules scarring and edema
      • Increased GFR (glomerular filtration rate)
      • Daily urine output above 400 ml
      • Possible electrolyte depletion from excretion of more water and osmotic effects of high blood urea nitrogen (BUN)
   2. Duration:
      • 7 to 14 days
4. Recovery phase: Tubular edema resolves and renal function improves.
   1. Features:
      • Decreased edema
      • Normalization of fluid and electrolyte balance
      • Return of GFR (glomerular filtration rate) to 70% or 80% of normal
   2. Duration:
      • Several months to 1 year.

Acute kidney injury classification system

RIFLE classification system

In 2004, the Acute Dialysis Quality Initiative work group set forth a definition and classification system for acute renal failure, described by the acronym RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease) ⁹. Investigators have since applied the RIFLE system to the clinical evaluation of AKI, although it was not originally intended for that purpose. AKI research increasingly uses RIFLE. See Table 1, below.

Table 1. RIFLE Classification System for Acute Kidney Injury (AKI)

Stage	GFR** Criteria	Urine Output Criteria	Probability
Risk	Serum creatinine increased × 1.5 or GFR decreased >25%	Urine output< 0.5 mL/kg/hour × 6 hour	High sensitivity (Risk >Injury >Failure)
Injury	Serum creatinine increased × 2 or GFR decreased >50%	Urine output < 0.5 mL/kg/hour × 12 hour
Failure	Serum creatinine increased × 3 or GFR decreased 75% or Serum creatinine ≥4 mg/dL; acute rise ≥0.5 mg/dL	Urine output < 0.3 mL/kg/hour × 24 hour (oliguria) or anuria × 12 hour
Loss	Persistent acute renal failure: complete loss of kidney function >4 week		High specificity
End-stage kidney disease	Complete loss of kidney function >3 months

Footnote: Patients can be classified by GFR criteria and/or urine output criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in serum creatinine is less than 3-fold, provided that the new serum creatinine is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L). When the failure classification is achieved by urine output criteria, the designation of RIFLE-FO is used to denote oliguria.

[Source ⁹ ]

Acute Kidney Injury Network (AKIN) classification system

The Acute Kidney Injury Network (AKIN) has proposed a staging system for AKI that is modified from RIFLE ¹⁰. In this system, either serum creatinine or urine output criteria can be used to determine stage. See Table 2, below.

Table 2. Acute Kidney Injury Network Classification/Staging System for Acute Kidney Injury (AKI)

Stage	Serum Creatinine Criteria	Urine Output Criteria
1	Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline	< 0.5 mL/kg/hour for >6 hour
2	>2-fold to 3-fold increase from baseline	< 0.5 mL/kg/hour for >12 hour
3*	>3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)	< 0.3 mL/kg/hour for 24 h or anuria for 12 hour

Footnote: *Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of renal replacement therapy (RRT).

[Source ¹⁰ ]

What causes acute kidney injury

The cause of acute kidney injury has always been traditionally divided into three categories: pre-renal, renal and post-renal. Each of these categories has several different causes associated with them ¹¹.

• Pre-renal acute kidney injury includes any reduced blood flow to the kidney. This may be part of a systemic hypoperfusion resulting from hypovolemia or hypotension; or may be due to selective hypoperfusion to the kidneys such as those resulting from renal artery stenosis, aortic dissection.
• Renal acute kidney injury includes acute tubular necrosis which can result from several different causes. Prolonged renal ischemia, sepsis, and nephrotoxins being the most common ones. It is worthwhile mentioning that pre-renal injury can convert into renal injury if the exposure to offending factor is prolonged enough to cause cellular damage.
• Post-renal acute kidney injury mainly includes obstructive causes which lead to congestion of the filtration system and thus eventually lead to shutting down of the kidneys. The most common ones being renal/ureteral calculi, tumors or any urethral obstruction. Another noteworthy fact is that a unilateral obstruction may not always present as acute kidney injury especially if the obstruction is gradual such as a tumor because a normal working contralateral kidney may be able to compensate for the function of the affected kidney. Therefore, the most common cause of post-renal acute kidney injury is bladder outlet obstruction.

