Acute Kidney Injury

AKI Classification

Acute kidney injury (AKI) is classified principally by change in kidney function over time, not by a single absolute creatinine value. In MRCP practice, the key classification is the KDIGO 2012 staging system, which harmonised the earlier RIFLE and AKIN criteria and remains the basis of NICE and international guidance. AKI is defined by any of the following: increase in serum creatinine by ≥26.5 micromol/L within 48 hours; increase in serum creatinine to ≥1.5 times baseline within the previous 7 days; or urine volume <0.5 mL/kg/hour for 6 hours. The definition deliberately combines biochemical and functional criteria because oliguria may precede creatinine rise, while creatinine may lag behind true fall in glomerular filtration rate.

KDIGO staging

Stage	Serum creatinine criterion	Urine output criterion	Clinical significance
Stage 1	Increase by ≥26.5 micromol/L within 48 h, or 1.5–1.9 × baseline	<0.5 mL/kg/h for 6–12 h	Associated with increased mortality despite apparently modest creatinine change
Stage 2	2.0–2.9 × baseline	<0.5 mL/kg/h for ≥12 h	Higher risk of complications, persistent dysfunction and need for renal support
Stage 3	3.0 × baseline, or creatinine ≥353.6 micromol/L with acute rise ≥26.5 micromol/L, or initiation of renal replacement therapy	<0.3 mL/kg/h for ≥24 h, or anuria for ≥12 h	Highest mortality risk; includes all patients requiring dialysis regardless of creatinine

For examination purposes, note that renal replacement therapy automatically classifies AKI as stage 3. Urine output criteria require accurate timing and weight-based assessment; in a 70 kg adult, the KDIGO oliguria threshold is approximately <35 mL/hour. Creatinine criteria require an estimate of baseline: ideally a stable outpatient value within the preceding 7–365 days, interpreted in context. Back-calculation from an assumed eGFR of 75 mL/min/1.73 m² has been used in epidemiological studies but is unreliable in older patients and those with chronic kidney disease.

Relationship to RIFLE and AKIN

The older RIFLE classification described severity as Risk, Injury, Failure, and outcomes as Loss and End-stage kidney disease. It used creatinine/eGFR and urine output thresholds: Risk approximates KDIGO stage 1, Injury stage 2, and Failure stage 3. AKIN modified RIFLE by adding the absolute creatinine rise of ≥26.5 micromol/L within 48 hours and removing eGFR criteria. KDIGO is preferred because it integrates these strengths and is more consistently used in trials, registries and guidelines.

System	Key contribution	Limitation
RIFLE	First widely adopted graded severity framework; linked AKI severity to outcome	Included eGFR change, problematic during non-steady-state creatinine kinetics
AKIN	Recognised small absolute creatinine rises as prognostically important	Required changes over 48 h, potentially missing slower-evolving AKI
KDIGO	Current standard; uses 48 h absolute and 7-day relative creatinine criteria plus urine output	Still dependent on imperfect biomarkers of filtration and urine measurement

Physiological and temporal classification

AKI should also be classified by anatomical-functional compartment: pre-renal, intrinsic renal and post-renal. This is a diagnostic framework rather than a severity scale. Pre-renal AKI denotes reduced effective renal perfusion with initially preserved tubular integrity; intrinsic AKI reflects parenchymal injury involving tubules, glomeruli, interstitium or renal vasculature; post-renal AKI reflects obstruction to urinary drainage. The distinction is clinically important because reversibility, urinary indices, imaging priorities and complications differ, but overlap is common: sustained pre-renal physiology may evolve into acute tubular injury, and obstruction may cause intrinsic tubular dysfunction if prolonged.

AKI may further be described as community-acquired or hospital-acquired, and as de novo or acute-on-chronic kidney disease. Acute-on-chronic kidney disease is particularly high risk because a small absolute fall in GFR may produce a large creatinine rise at low baseline renal reserve, and because drug accumulation, hyperkalaemia and acidosis occur earlier.

