Update on Lupus Nephritis Management

Investigators are making strides in understanding the pathogenesis and management of lupus nephritis. In the Annals of the Rheumatic Diseases, Dimitrios T. Boumpas, MD, of National and Kapodistrian University in Athens, Greece, and coauthors provided a synopsis of notable papers on lupus nephritis published in their journal 2019-2022. Here is a sample.

Pathogenesis

Genetics play a role in lupus nephritis development and progression. Patients with lupus nephritis who have a high genetic load have increased odds for end-stage kidney disease and death, according to a study by Lars Rönnblom, MD, of Uppsala University in Sweden and colleagues. STAT4 and TLRI genes carry risk variants for lupus nephritis. A study found that smoking in the presence of the STAT4 risk gene variant increases the risk for nephritis. Other research suggests a common pathway underlying systemic lupus erythematosus and lupus nephritis.

Decreases in species diversity in the intestinal microbiome may trigger lupus nephritis, according to a team led by Gregg J Silverman, MD, of New York University School of Medicine in New York, New York.

Diagnosis

The SLE Risk Probability Index (SLERPI) is a machine learning-based model that can predict SLE and lupus nephritis apart from other rheumatologic conditions. SLERPI assigns points for proteinuria greater than 500 mg/24 hours, positive ΑΝΑ, low C3 and low C4, and anti-DNA or antiphospholipid antibodies. The sensitivity of SLERPI for lupus nephritis is 98%, George K Bertsias, of the University of Crete School of Medicine in Heraklion, Greece, and peers reported.

Another study suggested that describing lupus nephritis class III/IV as proliferative does not sufficiently characterize the disease. Maddalena Maria Bolognesi, a PhD student at the University of Milan-Bicocca in Monza, Italy, and colleagues further identified membranoproliferative and vasculitis-like lesions as distinct phenotypes.

Strategy

Data continue to confirm that patients achieving the EULAR/ERA-EDTA guideline response criteria at 1 year have good long-term renal outcomes. Criteria include complete (proteinuria less than 0.5g/24 hours) or partial response (50% or more proteinuria reduction to subnephrotic levels) including near normal estimated glomerular filtration rate (eGFR).

Maintenance immunosuppression needs to be taken for at least 5 years to prevent relapses, according to investigators led by Noemie Jourde-Chiche, PhD, of Aix-Marseille Université in France. Their WIN Lupus trial showed that earlier discontinuation may increase the risk for severe flares.

Target blood pressure should be less than 130/80 mm Hg, other research confirms.

Drug options

Tacrolimus is an alternative to mycophenolate mofetil for induction therapy, Chi Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong and colleagues reported. The team found no difference in the risk for flares or kidney function decline between regimens at 10 years. Leflunomide can replace azathioprine for maintenance therapy, according to a study by Chunde Bao, MD, of Renji Hospital, Shanghai Jiao Tong University School of Medicine in China, and colleagues.

Sodium glucose contransporter-2 inhibitors provide renoprotection for patients with chronic kidney disease, including patients with lupus nephritis.

Novel Therapies

Obinutuzumab, a type II anti-CD20 antibody, demonstrates a good renal response compared with placebo and will be explored further, according to investigators led by Richard A. Furie, MD, of Northwell Health in Great Neck, New York.

Low-dose IL-2 can restore T cell regulation and ease lupus nephritis, Jing He, MD, of Peking University People’s Hospital Beijing China, and peers found.

An exploratory study hints that high-dose anti-interferon therapy with anifrolumab might improve renal response, but it is associated with higher rates of herpes zoster.

Several studies are exploring novel targets for lupus nephritis therapies.

Disclosure: Please see the original references for a full list of disclosures.

Reference

Kostopoulou M, Fanouriakis A, Bertsias G, Boumpas DT. Annals of the Rheumatic Diseases collection on lupus nephritis (2019-2022): novel insights and advances in therapy. Ann Rheum Dis. 2023 Jun;82(6):729-733. doi:10.1136/ard-2023-223880

This article originally appeared on Renal and Urology News