Impaired blood flow to the kidneys

Some diseases and conditions can slow blood flow to your kidneys and cause acute kidney injury.

These diseases and conditions include:

• Low blood pressure (called “hypotension”) or shock
• Blood or fluid loss (such as bleeding, severe diarrhea)
• Heart attack, heart failure, and other conditions leading to decreased heart function
• Organ failure (e.g., heart failure, liver failure)
• Overuse of pain medicines called “NSAIDs”, which are used to reduce swelling or relieve pain from headaches, colds, flu, and other ailments. Examples include ibuprofen, ketoprofen, and naproxen.
• Impaired blood flow to the kidneys
• Severe allergic reaction (anaphylaxis)
• Injury
• Infection
• Liver failure
• Major surgery
• Severe burns
• Severe dehydration

Direct Damage to the kidneys

Some disease and conditions can damage your kidneys and lead to acute kidney injury. Some examples include:

• A type of severe, life-threatening infection called “sepsis”
• A type of cancer called “multiple myeloma”
• A rare condition that causes inflammation and scarring to your blood vessels, making them stiff, weak, and narrow (called “vasculitis”)
• An allergic reaction to certain types of drugs (called “interstitial nephritis”)
• A group of diseases (called “scleroderma”) that affect the connective tissue that supports your internal organs
• Conditions that cause inflammation or damage to the kidney tubules, to the small blood vessels in the kidneys, or to the filtering units in the kidneys (such as “tubular necrosis,” “glomerulonephritis, “vasculitis” or “thrombotic microangiopathy”).
• Blood clots in the veins and arteries in and around the kidneys
• Cholesterol deposits that block blood flow in the kidneys
• Glomerulonephritis, inflammation of the tiny filters in the kidneys (glomeruli)
• Hemolytic uremic syndrome, a condition that results from premature destruction of red blood cells
• Infection
• Lupus, an immune system disorder causing glomerulonephritis
• Medications, such as certain chemotherapy drugs, antibiotics and dyes used during imaging tests
• Thrombotic thrombocytopenic purpura, a rare blood disorder
• Toxins, such as alcohol, heavy metals and cocaine
• Muscle tissue breakdown (rhabdomyolysis) that leads to kidney damage caused by toxins from muscle tissue destruction
• Breakdown of tumor cells (tumor lysis syndrome), which leads to the release of toxins that can cause kidney injury

Blockage of the urinary tract

In some people, conditions or diseases can block the passage of urine out of the body and can lead to acute kidney injury.

Blockage can be caused by:

• Bladder, prostate, or cervical cancer
• Enlarged prostate
• Problems with the nervous system that affect the bladder and urination
• Kidney stones
• Blood clots in the urinary tract

Risk factors for acute kidney injury

Acute kidney failure almost always occurs in connection with another medical condition or event. Conditions that can increase your risk of acute kidney injury include:

• Being hospitalized, especially for a serious condition that requires intensive care
• Advanced age
• Blockages in the blood vessels in your arms or legs (peripheral artery disease)
• Diabetes
• High blood pressure
• Heart failure
• Kidney diseases
• Liver diseases
• Certain cancers and their treatments

Pathophysiology of acute renal failure

The driving force for glomerular filtration is the pressure gradient from the glomerulus to the Bowman space. Glomerular pressure depends primarily on renal blood flow and is controlled by the combined resistances of renal afferent and efferent arterioles. Regardless of the cause of AKI, reductions in renal blood flow represent a common pathologic pathway for decreasing glomerular filtration rate (GFR). The cause of AKI consists of 3 main mechanisms: prerenal, intrinsic, and obstructive.

In prerenal failure, GFR is depressed by compromised renal perfusion. Tubular and glomerular function remain normal.

