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Key factors impacting the choice of immunosuppressive therapy for focal or diffuse lupus nephritis (LN) resistant to initial therapy

Key factors impacting the choice of immunosuppressive therapy for focal or diffuse lupus nephritis (LN) resistant to initial therapy
Factors Comments
Rapidly deteriorating kidney function and/or severe LN on biopsy (eg, extensive crescents, capillary necrosis) In such cases, some clinicians prefer a regimen that includes high-dose IV CYC. However, data to support this approach in this patient population are very limited as such patients were generally excluded from clinical trials.
Higher proteinuria (≥3 g/day) Such patients may benefit from triple therapy with glucocorticoids plus MMF and a CNI (voclosporin, tacrolimus, or cyclosporine). By contrast, belimumab may not be as effective in such patients.
Significantly reduced baseline kidney function (eGFR <45 mL/min/1.73 m2) In such patients, CNIs should be used with caution because of the potential nephrotoxicity of these drugs.
Difficulty with adherence In such patients, regimens involving IV therapies (eg, cyclophosphamide, belimumab, rituximab) may be preferable to those without IV therapies.
Prior courses of CYC In such patients, we advise calculating the total lifetime dose to avoid giving over 36 grams, which can predispose to future malignancies, and to consider fertility implications of repeated CYC.
Extrarenal manifestations The presence of extrarenal manifestations of SLE may influence the selection of therapy for LN. As examples:
  • Belimumab has been found to be helpful for patients with severe or refractory arthritis; thus, triple therapy with belimumab, glucocorticoids, and either MMF or CYC might be preferred over alternative regimens in that situation.
  • Regimens for LN that include IV CYC may be preferable in patients who have certain severe, potentially life-threatening manifestations of SLE (eg, inflammatory or demyelinating central nervous system disease, severe diffuse alveolar hemorrhage, and/or severe myocarditis).
For more information on choosing a treatment regimen, please refer to UpToDate content on the treatment of focal or diffuse lupus nephritis resistant to initial therapy.
CNI: calcineurin inhibitor; CYC: cyclophosphamide; eGFR: estimated glomerular filtration rate; IV: intravenous; LN: lupus nephritis; MMF: mycophenolate mofetil; SLE: systemic lupus erythematosus.
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