Sepsis Associated Acute Kidney Injury

Sepsis associated acute kidney injury is acute kidney injury that occurs in the presence of sepsis, defined by the development of kidney injury within 7 days of infection with a dysregulated host response. It affects about 40% to 50% of patients with septic shock and carries mortality of 40% to 60% when renal replacement is required.

The mechanism is not simply hypoperfusion. Renal blood flow may be normal or increased in early sepsis while the glomerular filtration rate falls. Injury arises from:

• Microcirculatory dysfunction with shunting and heterogeneous flow
• Inflammatory mediators and endotoxin acting on tubular epithelium
• Mitochondrial dysfunction and oxidative stress
• Tubular cell adaptive downregulation (a protective hibernation response)
• Endothelial dysfunction, glycocalyx damage and microthrombi
• Superimposed nephrotoxins (aminoglycosides, vancomycin, contrast, NSAIDs) and venous congestion from fluid overload

Histology is often surprisingly mild: patchy tubular vacuolation, brush border loss and leucocyte infiltration, with little necrosis. Recovery occurs in most survivors within 7 to 14 days, but a significant minority progress to chronic kidney disease.

• Fever or hypothermia, tachycardia, tachypnoea, leucocytosis or leucopenia, altered mentation
• Hypotension requiring vasopressors; lactate above 2 mmol/L
• Oliguria (below 0.5 mL/kg/h for 6 hours) frequently before creatinine rises
• Source: pneumonia, urinary tract infection, intra-abdominal sepsis, skin and soft tissue, meningitis, endocarditis, malaria, bacteraemia
• Associated organ dysfunction: thrombocytopenia, coagulopathy, hyperbilirubinaemia, hypoxaemia

Red flags: refractory shock, lactate above 4 mmol/L, potassium above 6.0 mmol/L, pH below 7.15, anuria, signs of necrotising infection, obstructed infected urinary tract (pyonephrosis).

• Sepsis recognition: organ dysfunction score increase of 2 or more; blood cultures (two sets) before antibiotics, urine, sputum, wound and other cultures
• Creatinine, urea, electrolytes, bicarbonate, lactate, hourly urine output
• Full blood count, coagulation, liver tests, C-reactive protein, procalcitonin
• Urinalysis and sediment: granular casts, tubular epithelial cells; urine sodium and fractional excretion are unreliable
• Imaging: ultrasound to exclude obstruction (pyonephrosis, abscess); CT when intra-abdominal source suspected, balancing contrast risk against diagnostic need
• Biomarkers (where available): urinary TIMP-2 multiplied by IGFBP7 above 2.0 (ng/mL)2/1000 indicates high short term risk

Differentials: hypovolaemia, cardiorenal syndrome, nephrotoxic injury, rhabdomyolysis, thrombotic microangiopathy, abdominal compartment syndrome, infection related glomerulonephritis.

Within the first hour

• Antibiotics within 1 hour of recognition of shock, within 3 hours if sepsis without shock. First doses are never reduced for renal function. Examples: ceftriaxone 2 g intravenously daily; piperacillin-tazobactam 4.5 g every 6 to 8 hours; meropenem 1 g every 8 hours (for resistant organisms or immunocompromise). Add vancomycin loading 25 to 30 mg/kg only when methicillin resistant Staphylococcus aureus is likely, avoiding the combination with piperacillin-tazobactam where alternatives exist.
• Crystalloid (balanced) 30 mL/kg within 3 hours for hypotension or lactate above 4 mmol/L; reassess with passive leg raise, capillary refill and ultrasound before further boluses.
• Source control within 6 to 12 hours: drain abscess, relieve urinary obstruction (nephrostomy or stent), debride necrotic tissue.

Haemodynamic support

• Noradrenaline 0.05 to 0.5 microg/kg/min, first line, target mean arterial pressure at least 65 mmHg (higher, 80 to 85 mmHg, may help in chronic hypertension).
• Add vasopressin 0.03 units/min if noradrenaline is above 0.25 microg/kg/min.
• Hydrocortisone 50 mg intravenously every 6 hours if vasopressor requirement persists for 4 hours or more.
• Dobutamine 2.5 to 10 microg/kg/min for low cardiac output.
• Avoid hydroxyethyl starch and gelatin; use albumin when large crystalloid volumes are needed.

Kidney specific

• Dose adjustment of antibiotics from the second day to eGFR; therapeutic monitoring of vancomycin (area under the curve 400 to 600 mg·h/L) and aminoglycosides.
• Stop NSAIDs, ACE inhibitors, angiotensin receptor blockers and diuretics until shock resolves.
• Diuretics only for established overload (furosemide 40 to 80 mg intravenously).
• Renal replacement therapy for refractory hyperkalaemia, pH below 7.15, overload impairing oxygenation, uraemic complications; routine early initiation without these indications offers no benefit. Continuous therapy is preferred for haemodynamically unstable patients, with effluent dose 20 to 25 mL/kg/h.
• Glucose 7.8 to 10 mmol/L with insulin; venous thromboprophylaxis with enoxaparin 20 mg daily when eGFR is below 30 mL/min/1.73 m2.

Follow up. Creatinine and albumin:creatinine ratio at 3 months; avoid nephrotoxins in the interim.