Intrinsic renal failure includes diseases of the kidney itself, predominantly affecting the glomerulus or tubule, which are associated with the release of renal afferent vasoconstrictors. Ischemic renal injury is the most common cause of intrinsic renal failure. Patients with chronic kidney disease may also present with superimposed AKI from prerenal failure and obstruction, as well as intrinsic renal disease.

Obstruction of the urinary tract initially causes an increase in tubular pressure, which decreases the filtration driving force. This pressure gradient soon equalizes, and maintenance of a depressed GFR then depends on renal efferent vasoconstriction.

Depressed renal blood flow

Depressed renal blood flow eventually leads to ischemia and cell death. This may happen before frank systemic hypotension is present and is referred to as normotensive ischemic AKI. The initial ischemic insult triggers a cascade of events, including production of oxygen free radicals, cytokines and enzymes; endothelial activation and leukocyte adhesion; activation of coagulation; and initiation of apoptosis. These events continue to cause cell injury even after restoration of renal blood flow.

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 renal blood flow, the kidneys are particularly vulnerable to further insults; this is when iatrogenic renal injury is most common. The following are common combinations:

• Radiocontrast agents, aminoglycosides, or cardiovascular surgery with preexisting renal disease (eg, elderly, diabetic, jaundiced patients)
• Angiotensin-converting enzyme (ACE) inhibitors with diuretics, small- or large-vessel renal arterial disease
• Non-steroidal anti-inflammatory drugs (NSAIDs) with chronic heart failure, hypertension, or renal artery stenosis

Acute tubular necrosis

Frank necrosis is not prominent in most human cases of acute tubular necrosis and tends to be patchy. Less obvious injuries include the following:

• Loss of brush borders
• Flattening of the epithelium
• Detachment of cells
• Formation of intratubular casts
• Dilatation of the lumen

Although these changes are observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated. In addition, the distal nephron may become obstructed by desquamated cells and cellular debris.

Apoptosis

In contrast to necrosis, the principal site of apoptotic cell death is the distal nephron. During the initial phase of ischemic injury, loss of integrity of the actin cytoskeleton leads to flattening of the epithelium, with loss of the brush border, loss of focal cell contacts, and subsequent disengagement of the cell from the underlying substratum.

Inflammatory response

Many endogenous growth factors that participate in the process of regeneration following ischemic renal injury have not been identified. However, administration of growth factors exogenously has been shown to ameliorate and hasten recovery from AKI.

Depletion of neutrophils and blockage of neutrophil adhesion reduce renal injury following ischemia, indicating that the inflammatory response is responsible, in part, for some features of acute tubular necrosis, especially in postischemic injury after transplant.

Vasoconstriction

Intrarenal vasoconstriction is the dominant mechanism for reduced GFR in patients with acute tubular necrosis. The mediators of this vasoconstriction are unknown, but tubular injury seems to be an important concomitant finding. Urine backflow and intratubular obstruction (from sloughed cells and debris) are causes of reduced net ultrafiltration. The importance of this mechanism is highlighted by the improvement in renal function that follows relief of such intratubular obstruction.

In addition, when obstruction is prolonged, intrarenal vasoconstriction is prominent in part due to the tubuloglomerular feedback mechanism, which is thought to be mediated by adenosine and activated when there is proximal tubular damage and the macula densa is presented with increased chloride load.

Apart from the increase in basal renal vascular tone, the stressed renal microvasculature is more sensitive to potentially vasoconstrictive drugs and otherwise-tolerated changes in systemic blood pressure. The vasculature of the injured kidney has an impaired vasodilatory response and loses its autoregulatory behavior.

This latter phenomenon has important clinical relevance because the frequent reduction in systemic pressure during intermittent hemodialysis may provoke additional damage that can delay recovery from acute tubular necrosis. Often, injury results in atubular glomeruli, where the glomerular function is preserved, but the lack of tubular outflow precludes its function.

Isosthenuria

A physiologic hallmark of acute tubular necrosis is a failure to maximally dilute or concentrate urine (isosthenuria). This defect is not responsive to pharmacologic doses of vasopressin. The injured kidney fails to generate and maintain a high medullary solute gradient, because the accumulation of solute in the medulla depends on normal distal nephron function.

