Lupus Nephritis: A New Approach to Treatment Goals – From Clinical to Immunologic Remission

Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE), affecting approximately 35–60% of patients. It can cause significant damage to kidney function, leading to chronic kidney disease (CKD) or end-stage renal disease (ESRD) if not properly managed.

For years, LN treatment has primarily focused on reducing proteinuria and stabilizing kidney function, but recent research suggests a paradigm shift—moving beyond clinical remission to immunologic remission, which may offer better long-term outcomes.

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1. The Limitations of Traditional Treatment: Why Reducing Proteinuria Isn’t Enough

(1) Conventional Treatment Approach

• Focuses on reducing proteinuria and stabilizing kidney function
• Uses corticosteroids, cyclophosphamide (CYC), mycophenolate mofetil (MMF), and other immunosuppressants

However, simply reducing inflammation does not fully eliminate persistent immune complex deposition or underlying autoimmunity. Studies show that even when proteinuria normalizes, many patients still have active inflammation in kidney biopsy results.

Case Study Example
A 30-year-old female patient was treated with steroids and MMF, leading to proteinuria reduction below 0.5 g/24 hours.
However, her anti-double-stranded DNA antibody (Anti-dsDNA) levels remained high, indicating ongoing immune activation.
A follow-up kidney biopsy confirmed residual inflammation, requiring additional immunomodulatory treatment to prevent relapse.

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2. Why Immunologic Remission Matters in Lupus Nephritis

(1) What is Immunologic Remission?

• Achieved when Anti-dsDNA levels normalize and C3/C4 complement levels recover
• Indicates that autoimmune activity is under control and immune complex formation is minimal

(2) Research Evidence

• A Kidney International study (2025) reports that achieving immunologic remission significantly reduces the risk of relapse and kidney damage【1】.
• Patients who only achieve clinical remission (normal proteinuria) but not immunologic remission still have a 35% chance of relapse within two years【1】.
• Immunologic remission is now considered a key predictor of long-term renal survival【1】.

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3. The Three Pillars of Lupus Nephritis Treatment: Inflammation, Immunity, and Kidney Protection

This table summarizes the ideal treatment goals for LN and their associated therapies.

Treatment Goal	Description	Main Therapies
Clinical Remission	Reduced proteinuria, stabilized kidney function	Corticosteroids, complement inhibitors, traditional immunosuppressants (MMF, CYC)
Immunologic Remission	Suppressed autoimmune activity, normalized antibodies	B-cell therapies (Rituximab, Obinutuzumab), immunomodulators
Kidney Protection	Prevents chronic kidney damage, maintains function	RAAS inhibitors (ACEi/ARB), SGLT-2 inhibitors, lifestyle modifications

 

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4. Practical Application: How to Implement This in Patient Care

(1) When to Consider Stopping Treatment

• Immunosuppressants are gradually tapered only if immunologic remission is maintained for at least one year.
• Steroids are reduced step by step to minimize long-term side effects.
• Regular monitoring ensures early intervention if relapse signs appear.

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5. Long-Term Management and Patient Education

1. Regular Testing: Monitor Anti-dsDNA, C3/C4 levels, urine protein levels, and kidney function.
2. Lifestyle Modifications: Low-sodium diet, proper hydration, moderate exercise.
3. Infection Prevention: Long-term steroid and immunosuppressant use increases infection risks, so vaccination is recommended.
4. Multidisciplinary Approach: Collaboration between rheumatology, nephrology, and immunology specialists ensures optimal patient outcomes.

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6. Conclusion: A New Era in Lupus Nephritis Treatment

• The goal of lupus nephritis treatment has evolved—it’s not just about reducing proteinuria anymore.
• Suppressing autoimmunity (immunologic remission) is crucial to preventing relapse and long-term kidney damage.
• Combining immune regulation, inflammation control, and kidney protection provides the best long-term prognosis.

“Our ultimate goal is not just stabilizing numbers, but achieving a state where patients can live relapse-free, normal lives.”

💡 Key Takeaway: Even if your proteinuria is under control, continue monitoring immune markers to ensure long-term remission and avoid unexpected relapses.

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🔖 References

1. De Vriese AS, Sethi S, Fervenza FC. Lupus nephritis: redefining the treatment goals. Kidney International (2025), 107: 198-211. DOI: 10.1016/j.kint.2024.10.018

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