Important limitations of creatinine-based staging

Serum creatinine is a delayed and context-dependent surrogate for GFR. It may not rise for 24–48 hours after abrupt nephron injury, and its concentration is influenced by muscle mass, volume status, diet, assay interference and tubular secretion. In critical illness, dilution from fluid resuscitation can mask AKI severity; conversely, low muscle mass may underestimate injury. Estimated GFR equations are not valid in evolving AKI because they assume steady-state creatinine kinetics. Thus, classification should be based on serial creatinine, urine output, clinical context and trajectory, rather than a single eGFR value.

AKI Causes

AKI is best approached aetiologically as pre-renal, intrinsic renal, or post-renal, recognising that these categories frequently coexist and may evolve sequentially: prolonged renal hypoperfusion causes ischaemic acute tubular injury, obstruction may precipitate infection, and sepsis produces both haemodynamic and inflammatory tubular injury. For MRCP purposes, the key discriminator is the dominant pathophysiological process: reduced renal perfusion pressure, primary parenchymal damage, or impaired urinary drainage.

Pre-renal AKI: reduced effective renal perfusion

Pre-renal AKI results from reduced renal blood flow or reduced glomerular filtration pressure with initially preserved tubular integrity. GFR is maintained by afferent arteriolar vasodilatation mediated by prostaglandins and efferent arteriolar vasoconstriction mediated by angiotensin II; drugs interfering with these compensatory mechanisms commonly precipitate AKI in vulnerable patients. The classic “triple whammy” is an ACE inhibitor or ARB plus a diuretic plus an NSAID, particularly in older adults, CKD, heart failure, cirrhosis, or intercurrent sepsis.

Pre-renal mechanism	Typical causes	Key pathophysiology
Absolute intravascular volume depletion	Haemorrhage, vomiting, diarrhoea, burns, excessive diuresis, osmotic diuresis	Reduced renal plasma flow and transglomerular filtration pressure; high neurohormonal activation
Reduced effective arterial blood volume	Heart failure, cirrhosis with ascites, nephrotic syndrome, sepsis	Renal hypoperfusion despite normal or increased total body water; RAAS and sympathetic activation
Renovascular or autoregulatory failure	Bilateral renal artery stenosis, solitary kidney stenosis, ACEi/ARB, NSAIDs, calcineurin inhibitors	Loss of efferent tone or afferent vasodilatation; vasoconstrictive endothelial injury with ciclosporin/tacrolimus

Hepatorenal syndrome-AKI is a functional renal failure in advanced cirrhosis with portal hypertension, driven by splanchnic vasodilatation, renal vasoconstriction, and intense RAAS activation. It is diagnosed after exclusion of shock, nephrotoxins, structural renal disease, and failure to respond to diuretic withdrawal plus albumin expansion, typically albumin 1 g/kg/day up to 100 g/day for 2 days.

Intrinsic renal AKI

Intrinsic AKI is subdivided anatomically into tubular, interstitial, glomerular, and vascular causes. The commonest hospital cause is acute tubular injury/necrosis, usually ischaemic or toxic. Sepsis-associated AKI is not merely “pre-renal”: inflammatory endothelial dysfunction, microcirculatory shunting, mitochondrial injury, tubular cell cycle arrest, and venous congestion all contribute, often with normal or increased renal blood flow.

