5.1 Acute Kidney Injury & KDIGO Staging

Acute Kidney Injury & KDIGO Staging

Acute Kidney Injury (AKI) represents an abrupt, potentially reversible decline in renal excretory function occurring over hours to days. It leads to the rapid retention of nitrogenous waste products (urea and creatinine), loss of electrolyte and acid-base homeostasis, and dysregulation of intravascular fluid volume. In the National Health Service (NHS), AKI complicates approximately 15–20% of all emergency hospital admissions and is associated with substantial in-hospital morbidity and mortality.

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1. Diagnostic Definition & KDIGO Staging Criteria

According to the internationally endorsed Kidney Disease: Improving Global Outcomes (KDIGO) consensus guidelines (adopted by UK NICE Guideline NG148), AKI is diagnosed if any one of the following criteria is fulfilled:

• A rise in serum creatinine by ≥ 26.5 µmol/L within 48 hours, OR
• A rise in serum creatinine to ≥ 1.5 times baseline, known or presumed to have occurred within the prior 7 days, OR
• A documented urine output of < 0.5 mL/kg/hour for at least 6 consecutive hours.

Staging Severity

Once diagnosed, AKI is stratified into three clinical stages according to the magnitude of serum creatinine elevation or the duration and severity of oliguria. When creatinine and urine output yield discordant stages, the higher (more severe) stage is always assigned.

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2. Aetiological Classification & Diagnostic Differentiation

AKI is mechanistically divided into three anatomical categories: pre-renal, intrinsic renal, and post-renal.

A. Pre-Renal Azotaemia (Renal Hypoperfusion)

Pre-renal AKI accounts for 60–70% of community-acquired cases. It is caused by reduced effective renal arterial perfusion without structural parenchymal damage. If hypoperfusion is rapidly reversed, glomerular filtration rate (GFR) normalises promptly.

• Absolute Hypovolaemia: Haemorrhage, gastrointestinal fluid loss (severe vomiting, choleraic diarrhoea), excessive diuresis, burns, severe dehydration.
• Relative Hypovolaemia / Vasodilation: Sepsis, anaphylaxis, neurogenic shock, liver cirrhosis with splanchnic arterial vasodilation.
• Cardiogenic Pump Failure: Severe acute decompensated heart failure, cardiogenic shock, massive acute myocardial infarction.
• Renal Haemodynamic Impairment: Bilateral renal artery stenosis (or unilateral stenosis in a solitary kidney); concurrent administration of ACE inhibitors or Angiotensin Receptor Blockers (which block angiotensin II-mediated efferent arteriolar vasoconstriction) combined with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs, which block prostaglandin-mediated afferent arteriolar vasodilation).

B. Intrinsic Renal AKI (Structural Parenchymal Injury)

Intrinsic AKI involves acute structural damage to the glomeruli, tubules, interstitium, or renal microvasculature:

1. Acute Tubular Necrosis (ATN): The most common cause of intrinsic AKI in hospitalised patients. Occurs secondary to prolonged, uncorrected renal ischaemia (severe shock, prolonged pre-renal state) or direct nephrotoxic exposure (exogenous toxins: aminoglycosides such as gentamicin, iodinated radiocontrast agents, amphotericin B, cisplatin; endogenous toxins: myoglobin in rhabdomyolysis, hemoglobin in massive intravascular haemolysis, light chains in multiple myeloma).
2. Acute Interstitial Nephritis (AIN): An immunologically mediated hypersensitivity reaction affecting the renal interstitium. Over 75% of cases are drug-induced, classically triggered by antibiotics (penicillins, cephalosporins, ciprofloxacin, rifampicin), Proton Pump Inhibitors (omeprazole, lansoprazole), NSAIDs, or allopurinol. Autoimmune causes include sarcoidosis, Sjögren's syndrome, and systemic lupus erythematosus (SLE). The classic clinical triad of fever, maculopapular rash, and peripheral eosinophilia is present in only 10–15% of patients (arthralgia may also occur), but urinalysis characteristically demonstrates sterile pyuria, white blood cell casts, and urinary eosinophils.
3. Acute Glomerulonephritis: Post-streptococcal GN, IgA nephropathy, ANCA-associated vasculitis (granulomatosis with polyangiitis), anti-GBM disease. Characterised by dysmorphic red cells, red cell casts, proteinuria, and active urinary sediment.
4. Rhabdomyolysis: Massive skeletal muscle necrosis releasing toxic myoglobin into the circulation. Classic causes include trauma, crush injuries, prolonged immobility ("long lie" after a fall in elderly individuals), grand mal seizures, severe exertion, hypothermia, and statin-fibrate interactions. Urinalysis demonstrates a strongly positive dipstick for blood in the complete absence of red blood cells on microscopy (because the reagent strip orthotolidine reaction detects the heme moiety of myoglobin). Serum creatine kinase (CK) is markedly elevated (typically > 10,000 U/L, often > 50,000 U/L). Associated electrolyte disturbances include hyperkalaemia, hyperphosphataemia, hyperuricaemia, and early hypocalcaemia (due to calcium precipitation in necrotic myocytes).

