Treatment of class III or IV lupus nephritis

IV: intravenous.
* Patients with concomitant thrombotic microangiopathy should receive therapy for the underlying etiology of thrombotic microangiopathy in addition to the treatment of lupus nephritis. Refer to UpToDate content on the management of acquired thrombotic thrombocytopenic purpura, complement-mediated thrombotic microangiopathy, or antiphospholipid syndrome.
¶ Oral glucocorticoid therapy (prednisone or equivalent) is typically started at 0.5 to 1 mg/kg per day (maximum 60 mg/day) for most patients. In patients with severe active disease (eg, acute kidney injury, crescentic glomerulonephritis, severe extrarenal disease), we administer IV pulse methylprednisolone (250 to 1000 mg given over 30 minutes daily for 1 to 3 days) prior to initiation of oral glucocorticoids to induce a rapid antiinflammatory effect. Some clinicians use IV pulse methylprednisolone in all patients as this may enable the use of lower doses of oral glucocorticoids. Refer to UpToDate content on glucocorticoid dosing and taper for focal or diffuse lupus nephritis.
Δ The efficacy of mycophenolate and cyclophosphamide as initial therapy for focal or diffuse lupus nephritis is comparable. Mycophenolate is preferred for patients with concerns about fertility since cyclophosphamide may adversely affect fertility. Conversely, IV cyclophosphamide may be preferred for patients with preexisting gastrointestinal conditions or who may have difficulty adhering to oral therapy. Refer to UpToDate content on dosing and duration of mycophenolate and cyclophosphamide for initial therapy.
◊ The role of combination regimens as initial therapy is not well established, and some experts reserve this approach for patients who do not demonstrate a clinical response within 3 to 4 months with either mycophenolate or cyclophosphamide. Others may choose to use these combination regimens as initial therapy. Refer to UpToDate content on alternative initial therapies for focal or diffuse lupus nephritis.
§ There is no consensus definition of complete or partial response in patients with focal or diffuse lupus nephritis. Most definitions of response have incorporated a substantial reduction in proteinuria, improvement or stabilization of serum creatinine, and improvement of the urinary sediment. Refer to UpToDate content on definitions of response in patients receiving treatment for focal or diffuse lupus nephritis.
¥ The timing of initiation of subsequent therapy depends upon the induction regimen used. Refer to UpToDate content on when to start maintenance therapy in patients with focal or diffuse lupus nephritis.
‡ Mycophenolate is preferred for subsequent therapy in most patients who achieve a renal response after initial therapy. Azathioprine is an alternative option, although the risk of relapse may be higher for azathioprine. However, azathioprine is preferred for females who want to become pregnant and is a reasonable choice for patients who are intolerant of mycophenolate or cannot afford the cost of mycophenolate. Mycophenolate is preferred for patients with gout who require treatment with allopurinol. Patients who receive belimumab or a calcineurin inhibitor as part of an alternative combination regimen for initial therapy may continue these agents as part of their subsequent therapy regimen.
† Patients who have not responded to initial therapy after 6 months should be assessed for adherence to therapy. Many cases of suspected treatment resistance are related to nonadherence rather than actual resistance to immunosuppressive therapy. Refer to UpToDate content on the treatment of focal or diffuse lupus nephritis resistant to initial therapy.