Treatment of focal or diffuse lupus nephritis resistant to initial therapy

CNI: calcineurin inhibitor.
* This algorithm does not apply to patients with pure class V lupus nephritis. Among patients with focal or diffuse lupus nephritis, resistant disease refers to the failure of initial immunosuppressive therapy to achieve either a complete or partial clinical response. Development of a complete response usually requires a minimum of 6 months and, in some patients, as long as 12 months or more after the initiation of initial therapy. Assessment of the patient's response should begin as early as 3 to 4 months after initial therapy to determine whether the patient is demonstrating a clinical response to therapy (ie, a reduction in proteinuria, improvement or stabilization of the serum creatinine, improvement of the urinary sediment).
¶ Many cases of suspected treatment resistance are related to nonadherence rather than actual resistance to immunosuppressive therapy. Refer to UpToDate content on the assessment of patient adherence to therapy in patients with focal or diffuse lupus nephritis suspected of being resistant to initial therapy.
Δ If nonadherence to therapy is likely contributing to the patient's lack of clinical response, we try to understand reasons for nonadherence and tailor our approach to the individual patient. Such patients are not considered to be resistant to therapy. If nonadherence is due to side effects (such as nausea or diarrhea), we would switch to an alternative therapy. If the patient has difficulty remembering to take their medications, we may suggest using a pill box/organizer, setting alarms on their smart phone, or switching to an injectable medication.
◊ A mycophenolate-based regimen refers to the use of mycophenolate alone or in combination with a CNI (voclosporin, tacrolimus, or cyclosporine) or belimumab. A cyclophosphamide-based regimen refers to the use of cyclophosphamide alone or in combination with belimumab. Glucocorticoids are generally given together with a mycophenolate- or cyclophosphamide-based regimen.
§ If the patient is already taking mycophenolate in combination with a CNI, belimumab, or rituximab, it is reasonable to switch to a different combination. As an example, if the patient is taking mycophenolate plus a CNI, they may be switched to mycophenolate plus rituximab.
¥ A rituximab-based regimen refers to the use of rituximab in combination with a CNI (voclosporin, tacrolimus, or cyclosporine), mycophenolate, or cyclophosphamide.