Next Lesson - Chronic Kidney Disease
Core
Acute kidney injury (AKI) is a clinical syndrome where there is an acute decline in the actual glomerular filtration rate (GFR). This results in an upset of extracellular fluid volume, electrolyte and acid-base homeostasis as well as the accumulation of nitrogenous waste. Acute kidney injury can be split into pre-renal, intrinsic and post-renal causes of renal failure.
- If a decline in GFR persists for between 7 days and 3 months, then it is defined as acute kidney disease, but if the decline in GFR remains after 3 months then it is defined as chronic kidney disease.
- Around 15% of patients in hospital will have an AKI (source), with the percentage increasing the sicker patients get.
AKI is clinically defined as:
- An increase in serum creatinine by ≥ 26.5μmol/L within 48 hours,
- An increase in serum creatinine by ≥ 1.5x baseline levels within 7 days, or
- Urine output of < 0.5ml/kg/hour for 6 hours
AKI can then be staged using the creatinine and urine output:
- Stage 1 - 1.5-1.9x baseline creatinine levels or urine output ≤ 0.5ml/kg/hour for > 6 hours.
- Stage 2 - 2-3x baseline creatinine levels or urine output ≤ 0.5ml/kg/hour for > 12 hours.
- Stage 3 - 3x baseline creatinine, creatinine > 354μmol/L, the patient is commenced on renal replacement therapy, urine output ≤ 0.3ml/kg/hour for > 24 hours, or anuria for 12 hours.
The raised serum creatinine is associated with worsening mortality.
The patient’s urine output is used to help define the stage as well as the cause of the AKI. There are three main descriptions of urine output that are used:
- Oliguria - where the patient produces a reduced volume of urine. It is defined as < 500ml of urine per day or < 20ml per hour.
- Anuria - where the patient produces a very reduced volume of urine. It is defined as < 100ml of urine per day. This usually indicates blockage of urine flow or very severe damage to the kidneys.
- Non-oliguria - where the patient produces a normal volume of urine (800 to 2000mls per day).
The symptoms of renal failure are quite generic but patients will typically present with reduced urine output. Other symptoms of renal failure include:
- Fluid retention and oedema
- Fatigue
- Loss of appetite
- Nausea
- Vomiting
- Shortness of breath
- Confusion
Pre-renal failure results from decreased renal perfusion leading to a reduction in the glomerular filtration rate. This causes acute kidney injury as there is reduced flow to the kidneys which decreases the filtration of blood and decreases urine output. The kidneys are not yet impaired in pre-renal failure, they are just unable to maintain adequate blood flow and so, they will often respond to careful fluid resuscitation (giving the patient intravenous fluids), provided the patient is hypovolaemic and does not have contraindications such as fluid overload or decompensated heart failure. This will increase the blood volume and therefore increase blood flow to the kidney.
In pre-renal AKI, the kidneys are unable to maintain the GFR as there is reduced blood flow to the kidneys, so they work to restore the blood flow and raise the filtration rate back to normal through a variety of mechanisms. The kidneys act as if the body was in hypovolaemia, and so they increase the reabsorption of salt and water through the activation of the renin-angiotensin-aldosterone system and anti-diuretic hormone release. This leads to urine becoming more concentrated with low sodium, as the body reabsorbs sodium and water. This factor can help to distinguish pre-renal failure from other causes of AKI.
With ageing, the body’s ability to maintain normal kidney perfusion decreases meaning it is unable to respond appropriately to changes in blood pressure. This is important as it explains why elderly patients are more susceptible to the pre-renal causes of AKI as the body is unable to appropriately adapt to changes in kidney perfusion.
Causes of pre-renal failure include:
- Hypovolaemia
- Hypotension
- Renal artery occlusion
- Cardiac failure
- Systemic vasodilation - causes include sepsis, cirrhosis and anaphylaxis.
- Impaired renal autoregulation - this can be caused by ACE inhibitors, angiotensin receptor blockers and NSAIDs.
- ACE inhibitors and angiotensin receptor blockers prevent vasoconstriction of the efferent arteriole and so prevent the kidney from increasing the glomerular capillary pressure. This stops the kidney from increasing the GFR.
- NSAIDs inhibit vasodilation of the afferent arteriole by preventing the production of prostaglandins which act to vasodilate the afferent arteriole to increase glomerular capillary pressure and the GFR.
Pre-renal failure can be distinguished from other types of acute kidney disease by the response to a fluid challenge. This involves giving the patient intravenous fluids to increase the perfusion to the kidney, which will cause an improvement in renal function in patients with pre-renal failure. Patients with other types of AKI will not respond as well.
