Last updated: Renal Transplant…
on 28 Jul 2013

Acute Kidney Injury (AKI)


Lisa Crowley 

Acute Kidney Injury (AKI) is a common and important clinical problem. Determining the precise incidence depends on the definition of AKI. There is a wide range of reported incidence in the literature as a result of using different definitions.


As mentioned above, advances in understanding the epidemiology of AKI have been hampered by the lack of a universal definition. The many different definitions have made it more difficult to assess true incidence and outcomes. Previously definitions overlooked the early stages of AKI; or did not consider them significant in terms of outcomes. More recent reports in the literature have started to demonstrate that even minor rises in serum creatinine are associated with worse outcomes.

In 2004 an international group of renal physicians and intensivists formed the Acute Dialysis Quality Initiative (ADQI). The ADQI proposed changing the term acute renal failure to acute kidney injury (AKI) to better describe the spectrum of injury occuring in the kidneys. This spectrum extends from early injury to severe injury resuting in organ failure and the need for renal replacement therapy. The ADQI also proposed a universal definition and staging system for AKI, termed RIFLE.

The purpose of the new definition and staging system was to increase awareness about AKI and to improve the recognition and response to the disease process at an earlier stage. Subsequently the RIFLE definition and staging system has been demonstrated to correlate with worse patient outcomes and has now been applied to over 500,000 patients.

RIFLE (Bellomo, 2004)
The Acute Dialysis Quality Initiative (ADQI) group, proposed the RIFLE criteria. It describes five stages of AKI:

  1. Risk: 1.5x rise in creatinine, or >25% decrease in GFR (or UO <0.5 ml/kg/h for 6 hours)
  2. Injury: 2x rise in creatinine, or >50% decrease in GFR (or UO <0.5 ml/kg/h for 12 hours)
  3. Failure: 3x rise in creatinine or creatinine >350 μmol/l (with an acute rise of ≥45 umol/L) or >75% decrease in GFR (or UO <0.3 ml/kg/h for 24 hours, or anuria >12 hours))
  4. Loss: persistent AKI or complete loss of kidney function for more than 4 weeks
  5. End-stage renal disease: complete loss of kidney function for more than 3 months

AKIN (Mehta, 2007)
Following the demonstration that even relatively minor rises in serum creatinine were associated with worse patient outcomes the Acute Kidney Injury Network (AKIN) proposed the following definition for AKI:

"An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 μmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours)"

And three stages of AKI:

  1. Stage 1: Increase in serum creatinine of more than or equal to 0.3 mg/dl (≥ 26.4 μmol/l) or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline (or UO < 0.5 ml/kg per hour for > 6h)
  2. Stage 2: Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold) from baseline (or UO < 0.5 ml/kg per hour for >12h)
  3. Stage 3: Increase in serum creatinine to more than 300% (> 3-fold) from baseline (or serum creatinine of more than or equal to 4.0 mg/dl [≥ 354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l]) (or UO < 0.3 ml/kg per hour for 24h, or anuria for 12h)

The Kidney Disease Improving Global Outcomes (KDIGO) international guideline group has most recently harmonised pevious definitions and defined AKI as any of the following:

  • Increase in SCr by 0.3 mg/dl (26.5 mcmol/l) within 48 hours; or
  • Increase in SCr to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
  • Urine volume <0.5 ml/kg/h for 6 hours

If these criteria are met the cause of AKI should be ascertained and staged as follows:

  1. Stage 1: serum creatinine 1.5–1.9 times baseline or >0.3 mg/dl (>26.5 mcmol/l) increase (or UO <0.5 ml/kg/h for 6-12h)
  2. Stage 2: serum creatinine 2.0–2.9 times baseline (or UO <0.5 ml/kg/h for >12h)
  3. Stage 3: serum creatinine 3.0 times baseline (or increase in serum creatinine to >4.0 mg/dl (353.6 mcmol/l); or initiation of renal replacement therapy; or in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m2 (or UO <0.3 ml/kg/h for >24h or anuria for >12 hours)

Simple Definition
Despite these efforts to create a precise definition of AKI, in normal clinical practice (rather than research) many physicians in the UK still use a simple definition, eg 'a rapidly rising creatinine (from baseline), over a period of hours or days'. For many patients who start from normal renal function this will mean 'a rapidly rising creatinine >120 mcmol/L, over hours or days'.


The incidence of AKI is determined by it's definition and the population studied. Previous estimates of the incidence have been based upon a variety of different definitions.

In a whole health economy study, Feest (1993) found an incidence of 140 ppm per year. Overall survival was 54% at three months and 34% at two years and was not significantly age related.

In a later whole health economy based study of AKI and AKI/CKD, including all patients requiring RRT or not, all patients with serum creatinine concentrations ≥150 µmol/L (male) or ≥130µmol/L (female) over a 6-month period, were identified (Ali, 2007). In this study, the incidence of AKI and AKI/CKD was alot higher: at 1811 and 336 per million population, respectively - ie, the incidence of AKI and AKI/CKD is nearly 20x incidence of patients with new ESRF. Median age was 76 years for AKI and 80.5 years for AKI/CKD. Sepsis was a precipitating factor in 47% of patients. Of the AKI patients, 8% required RRT, of which 57% died.

Conversely, in a hospital-based 12‐month prospective study of AKI in an UK population (of 593,000), 288 patients developed AKI (486 per million population/year) - ie was less common (Stevens, 2001). Mean age at presentation was 73 years (range 14–96). The overall survival was 56% at discharge from hospital, 35% at 1‐year follow‐up, 31% at 2 years, and 28% at 3 years. 18% were considered preventable, and 34% iatrogenic. The in-hospital mortality rate was 23.8%. In 2010, Van Berendoncks also pointed out that mortality rates were also high during the first and second year after discharge (23.0 and 7.6% respectively).

In another hospital based study, AKI not requiring dialysis was present in 5-10% of all medical and surgical admissions (Nash, 2002).  In this study of 4622 consecutive medical and surgical admissions, mortality was 19.4%, but was 37.8%, if creatinine reached >250 mcmol/L. AKI develops in upto 70% of intensive care unit (ICU) patients. Approximately 95% of consultations with nephrologists are related to AKI. A study from Canada showed a much higher incidence of AKI than in previous reports, 18.3% (7,856 of 43,008) in hospitalised patients (Pannu, 2011).

AKI is also expensive, both in terms of length of stay and cost. In a study of 19,982 patients, it was found that an increase in SCr ≥0.5 mg/dl was associated with a 6.5-fold increase in the odds of death, a 3.5-d increase in LoS, and nearly $7500 in excess hospital costs (Chertow, 2005). The cost of AKI has been estimated to be £400-600m/year in the UK.

