What is the target tacrolimus (FK506) trough level for lupus?

Target Tacrolimus Trough for Lupus Nephritis

For lupus nephritis maintenance therapy, target tacrolimus trough levels of 4-6 ng/mL (5-7.4 nmol/L). 1

Guideline-Based Recommendations

The 2024 KDIGO Clinical Practice Guideline for Lupus Nephritis explicitly states that tacrolimus should be maintained at trough blood levels of 4-6 ng/mL (5-7.4 nmol/L) when used as part of triple therapy maintenance regimens combined with prednisone. 1

This target range represents the optimal balance between:

• Efficacy: Adequate immunosuppression to prevent lupus nephritis flares 1
• Safety: Minimizing calcineurin inhibitor nephrotoxicity, particularly in patients with underlying chronic kidney disease 1

Clinical Context and Monitoring

When Tacrolimus is Used in Lupus Nephritis

Tacrolimus is typically employed in lupus nephritis for: 1

• Maintenance therapy after initial induction treatment, particularly in triple therapy regimens
• Refractory proteinuria in patients with inadequate response to mycophenolate mofetil and glucocorticoids, especially those with Class V (membranous) features 1
• Alternative maintenance option to azathioprine or mycophenolate 1

Monitoring Strategy

Trough levels should be measured 12 hours after the last dose (C12h), as this correlates well with drug exposure in lupus nephritis patients. 2 The 24-hour trough (C24h) is also a valid marker for therapeutic monitoring. 2

Evidence from Clinical Studies

Effective Dosing in Practice

Research studies support the guideline targets:

• Low-dose tacrolimus (2-3 mg/day) achieved complete or partial remission in 88% of cyclophosphamide-refractory lupus nephritis patients, with mean trough levels around 3-6 ng/mL. 3, 4
• A Japanese study using 3 mg/day tacrolimus achieved mean trough levels of 3.9 ng/mL with significant reduction in proteinuria and improvement in complement levels over one year. 5
• Case series using tacrolimus titrated to mean levels of 3-6 ng/dL (range 3-6.6 ng/dL) demonstrated complete remission in 75% of patients with refractory proteinuria. 4

Pharmacokinetic Considerations

In lupus nephritis patients, tacrolimus reaches maximum blood concentration 4-8 hours after oral administration (mean 6.7 hours), with significant inter-patient variability. 2 This supports the need for individualized dose adjustments based on trough monitoring rather than fixed dosing. 2

Critical Pitfalls to Avoid

• Chronic CNI nephrotoxicity: Exercise caution when adding tacrolimus for proteinuria reduction, particularly in patients with pre-existing chronic kidney disease who are more susceptible to calcineurin inhibitor toxicity. 1
• Overimmunosuppression: Avoid combining tacrolimus with multiple other immunosuppressants without clear indication, as this increases infection risk. 1
• Premature discontinuation: Most lupus nephritis patients require ≥36 months of total immunosuppression (induction plus maintenance) to prevent flares. 1
• Drug interactions: Tacrolimus is metabolized via CYP3A4, requiring careful monitoring when medications affecting this pathway are added or removed. 6

Comparison with Other Conditions

For context, tacrolimus targets differ by indication:

• Liver transplantation: 6-10 ng/mL first month, then 4-8 ng/mL thereafter 1
• Autoimmune hepatitis: Mean trough of 6 ng/mL for refractory disease 1
• Interstitial lung disease in autoimmune conditions: 5-10 ng/mL 1
• Steroid-resistant nephrotic syndrome in children: 5-7 ng/mL 1

The lower target range for lupus nephritis (4-6 ng/mL) reflects the need to minimize nephrotoxicity in patients with underlying kidney disease while maintaining adequate immunosuppression. 1