Treatment of relapsing lupus nephritis

MMF: mycophenolate mofetil; AZA: azathioprine; IV: intravenous.
* A relapse of focal or diffuse lupus nephritis may occur in the setting of reduction or cessation of immunosuppression or nonadherence to oral drug therapy. A kidney biopsy is frequently required to verify recurrent active lupus nephritis rather than nonimmunologic progression of kidney disease or an alternative diagnosis. Refer to UpToDate content on the diagnosis of relapse in patients with focal or diffuse lupus nephritis.
¶ Mild relapse is defined as increased activity of the urinary sediment and, possibly, a modest (eg, <50%) increase in urine protein excretion but with a stable serum creatinine. Moderate to severe relapse is defined as an active urinary sediment and a greater increase in proteinuria (eg, >50%) and, sometimes, with a rise in serum creatinine.
Δ Exceptions include patients who have received multiple prior courses of cyclophosphamide for whom there is concern for cumulative toxicity or risk of infertility; in such patients, it may be preferable to use a mycophenolate-based regimen. Patients who are not able to reliably adhere to oral medication regimens may have improved adherence if treated with IV cyclophosphamide.
Alternatively, some clinicians might choose to modify the initial therapy regimen rather than restart the previous initial therapy regimen. As an example, if a patient relapsed while on MMF alone for initial therapy, treating with MMF plus either a calcineurin inhibitor (voclosporin, tacrolimus, or cyclosporine) or belimumab would be a reasonable option for initial therapy after relapse.
◊ All patients who are treated for relapsing lupus nephritis should be monitored similarly to those receiving initial or subsequent therapy for focal or diffuse lupus nephritis. Refer to UpToDate content on monitoring the response to therapy in patients with focal or diffuse lupus nephritis.
§ Some clinicians choose to modify the subsequent therapy regimen in patients whose relapse occurred while on the original course of therapy. As an example, if a patient relapsed while on MMF alone for subsequent therapy, treating with MMF plus either a calcineurin inhibitor (voclosporin, tacrolimus, or cyclosporine) or belimumab would be a reasonable choice. Alternatively, some clinicians might try MMF plus rituximab.
¥ For patients who cannot increase the dose of their original immunosuppressive regimen (eg, patients with diabetes who do not wish to receive higher doses of glucocorticoids or patients on MMF or AZA with leukopenia at a high dose), switching to an alternative initial regimen is also an option. Refer to UpToDate content on treatment of mild relapse of focal or diffuse lupus nephritis.