Failure to excrete concentrated urine even in the presence of oliguria is a helpful diagnostic clue in distinguishing prerenal from intrinsic renal disease. In prerenal azotemia, urine osmolality is typically more than 500 mOsm/kg, whereas in intrinsic renal disease, urine osmolality is less than 300 mOsm/kg.

Restoration of renal blood flow and associated complications

Recovery from AKI is first dependent upon restoration of renal blood flow. Early renal blood flow 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 renal blood flow is restored, the remaining functional nephrons increase their filtration and eventually undergo hypertrophy. GFR recovery depends on the size of this remnant nephron pool. If the number of remaining nephrons is below a critical threshold, 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 AKI.

Acute kidney injury prevention

Acute kidney failure is often difficult to predict or prevent. But you may reduce your risk by taking care of your kidneys. Try to:

• Pay attention to labels when taking over-the-counter (OTC) pain medications. Follow the instructions for OTC pain medications, such as aspirin, acetaminophen (Tylenol, others), ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others). Taking too much of these medications may increase your risk of kidney injury. This is especially true if you have pre-existing kidney disease, diabetes or high blood pressure.
• Work with your doctor to manage kidney and other chronic conditions. If you have kidney disease or another condition that increases your risk of acute kidney failure, such as diabetes or high blood pressure, stay on track with treatment goals and follow your doctor’s recommendations to manage your condition.
• Make a healthy lifestyle a priority. Be active; eat a sensible, balanced diet; and drink alcohol only in moderation — if at all.

Acute kidney injury signs and symptoms

Signs and symptoms of acute kidney injury (AKI) differ depending on the cause and may include:

• Too little urine leaving your body (a decreased output of urine), although occasionally urine output remains normal
• Swelling in your legs, ankles, and around your eyes due to a build-up of fluid in your body
• Fatigue or tiredness
• Shortness of breath
• Confusion
• Nausea
• Irregular heartbeat
• Chest pain or pressure
• A sharp increase of creatinine and other toxins in your blood
• Seizures or coma in severe cases.

In some cases, acute kidney failure causes no symptoms and is only found through other tests done by your doctor. So it’s important to see your doctor for a Kidney Health Check if you become unwell.

See your doctor immediately or seek emergency care if you have signs or symptoms of acute kidney failure.

Acute kidney injury complications

Several complications may associate AKI with mortality. Some of these complications are directly associated with acute kidney injury and can easily be gauged (hyperkalemia [high blood potassium], volume overload, metabolic acidosis, hyponatremia [low blood sodium]); however, the effect of other complications on AKI-related mortality, such as inflammation and infection, is difficult to assess. Most common complications include metabolic derangements such as:

• Hyperkalemia (high blood potassium)– If severe, it can lead to arrhythmias because of which renal replacement therapy is required in cases of severe hyperkalemia.
• Metabolic acidosis– The kidney’s inability to excrete acids leads to metabolic acidosis and may necessitate systemic administration of bicarbonate or citrate buffers.
• Hyperphosphatemia (elevated level of phosphate in your blood)– can usually be prevented by decreasing dietary ingestion or using phosphate binders.
• Other effects include pulmonary edema from volume overload, peripheral edema from an inability to excrete body water. This is especially common in the low urine output (oliguric) phase of acute tubular necrosis. It may necessitate the use of diuretics or renal replacement therapy.

