Goal INR for Anticoagulation in Nephrotic Syndrome
The target International Normalized Ratio (INR) for patients with nephrotic syndrome requiring anticoagulation is 2-3. 1
Indications for Anticoagulation in Nephrotic Syndrome
Anticoagulation in nephrotic syndrome is indicated in two main scenarios:
Therapeutic anticoagulation for patients who have already experienced a thromboembolic event:
- Full-dose anticoagulation is required for 6-12 months and/or for the duration of nephrotic syndrome 1
- This includes treatment for venous thrombosis, arterial thrombosis, pulmonary embolism, or nonvalvular atrial fibrillation
Prophylactic anticoagulation for high-risk patients:
- Consider when serum albumin is <20-25 g/L (measured by bromocresol green) or <20 g/L (measured by bromocresol purple) 1
- Plus at least one of the following risk factors:
- Proteinuria >10 g/day
- BMI >35 kg/m²
- Heart failure (NYHA class III or IV)
- Recent orthopedic or abdominal surgery
- Prolonged immobilization
Risk Stratification for Thromboembolism
Thromboembolism risk varies by underlying cause of nephrotic syndrome:
- Membranous nephropathy carries particularly high risk 1, 2
- Risk increases with severity of hypoalbuminemia 3
Risk assessment should include:
- Serum albumin level (primary determinant)
- Proteinuria severity
- Additional risk factors (obesity, immobility, recent surgery)
- Bleeding risk assessment using validated tools (https://www.med.unc.edu/gntools/bleedrisk.html)
Anticoagulation Agent Selection
Warfarin (First Choice)
- Long-term experience makes warfarin the anticoagulant of choice 1
- Target INR: 2-3 1, 3
- Advantages:
- Extensive clinical experience in nephrotic syndrome
- Easily monitored
- Reversible
Special Considerations with Warfarin in Nephrotic Syndrome
- Higher than usual heparin dosing may be required initially due to antithrombin III urinary loss 1
- Intravenous heparin followed by bridging to warfarin is preferred when initiating therapy 1
- More frequent INR monitoring is necessary due to:
- Fluctuating serum albumin affecting warfarin-protein binding
- Potential drug interactions
- Changes in nutritional status
Direct Oral Anticoagulants (DOACs)
- Not systematically studied in nephrotic syndrome 1
- Concerns include:
- High protein binding (92-95% for rivaroxaban and apixaban)
- Unknown effects of hypoalbuminemia on drug pharmacokinetics
- Variable urinary clearance
- Lack of clinical trials in this population
Duration of Anticoagulation
- For therapeutic anticoagulation: 6-12 months and/or for the duration of nephrotic syndrome 1
- For prophylactic anticoagulation: Continue until serum albumin rises above 30 g/L 1
Monitoring Recommendations
- More frequent INR monitoring than in general population (at least weekly initially)
- Monitor serum albumin levels regularly
- Assess for bleeding complications
- Evaluate for resolution of nephrotic syndrome
Contraindications to Anticoagulation
- Patient preference/inability to adhere to treatment
- Bleeding diathesis
- CNS lesions
- Frailty with high fall risk
- Prior gastrointestinal bleeding
Practical Considerations
- Be vigilant for drug interactions with warfarin
- Educate patients to report any signs of bleeding
- Consider temporary discontinuation during procedures with high bleeding risk
- Reassess the need for anticoagulation regularly as nephrotic syndrome improves
Despite the availability of newer anticoagulants, warfarin remains the preferred agent for nephrotic syndrome due to established experience and the ability to monitor its effect through INR testing, with a clear target range of 2-3.