Prescribing in Acute Kidney Injury

Acute kidney injury is a rise in serum creatinine of 26.5 micromol/L or more within 48 hours, a rise to 1.5 times baseline or more within 7 days, or urine output under 0.5 mL/kg/h for 6 hours. Kidney function changes from day to day, and creatinine lags behind true filtration, so every dose is a provisional decision to be rechecked daily.

Estimating function. Creatinine based equations assume a steady state and are invalid while creatinine is moving. If creatinine is rising, true clearance is lower than the calculated value. If it is falling in recovery, clearance is higher than calculated.

Priorities. Correct the cause (hypovolaemia, sepsis, obstruction, nephrotoxins), hold medicines that harm the kidney or accumulate, and avoid underdosing life-saving drugs. The first dose of an antimicrobial is never reduced for kidney function.

Medicines to hold.

• ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, NSAIDs including COX-2 inhibitors, and diuretics unless the patient is volume overloaded.

• Metformin (lactic acidosis), SGLT2 inhibitors (euglycaemic ketoacidosis, volume depletion) and sulphonylureas (prolonged hypoglycaemia).

• Lithium, and any aminoglycoside, vancomycin, aciclovir, amphotericin or contrast exposure that can be avoided.

Analgesia. First line is paracetamol 1 g orally or intravenously, at least 6 hours apart (8 hours if clearance is under 10 mL/min), maximum 4 g daily. Under 50 kg use 15 mg/kg, maximum 60 mg/kg daily. Avoid NSAIDs, morphine, codeine and pethidine. If an opioid is needed, use fentanyl or low-dose oxycodone with a longer interval.

Antimicrobials. Choose agents that are not nephrotoxic where equal efficacy exists. Aminoglycosides are a last resort. Trimethoprim raises creatinine and potassium. Nitrofurantoin is unsuitable. Liposomal amphotericin is preferred over conventional amphotericin.

Thromboprophylaxis. Use unfractionated heparin 5000 units subcutaneously every 8 to 12 hours, or enoxaparin 20 mg subcutaneously once daily if clearance is under 30 mL/min.

Special groups.

• Children: dose by mg/kg, expect accumulation, and use age-specific creatinine ranges.

• Older adults: lower muscle mass hides severity, so a modest creatinine rise may represent a large fall in filtration.

• Pregnancy: avoid ACE inhibitors, angiotensin receptor blockers and NSAIDs.

• East Africa: ask about NSAID use, herbal and traditional remedies, and recent diarrhoea or malaria, all frequent contributors.

Work on the assumption that clearance is under 30 mL/min until the trend is clear.

Monitoring. Check creatinine, urea, potassium and bicarbonate at least daily, and every 6 to 12 hours if potassium is 6.0 mmol/L or over or the patient is unstable. Measure urine output hourly in stage 2 or 3 injury. Send drug levels (gentamicin, vancomycin, lithium, digoxin) before each redose.

Recovery. Step doses back up when creatinine falls on two consecutive measurements. Prolonged under-dosing after recovery is a common error.

Stop rules. Stop any suspected nephrotoxin if creatinine continues to rise. Do not restart ACE inhibitors, angiotensin receptor blockers or metformin until creatinine is stable or near baseline and the patient is eating and drinking.

Referral and escalation. Seek nephrology review urgently for stage 3 injury, an unclear cause, potassium 6.5 mmol/L or over or ECG changes, persistent pH under 7.2, pulmonary oedema unresponsive to diuretics, uraemic pericarditis or encephalopathy, oliguria under 0.3 mL/kg/h for 24 hours or anuria for 12 hours, or a dialysable toxin such as lithium or salicylate.

Common errors. Continuing an ACE inhibitor, NSAID or metformin; giving full-dose enoxaparin; trusting a single creatinine as steady state; and reducing the first antibiotic dose.