Acute kidney injury

Video by Dr Patrick Harnett - Consultant physician and nephrologist (2:57)


An acute kidney injury (AKI) is a clinical syndrome in which there is a rapid reduction in kidney function leading to a rise in serum creatinine and/or reduced urine output (oliguria). This leads to an inability to maintain electrolyte, acid-base and fluid homeostasis which can result in the following signs and symptoms:

This page will cover the aetiology and diagnosis of AKI.


2019 guidelines by the National Institute of Health and Care Excellence (NICE) defines the presence of an AKI with any one of the following criteria:

The above criteria have been created in line with the definitions of AKI as determined by the paediatric RIFLE classification, Acute Kidney Injury Network and Kidney Disease: Improving Global Outcomes organisation.


The causes of AKI are commonly divided into three major categories based on the anatomical location of pathophysiology behind the syndrome.

Prerenal AKI

The hallmark of a prerenal AKI is reduced renal perfusion. The most common cause is secondary to hypovolaemia (a decrease in circulating volume). Other causes include cardiogenic shock, distributive shock, impaired autoregulation, renal vessel occlusion and hepatorenal syndrome. There is no structural abnormality to the kidney and therefore a prerenal AKI will respond to a restoration of renal perfusion. It is the most common type of AKI.

A prolonged reduction in renal perfusion may lead to ischaemia and an acute tubular necrosis (see intrinsic AKI). This may not respond to a restoration of renal perfusion.

The first part of the renal nephron is known as the renal corpuscle. It consists of the glomerulus (a densely packed cluster of capillaries) and the Bowman’s capsule. Blood flows into the glomeruli via afferent arterioles and exits via efferent arterioles.

The hydrostatic pressure of the fluid on the capillary walls in the glomerulus causes filtration of blood plasma into the Bowman’s capsule. The hydrostatic pressure is determined by the blood pressure in the glomerulus. As a result, if there is decreased perfusion of blood into the glomeruli, whether this be due to hypovolaemia or hypotension, there will be a lower filtration pressure in the glomerulus and hence a drop in the eGFR.

This leads to reduced excretion of electrolytes, fluid and metabolic waste leading to the signs and symptoms of an acute kidney injury.


A reduction in circulating volume results in a decreased flow of plasma into the glomeruli. Hypovolaemia may be caused by four main mechanisms:

Other causes

If the blood pressure in the glomerulus drops, so does hydrostatic pressure and the filtration rate. In addition to hypovolaemia, are five major mechanisms by which this may occur:

The macula densa, located at the junction of the thick ascending limb and the distal convoluted tubule of the renal nephron, senses the concentration of sodium chloride (NaCl) in the nephron and helps regulate glomerular filtration via a mechanism known as tubuloglomerular feedback.

Both NSAIDs (which inhibit prostaglandin E2 production) and ACE inhibitors (which inhibits activity of the renin-angiotensin system) lead to a decrease in glomerular filtration predisposing patients to AKI.

In renal artery stenosis (renovascular disease), there is narrowing of the renal arteries due to atherosclerosis (90% cases) or fibromuscular dysplasia (an angiopathy in which there is abnormal growth of smooth muscle and collagen in the arterial wall).

This leads to a glomerular hypotension and reduced glomerular filtration. As a consequence of tubuloglomerular feedback (see the “impaired autoregulation” box above) there will be increased activity of the renin-angiotensin system (RAS); vasoconstriction of efferent arterioles will be essential to maintaining glomerular filtration. As a result of the increased RAS activity on other arteries in the body, patients with renal artery stenosis will have renovascular hypertension.

Use of an ACE inhibitor will cause efferent arteriole vasodilation as it impedes the effect of the RAS. This will result in a decrease in glomerular filtration. As a result, ACE inhibitors pose a significant risk to developing AKI in those with renal artery stenosis.

Intrinsic (renal) AKI

Intrinsic, or renal AKI is caused by structural injury to the kidney. As a result, restoration of renal perfusion will have no impact on its resolution. Injury may occur at the glomerulus, the renal tubule, the renal interstitium or the small vessels surrounding the nephrons. The damage may affect excretion and/or reabsorption of water, electrolytes and waste products leading to the features of AKI.


Glomerulonephritis an umbrella term used for many different diseases which cause inflammation of the glomeruli and surrounding structures.

