Authors Give Overview of the New ACR Lupus Nephritis Guideline

This year’s update to the ACR guideline for lupus nephritis (LN), expected to be published in 2025, is the first since 2012. The guideline summary is available now.

Lead author of the guideline, Lisa Sammaritano, MD, Professor of Clinical Medicine at Weill Cornell Medicine and Hospital for Special Surgery, discussed the development of the guideline and key recommendations in the Monday, Nov. 18, ACR Convergence session 2024 Updated ACR Guideline for the Diagnosis and Treatment of Lupus Nephritis. The session will be available on-demand to all registered ACR Convergence 2024 participants through Oct. 10, 2025, by logging into the meeting website.

For patients with suspected LN, the guideline recommends a prompt kidney biopsy and treatment with glucocorticoids while waiting for biopsy results. A kidney biopsy is recommended for patients with LN with proteinuria of more than 0.5 g/g, patients with impaired kidney function not otherwise explained, and patients with known LN who have a suspected flare or lack of response.

“For all lupus patients who do not have known LN, we recommend screening for proteinuria either at 6 or 12 months at a minimum or at the time of clinical flare,” Dr. Sammaritano said.

The guideline recommends hydroxychloroquine for all patients and the addition of renin-angiotensin-aldosterone system (RAAS) inhibitors for those with elevated proteinuria, she explained. Prompt glucocorticoid treatment is recommended for suspected LN to suppress acute inflammation while awaiting kidney biopsy results. A recent meta-analysis of glucocorticoid therapy for LN found that pulse glucocorticoid followed by a lower-dosage oral regimen maximized complete renal response while minimizing toxicity.

Maria Dall’Era, MD, Professor and Chief of Rheumatology at the University of California, San Francisco, discussed applying the updated guideline to patients with Class III/IV +/- V LN. She said the preferred first-line therapy is triple therapy.

“Which of the triple immunosuppressive therapies do you choose? This is where shared decision-making, preferences of our patients, and clinical clues in the actual case are important,” Dr. Dall’Era said.

The pivotal Belimumab International Study in Lupus Nephritis (BLISS-LN) trial assessed the efficacy of belimumab for LN and found that more patients treated with belimumab had a primary efficacy renal response and a complete renal response at week 104. A subgroup analysis found that belimumab was more efficacious in participants with baseline proteinuria levels of less than 3.

The AURORA1 trial assessed the efficacy of voclosporin for LN and found that patients treated with voclosporin had higher rates of complete renal response at week 52. A reduction in proteinuria was seen earlier in the voclosporin group.

Anca D. Askanase, MD, MPH, Professor of Medicine and Director of the Lupus Center, Columbia University Irving Medical Center, discussed applying the guideline to Class V LN.

In patients with active, newly diagnosed, or a flare of Class V LN with proteinuria greater than 1 g/24 hours, the guideline conditionally recommends mycophenolic acid plus a calcineurin inhibitor (CNI) over mycophenolic acid plus belimumab. In patients with active, newly diagnosed, or a flare of Class V LN with low-level proteinuria, the guideline conditionally recommends treatment.

“We’re saying don’t leave these patients untreated,” Dr. Askanase said. “They will progress to higher-grade proteinuria. Treat with either glucocorticoids and/or immunosuppressive therapy over no immunosuppressive treatment at all.”

The preferred first-line therapy for Class V LN is triple therapy. Post-hoc analyses support the use of voclosporin plus mycophenolic acid and low-dose glucocorticoids to achieve earlier reductions in proteinuria in patients with Class V LN.

Mary Beth Son, MD, Clinical Chief of Immunology at Boston’s Children’s Hospital, discussed applying the guideline to pediatric LN.

Pediatric systemic lupus erythematosus (SLE) has more prominent renal and neuropsychiatric manifestations. Further, these patients are at risk for higher cumulative dosing of glucocorticoids and increased damage accrual.

“This is the first time the ACR guidelines have included pediatric recommendations for LN,” Dr. Son said. “This was done because there was an acknowledged need for guidance given that kids are actually sicker and that the disease process and pathophysiology are the same, as are the clinical manifestations.”

The guideline recommends pediatric-appropriate dosages for glucocorticoids, because reduction of the cumulative dosing is important given the young age of the patients. Clinicians should monitor pediatric patients with LN for delayed pubertal onset and decreased growth velocity. A structured, intentional transition from pediatric to adult rheumatology care is needed to avoid poor outcomes, Dr. Son said.