Discuss the causes, clinical features, investigations and management of acute kidney injury, including acute tubular necrosis.

Definition

Acute kidney injury (AKI) is an abrupt (within hours to days) decline in glomerular filtration, causing retention of nitrogenous waste and dysregulation of fluid, electrolyte and acid-base balance.

KDIGO criteria — any one of:

• Rise in serum creatinine ≥ 0.3 mg/dL within 48 hours, or
• Rise in creatinine ≥ 1.5 times baseline within the prior 7 days, or
• Urine output < 0.5 mL/kg/hour for 6 hours

Staging 1 to 3 by the magnitude of creatinine rise and the duration of oliguria; stage 3 includes any patient requiring renal replacement therapy.

Classification and Causes

Note that pre-renal AKI progresses to ATN if hypoperfusion is prolonged — they are a continuum, not separate diseases.

Acute Tubular Necrosis

The commonest intrinsic cause of AKI, resulting from ischaemic or toxic injury to tubular epithelial cells.

Causes:

• Ischaemic — prolonged pre-renal states: sepsis (the commonest overall), major surgery, haemorrhage, burns, cardiac arrest, prolonged hypotension.
• Nephrotoxic:
• Exogenous — aminoglycosides, amphotericin B, cisplatin, contrast media, NSAIDs, vancomycin, tenofovir, and heavy metals
• Endogenous — myoglobin (RHABDOMYOLYSIS — crush injury, prolonged immobility, seizures, statins, snake bite), haemoglobin (intravascular haemolysis, blackwater fever, mismatched transfusion), uric acid and light chains (tumour lysis syndrome and myeloma), bilirubin

Pathophysiology: tubular cell injury and death → sloughing of cells forming casts that obstruct the tubular lumen, back-leak of filtrate across the damaged epithelium, and intrarenal vasoconstriction with medullary hypoxia — the outer medulla and the S3 segment of the proximal tubule are most vulnerable because of their high metabolic demand and marginal oxygen supply.

Three clinical phases:

1. Initiation — the insult occurs; injury is potentially reversible

2. Maintenance (1–2 weeks) — established oliguria with uraemia, fluid overload, hyperkalaemia and acidosis; this is when complications and death occur

3. Recovery (diuretic) phase — tubular regeneration with a massive polyuria as the concentrating mechanism recovers last, causing dehydration, hypokalaemia and hyponatraemia if fluids and electrolytes are not carefully replaced

Distinguishing Pre-renal Azotaemia from Atn

This distinction is the practical core of AKI assessment, because pre-renal disease reverses with fluid while ATN does not.

Important caveat: FENa is unreliable if the patient has received diuretics — use the fractional excretion of urea (FEUrea < 35% suggests pre-renal) instead.

Clinical Features

• Oliguria or anuria — though AKI may be non-oliguric, particularly with nephrotoxins, and non-oliguric AKI has a better prognosis.
• Fluid overload — oedema, raised JVP, pulmonary oedema, hypertension.
• Uraemic symptoms — nausea, vomiting, anorexia, confusion, asterixis, seizures, pericardial rub.
• Complications of electrolyte disturbance — hyperkalaemia with arrhythmia (the commonest immediate cause of death), metabolic acidosis with Kussmaul breathing, hyponatraemia, hyperphosphataemia, hypocalcaemia.
• Bleeding from uraemic platelet dysfunction.
• Features of the CAUSE — sepsis, hypovolaemia, rash and eosinophilia (interstitial nephritis), haematuria and hypertension (glomerulonephritis), palpable bladder and prostatic enlargement (obstruction), muscle tenderness and dark urine (rhabdomyolysis).

Investigations

• Serum creatinine, urea and electrolytes — with previous values, which are essential to establish whether the disease is acute or chronic.
• Urinalysis and microscopy — the "renal biopsy of the poor": muddy brown casts (ATN), red cell casts and dysmorphic red cells (glomerulonephritis), white cell casts and eosinophiluria (interstitial nephritis), crystals, and heavy proteinuria.
• Urine sodium, osmolality and FENa as above.
• CBC, blood gas, calcium, phosphate, uric acid, creatine kinase (rhabdomyolysis), LDH, coagulation profile, and blood cultures.
• ULTRASOUND OF THE KIDNEYS AND BLADDER IN EVERY PATIENT — to exclude obstruction (which is easily treatable and easily missed) and to assess kidney size, which distinguishes acute from chronic.
• Immunological screen where intrinsic disease is suspected: ANA, anti-dsDNA, ANCA, anti-GBM, complement, hepatitis serology, serum and urine electrophoresis with free light chains.
• Renal biopsy — where the cause is unexplained, particularly with suspected glomerulonephritis, vasculitis or interstitial nephritis.
• ECG — for hyperkalaemic changes; this should be immediate in any patient with significant AKI.

Management

1. Immediate — assess and treat life-threatening complications

• Hyperkalaemia — ECG, calcium gluconate, insulin-dextrose, salbutamol, binders, dialysis (see the hyperkalaemia answer).
• Pulmonary oedema — oxygen, sit up, nitrates, high-dose loop diuretic, non-invasive ventilation; dialysis if refractory.
• Severe metabolic acidosis — bicarbonate in selected cases, dialysis if severe.

2. Optimise perfusion and remove the insult

• Assess volume status carefully and correct hypovolaemia with balanced crystalloid, guided by clinical assessment, urine output and response — but avoid fluid overload, which independently worsens outcome in established AKI.
• Treat sepsis promptly with cultures and appropriate antibiotics (dose-adjusted for renal function).
• STOP nephrotoxic drugs — NSAIDs, ACE inhibitors and ARBs (temporarily), aminoglycosides, contrast; review and adjust all renally excreted drugs, including metformin.
• Relieve obstruction — catheterisation, nephrostomy or ureteric stenting; expect a post-obstructive diuresis and replace fluids and electrolytes accordingly.

3. Supportive management

• Strict fluid balance with daily weight and urine output charting — the single most useful monitoring tool.
• Dietary sodium, potassium and phosphate restriction with adequate calorie and protein intake — protein restriction to avoid dialysis is not appropriate and causes malnutrition.
• Treat hyperphosphataemia, hypocalcaemia and anaemia; stress ulcer prophylaxis; prevent infection.
• Note that "renal-dose dopamine", mannitol and routine loop diuretics do NOT prevent or treat AKI — diuretics are used only to manage fluid overload, not to convert oliguric to non-oliguric AKI.

4. Renal replacement therapy — indications ("AEIOU")

5. Recovery and follow-up

Anticipate and manage the polyuric recovery phase; monitor renal function after discharge — AKI is a strong risk factor for subsequent CKD, and survivors need long-term follow-up and avoidance of further insults.