Patient with biopsy-proven active class III or IV (with or without class V) lupus nephritis

CNI: calcineurin inhibitor; EC-MPS: enteric-coated mycophenolate sodium; eGFR: estimated glomerular filtration rate; MMF: mycophenolate mofetil; SLE: systemic lupus erythematosus.

* For more information on targeted therapy, refer to UpToDate content on specific SLE disease manifestations.

¶ Intravenous cyclophosphamide may be preferred in patients with active focal or diffuse lupus nephritis who additionally have certain severe, potentially life-threatening manifestations of SLE such as inflammatory or demyelinating central nervous system disease, severe diffuse alveolar hemorrhage, and/or severe myocarditis.

Δ Refer to UpToDate content on initial and subsequent therapy of focal or diffuse lupus nephritis for more detailed information on dosing and administration of suggested immunosuppressive therapy regimens.

◊ We typically administer IV pulse methylprednisolone (250 to 1000 mg daily for one to three days), followed by oral prednisone (or its equivalent) at 0.3 to 0.5 mg/kg per day (maximum of 40 mg/day), with a taper to ≤7.5 mg/day (and preferably to ≤5 mg/day) by three to six months.

§ Some UpToDate contributors prefer triple therapy with glucocorticoids + MMF + a CNI in patients with higher baseline proteinuria (≥3 g/day) based on data suggesting a benefit with the addition of a CNI to MMF in such patients. In patients who have significantly reduced kidney function (eg, eGFR <45 mL/min/1.73 m²), CNIs should be used with caution due to potential nephrotoxicity.

¥ During initial immunosuppressive therapy, we typically schedule follow-up visits every 2 to 4 weeks for the first three months. In stable patients, the duration between follow-up visits can then be extended to every 2 to 3 months. Once patients are transitioned from initial to subsequent therapy, we generally perform follow-up visits every 3 months.

• Proteinuria: We target a decrease in proteinuria of ≥25% by three months, ≥50% by six months, and proteinuria below 0.5 to 0.7 g/day by 12 months of initial therapy. Patients with nephrotic-range proteinuria at baseline may require an additional 6 to 12 months to reach complete clinical response goals for proteinuria.
• Kidney function: We target improvement or stabilization in eGFR, with no more than a 20% decline below the pre-flare value.
• Urine sediment: We aim for an inactive urinary sediment (ie, no or rare dysmorphic red blood cells (RBCs) and no RBC casts). In addition to a clinical response, some experts also aim for normalization of serum complement levels and anti-dsDNA antibody titers.

† The timing of initiation of subsequent therapy depends upon the induction regimen used. Subsequent therapy is typically administered for at least three years. Mycophenolate is preferred for subsequent therapy in most patients who achieve a renal response after initial therapy since the risk of relapse may be higher for azathioprine. Azathioprine is preferred for women who want to become pregnant and is a reasonable choice for patients who are intolerant of mycophenolate or cannot afford the cost of mycophenolate. Patients who receive belimumab or a CNI as part of initial therapy should continue these agents as part of their subsequent therapy regimen; however, the optimal duration of treatment with these agents is uncertain.