Acute tubular injury

• Ischaemic: prolonged hypotension, septic shock, major surgery, trauma, pancreatitis, postpartum haemorrhage, cardiac arrest. Renal medullary thick ascending limb and proximal tubule are vulnerable because of high ATP demand and low oxygen tension.
• Nephrotoxic drugs: aminoglycosides cause proximal tubular uptake via megalin/cubilin and lysosomal injury; risk rises with trough gentamicin concentrations >1 mg/L and therapy beyond 5–7 days. Vancomycin nephrotoxicity is exposure-related; contemporary monitoring targets AUC/MIC 400–600, as high trough-based dosing of 15–20 mg/L increases AKI risk. Amphotericin B causes afferent vasoconstriction and distal tubular toxicity; cisplatin causes dose-dependent proximal tubular injury.
• Pigment nephropathy: rhabdomyolysis from crush injury, seizures, statins, cocaine, malignant hyperthermia; myoglobin promotes tubular obstruction, vasoconstriction, and oxidative injury, with risk particularly when creatine kinase is >5,000 IU/L and dehydration/acidosis coexist. Haemolysis causes analogous haemoglobin-mediated injury.
• Crystal nephropathy: tumour lysis syndrome, aciclovir, indinavir, methotrexate, ethylene glycol. High-dose intravenous aciclovir, especially rapid infusion or dehydration, may cause intratubular precipitation.
• Iodinated contrast-associated AKI: now less common than historically suggested; risk is greatest with intra-arterial contrast, haemodynamic instability, diabetes with CKD, heart failure, and eGFR <30 mL/min/1.73 m². Modern guidance emphasises that many cases represent coincident AKI rather than direct contrast toxicity.

Interstitial nephritis

Acute interstitial nephritis is commonly drug-induced and typically delayed by days to weeks after exposure. Important causes include beta-lactams, rifampicin, sulfonamides, NSAIDs, proton pump inhibitors, immune checkpoint inhibitors, allopurinol, and diuretics. NSAID-associated AIN may present with nephrotic-range proteinuria due to minimal change disease. Systemic causes include sarcoidosis, Sjögren syndrome, IgG4-related disease, infections, and tubulointerstitial nephritis with uveitis.

Glomerular causes

Glomerular AKI should be suspected when AKI is driven by inflammatory capillary wall injury causing rapidly progressive glomerulonephritis. Core causes include ANCA-associated vasculitis, anti-GBM disease, lupus nephritis, IgA vasculitis/nephropathy, infection-related GN, cryoglobulinaemia, and endocarditis-associated immune complex GN. Anti-GBM disease is clinically critical because pulmonary haemorrhage may coexist and early treatment determines renal recovery.

Vascular causes

Renal vascular AKI includes large-vessel occlusion, malignant hypertension, thrombotic microangiopathy, cholesterol embolisation, and renal cortical necrosis. TMA causes endothelial injury with platelet-rich microthrombi: differential diagnoses include thrombotic thrombocytopenic purpura, Shiga-toxin HUS, complement-mediated atypical HUS, malignant hypertension, pregnancy-related syndromes, antiphospholipid syndrome, calcineurin inhibitors, quinine, and gemcitabine. Cholesterol embolisation follows vascular instrumentation or anticoagulation, typically in older patients with atherosclerosis, causing subacute AKI with livedo reticularis, blue toes, and eosinophilia.

Post-renal AKI: urinary tract obstruction

Post-renal AKI requires obstruction to both kidneys, a solitary functioning kidney, or obstruction distal to the bladder. It is common, reversible, and frequently missed. Causes include benign prostatic enlargement, prostate or pelvic malignancy, urethral stricture, blocked catheter, retroperitoneal fibrosis, bilateral ureteric stones, clot retention, neurogenic bladder, and severe constipation. Obstruction initially increases tubular pressure and reduces net filtration pressure; prolonged obstruction causes renal vasoconstriction, interstitial inflammation, tubular atrophy, and potentially irreversible fibrosis. In examinations, always consider post-renal AKI in older men, pelvic malignancy, anuria, loin pain, recurrent UTI, or new urinary retention.

AKI Investigations

Investigation of acute kidney injury (AKI) should proceed in parallel with resuscitation and management of immediately reversible threats. The aims are to confirm AKI and stage severity, identify pre-renal, intrinsic renal or post-renal patterns, detect complications, and define whether urgent renal replacement therapy or specialist intervention is required. NICE and KDIGO recommend that any patient with acute illness should have serum creatinine compared with baseline and urine output assessed; absence of a known baseline should prompt review of prior records rather than assuming normal renal function.

Confirmation and staging

KDIGO AKI stage	Serum creatinine criterion	Urine output criterion
Stage 1	Increase ≥26.5 micromol/L within 48 h, or 1.5–1.9 × baseline within 7 days	<0.5 mL/kg/h for 6–12 h
Stage 2	2.0–2.9 × baseline	<0.5 mL/kg/h for ≥12 h
Stage 3	≥3 × baseline, creatinine ≥353.6 micromol/L with acute rise, or initiation of renal replacement therapy	<0.3 mL/kg/h for ≥24 h or anuria for ≥12 h

Serum creatinine is an insensitive and delayed marker: it may not rise for 24–48 hours after a fall in glomerular filtration rate, is diluted by positive fluid balance, and is influenced by muscle mass, diet, tubular secretion and drugs such as trimethoprim or cimetidine. Urea rises disproportionately in catabolic states, gastrointestinal bleeding, corticosteroid use and volume depletion, but is useful when interpreted dynamically. eGFR equations are not valid in non-steady-state AKI and should not be used to dose rapidly changing renal function without clinical judgement.

Initial laboratory assessment

• Urea, creatinine and electrolytes: assess potassium, bicarbonate, sodium, calcium, phosphate and magnesium. Hyperkalaemia ≥6.0 mmol/L, severe acidosis with pH <7.1–7.2, or rapidly rising potassium are high-risk findings.
• Venous or arterial blood gas: quantifies metabolic acidosis, lactate and respiratory compensation; arterial sampling is reserved for hypoxaemia or shock.
• Full blood count: anaemia and thrombocytopenia suggest haemolysis, thrombotic microangiopathy or systemic disease; eosinophilia may support allergic interstitial nephritis but is insensitive.
• CRP, blood cultures and infection screen: guided by sepsis suspicion. Sepsis-associated AKI may occur without profound hypotension through microcirculatory and inflammatory tubular dysfunction.
• Creatine kinase: essential if rhabdomyolysis is possible; AKI risk rises markedly when CK exceeds 5,000 IU/L, particularly with hypovolaemia, acidosis or sepsis.
• Drug levels: lithium, gentamicin/amikacin/vancomycin and tacrolimus/ciclosporin where relevant. Aminoglycoside nephrotoxicity correlates with trough accumulation; gentamicin trough should usually be <1 mg/L.

Urine assessment

Accurate urine output measurement is central; insert a urinary catheter when monitoring is clinically necessary, balancing infection risk. Urinalysis is a high-yield MRCP investigation. Blood and protein suggest glomerulonephritis or vasculitis; leucocytes without bacteriuria may suggest interstitial nephritis; nitrites support Gram-negative urinary infection. Albumin:creatinine ratio helps quantify glomerular injury, though heavy proteinuria may also occur in acute tubular injury.

Test	Typical interpretation	Important limitations
Urine microscopy	Muddy brown granular casts: acute tubular necrosis; red cell casts/dysmorphic RBCs: glomerulonephritis; white cell casts: interstitial nephritis or pyelonephritis	Operator-dependent; absence of casts does not exclude intrinsic renal disease
Urine sodium	<20 mmol/L classically pre-renal; >40 mmol/L classically tubular injury	Unreliable after diuretics, CKD, adrenal insufficiency, contrast exposure or sepsis
Fractional excretion of sodium	FENa <1% supports pre-renal physiology; >2% supports ATN	Invalid with loop/thiazide diuretics and many mixed AKI states
Fractional excretion of urea	FEUrea <35% supports pre-renal physiology, including in some diuretic-treated patients	Altered by sepsis, catabolism, liver disease and osmotic diuresis

FENa is calculated as: urine sodium × plasma creatinine / plasma sodium × urine creatinine × 100. It should be treated as supportive rather than diagnostic, because modern AKI commonly involves overlapping haemodynamic, inflammatory and tubular mechanisms.

Imaging and obstruction

Renal tract ultrasound is indicated urgently where obstruction is suspected, in unexplained AKI, advanced AKI, solitary kidney, pelvic malignancy, renal colic, or failure to improve. Hydronephrosis supports obstruction but may be absent early, with dehydration, retroperitoneal fibrosis or encasing malignancy. Ultrasound also assesses renal size and chronicity: small echogenic kidneys suggest chronic kidney disease, whereas normal or enlarged kidneys may be seen in diabetic nephropathy, amyloid, myeloma, HIV nephropathy or acute interstitial processes. Non-contrast CT KUB is preferred for suspected ureteric stones; contrast-enhanced CT should be justified by diagnostic necessity rather than avoided reflexively, with volume status and nephrotoxin exposure optimised.