The renal corpuscule is made up of the glomerular capillaries which are surrounded by intraglomerular mesangial cells. A basement membrane envelopes the mesangium, separating it from the podocyte foot processes which make up the inner epithelial lining of the Bowman’s capsule.

Glomerular diseases cause injury to these structures. Proteins may pass through the cell membranes and into the Bowman’s capsule resulting in what is known as nephrotic syndrome (proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia).

Inflammation can result in basement membrane thinning and the creation of pores in the podocytes. This may allow further substances such as red blood cells to pass through and the patient will present with a nephritic syndrome (features of nephrotic syndrome + hypertension, haematuria, oliguria and/or uraemia). There is a marked reduction in glomerular filtration resulting in an intrinsic AKI.

The causes of glomerular disease may be classified by their histopathological effects:

Acute tubular necrosis

Acute tubular necrosis (ATN) is a disease in which there is death of tubular epithelial cells of the nephron. It is the most common reason for an intrinsic AKI. It can sometimes be difficult to reverse; the best management is to treat the aetiological factor:

Acute tubulointerstitial nephritis

Tubulointerstitial nephritis describes inflammation of the tubular interstitium, that is the space in between the renal tubules and capillaries. It is an inflammatory reaction that is almost always caused by drugs, such as antibiotics, proton pump inhibitors, NSAIDs and monoclonal antibodies. The patient may present with a fever, rash or arthralgia and will often have an eosinophilia.

Small vessel disease

Systemic small vessel disease can affect the capillaries surrounding the renal tubules. Causes include vasculitis, malignant hypertension, and thrombotic microangiopathies such as thrombotic thrombocytopaenic purpura and haemolytic uraemic syndrome.

Note that small vessel disease may affect the glomerulus. ANCA-associated vasculitides for example can cause a type III rapidly progressive glomerulonephritis.

Postrenal AKI

Postrenal AKI is caused by downstream obstruction to the flow of urine. As a result, there is swelling of the kidney (hydronephrosis), an increase in intratubular pressure and a decrease in glomerular filtration. Immediate relief of the obstruction will lead to a restoration of glomerular filtration with no structural damage.

Causes are usually mechanical in nature; however, they may also be secondary to pharmacological effects:

Note that a prolonged obstruction can cause glomerular, tubular and interstitial damage resulting in an intrinsic AKI.


Investigation of AKI must be tailored towards your differential diagnosis (see the “other investigations” box) below. As prerenal AKI is the most common cause of AKI, often fluid resuscitation is enough to manage the condition. However, in unresolving AKI a urine dipstick test, ultrasound scan and renal biopsy should be strongly considered.


An ECG will help identify or detect early signs of electrolyte abnormality.

Blood tests

Blood tests are essential for both detection of AKI and narrowing your differential diagnosis. A renal profile is essential in staging your AKI and detecting electrolyte abnormalities. Other tests you should consider are:


A urine protein:creatinine or albumin:creatinine ratio will be essential for diagnosis of a nephrotic syndrome. Urine sodium, creatinine and osmolality can help differentiate between a prerenal and intrinsic AKI.

If myeloma is suspected, consider urine electrophoresis.


  • Chest X-ray: To identify pulmonary oedema.
  • CT kidneys, ureter and bladder: If urolithiasis is suspected.
  • Urethrogram: If urethral injury is suspected/
  • In addition to renal ultrasound, you may wish to consider:


    This may be indicated if malignancy is suspected or, if there is urinary obstruction and a urethral/suprapubic catheterisation is contraindicated.

    Urine dip

    A urine dip will give information on urinary levels of blood, protein, leucocytes, nitrites and glucose. This will help to detect conditions such as glomerulonephritis (proteinuria, haematuria) and acute tubulointerstitial nephritis (haematuria, leucocytes).


    An ultrasound scan will identify any hydronephrosis and postrenal AKI.

    In AKI with no identifying cause, the NICE guideline development group recommend performing an ultrasound scan within 24 hours of assessment. If infection is also suspected, then the scan should be performed within 6 hours of assessment.

    Renal biopsy

    If prerenal and postrenal causes of AKI have been excluded, then a discussion with a nephrologist should be had. They may suggest performing a renal biopsy, which is the most useful test in identifying the cause of an intrinsic AKI.


    NICE recommends monitoring serum creatinine, monitoring urine output and using trigger systems (such as the National Early Warning Score 2) in all persons with or at risk of developing AKI.

    Risk factors

    Risk factors for developing an acute kidney injury include but are not limited to those with: