Acute kidney injury

Acute kidney injury (AKI) is an abrupt, usually reversible fall in glomerular filtration, manifest as a rise in creatinine or a fall in urine output. It is common, lethal when severe, and — critically for the emergency candidate — the window where intervention reverses the lesion is narrow and measured in hours. The Fellowship examiner tests three things: classification (KDIGO), the pre-renal versus intrinsic versus post-renal split and its urine-chemistry discriminators (BUN-to-creatinine ratio and FENa), and the resuscitation-plus-complication management (treat the cause, fluid challenge, avoid nephrotoxins, control hyperkalaemia, escalate to dialysis under AEIOU). The candidate who reaches for frusemide to "make urine" before securing perfusion fails the station and harms the kidney.[1][2]

Definition and classification

AKI is defined by the KDIGO 2012 criteria, which the candidate must reproduce verbatim. AKI is present when any one of the following holds: a rise in serum creatinine of at least 26.5 micromol per litre (0.3 mg per decilitre) within 48 hours; a rise in creatinine to at least 1.5 times the baseline value, known or presumed to have occurred within the prior seven days; or a urine volume of under 0.5 mL per kilogram per hour for six hours.[1][2]

Severity is then staged 1 to 3, and the stage predicts mortality and guides the threshold for renal replacement therapy. [1]

KDIGO unified the earlier RIFLE (Risk, Injury, Failure, Loss, End-stage) and AKIN (Acute Kidney Injury Network) schemes; the creatinine and urine-output thresholds overlap, and the examiner may use any of the three names. The change in nomenclature from "acute renal failure" to "acute kidney injury" was deliberate — it captures the spectrum from a mild, reversible rise in creatinine through to established tubular necrosis, and it underscores that the mild injury is itself dangerous and worth treating. [1]

Epidemiology and risk

AKI complicates roughly one in five adult hospital admissions and over half of intensive-care admissions; the multinational AKI-EPI study found AKI in approximately 57 per cent of ICU patients, with stage 2 to 3 disease in roughly a third.[3][4] Mortality tracks severity: stage 3 AKI in the critically ill carries a mortality approaching 50 per cent, and even stage 1 independently increases in-hospital death. Survivors carry a markedly elevated risk of progressing to chronic kidney disease. Risk is concentrated in the elderly, in patients with pre-existing CKD, diabetes, heart failure or sepsis, and after major surgery, hypovolaemia, or exposure to nephrotoxins (non-steroidal anti-inflammatories, ACE-inhibitors and angiotensin-receptor blockers, iodinated contrast, aminoglycosides, vancomycin, tenofovir). The commonest single emergency scenario is the volume-deplete septic patient on an ACE-inhibitor who has taken a NSAID and then had a contrast CT.

Pathophysiology — pre-renal, intrinsic, post-renal

AKI is classified by site into three compartments, and the site decides both the urine chemistry and the treatment. [1]

The unifying cellular mechanism is tubuloglomerular feedback: a fall in renal blood flow or a direct tubular toxin injures the proximal tubular cell, which releases mediators that constrict the afferent arteriole and collapse the glomerular filtration pressure. In pure pre-renal disease the tubule is structurally intact and simply underperfused, so it conserves sodium; once injury passes a threshold the tubule loses its sodium-pump integrity and becomes ATN — the point at which a fluid challenge no longer reverses the lesion.[1]

Clinical presentation

AKI is usually clinically silent and is discovered on the biochemistry or the urine-output chart, not at the bedside. When symptoms exist they reflect the cause (hypovolaemia, sepsis, obstruction), the uraemic state (nausea, anorexia, confusion, pruritus, pericarditic chest pain), or the complications (dyspnoea from fluid overload, weakness from hyperkalaemia, seizures from severe acidosis). The history interrogates fluid loss (vomiting, diarrhoea, haemorrhage, burns), sepsis source, recent surgery, drug list (NSAIDs, ACE-inhibitors, contrast, antibiotics), and urinary symptoms suggesting obstruction. The single most useful examination finding is the volume status: dry mucosae, low jugular venous pressure and a postural drop point to pre-renal disease and predict a response to fluid, whereas a raised jugular venous pressure, basal crackles and oedema argue against further boluses. [1]

Differential diagnosis

The differential is not a list of diseases but the mechanistic split above, plus the AKI-versus-CKD distinction. AKI on a background of CKD ("acute-on-chronic") is the rule rather than the exception in the elderly renal patient — small kidneys on ultrasound, an anaemia out of proportion to the acute event, and a known baseline creatinine all flag chronicity. The distinguishing features: [1]

Bedside assessment

Assess and resuscitate in parallel. Secure airway and breathing, attach cardiac monitoring (hyperkalaemia is the lethal complication), and establish intravenous access. Establish the volume status from mucous membranes, jugular venous pressure, capillary refill, lung bases and peripheral oedema, and look for the cause: fever and a source for sepsis, a palpable bladder and an enlarged prostate or pelvic mass for obstruction, a drug chart laden with nephrotoxins, and stigmata of chronic liver or heart failure. Examine for the complications — a pericardial rub (uraemic pericarditis), asterixis (uraemic encephalopathy), and fluid overload. [1]

Send blood for urea and electrolytes with a venous gas (to confirm the potassium and the acid-base immediately), full blood count, creatinine kinase for rhabdomyolysis, calcium, magnesium, phosphate, albumin, coagulation, and a beta-human chorionic gonadotropin in women. Send urine for dipstick, microscopy (casts) and a spot sodium and creatinine for FENa. A bladder scan or in-out catheter excludes retention at the bedside. [1]

Investigations and the discriminators

The venous blood gas delivers the potassium and pH within minutes and sets the urgency. The serum creatinine confirms AKI against a baseline (use the lowest known value in the prior three months); remember creatinine lags the injury and under-represents severity in the small, malnourished patient. Urinalysis narrows the mechanism: bland concentrated urine suits pre-renal disease; muddy brown granular casts and renal tubular epithelial cells on microscopy are the signature of ATN; haematuria and proteinuria with red-cell casts suggest glomerulonephritis; eosinophils and white-cell casts suggest acute interstitial nephritis. [1]

Two urine-chemistry ratios distinguish pre-renal from intrinsic disease and must be reproduced. [1]

The fractional excretion of urea (FEUrea) is the diuretic-resistant cousin of FENa and the discriminator the candidate must reach for whenever the patient has received frusemide. Urea is reabsorbed passively and partly independently of the sodium-pump that frusemide blocks, so it retains discriminating power after a loop diuretic. Carvounis' landmark Kidney International study showed FEUrea under 35 per cent correctly identified pre-renal azotemia in the diuretic-treated patient where FENa failed.[13] FEUrea = (urine urea × plasma creatinine) ÷ (plasma urea × urine creatinine) × 100.

Renal tract ultrasound is mandatory in any AKI without a clear pre-renal cause to exclude obstruction (hydronephrosis) and to gauge kidney size and cortical thickness (small kidneys support CKD). A chest radiograph assesses fluid overload, and an electrocardiogram screens for hyperkalaemic change. [1]

Immediate management and resuscitation

The principles are treat the cause, restore perfusion, stop nephrotoxins, and manage the complications in parallel. Do not reach for frusemide to generate urine before the patient is resuscitated — it converts a hypovolaemic pre-renal state into established ATN. [1]

Treat the cause at the source: control haemorrhage, give antibiotics and source control for sepsis within the hour, drain obstruction with a catheter or nephrostomy, and stop the offending drug. Stop every nephrotoxin on presentation — non-steroidal anti-inflammatories, ACE-inhibitors and angiotensin-receptor blockers, iodinated contrast unless essential, aminoglycosides (switch to a renal-safe regimen), and potassium-sparing agents. Withhold metformin in any AKI (lactic-acidosis risk). [1]

Give a fluid challenge to the volume-deplete patient — 250 to 500 mL of balanced crystalloid (Hartmann's or Plasma-Lyte) over 15 to 30 minutes, and reassess the response by urine output, jugular venous pressure and lung bases before repeating. Normal saline in large volumes causes hyperchloraemic acidosis and worsens renal perfusion, so prefer a balanced solution. The fluid challenge is diagnostic as well as therapeutic: a pre-renal kidney responds within hours; failure to respond means established intrinsic disease or ongoing obstruction, and further blind boluses only cause pulmonary oedema.[6]

Definitive management and the escalation ladder

Once resuscitated and the cause addressed, definitive management is supportive while the tubule recovers: maintain perfusion with balanced fluids matched to output, correct electrolyte and acid-base disturbances, treat infection, and nutritionally support. Loop diuretics (frusemide 40 to 80 mg IV) have no role in treating AKI itself — they do not shorten the course or reduce mortality — but may relieve symptomatic fluid overload in the polyuric or responsive patient, and never substitute for dialysis when dialysis is indicated. [1]

Hyperkalaemia is the lethal complication and is treated up the antidote ladder (the candidate must know the order): calcium chloride 10 mL of 10 per cent IV first to stabilise the cardiac membrane whenever there is any ECG change (peaked T, widened QRS, sine wave); then insulin 10 units of soluble insulin with 50 mL of 50 per cent dextrose IV to shift potassium into cells, lowering it by roughly 1 mmol per litre over 15 to 30 minutes; add salbutamol 10 to 20 mg nebulised as a synergistic beta-2 shifter; and remove potassium with gastrointestinal cation-exchange resins or, definitively, haemodialysis.[1]