For all of these reasons, Thomas (2011) developed an electronic early warning system to spot AKI at an earlier stage (and treat appropriately) - though a similar mortality (36%) was seen. In another hospital-based study (Selby, 2012), a similar electronic reporting system was described in a large general hospital. The results showed that there were 3202 AKI episodes in 2619 patients during the 9-month study period (5.4% of hospital admissions).

But AKI, requiring dialysis, is rare. In one study, incidence was approximately 203 patients/million/yr (nearly 2x the incidence of new ESRF). It had a very high mortality. In one study 73.5% of patients receiving RRT for AKI died within 90 days. 23.5% became independent of RRT (Metcalfe, 2002). The median duration of hospital admission was 19 days.

Key Point: New cases of AKI are unsual but not rare, affecting approximately 0.1% of the UK population per year (2000 ppm/year), 20x incidence of new ESRD. AKI requiring dialysis (10% of these) is rare (200 ppm/year), 2x incidence of new ESRD.

So. An average GP in the UK with 2000 patients, will see 10 per year. 9 patients (90%) will not require RRT. 1 patient (10%) will die. Of the patients (one) that will require RRT, 50% will die, and 5-10% will remain on dialysis. In other words, AKI that is bad enough to require nephrology input, still has a very high mortality and poor prognosis.





AKI can be simply classified into 3 groups: pre-renal, intrinsic and post-renal. Pre-renal is due to ineffective perfusion of the kidneys that are otherwise structurally normal. Intrinsic renal AKI results from structural damage to the glomeruli or renal tubules, or both. Post-renal is due to obstruction of the urinary tract anywhere from the calyces to the urethral meatus.

The pathogenesis of AKI is complicated. It has been summarised recently by Barratt and Ostermann (2012).

Pre-renal AKI

Pre-renal AKI, is caused by underperfusion of an otherwise normal kidney. The hallmark of pre-renal failure is that it is quickly reversible with appropriate therapy. Thus, it can be thought of as 'a good kidney looking at a bad world'.

Pre-renal AKI and ischaemic acute tubular necrosis occur on a continuum of the same pathological process and together account for approximately 95% of hospital-acquired and 75% of community-acquired AKI (Lamiere, 2005).

Pre-renal AKI, in which the integrity of the renal tissue is preserved, is an appropriate physiological response to renal hypoperfusion associated with sepsis, hypovolaemia or cardiac failure (Prowle, 2009). Responses of the ageing kidney leave it more vulnerable to AKI. The kidney shrinks with age and with anatomical changes including:

• Cortical atrophy
• Decreased glomeruli
• Proximal tubule numbers
• Glomerular scarring
• Intimal thickening of renal arterioles

Functional changes include a decrease in renal blood flow and in GFR. Baseline 'normal' GFR is not known but in one study, median eGFR (using the MDRD equation) decreased from 90–100 ml/min (age 18–24 years) to 60–65 ml/min (age 85+ years) (Wetzels, 2007).

Pre-renal AKI is most often caused by volume depletion; eg gastrointestinal fluid loss, haemorrhage, poor oral intake, diuretic treatment, and 'third space' losses (eg pancreatitis). All of these cause 'true hypovolaemia'. Three other mechanisms can cause reduction in effective circulating volume ('pseudo-hypovolaemia'): poor cardiac output (heart failure), systemic vasodilatation and afferent arteriolar vasoconstriction (often for haemodynamic reasons relating to drugs). Further examples are listed below. The urinalysis is bland and the urinary sodium level is low, but urine osmolality is high - ie the body is trying to retain Na and water.

Causes of Pre-renal AKI

Volume depletion
• Renal losses (diuretics, polyuria)
• GI losses (vomiting, diarrhoea)
• Cutaneous losses (burns, Stevens-Johnson syndrome)
• Haemorrhage
• Pancreatitis ('third-space' loss, ie pseudo-hypovolaemia)

Decreased cardiac output
• Heart failure
• Pulmonary embolus
• Acute myocardial infarction
• Severe valvular disease
• Abdominal compartment syndrome (tense ascites)

Systemic vasodilation
• Sepsis
• Anaphylaxis
• Anaesthetics
• Drug overdose

Afferent arteriolar vasoconstriction
• Hypercalcaemia
• Drugs (NSAIDs, ACEi/ARBs, amphotericin B, calcineurin inhibitors, norepinephrine, radiocontrast agents)
• Hepatorenal syndrome

Pre-renal failure is often multifactorial, eg a patient may be septic and dehydrated post-operatively, on the background of a recent anaesthetic causing hypotension, and has just been given an NSAID. Therefore treatment of pre-renal failure has to address all these factors, eg IV fluids, adrenaline and antibiotics, and withdrawal of the nephrotoxic drug (NSAID). Treatment of all causes of pre-renal AKI is imperative, because continued renal hypoperfusion can progress to intrinsic renal failure
Note: none of these treatments will be effective, if the underlying problem is not addressed (eg the patient needs an operation)

Drug Causes
The kidney responds to changes in renal perfusion pressure by closely regulating renal blood flow. A decrease in perfusion leads to dilatation of afferent glomerular arterioles mediated through prostaglandins and vasoconstriction of efferent glomerular arterioles through angiotensin II thereby maintaining hydrostatic pressure in the glomerulus and adequate filtration. Drugs that interfere with this regulatory mechanism can precipitate AKI.

Acute inhibition of cyclo-oxygenase (type I or II) by non-steroidal anti-inflammatory drugs (NSAIDs) results in decreased prostaglandins and an inadequate dilatation of the afferent arteriole. This loss of pre-renal blood flow leads to a decreased glomerular pressure and a reduced GFR is particularly common in these clinical situations: atherosclerotic cardiovascular disease in a patient older than 60 years, pre-existing chronic renal insufficiency, and states of renal hypoperfusion such as in sodium depletion, diuretic use, hypotension, and sodium-avid states such as cirrhosis, nephrotic syndrome, and congestive heart failure.

Hyperkalaemia, sometimes out of proportion to the degree of renal impairment, can occur when these patients are concomitantly treated with potassium-sparing diuretics, inhibitors of angiotensin-converting enzyme (ACEi), or angiotensin receptor blockers (ARBs). There is little evidence that NSAIDs can acutely impair renal function in otherwise healthy individuals.

Drugs that block the action of Angiotensin Converting Enzyme (ACE-i and ARBs) cause inadequate constriction of the efferent arteriole resulting in decreased hydrostatic pressure across the glomerulus and a decreased GFR - especially in patients with stenosis of the renal artery in a solitary kidney or with bilateral renal-artery stenosis. But patients with hypovolaemia, severe CCF, polycystic kidney disease, or intrarenal nephrosclerosis without renal artery stenosis are also at risk. The frequency of AKI induced by ACE inhibitors varies between 5% and 20% in patients with bilateral renal-artery stenosis and increases to 40% in patients with unilateral stenosis in a single kidney.

Intrinsic AKI

Once pre-renal and post-renal causes are ruled out, intrinsic renal failure is likely. There are a number of different causes:

• Acute tubular necrosis (ATN)
• Drugs (eg aminoglycosides, contrast nephropathy)
• Rhabdomyolysis (recreational drugs, alcohol, long lie), tumour lysis syndrome
• Acute glomerulonephritis/Vasculitis (eg Lupus nephritis, ANCA positive vasculitis)
• Interstitial nephritis (penicillins, cephalosporins, diuretics)
• Myeloma (should be actively excluded in all cases of AKI)
• Microangiopathic haemolytic anaemia (MAHA) (eg many causes including Haemolytic Uraemic Syndrome, HUS)

Intrinsic AKI, ie disease of the renal parenchyma, has many causes. Acute Tubular Necrosis (ATN) is the commonest. However, disorders may involve the glomeruli, tubules, or interstitium. Glomerular disease reduces GFR and increases glomerular capillary permeability to proteins; it may be inflammatory (glomerulonephritis) or the result of vascular damage from ischaemia or vasculitis. Tubules also may be damaged by ischaemia and may become obstructed by cellular debris, protein or crystal deposition, and cellular or interstitial oedema. Tubular damage impairs reabsorption of Na, so urinary Na tends to be elevated, which is helpful diagnostically. Interstitial inflammation (nephritis) usually involves an immunologic or allergic phenomenon.

There are multiple processes that combine to result in ATN. These include a vascular component (intrarenal vasoconstriction, endothelial injury, microvascular disruption, vascular congestion in the outer medulla); and a tubular component (hypoxia and obstruction). New concepts such as sublethal cell injury, apoptosis, and cell repair after injury are emerging (see Lamiere, 2005).

ATN is most often the consequence of untreated prerenal AKI (renal hypoperfusion and renal ischaemia). Other causes include various endogenous nephrotoxic substances (eg myoglobin and haemoglobin after trauma; cellular products in tumour lysis syndrome; crystals of uric acid, calcium, or oxalate) and a host of exogenous substances.

If a patient develops ATN, all medication (prescribed and non-prescribed) must be reviewed for the possibility of nephrotoxicity. It should not be assumed that the 'usual suspects' (eg ACEi) are the cause. There may be more than one drug cause. If in doubt, stop most or all drugs.

ATN usually behaves in a particular way with 3 phases:

  • Prodrome. This phase, with usually normal urine output, varies in duration depending on causative factors. Urea and creatinine rise acutely
  • Oliguria. In this phase, urine output is typically between 50 and 400 mL/day. It lasts an average of 10 to 14 days but varies from 1 day to 8 weeks. In an ITU study, the average duration of RRT was 7 days (Schiffl, 2005). However, many patients are never oliguric. Non-oliguric patients have lower mortality and morbidity and less need for dialysis
  • Recovery. In this post-oliguric phase, urine output gradually returns to normal, but serum creatinine and urea levels may not fall for several more days. Tubular dysfunction may persist and is manifested by Na wasting, polyuria (sometimes massive) unresponsive to vasopressin, and hyperchloraemic metabolic acidosis

The phrase 'ATN' is now being rethought. In an autopsy study of patients with septic shock by Hotchkiss (1999), only 1/20 (5%) patients had pathological evidence of necrosis. The phrase 'acute tubular damage' has been suggested and may be more descriptive of this syndrome. This and other papers have been described by Langenburg (2008) in a review of septic AKI pathology.

AKI secondary to glomerulonephritis is the least common cause of AKI but beware rapidly progressive glomerulonephritis/vasculitis as this requires urgent treatment. Myeloma is more common and should be excluded with the same degree of urgency as glomerulonephritis/vasculitis.

Post-renal AKI

Post-renal AKI is caused by obstruction of the urinary tract. This may occur anywhere along the urinary tract and includes:

• Prostate (malignancy, benign prostatic hypertrophy)
• Bladder (malignancy)
• Ureter (calculi, extrinsic compression eg retroperitoneal fibrosis)
• Pelvic tumour

Obstructive nephropathy is more common in selected populations such as older men with prostatic disease; patients with a single kidney; or intra-abdominal cancer - particularly pelvic cancer. Severe ureteral obstruction is also caused by retroperitoneal fibrosis. This can be associated with neoplasia (eg lymphoma) or small inflammatory aortic aneurysms, or be idiopathic. If idiopathic, this type of obstruction can be successfully treated with corticosteroids. Ureteric stents are not always necessary. Most causes of post-renal AKI are amenable to therapy and the prognosis is generally good, depending on the underlying disease.

Important clinical sequelae of post-renal AKI are post-obstructive diuresis and the presence of hyperkalaemic renal tubular acidosis. Severe diuresis can occur after the release of the obstruction, especially if both kidneys, or a single functioning kidney, are completely obstructed. The period of total obstruction is short in most cases, a few days to a maximum of a week. Once the obstruction is relieved, the urine output generally ranges from 4 L to 20 L per day. This diuresis must be closely monitored as it can precipitate pre-renal AKI due to volume depletion, delaying renal recovery.

The development of hyperkalaemic hyperchloraemic tubular acidosis is indolent in most cases, and the abnormality tends to persist after correction of the obstruction. Patients in whom the hyperkalaemia is not corrected as their AKI is reversed by treatment of the obstructive lesion, should be investigated for the presence of tubular acidosis.

The pathophysiology of obstructive nephropathy is complicated. It affects renal blood flow, initially increasing the flow and pressure in the glomerular capillary by reducing afferent arteriolar resistance. However, within 3 to 4 hours, the renal blood flow is reduced, and by 24 hours, it has fallen to < 50% of normal because of increased resistance of renal vasculature. Renovascular resistance may take up to a week to return to normal after relief of a 24 hour obstruction.

Treatment should focus on removing the obstruction. Techniques vary with the type of obstruction, but may include bladder catheterisation, nephrostomy and placement of urinary stents (either retrograde or antegrade).









Clinical Features

The differential diagnosis of AKI is extensive. Therefore history and examination should aim to distinguish between pre-renal, intrinsic and post-renal causes.

An important skill is to recognise patients at risk of developing AKI. Consider recent events in the individual's history and highlight those that will put them at risk of AKI. For example, the post-operative surgical patient may have suffered multiple nephrotoxic insults; such as volume depletion, sepsis, CT with contrast, and may be on nephrotoxic drugs. Often, predominant symptoms are those of the underlying illness or those caused by the surgical complication that precipitated renal deterioration. Initially, weight gain and peripheral oedema may be the only findings.

Later, as nitrogenous products accumulate, symptoms of uraemia may develop, including anorexia, nausea and vomiting, weakness, myoclonic jerks, seizures, confusion, and coma; asterixis and hyperreflexia may be present on examination. A 'jittery' patient may be about to have a seizure. In causes of Micro-angiopathic Haemolytic Anaemia (MAHA) - especially pre-eclampsia and eclampsia - cerebral deterioration can occur rapidly, with very serious consequences. You may need to act quickly.

Chest pain (typically worse with inspiration or when recumbent), a pericardial friction rub, and findings of pericardial tamponade may occur if uraemic pericarditis is present.

Symptoms of hypocalcaemia are rare but may be profound in patients with rhabdomyolysis, apparently because of the combined effects of Ca deposition in necrotic muscle, reduced calcitriol production, and resistance of bone to parathyroid hormone (PTH). During recovery from AKI, hypercalcaemia may supervene as renal calcitriol production increases, the bone becomes responsive to PTH, and Ca deposits are mobilised from damaged tissue.

Anuria. Complete anuria is very rare, and has only three common causes:

  • Obstruction. Put a catheter in now
  • Vascular catastrophe. Eg aortic dissection, or thromboembolism in a single kidney
  • Acute severe glomerulonephritis/vasculitis

Note 1: unless it is 1, and can be rectified simply, a consultant needs to see the patient ASAP
Note 2: occasionally patient with acute tubular necrosis will be anuric for a few hours


Pre-renal AKI
Symptoms related to hypovolaemia include increased thirst, decreased urine output and postural dizziness whilst simple causes of hypovolaemia are easy to explore – diarrhoea, vomiting, haemorrhage and reduced oral intake.

Drug history is vital. If you are going to do ONE thing .. TAKE A DRUG HISTORY.

The past medical history is important, particularly looking for conditions such as ischaemic heart diasease, cerebrovascular disease, peripheral vascular disease and diabetes mellitus that would suggest renovascular disease. These risk factors are especially important for prerenal causes.

Intrinsic AKI
ATN is suggested by prolonged renal failure and hypotension, symptoms of sepsis, exposure to nephrotoxic drugs and situations with potential for muscle injury – prolonged lying, seizures, alcohol and excessive exercise – that may lead to rhabdomyolysis.

Ask about recent procedures such as angiography or CT scans that may have exposed the patient to nephrotoxic contrast.

Clues to glomerular disease include upper respiratory tract infection, rash, fever, haemoptysis and sore throat (post-streptococcal glomerulonephritis) whilst more systemic symptoms should be looked for in diseases such as Systemic Lupus Erythematous (SLE) and the vasculitides.

Post-renal AKI
For post-renal AKI it is important to assess preceeding symptoms of prostatism (hesitancy, poor flow, dribbling and nocturia), lower abdominal pain, constipation and an inability to pass urine. Also look for symptoms suggesting covert malignancy such as weight loss and decreased appetite.


A comprehensive physical examination is vital focusing on an accurate assessment of fluid status. The JVP is the most important sign in nephrology. If the patient has an obese neck, measurement of CVP should be considered. Assess skin turgor, mucous membranes and closely monitor heart rate.

What is the blood pressure? This is a simple but vital observation.

Normal blood pressure does not exclude hypovolaemia. A postural drop, when moving the patient from a lying to standing position, may demonstrate hypotension (and hypovolaemia) when the lying blood pressure is normal. This is not always easy in a frail, ill or obese patient. It may be easier to carry out a lying-to-sitting BP.

A high or low temperature (>38C or <36C) with tachycardia or tachypnoea defines the systemic inflammatory response syndrome (SIRS) and evidence of infection should make you strongly consider sepsis as your underlying cause for AKI. If in doubt, treat.

Systematically examine the different systems looking for complications of AKI such as pulmonary oedema, and causes of it (recent MI, AF). A palpable bladder suggests post-renal obstruction and necessitates a rectal examination looking for constipation and prostatic enlargement. Listen for adbominal and femoral bruits (reno-vascular disease).

Remember that AKI can be a complication of many systemic conditions (or their investigation and treatment); therefore clues to aetiology will be given by thorough examination.



Urea, Electrolytes and Creatinine

In the early stages of AKI, serum creatinine levels may rise within the ‘normal’ range despite a significant reduction in GFR - especially in an elderly patient, with poor muscle mass. Occasionally it is necessary to dialyse a patient with a creatinine that is in the normal range, or just above it.

A progressive daily rise in serum creatinine is diagnostic of AKI. Serum creatinine can increase by as much as 200 mcmol/L/day, depending on the amount of creatinine produced (which varies with lean body mass) and total body water. A rise of >200 mcmol/L per day suggests overproduction due to catabolic causes of AKI including rhabdomyolysis and tumour lysis syndrome.

Estimating GFR from serum creatinine should not be done, because the rise in serum creatinine concentration is a delayed response to GFR decline.

Serum urea may increase by 3.5 to 7 mmol per day. But the urea level may be misleading because it is frequently elevated in response to increased protein catabolism resulting from surgery, trauma, corticosteroids, burns, transfusion reactions, parenteral nutrition or GI or internal bleeding.
Note: the fact that it is inappropriately raised in dehydration is useful, though, as a diagnostic tool

New Biomarkers

Efforts to identify biomarkers to assist with the early diagnosis of AKI have yielded many promising candidates, such as KIM-1, NGAL, IL-18, Cys-C, clusterin, FABP, and osteopontin (Vaidya, 2010). None of these have reached clinical practice.

Blood Gases

Whilst sending blood samples to the laboratory, also take a sample to go through the blood gas machine. This allows rapid evaluation of pH, potassium and lactate – all of which can signify the need for immediate intervention. Serum should be sent to haematology, biochemistry, immunology and microbiology. It is vital to know the potassium level as soon as possible.

Other laboratory findings are progressive metabolic acidosis, hypernatraemia or hyponatraemia, and anaemia. Acidosis is normally moderate, with a plasma HCO3 content of 15 to 20 mmol/L. Serum K concentration increases slowly, but when catabolism is markedly accelerated, it may rise by 1 to 2 mmol/L/day. Inappropriately high or rapidly rising K suggests catabolic causes of AKI including rhabdomyolysis and tumour lysis syndrome.

Hyponatraemia, if present, is usually moderate (Na 125-135 mmol/L) and correlates with a surplus of water. If the patient is dehydrated, sodium can be very high (>160 mmol/L).


Mild normochromic-normocytic anemia with an haematocrit of 25 to 30% is typical. A rapidly falling or severe anaemia has three main causes: haemorrhage, myeloma and haemolytic uraemic syndrome/thrombotic thrombocytopenia purpura (HUS/TTP). In the latter case, a blood film should also be sent.

Raised inflammatory markers, ESR or CRP, imply infection or an underlying systemic disorder. Peripheral eosinophilia may be seen in interstitial nephritis. In sepsis, CRP can be normal in the elderly; or even in the non-elderly, normal on day one. In Black patients a sickle cell screen should be performed.


Hypercalcaemia suggests myeloma, sarcoidosis (or TB) or malignancy. Hypocalcaemia is common and may be profound in patients with rhabdomyolysis.

Amylase, and Other 'False Positive' Tests
Mild hyperamylasaemia commonly is seen in AKI (2-3 times controls). Elevation of baseline amylase can complicate the diagnosis of pancreatitis in patients with AKI. Lipase, which commonly is not elevated in AKI, often is necessary to make the diagnosis of pancreatitis. Pancreatitis has been reported as a concurrent illness with AKI in patients with atheroemboli, vasculitis, and sepsis from ascending cholangitis. Troponin T can also be falsely raised in AKI, complicating the diagnosis of myocardial disease.

Urine Tests

Urine dipstick should be done early. The presence of blood and protein is highly suggestive of glomerulonephritis or vasculitis whereas their absence almost excludes it. This sample should be sent for microscopy, culture and sensitivity. The presence of red cell casts is diagnostic of glomerulonephritis. Pyuria (the presence of white cells) is suggestive of urinary tract infection or tubulointerstitial nephritis.

Urine osmolality and electrolytes are helpful in distinguishing between pre-renal and intrinsic AKI. In intrinsic renal injury, there is an inability to concentrate urine. Therefore urine will be dilute (<300mOsm/kg) with a urinary sodium of <40 mmol/L. This compares to the concentrated urine of pre-renal kidney injury (>500mOsm/kg) (with increased sodium reabsorption), with a urinary Na of <10 mmol/L in a healthy adult, and <20 in the elderly. A urinary Na of 20-40 mmol/L is harder to interpret.

Other Tests

An ECG is important to look for changes of hyperkalaemia (absent p-wave, tall tented T-wave, wide QRS complex becoming sinusoidal) and those of pericarditis (diffuse saddle-shaped ST segments). A CXR is also important, looking for pulmonary oedema, pericardial effusion and pulmonary haemorrhage.

Renal Imaging
After immediate investigation and initial management has been implemented, a renal ultrasound is indicated. Early identification of AKI secondary to obstruction is essential. Dilatation of any part of the renal tract will indicate obstruction whilst bilateral small kidneys suggest chronic renal disease.

Renal ultrasonography, when used to detect obstruction, has a sensitivity and specificity of 90-95%. Unfortunately, it is also highly operator-dependent, so it should be performed by a highly experienced radiologist.
Note: the result of renal US should be known in no more than 24 hours ftom referral, preferably that day

Furthermore, false positives and negatives can occur. For example, false-negative results can occur if the obstruction is caused by retroperitoneal fibrosis or certain malignancies that encase the entire system. It might also fail to detect an obstruction in extremely volume-depleted patients who do not have enough fluid buildup to reveal the obstruction. Conversely, dilatation of the urinary tract can occur without obstruction (eg pregnancy, and in a transplant ureter).

Key point: a 'normal' renal US does not exclude obstruction, and dilatation (hydronephrosis) can occur without obstruction

In other words, non-dilated obstruction and non-obstructed dilatation, can occur. For thess reasons, specialist imaging techniques (eg cystoscopy and retrograde pyelograms) may be necessary. Then, if the diagnosis is still unclear, relieving the obstruction and seeing if renal function improves may be necessary.

Summary of Investigations

• Full Blood Count
   - Eosinophilia (cholesterol emboli, vasculitis)
   - Thrombocytopenia (with normal clotting, HUS/TTP; with deranged clotting, DIC)
• Clotting
• Venous/arterial (if ?hypoxic) blood gas
Note: if you are going to do ONE test, do the VBG

• Urea and electrolytes
• LFTs (bilirubin raised in liver disease, and leptospirosis; low albumin in nephrotic syndrome, cirrhosis)
• Bone (hypercalcaemia in myeloma, sarcoidosis and malignancy)
• Glucose
• Creatinine kinase (rhabdomyolysis)

• Dipstick (proteinuria suggestive of glomerular disease? infection?)
• Microscopy (infection?)
• Culture and sensitivity

• Chest xray (pulmonary oedema or haemorrhage)
• ECG (hyperkalaemia)

Summary of Specialist Investigations (selected patients)

• Blood film (fragments in HUS/TTP and DIC; malarial parasites)
• Haemoglobin electrophoresis (sickle cell disease)

• LDH (raised in haemolysis, malignancy)
• Haptoglobins (reduced in haemolysis)
• Uric acid (raised in tumour lysis syndrome)

• Immunoglobulins (A, G, M) (IgA nephropathy, myeloma)
• Protein electrophoresis (myeloma)
• Serum free light chains (myeloma)
• ANA and dsDNA (SLE)
• Complement factors (C3 and C4):
   - Low C3 and/or C4 (SLE)
   - Low C4 (cryoglobulinaemia)
   - Low serum complement activity (CH50) (post-infectious GN, Type II mesangiocapillary glomerulonephritis, cryoglobulinaemia, infective endocarditis, 'shunt' nephritis)
• Anti-neutrophil cytoplasmic antibodies MPO and PR3 (ANCA) (vasculitis)
• Anti-glomerular basement membrane antibodies (AGBM) (Goodpastures Syndrome)
• Anti-streptolysin O titre (ASOT) (post-infectious glomerulonephritis). This is done to test for exposure to streptococci. It has poor specificity
• Angiotensin converting enzyme (ACE) (raised in sarcoidosis)
• Cryoglobulins

Microbiology and virology
• Blood cultures
• Throat swab (post-infectious glomerulonephritis)
• Hepatitis B, C (cryoglobulinaemia, and transmission risk on haemodialysis)
• HIV (FSGS and increased risk of AKI on HAART)

• Bence-Jones protein (myeloma)
• Sodium and osmolality
• Microscopy (sediment: red cell casts (glomerulonephritis); eosinophiluria (interstitial nephritis))
• Leptospirosis, legionella

• Renal ultrasound

Consultant Decisions (minority of patients)

• Renal biopsy
• Renal angiogram
• Cystoscopy and retrograde pyelogram
• Occasionally CT-KUB (stones or sloughed papillae), CT abdomen or CT angiogram


Principles of Management

Prerenal failure is often multifactorial, eg a patient may be septic and dehydrated post-operatively, on the background of a recent anaesthetic causing hypotension, and has just been given a NSAID. Therefore treatment of pre-renal failure has to address all these factors, eg IV fluids, adrenaline and antibiotics, and withdrawal of the nephrotoxic drug (NSAID). Treatment of all causes of pre-renal AKI is imperative, because continued renal hypoperfusion can progress to intrinsic renal failure. None of these treatments will be effective, if the underlying problem is not addressed (eg the patient needs an operation).

Key point: in terms of treatment, removing the nephrotoxic event or agent(s) - whether it a bleeding source, or drug - is often the most important intervention. This may be a drug, incorrect IV therapy, untreated trauma, bleeding or sepsis. If there is an abscess, does the patient need an operation? 'Where there is pus, let it out'.

A nephrologist always looks at the front and back of the drug card, and the Emergency Department record. The nephrotoxins may be hidden. Ring the GP.

The Renal Pharmacy Group have published a toolkit to advise on which drugs to stop or reduce the dose of, in AKI.

General Measures

Nephrotoxic drugs should be stopped. The dose of all drugs excreted by the kidneys (eg digoxin, some antibiotics) should be adjusted; serum levels are useful. Patients that need, or may need dialysis, should be transferred without delay to a renal ward (or ITU if unstable).

Fluid Balance
If the patient is fluid overloaded, daily water intake is restricted to a volume equal to the previous day's urine output plus measured extrarenal losses (eg vomit) plus 500 mL/day for insensible loss. Water intake may need to be increased in a dry patient, especially if hypernatraemic.

Na and K intake should be minimised in most patients. Don’t forget the importance of nutritional support to patients with AKI. They will often be hypercatabolic with high nutritional requirements. Elderly patients are at particular risk of malnutrition. An adequate diet should be provided, including daily protein intake of about 0.8-1 g/kg.

If oral or enteral nutrition is impossible, parenteral nutrition should be used. But it should be remembered in AKI, risks of fluid overload, hyperosmolality, and infection are increased by IV nutrition.

Calcium and Phosphate
Calcium salts (carbonate, acetate) before meals help maintain serum phosphate at < 1.8 mmol/L.

Urinary Catheter
An indwelling bladder catheter is often needed, accepting the risks of UTI and urosepsis. It should be removed as soon as possible.

Treatment of Pulmonary Oedema

Pulmonary oedema must be managed very carefully. It can be directly due to AKI but is often present because of over-zealous fluid resuscitation. Initially give supplemental oxygen therapy and sit the patient upright. Pharmacological therapy including loop diuretics (furosemide), opiates (morphine) and nitrates is the next stage of management. If the patient is refractory to these treatments then they will need dialysis.

Treatment of Hyperkalaemia

Hyperkalaemia should be teated as needed with an IV infusion of 10 ml of 10% Calcium Gluconate (to stabilise the heart), and 50 mls of IV 50% Dextrose, containing 10 units of Insulin. Calcium Gluconate is a quick acting cardioprotective measure used as a prelude to dialysis. Nebulised Salbutamol 10 mg is also used.

These drugs do not reduce total body K. They move K back into the cells. So further (but slower acting) treatment with 15-30g of oral or rectal Calcium Resonium, to remove K from the body, is also needed. If K is not controlled (<6.5 mmol/L) by two rounds of insulin/dextrose, dialysis should be considered.

It is important to note that these treatments are not appropriate in an anuric-oliguric patient; as they are ‘temporary fixes’ to the problem of hyperkalaemia (and do not reduce the amount of K+ in the body). This seems rather obvious but it is something that gets overlooked, especially by juniors.

Treatment of Metabolic Acidosis

Metabolic acidosis is common in AKI. Correction of a high anion gap metabolic acidosis (which is the norm in AKI) with NaHCO3 is controversial. Small amounts of sodium bicarbonate can be given if serum bicarbonate falls below 15mmol/L but this should only be done under close supervision. When metabolic acidosis is not controlled by medical therapy, this is another indication for dialysis - especially if they are oligo-anuric or fluid overloaded.

There are acidotic circumstances (sometimes with normal renal function) that may be immediate indications for dialysis, eg Metformin (lactic acidosis), Aspirin and Ethylene glycol. Renal tubular acidosis is rare, and often missed. So nephrologists need to be on the 'look out' for it.

Treatment Algorithm

Once venous access is established, if the patient is dry, an intravenous fluid challenge should be commenced to increase renal perfusion. A measured approach to initial fluid replacement should be taken depending on the patients heart rate, blood pressure, capillary refill time and venous filling. Overzealous fluid replacement can lead to pulmonary oedema especially in those with a cardiac history.

Aggressive fluid replacement (over-zealous fluid replacement)?
In a post hoc analysis of the Fluid and Catheter Treatment Trial (FACTT, 2006), which examined liberal versus conservative fluid management in intubated ICU patients, fluid balance and diuretic use were identified as prognostic factors for mortality in individuals with AKI (Grams, 2011). Specifically, greater cumulative fluid accumulation over an average of 6 days was associated with a higher mortality (10.2L vs 3.7L in the liberal vs conservative group), and higher furosemide use was associated with a lower mortality (cumulatively 562 mg vs 159 mg).
Note: high dose loop diuretics have no effect on outcome (dialysis or death), but can 'buy time' my maintaining urine output and controlling pulmonary oedema) (Bennett-Jones D, 2006) (Bagshaw, 2007).

Of note, more than one half of the individuals had Stage 1 AKI (AKIN criteria), so whether these results apply to more severe stages of AKI is not clear. One interpretation of this study is that patients who can be stabilised with less volume resuscitation fare better. From a practical standpoint, one conclusion is that aggressive prolonged volume resuscitation does not improve prognosis in AKI in the ICU setting.
Note: careful rather than aggressive fluid replacement may be preferable. This contradicts standard renal dogma (give alot of fluids to a patient with prerenal failure)

The failure of a response in urine output (minimum 0.5 ml/kg/hour) to the correction of hypovolaemia should make you consider an intrinsic or post-renal problem. If unsure, in the oliguric-anuric patient, pass a urinary catheter. If this produces a large residual volume then the patient has a lower-tract post-renal problem. But. If the urinary catheter does not drain a significant volume of urine, then the diagnosis is either a pre-renal problem (that you have insufficiently corrected), an intrinsic renal problem, or upper-tract obstruction. So, both lack of diuresis post catheterisation and 'lack' of obstruction on ultrasound do not exclude obstruction. If in doubt, ask for a urological opinion (leading to nephrostomy or ureteric stent placement). Leave the catheter in-situ as accurate monitoring of urine output is vital.

If the patient does not improve with this approach, and life-threatening complications of AKI are still present (eg fluid overload and hyperkalaemia) dialysis should be started, either in the form of haemodialysis or haemofiltration (which is usually carried out on ITU). There is no evidence that one form of RRT leads to better results than another.

Urea and creatinine levels alone are not the best guides for initiating dialysis in AKI. In asymptomatic patients who are not seriously ill, particularly those in whom return of renal function is considered likely, dialysis can be deferred until symptoms occur (or K is uncontrolled), thus avoiding placement of a dialysis catheter with its attendant complications. In these patients, daily bloods and senior review is necessary.


  • Treat underlying cause
  • Oxygenation
  • Maintain BP
  • Correct hyperkalaemia and metabolic acidosis
  • Urinary catheter – exclude obstruction and monitor urine output
  • Does this patient need dialysis?

Indications for Dialysis

  • Pulmonary oedema unresponsive to medical treatment
  • Hyperkalaemia (>6.5 mmol/L) unresponsive to treatment
  • Metabolic acidosis (pH <7.2) unresponsive to treatment
  • Pericarditis
  • Encephalopathy

Management of Specific Causes of AKI

Diuresis in Recovery Phase of ATN and Obstruction
In many patients, a brisk and even dramatic diuresis after relief of obstruction or recovery of ATN, is a physiologic response to the expansion of ECF during early stage of AKI. In some patients, polyuria accompanied by the excretion of large amounts of Na, K, Mg, and other solutes may cause hypokalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, or marked contraction of ECF volume with peripheral vascular collapse.