Acute tubular injury (ATN) is the most common acute kidney injury that causes intrinsic renal failure (where the pathology lies within the kidney itself). Although it is called acute tubular necrosis, there is typically minimal necrosis to the kidney tubules. ATN is commonly seen in hospital and is associated with a high morbidity and mortality so needs to be identified quickly.
In ATN there is damage to the tubule cells of the nephron that is either reversible or irreversible. It is caused by ischaemia, nephrotoxins or sepsis, often being a combination of two or more of these. The damaged cells are unable to reabsorb salt and water effectively because of this damage, and this factor can help to determine whether a patient has a pre-renal AKI or if they have ATN.
There are three phases in ATN: initiation, maintenance and recovery. In the initiation phase, there is a decrease in the glomerular filtration rate (i.e. the patient develops AKI), which continues in the maintenance phase where the reduction in GFR persists, often for days to weeks, depending on the severity and cause. The recovery phase is characterised by the return of normal tubular function with urine output returning to pre-ATN levels.
Ischaemic causes of ATN are very similar to pre-renal causes of AKI, as they reduce the blood flow to the kidney and cause ischaemia. Some examples include hypovolaemia (e.g. dehydration, haemorrhage, diuretics), heart failure (oedema can reduce renal perfusion) and anaphylaxis.
In sepsis, systemic vasodilation and the release of toxins occur which together cause ATN. Both damage the kidneys either by direct damage to the tubule cells or by causing ischaemia of these tubule cells.
Nephrotoxins damage the tubule cells to cause cell injury and cell death. The risk of acute tubular necrosis is increased if there is decreased perfusion to the kidney alongside the nephrotoxic damage. Nephrotoxins can either be endogenous or exogenous. Endogenous nephrotoxins include urate, bilirubin and myoglobin (high levels of myoglobin released in rhabdomyolysis is a well-known cause of ATN). Exogenous nephrotoxins include aminoglycosides, radiographic contrast media, cisplatin, acyclovir and calcineurin inhibitors.
Recovery from acute tubular necrosis can take several weeks and the treatment is mainly supportive, via maintaining kidney perfusion, avoiding nephrotoxins and treating any identifiable cause.
Pre-Renal Acute Kidney Injury vs Acute Tubular Necrosis
Pre-renal AKI and acute tubular necrosis can present very similarly, but there are some key differences that can help to differentiate them from each other, particularly the urine osmolality and urinary sodium levels, although these are not always reliable in isolation. Pre-renal AKI has a high urinary osmolality and a low urinary sodium whereas ATN has a low urine osmolality and a high urinary sodium. Pre-renal AKI has a low urinary sodium as the body tries to retain sodium to increase the blood pressure and so there is an increased reabsorption of sodium. In ATN, the damaged tubule cells cannot reabsorb sodium so it is lost in the urine.
Table - The differences between pre-renal AKI and ATN. This can be used to determine if a patient has pre-renal AKI or if they have ATN
SimpleMed original by Dr. Thomas Burnell
Intrinsic renal failure is an AKI where something damages the glomerulus or the tubule causing tissue injury and so decreases the glomerular filtration rate. Some examples of intrinsic AKI causes include glomerulonephropathies (e.g. IgA glomerulonephritis), nephrotoxins, renal ischaemia, systemic lupus erythematosus and infection.
With intrinsic renal failure, there is damage to the cells lining the nephron leading to a decrease in the reabsorption of substances from the filtrate. This means the urine is similar to the urine seen in acute tubular necrosis, with a high urine sodium and a low urine osmolality as the kidneys lose the ability to concentrate the urine.
Acute interstitial nephritis is acute immune-mediated inflammation of the renal tubule interstitium. It presents similar to other causes of acute renal failure and so acute interstitial nephritis can be difficult to distinguish from other causes of AKI. If a patient is thought to have acute interstitial nephritis then it is important to identify potential causes and manage them appropriately, such as removing any offending nephrotoxic medication.
Acute interstitial nephritis is caused by:
- Medications - examples include penicillin, proton pump inhibitors, NSAIDs and furosemide.
- Infections - examples include acute bacterial pyelonephritis, renal tuberculosis and fungal nephritis.
- Autoimmune Diseases - examples include systemic lupus erythematosus, granulomatosis with polyangiitis and Sjögren’s syndrome.
Post-renal failure is AKI caused by obstruction downstream of the kidneys, either of the ureter or urethra. An obstruction leads to a build-up of back pressure within the urinary tract that extends to the kidneys which causes damage to them and prevents the removal of waste products and excess water from the body.
For post-renal failure to cause acute kidney injury, it must either block both kidneys or block one kidney in a patient who has a single functioning kidney.