Immunological and disease-specific investigations

Intrinsic renal AKI with active urinary sediment, pulmonary haemorrhage, purpura, systemic features or rapidly progressive renal failure requires urgent serology: ANCA, anti-GBM antibody, ANA, anti-dsDNA, complement C3/C4, serum immunoglobulins, serum free light chains, protein electrophoresis, hepatitis B/C and HIV testing. Low complement suggests lupus nephritis, infection-related GN, cryoglobulinaemia or membranoproliferative patterns. Suspected thrombotic microangiopathy requires blood film for schistocytes, LDH, haptoglobin, reticulocytes, coagulation screen and ADAMTS13 activity if TTP is possible.

Renal biopsy and biomarkers

Renal biopsy is considered when the result will alter management: unexplained intrinsic AKI, suspected rapidly progressive glomerulonephritis, vasculitis, interstitial nephritis not resolving after drug withdrawal, myeloma-related renal disease, or transplant dysfunction. Contraindications include uncontrolled hypertension, bleeding diathesis, active infection at the biopsy site, uncooperative patient and often a solitary native kidney. Novel biomarkers such as NGAL, KIM-1 and TIMP-2·IGFBP7 detect tubular stress earlier than creatinine, but availability and outcome-changing evidence remain limited; they are not routine MRCP-level decision tests in standard NHS practice.

AKI Complications

Complications of acute kidney injury (AKI) arise from abrupt loss of excretory, endocrine and homeostatic renal functions, compounded by systemic inflammation and drug accumulation. In MRCP-style questions, complications are often tested through recognition of urgent indications for renal replacement therapy (RRT), particularly refractory hyperkalaemia, pulmonary oedema, severe acidosis and uraemic manifestations.

Life-threatening metabolic and fluid complications

Complication	Mechanism	Key thresholds / exam points	Immediate management principles
Hyperkalaemia	Reduced distal tubular potassium secretion, acidosis-driven extracellular shift, tissue breakdown, RAAS blockade, potassium-sparing drugs.	K+ >6.0 mmol/L is significant; >6.5 mmol/L or ECG changes is a medical emergency. ECG: peaked T waves, PR prolongation, QRS widening, sine-wave pattern.	Cardiac membrane stabilisation with calcium; intracellular shift; potassium removal; consider urgent RRT if refractory.
Metabolic acidosis	Failure of ammoniagenesis and acid excretion; lactic acidosis in sepsis/shock; accumulation of unmeasured anions.	Severe if pH <7.1 or bicarbonate <10 mmol/L, especially with haemodynamic compromise or hyperkalaemia.	Treat cause, optimise perfusion; bicarbonate selectively; RRT if refractory/severe.
Fluid overload and pulmonary oedema	Salt and water retention, capillary leak, excessive resuscitation, oliguria/anuria.	Hypoxaemia, raised JVP, crackles, CXR interstitial/alveolar oedema; fluid overload independently predicts mortality in ICU AKI.	Oxygen/CPAP, fluid restriction, loop diuretics if responsive, RRT for refractory pulmonary oedema.
Uraemic complications	Retention of middle molecules, guanidines, phenols and inflammatory mediators.	Encephalopathy, pericarditis, platelet dysfunction, nausea/vomiting, pruritus. Uraemic pericarditis is an urgent dialysis indication.	RRT; avoid anticoagulation if active pericarditis/bleeding risk.

Hyperkalaemia: pharmacological details

Hyperkalaemia is the most immediately fatal biochemical complication because extracellular potassium depolarises myocardial resting membrane potential and promotes malignant arrhythmia. Treatment is guided by potassium level, rate of rise, renal excretory capacity and ECG changes rather than the absolute value alone.