In this post-oliguric phase, close attention to fluid and electrolyte balance is mandatory. When post-oliguric diuresis occurs, replacement of urine output (with the correct fluid for the patient, eg 0.45% saline) at about 75% of the previous day's urine output prevents volume depletion.

The prognosis of Sepsis-related AKI in the critically ill, is worse than non-sepsis related (Bagshaw, 2007). So, specific therapies should be considered in patients with sepsis-related AKI (Ronco C, 2008).


(Lameire, 2003) AKI can often be prevented by maintaining normal fluid balance, blood volume, and BP in patients with trauma, burns, or major haemorrhage and in those undergoing major surgery. Infusion of isotonic saline and blood may be helpful. Use of contrast agents should be minimised, particularly in at-risk groups (eg the elderly and those with preexisting CKD, volume depletion, diabetes, myeloma or heart failure). However Katzberg (2010) has questioned the risk of AKI associated with contrast media.

If contrast agents are necessary, risk can be lowered by minimising volume of the IV contrast agent, using nonionic and low osmolar or iso-osmolar contrast agents, avoiding NSAIDs, and pretreating with normal saline at 1 ml/kg/h IV for 12 hours before the test. Isotonic NaHCO3 is used instead of normal saline in some patients. PO N-acetylcysteine 600 mg bd the day before and the day of IV contrast administration has been used to prevent contrast nephropathy, but reports of its efficacy are conflicting. Kelly (2008) carried out a meta-analysis of the interventions that have been used to prevent contrast nephropathy, and considers n-acetylcysteine to be effective.

Before cytotoxic therapy is initiated in patients with certain neoplastic diseases (eg lymphoma, leukaemia), treatment with allopurinonol should be considered along with increasing urine flow by increasing oral or IV fluids to reduce urate crystalluria. Some units use IV Rasburicase, to prevent tumour lysis (Ueng, 2005). Making the urine more alkaline (by giving oral or IV NaHCO3 or acetazolamide) has been recommended by some but is controversial because it may also induce urinary Ca phosphate precipitation and crystalluria, which may cause AKI.

The renal vasculature is very sensitive to endothelin, a potent vasoconstrictor that reduces renal blood flow and GFR. Endothelin is implicated in progressive renal damage, and endothelin receptor antagonists have successfully slowed or even halted experimental renal disease. Anti-endothelin antibodies and endothelin-receptor antagonists are being studied to protect the kidney against ischaemic AKI

Prognosis and Follow-up .

Short-term Mortality
Although many causes are reversible if diagnosed and treated early, the overall survival rate of dialysis-requiring AKI remains high about 50% (30% for non-ITU patients); perhaps because many patients with AKI have significant underlying disorders (eg sepsis, respiratory failure). Mortality may exceed 70% in patients that require ITU. Conversely, the mortality of AKI that does not require dialysis is approximately 10%. Death in all these patient groups, is usually the result of these disorders rather than the renal failure itself.

Factors Affecting Prognosis

  • Older age
  • Pre-existing CKD
  • Cause of AKI (eg sepsis)
  • Multiorgan failure (ie, the more organs that fail, the worse the prognosis)
  • Oliguria
  • Hypotension
  • Vasopressor support

Short-term Renal Outcomes
The duration and severity of AKI predicts the development of progressive chronic kidney disease (CKD). In a large ITU follow-up study, patients who have suffered AKI, 57% returned to normal renal function, 33% had mild to moderate CKD and 10% (Schiffl, 2005) severe renal failure.

Even if serum creatinine returns towards baseline value but remains a poor marker of the residual tubular and vascular damage. The ensuing CKD is associated with an increase in cardiovascular disease.

Long-term Outcomes
Coca (2009) has published a very good meta-analysis of long-term outcomes in AKI. Mortality was 8.9 per 100 person-years in survivors of AKI and was 4.3 per 100 patient-years in survivors without AKI. The incidence rate of CKD after an episode of AKI was 7.8 per 100 patient-years and the rate of ESRD was 4.9 per 100 patient-years.

Key Point: All cases of AKI that are accepted by a renal service will require follow-up, within 4 weeks of discharge, by a nephrologist (or in some cases by the GP)






  1. Acute Kidney Injury (AKI) is traditionally referred to as a rapid decrease in renal function over hours to days, resulting in a failure to regulate fluid, electrolyte and acid-base balance. Patients are at risk of a number of complications and have an increased mortality
  2. New definitions based on rises in serum creatinine or reductions in urine output have been proposed, which should provide improved epidemiological data
  3. The most common forms of AKI are secondary to hypoperfusion injury, sepsis and nephrotoxins. Therapy is supportive and consists of rapid correction of hypovolaemia, prompt treatment of sepsis and withdrawal of nephrotoxic medication
  4. Prevention of AKI is of paramount importance and is dependent upon recognition of patients with risk factors. It has been estimated that 30% of cases of AKI could be prevented
  5. The cause of AKI must always be established to ensure that rarer forms (vasculitis) are not overlooked. Specific therapies are available and must be initiated as soon as possible
  6. The duration and severity of AKI predicts the development of progressive chronic kidney disease (CKD)
  7. Following AKI, serum creatinine may return towards the baseline value but remains a poor marker of the residual tubular and vascular damage. The ensuing CKD is associated with an increase in cardiovascular disease
  8. The mortality associated with AKI has remained unacceptably high. The mortality of dialysis-dependent AKI (if ITU patients are included) is 50% (and 30% if the ITU patients are not included). Approximately 50% will have normal renal function. a third mild-moderate CKD and 5-10% of patients will remain on dialysis
  9. The cost of AKI has been estimated to be £400-600m/year in the UK
  10. There is renewed interest in developing specific therapies to prevent AKI and major investment is occurring from the pharmaceutical industry (especially with regard to biomarkers)



Ali et al. Incidence and Outcomes in Acute Kidney Injury: A Comprehensive Population-Based Study. J Am Soc Nephrol 2007; 18: 1292-1298

Bagshaw SM et al. Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resusc 2007; 9(1): 60-8

Bagshaw SM et al. Septic Acute Kidney Injury in Critically Ill Patients: Clinical Characteristics and Outcomes. CJASN 2007; 2 (3): 431-439

Barrett NA, Ostermann M.The Pathogenesis of Acute Kidney Injury. "Renal Failure - The Facts", book edited by Momir Polenakovic, ISBN 978-953-51-0630-2, Published: May 23, 2012 
This is an extremely good review article

Bywaters EGI, Beall D. Crush injuries with impairment of renal function. BMJ 1941;1: 427-32

