Cardiac Surgery Associated Acute Kidney Injury

Cardiac surgery associated acute kidney injury is acute kidney injury developing within 7 days of cardiac surgery, particularly with cardiopulmonary bypass. It affects 20% to 30% of patients, with 1% to 5% requiring renal replacement therapy, and it is among the strongest predictors of death after cardiac surgery: mortality is 2 to 5 times higher with stage 1 injury and up to 40% to 60% when dialysis is required.

Injury arises from several simultaneous insults:

• Ischaemia reperfusion: reduced renal perfusion during bypass with nonpulsatile flow and mean arterial pressure typically 50 to 70 mmHg, aortic cross-clamping, low cardiac output, vasoplegia, hypothermia and rewarming
• Haemolysis: mechanical red cell injury in the bypass circuit releases free haemoglobin and iron, overwhelming haptoglobin and producing pigment mediated tubular injury
• Inflammation: contact of blood with circuit surfaces, complement activation, cytokine release and oxidative stress
• Haemodilution and anaemia: bypass priming volume and reduced oxygen delivery to the renal medulla
• Atheroembolism from aortic manipulation and cannulation
• Nephrotoxins: contrast during angiography, NSAIDs, aminoglycosides, vancomycin
• Postoperative: low output state, tamponade, bleeding, vasoplegia, sepsis, intra-abdominal hypertension, mechanical ventilation with high positive end expiratory pressure raising venous pressure

Risk factors: preoperative eGFR below 60 mL/min/1.73 m2, diabetes, age above 70 years, left ventricular ejection fraction below 35%, emergency surgery, combined valve and coronary surgery, redo surgery, intra-aortic balloon pump, preoperative anaemia (haemoglobin below 120 g/L), peripheral vascular disease, bypass time above 120 minutes, cross-clamp time above 90 minutes, and transfusion of red cells.

• Oliguria (below 0.5 mL/kg/h for 6 hours or more) in the first 24 hours; creatinine peaks at 2 to 4 days
• Low output syndrome: hypotension, cold peripheries, raised lactate (above 2 mmol/L), high central venous pressure
• Vasoplegia: low systemic vascular resistance, high cardiac output, need for noradrenaline above 0.2 microg/kg/min
• Fluid overload, pulmonary oedema, ventilatory difficulty, weight gain above 10% of baseline
• Hyperkalaemia, metabolic acidosis, hyperphosphataemia
• Bleeding, tamponade, abdominal distension
• Dark urine from haemoglobinuria, positive dipstick without red cells

Red flags: anuria after bypass, lactate above 4 mmol/L, noradrenaline above 0.3 microg/kg/min, potassium above 6.0 mmol/L, pH below 7.15, central venous pressure above 15 mmHg with oliguria, cardiac tamponade, abdominal compartment syndrome, creatinine rising by more than 26.5 micromol/L in 48 hours.

• Preoperative creatinine and eGFR; postoperative creatinine at 6, 12, 24, 48 hours and daily; hourly urine output.
• Urinary biomarkers where available: TIMP-2 multiplied by IGFBP7 measured 4 hours after bypass (above 0.3 (ng/mL)2/1000 indicates risk; above 2.0 high risk); NGAL; cystatin C.
• Lactate, electrolytes, blood gas, haemoglobin, plasma free haemoglobin, haptoglobin, lactate dehydrogenase.
• Echocardiography for ventricular function, tamponade, right heart failure; pulmonary artery catheter or cardiac output monitoring.
• Central venous pressure and bladder pressure measurement.
• Renal ultrasound with Doppler for obstruction or vascular occlusion; CT with contrast only when it alters management.
• Urinalysis and microscopy (muddy brown casts).

Differentials: prerenal azotaemia from low output, pigment nephropathy, atheroembolic disease, nephrotoxic injury, sepsis, abdominal compartment syndrome, obstruction.

Prevention

• Preoperative: delay elective surgery for 24 to 72 hours after contrast angiography if eGFR is below 60 mL/min/1.73 m2; stop NSAIDs; hold ACE inhibitors and angiotensin receptor blockers for 24 hours before surgery; correct anaemia (haemoglobin at least 120 g/L, with iron 1 g intravenously if deficient); optimise glucose.
• Bypass: mean arterial pressure at least 65 to 70 mmHg (75 to 80 mmHg in chronic hypertension), flow index 2.4 L/min/m2, avoid prolonged hypothermia and haemodilution (haematocrit at least 24%), minimise bypass and cross-clamp time, use off pump or minimal extracorporeal circulation in high risk patients when appropriate.
• Intraoperative: balanced crystalloid, avoid hydroxyethyl starch, tight glucose control (6 to 10 mmol/L), meticulous haemostasis, restrictive transfusion (haemoglobin below 75 g/L).
• Postoperative bundle for patients with positive urinary biomarkers: avoid nephrotoxins, maintain perfusion pressure and optimise volume, monitor creatinine and urine output closely, avoid hyperglycaemia and avoid radiocontrast.
• Agents that do not prevent injury: furosemide, mannitol, dopamine, fenoldopam, atrial natriuretic peptide, N-acetylcysteine, sodium bicarbonate, erythropoietin and statins (loading) have not been shown to reduce injury.

Haemodynamic management

• Target mean arterial pressure 65 to 80 mmHg and central venous pressure below 12 mmHg; avoid venous congestion.
• Low output: dobutamine 2.5 to 10 microg/kg/min or milrinone 0.25 to 0.5 microg/kg/min (reduce dose to 0.2 to 0.3 microg/kg/min in eGFR below 30), adrenaline 0.02 to 0.1 microg/kg/min; correct tamponade, ischaemia and arrhythmia; intra-aortic balloon pump or mechanical support for refractory shock.
• Vasoplegia: noradrenaline first, add vasopressin 0.01 to 0.06 units/min, then methylene blue 1.5 to 2 mg/kg intravenously over 20 to 30 minutes, or hydroxocobalamin 5 g intravenously over 15 minutes; avoid methylene blue with serotonergic drugs.
• Volume: fluid boluses of 250 mL balanced crystalloid with reassessment; avoid more than 10% positive balance.

Established injury

• Stop nephrotoxins; renally adjust drugs; no ACE inhibitors or angiotensin receptor blockers until recovery.
• Haemolysis: maintain urine output above 1 mL/kg/h with crystalloid; treat hyperkalaemia and acidosis.
• Hyperkalaemia: calcium gluconate 10% 10 mL, insulin 10 units with glucose 25 g, salbutamol 10 to 20 mg nebulised, sodium zirconium cyclosilicate 10 g three times daily for up to 48 hours.
• Diuretics only for overload: furosemide 40 to 80 mg intravenously, infusion 5 to 20 mg/h.
• Renal replacement therapy for refractory hyperkalaemia, pH below 7.15, overload with respiratory compromise, uraemic complications; continuous venovenous haemodiafiltration at effluent 20 to 25 mL/kg/h in unstable patients. Routine early initiation does not improve survival.
• Intra-abdominal hypertension: decompress when pressure is above 20 mmHg with organ failure.

Recovery and follow up. Most patients recover within 2 weeks. Check creatinine and albumin:creatinine ratio at 3 months; nephrology follow up for stage 2 or 3 injury, dialysis requirement or incomplete recovery; restart renin angiotensin blockade once creatinine is stable and blood pressure allows.

Special groups. Pre-existing chronic kidney disease: avoid contrast within 72 hours before surgery, dose reduce antibiotics, and consider modifying cardiopulmonary bypass strategy. Children: bypass related injury is common; use age appropriate urine output targets of 1 mL/kg/h.