Intervention	Typical adult dose	Onset / duration	Key cautions
Calcium gluconate 10%	10 mL IV over 2–5 min; repeat after 5 min if ECG changes persist	Onset 1–3 min; duration 30–60 min	Stabilises myocardium but does not lower K+; caution with digoxin toxicity, though life-threatening hyperkalaemia still warrants calcium.
Soluble insulin with glucose	10 units IV insulin with 25 g glucose, e.g. 50 mL of 50% dextrose or local equivalent	Onset 15–30 min; K+ reduction ~0.6–1.0 mmol/L; duration 4–6 h	Check capillary glucose at baseline and for at least 6 h; hypoglycaemia is common in renal failure.
Nebulised salbutamol	10–20 mg nebulised	Onset 30 min; reduction ~0.5–1.0 mmol/L	Non-response occurs in up to 40%; causes tachycardia and tremor.
Sodium bicarbonate	Consider 50 mmol IV in severe metabolic acidosis	Variable potassium effect; more effective if acidotic	Sodium load, hypocalcaemia, paradoxical intracellular acidosis; not routine for isolated hyperkalaemia.
Potassium binders	Sodium zirconium cyclosilicate 10 g three times daily for up to 72 h; patiromer 8.4 g daily	Hours, not minutes	Adjuncts, not sole emergency therapy; check local formulary.

Indications for renal replacement therapy

KDIGO recommends initiating RRT emergently when life-threatening changes in fluid, electrolyte or acid-base balance exist, rather than using urea or creatinine thresholds alone. Traditional exam shorthand is AEIOU: Acidosis refractory to medical therapy; Electrolyte disturbance, especially refractory hyperkalaemia; Intoxications with dialysable toxins; Overload causing pulmonary oedema; Uraemic complications such as encephalopathy, pericarditis or bleeding.

Large ICU trials have refined timing. AKIKI and STARRT-AKI did not show mortality benefit from accelerated RRT initiation in the absence of urgent indications; STARRT-AKI reported 90-day mortality 43.9% with accelerated versus 43.7% with standard initiation, with more dialysis dependence among survivors in the accelerated arm. Thus, exam answers should favour urgent RRT for complications, not for creatinine elevation alone.

Other biochemical and systemic complications

• Hyponatraemia: usually dilutional from impaired free-water excretion and hypotonic fluid administration; severe symptoms occur with cerebral oedema. Avoid correction >8–10 mmol/L per 24 h to reduce osmotic demyelination risk.
• Hyperphosphataemia and hypocalcaemia: phosphate retention binds calcium and suppresses calcitriol generation. Severe hypocalcaemia may cause tetany, seizures or QT prolongation, but calcium replacement is cautious if phosphate is markedly elevated because of metastatic calcification.
• Hypermagnesaemia: particularly with magnesium-containing antacids/laxatives; causes hyporeflexia, bradyarrhythmia and respiratory depression. Calcium gluconate antagonises acute toxicity; dialysis removes magnesium.
• Bleeding tendency: uraemic platelet dysfunction impairs adhesion and aggregation despite normal platelet count. Desmopressin 0.3 micrograms/kg IV may transiently improve haemostasis before procedures; effect begins within 1 h and tachyphylaxis occurs after repeated doses.
• Drug toxicity: reduced renal clearance increases exposure to aminoglycosides, vancomycin, digoxin, lithium, metformin, DOACs, LMWH and opioids such as morphine. Dose adjustment should use current renal function and drug levels where available, recognising creatinine-based eGFR is unreliable during rapidly changing AKI.
• Infection and immune dysfunction: AKI is associated with impaired neutrophil and lymphocyte function, catheter-related infection risk and higher sepsis mortality.
• Cardiovascular complications: arrhythmias, myocardial injury, hypertension or hypotension, and pericarditis. AKI is independently associated with subsequent heart failure and major adverse cardiovascular events.
• Progression to CKD: incomplete tubular repair, nephron loss, capillary rarefaction and interstitial fibrosis increase later CKD and ESRD risk. KDIGO advises reassessment at 3 months after AKI for renal recovery, proteinuria and CKD classification.