C. Post-Renal AKI (Obstructive Uropathy)

Occurs when acute mechanical obstruction to urinary outflow elevates retrograde hydrostatic pressures within Bowman's space, opposing glomerular filtration:

• Bladder Outflow Obstruction: Benign Prostatic Hyperplasia (BPH), prostate adenocarcinoma, blocked urethral catheter, neurogenic bladder, urethral strictures.
• Ureteric Obstruction: Bilateral ureteric calculi (or unilateral calculus in a single functional kidney), retroperitoneal fibrosis, retroperitoneal lymphadenopathy, pelvic malignancies (cervical, colorectal, or ovarian carcinoma).
• Diagnostic Investigation: Urgent renal tract ultrasound must be performed within 24 hours of presentation (or within 6 hours in suspected pyonephrosis, sepsis, or solitary kidney) to identify pelvicalyceal dilatation (hydronephrosis and hydroureter).

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3. Pre-Renal Azotaemia vs. Acute Tubular Necrosis (ATN)

Distinguishing pre-renal hypoperfusion from established ATN is critical because pre-renal failure responds rapidly to fluid resuscitation, whereas established ATN carries a damaged tubular epithelium that cannot concentrate urine or reabsorb sodium, placing the patient at high risk of fluid overload if excessive fluids are given.

$\text{FeNa} (\%) = \frac{\text{Urinary Sodium} \times \text{Serum Creatinine}}{\text{Serum Sodium} \times \text{Urinary Creatinine}} \times 100$

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4. Acute Clinical Management Protocol

Management of AKI follows a structured, evidence-based algorithm:

Step 1: Medication Review & Cessation of Nephrotoxins (DAMN Mnemonic)

Immediate discontinuation of all potentially nephrotoxic or renally cleared agents is mandatory. Remember the DAMN mnemonic:

• D – Diuretics: Furosemide, bumetanide, indapamide, spironolactone (withhold immediately unless pulmonary oedema is present).
• A – ACE inhibitors / ARBs: Ramipril, lisinopril, losartan, candesartan (withhold; their efferent arteriolar vasodilation lowers glomerular filtration pressure, which worsens GFR when renal perfusion is already reduced).
• M – Metformin: Withhold immediately! Metformin is cleared by the kidneys; accumulation during AKI induces life-threatening Metformin-Associated Lactic Acidosis (MALA).
• N – NSAIDs: Ibuprofen, naproxen, diclofenac, meloxicam (stop immediately; inhibits vasodilatory prostaglandins at afferent arterioles).
• Additional agents to stop or dose-adjust: Aminoglycosides (gentamicin), vancomycin, amphotericin, iodinated contrast agents, and direct oral anticoagulants (DOACs).

Step 2: Haemodynamic Assessment & Fluid Resuscitation

• Hypovolaemic AKI: Administer 500 mL boluses of intravenous balanced crystalloid (e.g. Plasma-Lyte 148 or Hartmann's solution) over 15 minutes, followed by clinical reassessment (pulse, blood pressure, capillary refill time, JVP, chest auscultation). Avoid large volumes of 0.9% normal saline, which induce hyperchloraemic metabolic acidosis and renal vasoconstriction.
• Euvolaemic or Hypervolaemic AKI: Fluid boluses are harmful. Restrict maintenance fluid to insensible losses (30–50 mL/h) plus measured urinary output.

Step 3: Urgent Catheterisation & Bladder Decompression

Insert a Foley urinary catheter if urinary retention is suspected, if the patient is haemodynamically unstable, or to enable accurate hourly urine output monitoring in KDIGO Stage 2 or 3 AKI.

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5. Emergency Indications for Renal Replacement Therapy: The AEIOU Mnemonic

When conservative medical management fails, urgent nephrology referral for Renal Replacement Therapy (RRT / Haemodialysis) is lifesaving. The emergency indications are memorised using the AEIOU mnemonic:

• A – Acidosis (Metabolic): Severe refractory metabolic acidosis with arterial pH < 7.15 or serum bicarbonate < 10 mmol/L, unresponsive to medical therapy.
• E – Electrolytes (Hyperkalaemia): Refractory hyperkalaemia with serum potassium > 6.5 mmol/L or rapidly rising levels associated with toxic ECG changes, refractory to insulin-dextrose and calcium gluconate.
• I – Ingestions / Toxins: Poisoning with dialysable toxins (mnemonic SLIME: Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol).
• O – Overload (Fluid): Intractable, diuretic-resistant acute pulmonary oedema causing respiratory failure in an oliguric or anuric patient.
• U – Uraemia (Complications): Life-threatening end-organ uraemic manifestations: uraemic pericarditis (pericardial friction rub, risk of haemorrhagic tamponade), uraemic encephalopathy (confusion, asterixis, myoclonus, seizures, coma), or uraemic bleeding diathesis secondary to platelet dysfunction.