Ischaemic Acute Tubular Injury

Ischaemic acute tubular injury is tubular epithelial damage caused by inadequate renal oxygen delivery, followed by reperfusion injury. It is the dominant form of acute tubular injury after hypotension, shock, major surgery and cardiac arrest.

The kidney receives about 20% of cardiac output but has an inner medulla with oxygen tension of only 10 to 20 mmHg, leaving little reserve. When mean arterial pressure drops under the autoregulatory range (about 65 mmHg, higher in chronic hypertension), filtration falls and medullary hypoxia deepens. The proximal S3 segment and medullary thick ascending limb suffer first. Reperfusion adds oxidative injury, inflammation and endothelial dysfunction that extends damage and causes persistent medullary vascular congestion.

Typical settings:

• Septic or cardiogenic shock, haemorrhage, anaphylaxis, severe dehydration
• Cardiac surgery with cardiopulmonary bypass
• Aortic cross-clamping, major vascular and abdominal surgery
• Cardiac arrest
• Heat stroke
• Pre-existing risk: chronic kidney disease, diabetes, older age, anaemia, hypoxaemia

Prolonged or severe ischaemia may cause bilateral cortical necrosis.

• Oliguria or anuria after a hypotensive episode; creatinine typically peaks at 3 to 7 days
• Features of shock or the precipitating event
• Volume overload, hyperkalaemia, metabolic acidosis, uraemia
• Prolonged course: creatinine plateau for 1 to 2 weeks, then recovery

Red flags: hypotension for more than 30 to 60 minutes, lactate above 4 mmol/L, anuria beyond 24 hours (cortical necrosis if complete and prolonged), potassium above 6.5 mmol/L, pH below 7.15.

• Identify the ischaemic insult: duration and depth of hypotension (mean arterial pressure below 60 mmHg for 30 minutes or more), surgical details, vasopressor dose
• Creatinine, urea, electrolytes, bicarbonate, lactate, creatine kinase, haemoglobin
• Urinalysis: muddy brown casts; fractional excretion of sodium above 2%; urine osmolality below 350 mOsm/kg
• Lack of recovery within 48 to 72 hours of restoring perfusion and volume
• Renal ultrasound with Doppler: kidneys normal or enlarged, resistive index above 0.7 in established injury, exclude obstruction and arterial occlusion
• Contrast enhanced CT or magnetic resonance angiography if renal artery occlusion is suspected
• Biomarkers (NGAL, TIMP-2 multiplied by IGFBP7 above 2.0) support early diagnosis

Differentials: prerenal azotaemia, nephrotoxic injury, renal artery or vein thrombosis, atheroembolic disease, abdominal compartment syndrome, cardiorenal syndrome.

Restore perfusion

• Identify and correct the cause: stop bleeding, treat sepsis, restore cardiac output.
• Mean arterial pressure at least 65 mmHg; target 75 to 85 mmHg in chronic hypertension when there is oliguria. Noradrenaline 0.05 to 0.5 microg/kg/min is first line vasopressor; add vasopressin 0.03 units/min if noradrenaline is above 0.25 microg/kg/min.
• Fluids: balanced crystalloid in 250 to 500 mL aliquots with reassessment; avoid overload. Blood to haemoglobin 70 to 80 g/L.
• Optimise cardiac output with dobutamine 2.5 to 10 microg/kg/min in low output.
• Correct hypoxaemia and anaemia.

Prevent additional insults

• Avoid nephrotoxins (NSAIDs, aminoglycosides, vancomycin dosing to area under the curve 400 to 600 mg·h/L, amphotericin B).
• Hold ACE inhibitors, angiotensin receptor blockers, diuretics and SGLT2 inhibitors until recovery.
• Iodinated contrast only when essential; isotonic crystalloid 1 mL/kg/h for 6 to 12 hours before and after in eGFR below 30 mL/min/1.73 m2 if volume status allows.

Supportive care and renal replacement

• Hyperkalaemia: calcium gluconate 10% 10 mL intravenously, insulin 10 units with glucose 25 g, salbutamol 10 to 20 mg nebulised. Acidosis: sodium bicarbonate 500 mg to 1 g orally two to three times daily. Overload: furosemide 40 to 80 mg intravenously.
• Renal replacement therapy for refractory hyperkalaemia (potassium above 6.5 mmol/L), pH below 7.15, overload, uraemic complications; continuous therapy for unstable patients.
• No benefit from dopamine, fenoldopam, atrial natriuretic peptide, mannitol or high dose loop diuretics to prevent or shorten ischaemic injury.

Prognosis and follow up. Most patients recover over 1 to 3 weeks; cortical necrosis and severe or repeated episodes lead to chronic kidney disease. Check creatinine and albumin:creatinine ratio at 3 months; annual review for incomplete recovery.

Refer to nephrology if oliguria persists beyond 48 hours after restored perfusion or if renal replacement is anticipated.