Anticoagulation in Kidney Disease

Kidney impairment raises both clotting and bleeding risk, and reduces clearance of most anticoagulants. Dose selection is based on creatinine clearance by the Cockcroft-Gault equation, not estimated glomerular filtration rate, and agents with less kidney clearance are preferred as function falls.

Kidney clearance. Dabigatran about 80%, edoxaban about 50%, rivaroxaban about 35%, apixaban about 27%, low molecular weight heparins mostly kidney, fondaparinux mostly kidney, and unfractionated heparin and warfarin are not kidney cleared.

• Creatinine clearance over 50 mL/min: usual doses of all direct oral anticoagulants.
• 30 to 50 mL/min: apixaban usual dose (reduce if criteria are met); rivaroxaban 15 mg once daily in atrial fibrillation; edoxaban 30 mg once daily; dabigatran 110 to 150 mg twice daily with caution; enoxaparin treatment 1 mg/kg twice daily with anti-Xa monitoring.
• 15 to 29 mL/min: apixaban 2.5 mg to 5 mg twice daily with caution; rivaroxaban 15 mg once daily for atrial fibrillation and with caution for venous thromboembolism; edoxaban 30 mg once daily; dabigatran contraindicated; enoxaparin 1 mg/kg once daily; fondaparinux avoided; unfractionated heparin or warfarin preferred.
• Under 15 mL/min or dialysis: warfarin (INR 2.0 to 3.0) or unfractionated heparin; apixaban 2.5 to 5 mg twice daily has been used in atrial fibrillation under specialist direction; avoid dabigatran, rivaroxaban and edoxaban.
• Prophylaxis: enoxaparin 20 mg daily at 15 to 30 mL/min; unfractionated heparin 5000 units every 8 to 12 hours under 15 mL/min.
• Unfractionated heparin infusion: 80 units/kg bolus then 18 units/kg/h, adjusted to aPTT 1.5 to 2.5 times control.

Haemodialysis circuit. Unfractionated heparin 1000 to 2000 units bolus then 500 to 1500 units/h, or low molecular weight heparin 0.5 to 1 mg/kg once at the start, under the dialysis team.

Nephrotic syndrome. Increased clot risk when albumin is under 25 g/L (under 20 g/L in membranous disease); prophylactic anticoagulation is considered.

Acute kidney injury. Recalculate clearance daily and adjust or switch agent.

Older adults and low weight. Creatinine clearance overestimates function in low muscle mass, so use caution.

Interactions. Warfarin dose needs fall in kidney disease. Avoid combining with non-steroidal drugs.

Special groups. In East Africa, kidney disease from HIV, hypertension, diabetes and glomerulonephritis presents late, and warfarin or unfractionated heparin is the realistic option where monitoring is available.

Monitoring. Creatinine clearance at baseline and every 3 months (monthly if under 30 mL/min), haemoglobin, and anti-Xa activity for low molecular weight heparin beyond 5 days (peak 0.6 to 1.0 units/mL twice daily dosing). INR weekly until stable on warfarin.

Referral and escalation. Seek nephrology and haematology advice for clearance under 30 mL/min, dialysis, recurrent clots on treatment and bleeding.

Stopping. Stop or change the agent when clearance falls under the agent’s limit, and restart after the acute illness resolves.