Lupus Nephritis When Initial Immunosuppressive Therapy Has Not Achieved Kidney Response
This protocol applies to patients with lupus nephritis whose first-line treatment course did not achieve the defined kidney response targets. A structured next-line regimen addresses this scenario.
First-Line Treatment — Goals Not Achieved
The prior regimen — corticosteroids (methylprednisolone, prednisone) combined with immunosuppressive and/or biologic agents (mycophenolate mofetil, belimumab, cyclophosphamide, voclosporin, tacrolimus, obinutuzumab, azathioprine, or hydroxychloroquine) — did not meet the following targets:
- GFR preserved or improved to ≥80% of baseline within 3 months
- Proteinuria reduced ≥25% by 3 months and ≥50% by 6 months
- Urine protein-to-creatinine ratio <700 mg/g by 12 months
- Complete renal response: urine protein-to-creatinine ratio <500 mg/g
Goals of This Protocol
- Preservation or improvement of kidney function — GFR ≥80% of baseline within 3 months
- Proteinuria reduction ≥25% by 3 months, ≥50% by 6 months
- Urine protein-to-creatinine ratio <700 mg/g by 12 months
- Complete renal response: urine protein-to-creatinine ratio <500 mg/g
Treatment Approach (Partial Overview)
The next step involves switching to an alternative immunosuppressive and/or biologic regimen; where the prior course used a single agent, combination therapy is now strongly considered. Referral to specialist centres is also recommended. The full protocol — agent selection, sequencing, and decision criteria — is available via the link below.
References
DOI: 10.1016/j.ard.2025.09.007
- For patients with persistently active or relapsing disease, switching among different immunosuppressive and/or biologic drugs and referral to experts is recommended.
- Any of the alternative regimens outlined in recommendation #4 can be tried.
- In cases of monotherapy with MPAA or CYC used as initial therapy, combination therapy should now be strongly considered.
- In 2019, a recommendation for rituximab was also made in cases of nonresponding disease, based on observational evidence.
- Rituximab may still be considered if other options have failed and obinutuzumab is unavailable.
- Treatment should aim for optimisation (preservation or improvement) of kidney function within 3 months, accompanied by a reduction in proteinuria of at least 25% by 3 months, 50% by 6 months, and a UPCR target <700 mg/g by 12 months, and as low as possible afterwards.
- Together with proteinuria, stabilisation (if not improvement) of GFR to ≥80% of baseline value is desirable within the first 3 months to ensure that the patient is not deteriorating and in need of reevaluation of the treatment regimen.
- Complete renal response should be defined as UPCR <500 mg/g at any time point.
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