Renal replacement therapy is indicated when conservative measures fail. The indications are encoded by AEIOU: [1]

The modality — intermittent haemodialysis, continuous renal replacement therapy (CVVHDF), or sustained low-efficiency dialysis — is chosen with the renal and intensive-care teams by haemodynamic stability; continuous therapy suits the shocked patient. Timing of initiation is nuanced: dialyse for an indication, not for a creatinine number alone.[5]

Renal replacement therapy timing — the evidence

The single most examined AKI controversy of the last decade is when to start RRT in the critically ill patient without an absolute indication. Three large multicentre randomised trials frame the modern answer, and the candidate must hold them in the same hand. ELAIN suggested a benefit to early initiation; AKIKI and the much larger STARRT-AKI found no benefit and a signal toward harm (more RRT dependence) with the early strategy. The synthesis: initiate RRT for an indication (AEIOU), not for a creatinine number, and tolerate a period of observation with conservative support in the patient with severe AKI but no absolute indication. [1]

Subtypes and special scenarios

Contrast-associated AKI follows iodinated contrast in the at-risk patient (CKD, diabetes, hypovolaemia); prevention is volume expansion with isotonic fluid and avoidance of nephrotoxins, not prophylactic N-acetylcysteine (the evidence is equivocal). Rhabdomyolysis-induced AKI (creatine kinase in the thousands, pigment casts, myoglobin) demands aggressive isotonic fluid expansion to drive a urine output of 1 to 2 mL per kilogram per hour; alkaline diuresis is now debated. Acute interstitial nephritis (eosinophiluria, rash, fever, after a beta-lactam, NSAID or proton-pump inhibitor) requires drug cessation and, for severe disease, corticosteroids. Hepatorenal syndrome in cirrhosis is a pre-renal physiology unresponsive to fluid, treated with albumin and terlipressin. Glomerulonephritis (red-cell casts, hypertension, oedema) demands urgent renal referral, serology and biopsy. [1]

Contrast-associated AKI and the PRESERVE verdict

The earlier enthusiasm for prophylactic N-acetylcysteine and sodium bicarbonate infusions before iodinated contrast was overturned by the PRESERVE trial: in 5177 high-risk patients undergoing angiography, neither intravenous sodium bicarbonate nor acetylcysteine reduced the risk of contrast-associated AKI, dialysis, or death compared with isotonic saline and placebo. The prevention of contrast-associated AKI is now isotonic volume expansion and the avoidance of other nephrotoxins — bicarbonate and N-acetylcysteine add nothing.[14]

Aetiology memory aids by compartment

Complications and pitfalls

The complications are fluid, electrolyte and acid-base: hyperkalaemia (the killer), metabolic acidosis (a high anion gap from retained acids), fluid overload and pulmonary oedema, uraemic pericarditis and encephalopathy, anaemia from blunted erythropoietin, infection (the leading cause of death), and bleeding from platelet dysfunction. The pitfalls are the mirror of the management: reaching for frusemide before resuscitating; continuing ACE-inhibitors or NSAIDs in an evolving AKI; missing a drainable obstruction; trusting a FENa taken after a diuretic; over-resuscitating into pulmonary oedema; and delaying dialysis when the hyperkalaemic ladder has failed. [1]

Prognosis and disposition

Outcome tracks severity, cause, and the speed of correction. Pre-renal and post-renal AKI recover fully when the insult is removed promptly; ATN recovers over one to three weeks but carries a mortality that rises with stage. Disposition: stage 1 AKI with a reversible cause may be managed on a ward with daily biochemistry; stage 2 to 3 disease, hyperkalaemia, fluid overload, or any dialysis indication is admitted to a high-dependency or intensive-care bed with continuous monitoring. Survivors need follow-up creatinine, as even recovered AKI raises the long-term risk of chronic kidney disease.[3][4]

Special populations

The elderly have less renal reserve and accumulate nephrotoxins; a small creatinine rise in an 80-year-old is a large loss of filtration. Pre-existing CKD is the single strongest risk factor and is usually the substrate for acute-on-chronic injury. Sepsis is the commonest ICU cause and combines vasodilatory pre-renal hypoperfusion with direct tubular injury. Post-operative patients (especially cardiac and major abdominal surgery) develop AKI from hypoperfusion and third-spacing. Cirrhosis brings hepatorenal physiology. The diabetic on metformin needs the drug withheld and lactic acidosis considered when AKI coexists. [1]

