Applying the latest ACR guideline to the diagnosis & treatment of lupus nephritis
CHICAGO—During ACR Convergence 2025, three lupus experts presented a session titled, Bench to Bedside in the Diagnosis and Treatment of Lupus Nephritis. The talk highlighted new biomarkers for lupus nephritis and a practical approach on how to apply the 2024 ACR Guideline for the Screening, Treatment and Management of Lupus Nephritis to patients refractory to treatment.
Novel Urinary Biomarkers
Dr. Fava
Andrea Fava, MD, assistant professor of medicine and director of Lupus Translational Research at Johns Hopkins School of Medicine, Baltimore, spoke on applying promising new data from the AMP program clinically.
Lupus nephritis carries a 20% risk of end-stage kidney disease within 20 years. Current practice patterns include serial screening for proteinuria. “We react with a kidney biopsy if proteinuria is above a ‘magic threshold’ of 500 mg per 24 hours,” Dr. Fava said.
However, the use of proteinuria as a measure of disease activity has several limitations. Dr. Fava explained how proteinuria has been shown to have no correlation with inflammation, is a lagging indicator and cannot distinguish treatable inflammation from chronic damage.
Michelle Petri, MD, MPH
A plenary given at ACR Convergence 2025 by Michelle Petri, MD, from Johns Hopkins School of Medicine demonstrated among patients with SLE and proteinuria from 0.25–0.499g/g nearly half had evidence of actionable lupus nephritis (21% had Class III/IV +/- V and 25% with Class V) even despite proteinuria below the 500 mg threshold.1
Dr. Fava also highlighted in a study of patients with systemic lupus erythematosus (SLE) nephritis treated for three years and in complete renal remission who underwent repeat kidney biopsy. In the study, 20% of patients in proteinuric remission for greater than one year still had persistent histologic activity.2
Dr. Fava discussed his work in urine proteomics, quantifying over 1,000 proteins in the urine and identifying ones that correlated with intra-renal immunologic activity.3 Urinary biomarkers of immunologic response, such as interleukin 16, CD163 and CD206, decreased in responders and predicted one-year response, suggesting effective immunosuppression reduces intrarenal inflammation early.
Many urine protein biomarkers outperform proteinuria in predicting poor long-term outcomes (Fig. 1, below). Urinary tenascin C was a novel marker discovered—and involved in matrix remodeling—whose persistence along with other markers emerged as a robust predictor of kidney function loss in lupus nephritis. A 12-protein panel and urinary proteomics-based score were presented, which outperformed UPCR and helped stratify high-risk individuals, regardless of the proteinuria response.4
