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)
314262
We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus any one of the following:
mycophenolic acid analogs (MPAA) (1, B)
314262
low-dose intravenous cyclophosphamide (1B) (1, B)
314262
belimumab and either MPAA or low-dose intravenous cyclophosphamide (1, B)
314262
MPAA and a calcineurin inhibitor (CNI) when kidney function is not severely impaired (i.e., estimated glomerular filtration rate ≤45 ml/min per 1.73 m2) (1, B)
314262
We recommend that after completion of initial therapy, patients should be placed on MPAA for maintenance. (1, B)
314262

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.

Recommendation Grading

Abbreviations

  • LN: Lupus Nephritis
  • MMF: Mycophenolate Mofetil
  • MPA: Mycophenolic Acid
  • MPAA: Mycophenolic Acid Analogs
  • SLE: Systemic Lupus Erythematosus
  • eGFR: Estimated Glomerular Filtration Rate

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Management of Lupus Nephritis

Authoring Organization

Publication Month/Year

January 3, 2024

Last Updated Month/Year

February 20, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

The 2024 Clinical Practice Guideline for the Management of Lupus Nephritis is a focused update of the lupus nephritis (LN) chapter of The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Drawing from the latest approvals of belimumab and voclosporin by the FDA and EMA, the guideline provides updated recommendations and practice points for using these new therapies as add-on immunosuppressive agents in the management of LN. The development of the guideline followed an explicit process of evidence review and appraisal.

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D008181 - Lupus Nephritis

Keywords

lupus, lupus nephritis, glomerulonephritis, nephrotic syndrome, glomerular diseases

Source Citation

Kidney Disease: Improving Global Outcomes (KDIGO) Lupus Nephritis Work Group. KDIGO 2024 Clinical Practice
Guideline for the Management of Lupus Nephritis. Kidney Int. 2024;105(1S):S1–S69.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
370
Literature Search Start Date
July 1, 2022
Literature Search End Date
April 1, 2023