What are the factors to transition from induction to maintenance therapy in lupus nephritis?

Transition from Induction to Maintenance Therapy in Lupus Nephritis

Patients with lupus nephritis should transition to maintenance therapy after completing initial induction therapy, typically within 6-12 months, regardless of whether they achieve complete or partial remission, as long as they demonstrate adequate treatment response. 1

Key Factors Determining Transition Timing

Treatment Response Assessment (6-12 Months)

The decision to transition is primarily based on achieving either complete or partial renal response by 6-12 months: 1

Complete Response Criteria:

• Proteinuria <0.5 g/g (50 mg/mmol) on protein-creatinine ratio 1
• Stabilization or improvement in kidney function (±10-15% of baseline) 1
• No use of rescue therapy for treatment failure 1

Partial Response Criteria:

• Reduction in proteinuria by ≥50% AND to <3 g/g (300 mg/mmol) 1
• Stabilization or improvement in kidney function (±10-15% of baseline) 1

Duration of Induction Therapy

The typical induction phase lasts 6 months, though complete response may take up to 12 months or longer. 1 The KDIGO 2024 guidelines emphasize that patients should not be kept on induction therapy indefinitely—transition to maintenance should occur after completing the initial treatment course, even if only partial remission is achieved. 1

Critical Pitfalls to Avoid

Do Not Wait for Perfect Response

A common error is delaying transition to maintenance therapy while waiting for complete remission. 1 Patients achieving partial response should still transition to maintenance therapy, as prolonged high-intensity induction therapy increases toxicity without proven additional benefit. 1

Assess for Non-Response Early

If patients show worsening lupus nephritis (rising serum creatinine, worsening proteinuria) during the first 3 months, consider changing to an alternative induction regimen or performing repeat kidney biopsy rather than continuing the same therapy. 1 This represents treatment failure, not a reason to delay transition—it's a reason to change induction strategy. 1

Verify Adherence and Adequate Dosing

Before labeling a patient as having unsatisfactory response, the KDIGO guidelines mandate: 1

• Verify medication adherence 1
• Ensure adequate immunosuppressive dosing by measuring plasma drug levels (check mycophenolic acid levels if on mycophenolate analogs) 1
• Consider repeat biopsy if concern exists for chronicity versus active inflammation 1

Management Algorithm for Transition Decision

Step 1: Assess Response at 6 Months

• Measure proteinuria (protein-creatinine ratio) and serum creatinine 1
• Compare to baseline values 1

Step 2: Categorize Response

• Complete response: Transition to maintenance therapy 1
• Partial response: Transition to maintenance therapy 1
• No response: Verify adherence, check drug levels, consider repeat biopsy, then switch to alternative induction regimen 1

Step 3: Initiate Maintenance Therapy

• First-line: Mycophenolate (MMF 750-1000 mg twice daily or MPA 540-720 mg twice daily) plus low-dose glucocorticoids 1
• Alternative: Azathioprine if mycophenolate not tolerated, unavailable, or pregnancy planned 1
• Triple therapy continuation: If belimumab or calcineurin inhibitor used during induction, continue as triple maintenance regimen 1

Special Considerations

Patients on Triple Immunosuppression

Those treated with belimumab or calcineurin inhibitors (voclosporin, tacrolimus) plus standard therapy during induction should continue the triple regimen during maintenance rather than de-escalating. 1 The BLISS-LN trial demonstrated sustained efficacy with belimumab-containing triple therapy through 100 weeks. 1

Glucocorticoid Tapering

Begin tapering glucocorticoids to the lowest possible dose during the maintenance phase. 1 Discontinuation can be considered only after patients maintain complete clinical renal response for ≥12 months, unless glucocorticoids are required for extrarenal lupus manifestations. 1

Total Treatment Duration

The combined duration of induction plus maintenance immunosuppression should be ≥36 months for proliferative lupus nephritis. 1 This recommendation is based on evidence showing increased flare rates with earlier discontinuation: 1

• The WIN-Lupus trial showed more severe SLE flares when immunosuppression was discontinued before 36 months 1
• Chinese cohorts demonstrated increased disease flares when MMF was stopped before 2 years 1
• 28-50% of patients show persistent histologic inflammation despite clinical remission at 36 months 1

Histologic Versus Clinical Response

Clinical response does not correlate completely with ongoing kidney inflammation. 1 Consider repeat kidney biopsy before discontinuing maintenance therapy, particularly in patients with only partial clinical remission, as many have resolution of histologic activity despite persistent proteinuria from chronic kidney damage. 1

Evidence Quality Note

The 2024 KDIGO guidelines represent the highest quality and most recent evidence available, superseding the 2014 Canadian Society of Nephrology commentary. 1 The recommendation for mycophenolate as first-line maintenance therapy is graded 1B (strong recommendation, moderate quality evidence). 1 Meta-analyses confirm MMF superiority over azathioprine for preventing relapse during maintenance (OR 1.83 for relapse with azathioprine). 2, 3