Bywaters EGL, Joekes AM. The Artificial Kidney: Its Clinical Application in the Treatment of Traumatic Anuria. Proc R Soc Med 1948; 41(7): 420–426

Bellomo R et al (RIFLE). 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 2004; 8: R204-R212

Bennett-Jones D. Early intervention in acute renal failure: Give intravenous fluids, not loop diuretics. BMJ. 2006; 333(7565): 406–407

Calvert S, Shaw A. Perioperative acute kidney injury. Perioperative Medicine 2012, 1:6

Cameron JS. Nephrologist extraordinary—Michael Darmady (1906–1989). Nephrol Dial Transplant 2007; 22 (3): 715-721

Chertow GM et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005; 16(11): 3365-70

Cheung AK, Lysaght M, Bergstrom J. The Career of Lee W. Henderson. JASN 2002; 13 (Suppl 1, S1-S2)
A description of the career of Lee Henderson

Cheung MC, Ponnusamy A and Anderton JG. Management of Acute Renal Failure in the Elderly Patient: A Clinician's Guide. Drugs Aging 2008; 25(6) :455-76

Coca SG et al. Long-term Risk of Mortality and Other Adverse Outcomes After Acute Kidney Injury: A Systematic Review and Meta-analysis. Am J Kidney Dis 2009; 53(6): 961–973

Comparison of Two Fluid-Management Strategies in Acute Lung Injury. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. N Engl J Med 2006; 354: 2564-2575

Feest TG, Round A, Hamad S. Incidence of severe acute renal failure in adults: results of a community based study. BMJ 1993; 306(6876): 481-3

Grams ME, Estrella MM, Coresh J, Brower RG, Liu KD. Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury. Clin J Am Soc Nephrol 2011; 6(5): 966-973

Henderson L, Besarab A, Michaels A, Bluemle LW Jr. Blood purification by ultrafiltra- tion and fluid replacement (diafiltration). Trans Am Soc Artif Int Organs 1967; 13: 216

Henderson L et al. Hemofiltration (1986)
A long article/short book with a good historical section regarding the history of haemofiltration

Hilton R. Acute renal failure. BMJ 2006; 333: 786

Hotchkiss RS et al. Apoptotic cell death in Intravenous in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999, 27:1230-1251

Katzberg RW, Jeffrey HN. Contrast Medium–induced Nephrotoxicity: Is the Medical Risk Really as Great as We Have Come to Believe? Radiology 2010; 256: 21-28

Kelly AM et al, Meta-analysis: Effectiveness of Drugs for Preventing Contrast-Induced Nephropathy. Ann Intern Med. 2008; 148: 284-294

Kramer P, Kaufhold C, Grone HJ, Wigger W, Rieger D. Management of anuric intensive-care patients with arteriovenous hemofiltration. Int J Artif Organs 1980; 3: 225-230

Lameire et al. Prevention and nondialytic treatment of acute renal failure. Current Opinion in Critical Care 2003; 9: 481–490

Lameire N, Wim Van Biesen W, Vanholder R. Acute renal failure. Lancet 2005; 365: 417–30. This is a good review article

Langenberg C et al. The histopathology of septic acute kidney injury: a systematic review. Critical Care 2008, 12:R38

Mehta RL et al (AKIN). Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Critical Care 2007; 11: R31

Metcalfe et al. Acute renal failure requiring renal replacement therapy: incidence and outcome. QJM 2002; 95 (9): 579-583

Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002; 39(5): 930-6

Joslin J, Ostermann M. Care of the Critically Ill Emergency Department Patient with Acute Kidney Injury. Emerg Med Int 2012; 2012

Pannu N, James M, Hemmelgarn BR, Dong J, Tonelli M, Klarenbach S. Modification of Outcomes After Acute Kidney Injury by the Presence of CKD. Am J Kidney Dis 2011; 58(2) :206-13

Phu NH et al. Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. N Engl J Med 2002;19; 347(12): 895-902

Prowle JR et al. Fluid balance and acute kidney injury. Nature Reviews Nephrology 2009; 6: 107-115

Ricci Z et al (RIFLE and AKIN). Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria. Nature Reviews Nephrology 2011; 7: 201-208

Ronco C et al. Potential Interventions in Sepsis-Related Acute Kidney Injury. CJASN March 2008; (3, 2): 531-544 

Schiffl H. Renal recovery from acute tubular necrosis requiring renal replacement therapy: a prospective study in critically ill patients. Nephrol Dial Transplant 2006; 21 (5): 1248-1252

Selby NM et al. Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients. Clin J Am Soc Nephrol 2012; 7(4): 533-40

Silverstein ME, Ford CA, Lysaght MJ, Henderson LW. The treatment of intractable fluid overload. N Engl J Med 1974; 291: 747

Smith HW. The Kidney: Structure and Function in Health and Disease. New York: Oxford University Press, 1951

Stevens PE et al. Non-specialist management of acute renal failure. QJM 2001;94(10): 533-40

Srisawat N, Kellum JA. Acute Kidney Injury—Definition and Classification. 2009
A good review of definition and classification of AKI

Thomas M et al. The initial development and assessment of an automatic alert warning of acute kidney injury. Nephrol Dial Transplant 2011; 26(7): 2161-8

Ueng S et al. Rasburicase (Elitek): a novel agent for tumor lysis syndrome. Proc (Bayl Univ Med Cent) 2005; 18(3): 275–279

Van Berendoncks AM et al. Outcome of acute kidney injury with different treatment options: long-term follow-up. Clin J Am Soc Nephrol 2010; 5(10): 1755-62

Vaidya et al. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008; 48: 463-93

Waikar SS and Bonventre JV. Creatinine Kinetics and the Definition of Acute Kidney Injury. JASN 2009, 20 (3): 672-679

Wetzels JFM et al. Age- and gender-specific reference values of estimated GFR in Caucasians: The Nijmegen Biomedical Study. Kidney Int 2007; 72(5): 632–7


Global/Cochrane. Reviews (10). Acute Kidney Failure

Global/KDIGO. Acute Kidney Injury (AKI). March 2012

UK/GAIN. Northern Ireland Guidelines for Acute Kidney Injury (AKI). 2010

UK/NICE. CG24: Acute kidney injury: prevention, detection and management of acute kidney injury up to the point of renal replacement therapy. August 2013

UK/NCEPOD. National Confidential Enquiry into Patient Outcome and Death (NCEPOD) “Acute Kidney Injury: Adding Insult to Injury”. 2009

UK/Renal Association. Acute Kidney Injury (AKI). Lewington A, Kanagasundaram S. 8.3.11

UK/Renal Pharmacy Group. Acute Kidney Injury - Medication Optimisation Toolkit. March 2012


Acute Dialysis Quality Initiative (ADQI)

Acute Kidney Injury Network (AKIN)

An account of AKI for junior doctors can be found in AcuteMed