Recommendations for screening, treatment, and management of lupus nephritis: New ACR guideline summary

Washington: During ACR Convergence 2024, the American College of Rheumatology (ACR) unveiled a summary of the 2024 Guideline for the Screening, Treatment, and Management of Lupus Nephritis. This marks the ACR’s first updated lupus nephritis guideline since 2012, offering evidence-based, expert recommendations for managing the condition in both adults and children. The goal of lupus nephritis treatments is to preserve kidney function and reduce morbidity and mortality of chronic kidney disease while minimizing medication-related toxicities.

"At the time the ACR released its last lupus nephritis clinical practice guidelines, recommendations called for induction therapy with high-dose glucocorticoids plus immunosuppressant medications like mycophenolate mofetil or cyclophosphamide and endorsed mycophenolate for maintenance therapy,” said Lisa Sammaritano, MD, lead author on the guideline, professor of clinical medicine at Weill Cornell Medicine, and an attending physician in the Hospital for Special Surgery Division of Rheumatology. “Since then, belimumab and voclosporin have been approved by the US Food and Drug Administration for treatment, prompting a conceptual shift from induction and maintenance therapy to one of combination, ongoing therapy targeting different parts of the immune system.”

The guideline summary provides 41 recommendations and good practice statements. Key recommendations include:

Screening

• Strong recommendation to screen at least every six to 12 months for protein in the urine (proteinuria) in patients with SLE without known kidney disease, or when experiencing extra-renal flares.

• Conditional recommendation to perform a kidney biopsy in patients with SLE who have high levels of protein in the urine (> 0.5 g/g) and/or impaired kidney function not otherwise explained.

Treatment

• Conditional recommendation for a triple immunosuppressive regimen in patients with active Class III & IV lupus nephritis: Triple therapy for Class III/IV lupus nephritis includes glucocorticoid, and one of three immunosuppressive combination regimens: mycophenolate plus belimumab, mycophenolate plus calcineurin inhibitor therapy, or low dose cyclophosphamide plus belimumab.

• Conditional recommendation for treatment with a specific “triple therapy” as the most desirable therapy for pure Class V lupus nephritis with proteinuria greater than 1 g/g: Triple therapy for Class V lupus nephritis includes glucocorticoid, mycophenolate, and calcineurin inhibitor therapy.

• Conditional recommendation for a lower dose glucocorticoid regimen (after initial intravenous pulse therapy) to minimize toxicity, starting at 0.5 mg/kg/day prednisone (maximum of 40 mg daily) with taper to a prednisone goal of less than or equal to 5 mg/day by six months of treatment.

Monitoring

• Strong recommendations to quantify proteinuria at least every three months in patients with lupus nephritis who have not achieved complete renal response and every three to six months in patients with sustained complete renal response.

Lupus nephritis occurs in people with lupus when autoantibodies affect the kidneys causing inflammation that may result in scarring. This can lead to blood or protein in the urine, high blood pressure, poorly functioning kidneys, or even kidney failure.

Lupus nephritis manifests in close to half of SLE patients and carries a mortality rate of up to 30% at 10 years. Ten to 22 percent of patients with the condition will develop end-stage kidney disease (ESKD). Among those with SLE, those who are male, younger in age, and are of African, Hispanic, American Indian/Alaska Native, and Asian ancestry have an increased likelihood of developing lupus nephritis and ESKD. Additionally, socially disadvantaged individuals in medically underserved areas have worse kidney outcomes.

“We also acknowledge that therapeutic decisions will vary depending on clinical presentation and patient preferences and may be limited by access to specialists, procedures, and medications,” Dr. Sammaritano continued. “When recommended medications are unavailable, this guideline should not preclude using available traditional therapies.”

Guideline recommendations are based on systematic evidence reviews, values and preferences from a lupus nephritis patient panel, and input from adult and pediatric rheumatologists and nephrologists and a rheumatology physician assistant. The recommendations are intended to promote optimal outcomes for the most commonly encountered lupus nephritis scenarios. The guideline includes therapies available in the United States as of fall 2024 and applies to lupus nephritis in adults, children, and adolescents. This is the first time the ACR has included children and adolescents in their lupus treatment guidelines. The systematic literature search included all age ranges, and pediatric providers were included in every stage of the guideline development process allowing creation of pediatric specific guidance.