Evidence and regional guidelines

The contemporary framework is the KDIGO 2012 Clinical Practice Guideline for Acute Kidney Injury, summarised operationally by Kellum and Lameire, which codifies the diagnostic criteria, staging, the work-up, and the management principles reproduced above, and is endorsed across ANZ, UK and US practice.[7] The definitive reviews of classification, pathophysiology and management are the Ronco–Bellomo–Kellum Lancet seminar and the Lameire–Vanholder Lancet review; the epidemiology is captured by the world-incidence meta-analysis and the AKI-EPI multinational ICU study.[1][2][3][4] The modern answer to when to start RRT is settled by the three large timing trials — AKIKI and the much larger STARRT-AKI showed no benefit and a harm signal with the early strategy, while the single-centre ELAIN remains the unreproduced positive outlier, and AKIKI-2 added nuance to the delayed arm — together establishing the indication-based consensus.[8][9][10][15] The fluid choice is settled by the SMART and SALT-ED trials in favour of balanced crystalloid over saline for the AKI resuscitation, and the contrast-associated AKI prophylaxis is settled by PRESERVE in favour of isotonic saline alone (no bicarbonate, no N-acetylcysteine).[11][12][14] The timing of dialysis more broadly is addressed in the Macedo–Mehta review, and the harm of fluid overload is detailed in the O'Connor–Prowle review.[5][6] The fractional excretion of urea as the diuretic-resistant discriminator was validated by Carvounis.[13]

Exam pearls

• KDIGO verbatim — at least 26.5 micromol per litre creatinine rise in 48 hours, OR at least 1.5 times baseline in seven days, OR urine output under 0.5 mL per kilogram per hour for six hours. Stage 3 includes the initiation of renal replacement therapy.
• Pre-renal vs ATN urine chemistry — FENa under 1 per cent, urine sodium under 20, BUN:Cr over 20 to 1, urine osmolality over 500 is pre-renal; the reverse is ATN. Diuretics invalidate FENa — switch to FEUrea under 35 per cent.
• Muddy brown granular casts equal ATN — the single best microscopy discriminator for intrinsic tubular injury.
• First drug in hyperkalaemic AKI with ECG change is calcium — chloride 10 mL of 10 per cent IV; it stabilises the membrane but does not lower potassium, so always pair it with insulin-dextrose.
• Frusemide does not treat AKI — it relieves overload and does not shorten recovery; never substitute it for resuscitation or dialysis.
• AEIOU — Acidosis, Electrolytes, Intoxication, Overload, Uraemia — the dialysis indications.
• RBC casts equal glomerulonephritis, WBC casts plus eosinophils equal acute interstitial nephritis — pair the cast to the mechanism; AIN follows penicillins, NSAIDs and PPIs.
• Sepsis is the commonest cause of AKI in the ICU — it combines vasodilatory pre-renal hypoperfusion with direct tubular injury, and is the master diagnosis to exclude.
• NSAIDs constrict the afferent arteriole, ACE-inhibitors dilate the efferent — both drop the glomerular filtration pressure and tip the borderline kidney into AKI; stop both on presentation.
• FEUrea under 35 per cent is the diuretic-resistant discriminator — Carvounis showed it identifies pre-renal azotemia where FENa fails after frusemide.
• Post-renal AKI needs bilateral obstruction (or a single kidney) to raise creatinine — BPH, prostate or cervical cancer, bilateral stones, retroperitoneal fibrosis; drain it and it recovers.
• Creatinine lags the injury — a normal creatinine in the small, malnourished or early patient does not exclude a large loss of filtration; the urine output and the trend are the frontline.
• Normal saline in large volume causes hyperchloraemic acidosis — the SMART and SALT-ED trials made balanced crystalloid (Hartmann, Plasma-Lyte) the default for the AKI fluid challenge.
• PRESERVE killed the bicarbonate-and-N-acetylcysteine reflex — isotonic saline volume expansion and holding nephrotoxins are the only proven prevention for contrast-associated AKI.
• AKIKI and STARRT-AKI settled the RRT-timing question — start dialysis for an AEIOU indication, not for a creatinine number; the early strategy adds catheter harm and RRT dependence without a survival gain. ELAIN is the unreproduced positive outlier.
• Withhold metformin in any AKI — the renally-cleared drug accumulates and precipitates lactic acidosis; check the lactate and the pH in the metformin-treated patient.
• Hydroxyethyl starch is contraindicated in AKI — colloids add no outcome benefit over crystalloid and the starches increase the renal injury and the need for RRT.
• A single normal creatinine never rules out AKI in the elderly — the 80-year-old loses a large filtration fraction for a small creatinine rise; stage by KDIGO and trend the urine output. [1]

Exam practice

Red flags