Management of Lupus Nephritis

Publication Date: January 3, 2024
Last Updated: January 3, 2024

Summary of Recommendations

We recommend that patients with SLE, including those with lupus nephritis (LN), be treated with hydroxychloroquine or an equivalent antimalarial unless contraindicated. (1, C)

Summary of Practice Points

  • A regimen of reduced-dose glucocorticoids following a short course of methylprednisolone pulses may be considered during the initial treatment of active LN when both the kidney and extrarenal disease manifestations show satisfactory improvement.
  • Intravenous cyclophosphamide can be used as the initial therapy for active Class III and Class IV LN in patients who may have difficulty adhering to an oral regimen.
  • An MPAA-based regimen is the preferred initial therapy of proliferative LN for patients at high risk of infertility, such as patients who have a moderate-to-high prior cyclophosphamide exposure.
  • Initial therapy with an immunosuppressive regimen that includes a CNI (voclosporin, tacrolimus, or cyclosporine) may be preferred in patients with relatively preserved kidney function and nephroticrange proteinuria likely due to extensive podocyte injury, as well as patients who cannot tolerate standard-dose MPAA or are unfit for or will not use cyclophosphamide-based regimens.
  • A triple immunosuppressive regimen of belimumab with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be preferred in patients with repeated kidney flares or at high-risk for progression to kidney failure due to severe chronic kidney disease.
  • Other therapies, such as azathioprine or leflunomide combined with glucocorticoids, may be considered in lieu of the recommended initial drugs for proliferative LN in situations of patient intolerance, lack of availability, and/or excessive cost of standard drugs, but these alternatives may be associated with inferior efficacy, including increased rate of disease flares and/or increased incidence of drug toxicities.
  • Newer biologic and non-biologic therapies are under development and may offer future options for the treatment of active LN. Rituximab may be considered for patients with persistent disease activity or inadequate response to initial standard-of-care therapy.
  • Azathioprine is an alternative to MPAA after completion of initial therapy in patients who do not tolerate MPAA, who do not have access to MPAA, or who are considering pregnancy.
  • Glucocorticoids should be tapered to the lowest possible dose during maintenance, except when glucocorticoids are required for extrarenal lupus manifestations; discontinuation of glucocorticoids can be considered after patients have maintained a complete clinical renal response for ≥12 months.
  • The dose of mycophenolate mofetil in the early maintenance phase is approximately 750–1000 mg twice daily, and for mycophenolic acid, approximately 540–720 mg twice daily.
  • The total duration of initial immunosuppression plus combination maintenance immunosuppression for proliferative LN should be ≥36 months.
  • Patients treated with triple immunosuppressive regimens that include belimumab or a CNI in addition to standard immunosuppressive therapy can continue with a triple immunosuppressive regimen as maintenance therapy.
  • If MPAA and azathioprine cannot be used for maintenance, CNIs or mizoribine or leflunomide can be considered.
  • An algorithmic approach to patients whose response to therapy is deemed unsatisfactory is provided:
    1. Verify adherence to treatment
    2. Ensure adequate dosing of immunosuppressive medications by measuring plasma drug levels if applicable or available (check mycophenolic acid level if on mycophenolic acid analogs/check infusion records if on cyclophosphamide)
    3. Repeat biopsy if concern for chronicity or other diagnosis (e.g., thrombotic microangiopathy)
    4. Consider switching to an alternative recommended treatment regimen when there is persistent active disease
    5. Consider the following in patients refractory:
      • Addition of rituximab or other biologic therapies
      • Extended course of i.v. pulse cyclophosp
      • Enrollment in clinical trials if eligible
  • After a complete or partial remission has been achieved, LN relapse should be treated with the same initial therapy used to achieve the original response, or an alternative recommended therapy.
  • Patients with active LN should be counseled to avoid pregnancy while the disease is active or when treatment with potentially teratogenic drugs is ongoing, and for ≥6 months after LN becomes inactive.
  • To reduce the risk of pregnancy complications, hydroxychloroquine should be continued during pregnancy, and low-dose aspirin should be started before 16 weeks of gestation.
  • Glucocorticoids, hydroxychloroquine, azathioprine, tacrolimus, and cyclosporine are considered safe immunosuppressive treatments during pregnancy.
  • Treat pediatric patients with LN using immunosuppression regimens similar to those used in adults, but consider issues relevant to this population, such as dose adjustment, growth, fertility, and psychosocial factors, when devising the therapy plan.
  • Patients with LN who develop kidney failure may be treated with hemodialysis, peritoneal dialysis, or kidney transplantation; and kidney transplantation is preferred to long-term dialysis.



Management of Lupus Nephritis

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