Lupus Nephritis

Secondary GNmedium

A 26-year-old woman with SLE had Class IV lupus nephritis treated with IV cyclophosphamide plus glucocorticoids, complicated by severe leukopenia and hemorrhagic cystitis. She achieved only a partial response on maintenance mycophenolate. She now has a biopsy-confirmed active proliferative relapse. Among the following choices, which is the most reasonable treatment option?

  1. A.Rituximab, an anti-CD20 antibodyCorrect
  2. B.Azathioprine, a maintenance agent
  3. C.Repeat high-dose IV cyclophosphamide
  4. D.Methotrexate, an antifolate agent

Explanation

In a patient with active relapsing/proliferative lupus nephritis who had major cyclophosphamide toxicity and an inadequate response to mycophenolate, rituximab is a reasonable rescue option among the choices and is specifically discussed by KDIGO 2024 for persistent disease activity or inadequate response to standard therapy. It should not be described as universally preferred, because the evidence base is less robust than for established standard regimens and treatment must be individualized. Azathioprine is mainly a maintenance drug, repeating high-dose cyclophosphamide is unattractive after severe toxicity, and methotrexate is not a lupus nephritis therapy. Since October 2025, obinutuzumab is also FDA-approved for adults with active lupus nephritis receiving standard therapy, further broadening current B-cell-directed options.

Why each option

A.
Correct. Rituximab is a preferred option for refractory or relapsing proliferative lupus nephritis, especially after cyclophosphamide toxicity and incomplete mycophenolate response.
B.
Azathioprine is a maintenance immunosuppressant and is inadequate to treat an active proliferative relapse.
C.
Repeat high-dose cyclophosphamide is relatively contraindicated after severe prior toxicity (cytopenia, hemorrhagic cystitis) in a woman of reproductive age.
D.
Methotrexate has no established role in lupus nephritis and is contraindicated with impaired kidney function.

Reference: KDIGO 2024 Lupus Nephritis Guideline; FDA GAZYVA (obinutuzumab) lupus nephritis indication, October 2025.

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