The other organ-related complications include:

• Cardiovascular – Heart failure secondary to fluid overload is attributable to oliguric AKI, arrhythmias secondary to acidotic state and electrolyte abnormalities, cardiac arrest due to metabolic derangements, and myocardial infarction (heart attack), and rarely pericarditis.
• Gastrointestinal (GI) – Nausea, vomiting, GI bleeding, and anorexia. A mildly raised level of amylase is commonly found in patients suffering from AKI. Elevation of amylase concentration can make the diagnosis of pancreatitis difficult, therefore measuring lipase, which is not raised in AKI, is necessary to establish AKI diagnosis.
• Neurologic – central nervous system (CNS)-related signs of uremic burden are common in AKI, and they include lethargy, somnolence, disturbed sleep-wake cycle, and cognitive impairment.
• Chest pain. If the lining that covers your heart (pericardium) becomes inflamed (pericarditis), you may experience chest pain.
• Muscle weakness. When your body’s fluids and electrolytes — your body’s blood chemistry — are out of balance, muscle weakness can result.
• Permanent kidney damage. Occasionally, acute kidney failure causes permanent loss of kidney function, or end-stage renal disease. People with end-stage renal disease require either permanent dialysis — a mechanical filtration process used to remove toxins and wastes from the body — or a kidney transplant to survive.
• Death. Acute kidney failure can lead to loss of kidney function and, ultimately, death.

Acute kidney injury diagnosis

Depending on the cause of your acute kidney injury, your healthcare provider will run different tests if he or she suspects that you may have acute kidney injury. It is important that acute kidney injury is found as soon as possible because it can lead to chronic kidney disease, or even kidney failure. It may also lead to heart disease or death.

The following tests may be done:

• Measuring urine output: Your healthcare provider will track how much urine you pass each day to help find the cause of your acute kidney injury.
• Urine tests: Your healthcare provider will look at your urine (urinalysis) to find signs of kidney failure
• Blood tests: Blood tests will help find levels of creatinine, urea nitrogen phosphorus and potassium should be done in addition to blood tests for protein in order to look at kidney function.
• GFR (glomerular filtration rate): Your blood test will also help find your GFR (glomerular filtration rate) to estimate the decrease in kidney function
• Imaging tests: Imaging tests, such as ultrasound, may help your doctor see your kidneys and look for anything abnormal.
• Kidney biopsy: In some situations, your healthcare provider will do a procedure where a tiny piece of your kidney is removed with a special needle, and looked at under a microscope.

Acute kidney injury treatment

Treatment for acute kidney injury involves identifying the illness or injury that originally damaged your kidneys. Your treatment options depend on what’s causing your acute kidney injury. Treatment for acute kidney injury usually requires you to stay in a hospital. Most people with acute kidney injury are already in the hospital for another reason. How long you will stay in the hospital depends on the cause of your acute kidney injury and how quickly your kidneys recover. In more serious cases, dialysis may be needed to help replace kidney function until your kidneys recover. The main goal of your healthcare provider is to treat what is causing your acute kidney injury. Your healthcare provider will work to treat all of your symptoms and complications until your kidneys recover.

With the exception of post-renal acute kidney injury, most cases are an overlap between pre-renal and acute tubular necrosis type of acute kidney injury ¹². The best way to determine if the acute kidney injury is pre-renal or not is a fluid challenge. If the clinical scenario doesn’t contradict it, all patients with acute renal dysfunction should receive a fluid challenge. They require close monitoring of the urine output and renal function. If the renal function improves with fluid, that is the best indicator of a pre-renal acute kidney injury. Acute tubular necrosis is very slow to recover and can take weeks to months for complete recovery of renal function. It may not normalize at all sometimes. Another important thing to consider for these patients is to avoid any further insult to the kidneys such as nephrotoxic drugs. Any and all medications need to be renally dosed once a patient develops acute kidney injury. Sometimes, acute kidney injury may need short-term renal replacement therapy till the kidney function recovers. This is seen especially in the oliguric phase of acute tubular necrosis, where the patient is prone to develop multiple electrolyte and acid-base abnormalities as well as fluid overload ¹³.