Some causes of post-renal AKI include benign prostatic hyperplasia, renal stones, urethral obstruction, blood clots in the urinary tract and urological malignancy.
For more information about the causes of obstruction in the urinary tract, check out our article on urinary obstruction.
The main investigations that must be done to identify the cause of acute kidney injury include testing the urine (e.g. urinalysis and urine microscopy), imaging (e.g. ultrasound scan and chest x-ray) and blood tests (e.g. urea and electrolytes, arterial blood gas and calcium levels).
Urine Testing
Patients identified as having an AKI must undergo urinalysis to help determine the underlying cause. Urine microscopy can also help, particularly if the initial dipstick is positive, as this can suggest an infection or a glomerulonephropathy, and microscopy can help identify what else is present in the urine.
Urinalysis (either formal analysis in a hospital or a dipstick ) will test for the presence of blood, protein and leukocytes, and this will help in determining the underlying cause of the AKI. For example, if there is a large concentration of protein and blood on the dipstick, then an intrinsic renal disease is more likely.
Imaging
The role of imaging in investigating AKI is to identify an obstruction if a post-renal failure is suspected. An ultrasound scan can be used to identify either an obstruction or the complications of an obstruction such as hydronephrosis or dilated ureters. If an ultrasound scan cannot find the obstruction then a CT scan or MRI can be performed if an obstruction is still suspected. A chest x-ray can also be performed to look for pulmonary oedema if a patient with AKI presents with shortness of breath.
Blood Tests
The patient’s serum biochemistry is used to identify, stage and look for any complications of AKI. The main results to pay attention to on a patient’s blood test are the concentrations of urea, creatinine, calcium, potassium, sodium and phosphate. In AKI there is typically hyperkalaemia, hyponatraemia, hypocalcaemia and hyperphosphataemia.
In AKI there will be an increased urea and an increased creatinine concentration. The amount of increase in creatinine can be used to stage the level of AKI. This will happen in any cause of AKI and is caused by a decreased excretion of these substances from the body.
The management of acute kidney injury varies and depends on the underlying cause, but may involve fluid resuscitation where there is evidence of hypovolaemia, with the aim of improving renal perfusion and supporting recovery of kidney function. For example, pre-renal failure is treated by the restoration of renal perfusion while post-renal failure will be treated by the removal of, or bypassing the urinary tract obstruction.
Dialysis can be used in the management of AKI when indicated, particularly if conservative treatments do not adequately control complications or support kidney function. Haemodialysis is used to treat AKI by filtering the blood to maintain homeostasis of the blood components.
The complications of AKI must also be treated as they can increase the risk of mortality. One of the main complications is hyperkalaemia which must be treated urgently as it can trigger arrhythmias and death. The main complications that can occur with acute kidney injury are:
- Hyperkalaemia - to see the signs, symptoms and treatment of hyperkalaemia check out our article on the control of potassium.
- Pulmonary Oedema - patients will present with shortness of breath and will have pulmonary oedema visible on a chest x-ray. It is mainly treated with diuretics to remove water from the body and lungs.
- Acidosis - acidosis is where the blood has an acidic pH. It is diagnosed using an arterial blood gas which can measure the pH of blood. Management depends on severity and cause, and may include sodium bicarbonate in selected cases. For more information on acidosis check out our article on acid and base balance.
Once a patient is identified as having acute kidney injury, their medications must be reviewed to stop any that could worsen renal function or could reach toxic levels because of reduced excretion of the drug.
- Drugs to stop in AKI due to worsening renal function include NSAIDs, ACE inhibitors, angiotensin receptor blockers, diuretics and aminoglycosides (e.g. gentamicin).
- Drugs to stop in AKI due to drug toxicity include metformin, lithium and digoxin.
Dialysis should be considered if the patient is not responding to treatment and the kidney can no longer adequately maintain the acid-base balance or if it cannot excrete salt, water, potassium or other waste products. Other indications for dialysis:
- Hyperkalaemia resistant to treatment
- Metabolic acidosis resistant to treatment
- Fluid overload resistant to diuretics
- Pulmonary oedema resistant to treatment
- Signs of uraemia - These include pericarditis, a decreased level of consciousness, intractable nausea and vomiting, and drowsiness.
- Presence of a dialyzable nephrotoxin such as aspirin, ethylene glycol, salicylates or lithium overdose.
For more information on dialysis, check out the article on chronic kidney disease as it explains the different types of dialysis.
Edited by: Dr. Tom Bradley
Reviewed by: Dr. Marcus Judge
In this article
Acute kidney injury is an acute decline in the actual glomerular filtration rate and is defined by either an increase in serum creatinine or a decrease in…
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