Treatments that help prevent complications include:

• Treatments to balance the amount of fluids in your blood. If your acute kidney failure is caused by a lack of fluids in your blood, your doctor may recommend intravenous (IV) fluids. In other cases, acute kidney failure may cause you to have too much fluid, leading to swelling in your arms and legs. In these cases, your doctor may recommend medications (diuretics) to cause your body to expel extra fluids.
• Medications to control blood potassium. If your kidneys aren’t properly filtering potassium from your blood, your doctor may prescribe calcium, glucose or sodium polystyrene sulfonate (Kionex) to prevent the accumulation of high levels of potassium in your blood. Too much potassium in the blood can cause dangerous irregular heartbeats (arrhythmias) and muscle weakness.
• Medications to restore blood calcium levels. If the levels of calcium in your blood drop too low, your doctor may recommend an infusion of calcium.
• Dialysis to remove toxins from your blood. If toxins build up in your blood, you may need temporary hemodialysis — often referred to simply as dialysis — to help remove toxins and excess fluids from your body while your kidneys heal. Dialysis may also help remove excess potassium from your body. During dialysis, a machine pumps blood out of your body through an artificial kidney (dialyzer) that filters out waste. The blood is then returned to your body.

After having acute kidney injury, your chances are higher for other health problems (such as kidney disease, stroke, heart disease) or having acute kidney injury again in the future. The chances for developing kidney disease and kidney failure increase every time acute kidney injury occurs. To protect yourself, you should follow up with your healthcare provider to keep track of your kidney function and recovery. The best ways to lower your chances of having kidney damage and to save kidney function are to prevent acute kidney injury or to find and treat it as early as possible.

Acute kidney injury diet

During your recovery from acute kidney injury, your doctor may recommend a special diet to help support your kidneys and limit the work they must do. Your doctor may refer you to a dietitian who can analyze your current diet and suggest ways to make your diet easier on your kidneys.

Depending on your situation, your dietitian may recommend that you:

• Choose lower potassium foods. Your dietitian may recommend that you choose lower potassium foods. High-potassium foods include bananas, oranges, potatoes, spinach and tomatoes. Examples of low-potassium foods include apples, cauliflower, peppers, grapes and strawberries.
• Avoid products with added salt. Lower the amount of sodium you eat each day by avoiding products with added salt, including many convenience foods, such as frozen dinners, canned soups and fast foods. Other foods with added salt include salty snack foods, canned vegetables, and processed meats and cheeses.
• Limit phosphorus. Phosphorus is a mineral found in foods, such as whole-grain bread, oatmeal, bran cereals, dark-colored colas, nuts and peanut butter. Too much phosphorus in your blood can weaken your bones and cause skin itchiness. Your dietitian can give you specific recommendations on phosphorus and how to limit it in your particular situation.

As your kidneys recover, you may no longer need to eat a special diet, although healthy eating remains important.

Acute kidney injury prognosis

Most acute kidney injury cases recover entirely with supportive management; however, the prognosis mostly depends on the cause of AKI and the presence or absence of antecedent kidney disease or declined estimated glomerular filtration rate (eGFR). Most pre-renal AKI cases recover completely with correction of the underlying insult if caught early; however, the persistence of underlying insult may lead to acute tubular necrosis, in which case the damage may not be completely reversible ¹⁴. The other consideration to keep in mind is that although recovery from individual episodes may be complete or partial, repeated AKI can lead to a cumulative worsening of renal function. Therefore, it is essential to follow these patients either to the normalization of renal function or until it can be decided that this will be their new baseline renal function. The in-hospital mortality rate for AKI is 40-50%, and the mortality for ICU patients is more than 50%. Other prognostic factors include ¹⁴:

• Older age
• Duration of illness
• Fluid balance
• Diuretic use
• The decline in urine output
• Hypotension
• Inotropic support
• Multiorgan involvement
• Sepsis
• Number of transfusions.

It is now known that survivors of AKI do not universally have a benign course. Over the long term (1-10 years), at least 12-15% of patients with acute kidney injury may require permanent dialysis; rates range widely, from 1-64%, depending on the patient population ¹⁵. From 19-31% of survivors experience partial recovery of kidney function and have chronic kidney disease ¹⁶. Mortality is increased in patients with high APACHE lll score, advanced age and persistent elevation of creatinine ¹⁷.

In a long-term follow-up study of 350 patients from the randomized RENAL trial who survived AKI in the intensive care unit, researchers found that the overall mortality rate was 62% at a median of 42.4 months after randomization ¹⁸. Median survival did not significantly differ between patients who received high- or low-intensity renal replacement therapy. At follow-up, 42.1% of the surviving patients had microalbuminuria or macroalbuminuria. Only 5.4% of the patients surviving at day 90 required maintenance dialysis. Predictors of long-term mortality included age, APACHE III score, and serum creatinine levels at baseline ¹⁸.

References

1. Goyal A, Bashir K. Acute Kidney Injury (Acute Renal Failure) [Updated 2019 Apr 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441896
2. Muroya Y, He X, Fan L, Wang S, Xu R, Fan F, Roman RJ. Enhanced renal ischemia-reperfusion injury in aging and diabetes. Am. J. Physiol. Renal Physiol. 2018 Dec 01;315(6):F1843-F1854
3. 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. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup. Crit Care. 2004 Aug; 8(4):R204-12.
4. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network. Crit Care. 2007; 11(2):R31.
5. Kidney Disease Outcomes Quality Initiative KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1–138. doi: 10.1038/kisup.2012.1
6. Doi K, Nishida O, Shigematsu T, et al. The Japanese clinical practice guideline for acute kidney injury 2016. Clin Exp Nephrol. 2018;22(5):985–1045. doi:10.1007/s10157-018-1600-4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154171
7. Winther-Jensen M, Kjaergaard J, Lassen JF, Køber L, Torp-Pedersen C, Hansen SM, Lippert F, Kragholm K, Christensen EF, Hassager C. Use of renal replacement therapy after out-of-hospital cardiac arrest in Denmark 2005-2013. Scand. Cardiovasc. J. 2018 Oct;52(5):238-243
8. Acute Renal Failure. https://www.medscape.com/viewarticle/414667_1
9. Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L., Palevsky, P., & Acute Dialysis Quality Initiative workgroup (2004). 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. Critical care (London, England), 8(4), R204–R212. https://doi.org/10.1186/cc2872
10. Mehta, R. L., Kellum, J. A., Shah, S. V., Molitoris, B. A., Ronco, C., Warnock, D. G., Levin, A., & Acute Kidney Injury Network (2007). Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Critical care (London, England), 11(2), R31. https://doi.org/10.1186/cc5713
11. Moresco RN, Bochi GV, Stein CS, De Carvalho JAM, Cembranel BM, Bollick YS. Urinary kidney injury molecule-1 in renal disease. Clin. Chim. Acta. 2018 Dec;487:15-21.
12. Azzalini L, Vilca LM, Lombardo F, Poletti E, Laricchia A, Beneduce A, Maccagni D, Demir OM, Slavich M, Giannini F, Carlino M, Margonato A, Cappelletti A, Colombo A. Incidence of contrast-induced acute kidney injury in a large cohort of all-comers undergoing percutaneous coronary intervention: Comparison of five contrast media. Int. J. Cardiol. 2018 Dec 15;273:69-73
13. Cahn A, Melzer-Cohen C, Pollack R, Chodick G, Shalev V. Acute renal outcomes with sodium-glucose co-transporter-2 inhibitors: Real-world data analysis. Diabetes Obes Metab. 2019 Feb;21(2):340-348
14. Goyal A, Daneshpajouhnejad P, Hashmi MF, et al. Acute Kidney Injury. [Updated 2021 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441896
15. Acute Kidney Injury. https://emedicine.medscape.com/article/243492-overview#a7
16. Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019 Nov 23. 394 (10212):1949-1964.
17. Huang ST, Ke TY, Chuang YW, Lin CL, Kao CH. Renal complications and subsequent mortality in acute critically ill patients without pre-existing renal disease. CMAJ. 2018 Sep 10;190(36):E1070-E1080.
18. Gallagher M, Cass A, Bellomo R, Finfer S, Gattas D, Lee J, et al. Long-term survival and dialysis dependency following acute kidney injury in intensive care: extended follow-up of a randomized controlled trial. PLoS Med. 2014 Feb. 11(2):e1001601.