TOPLINE:

Low-grade proteinuria (< 1 g/24 h) did not predict better renal outcomes or treatment response in patients with lupus nephritis, despite being associated with milder disease phenotypes. Glomerulosclerosis emerged as a key predictor of renal function decline, particularly in patients with relapsing lupus nephritis, highlighting the importance of early biopsy and personalized therapy.

METHODOLOGY:

• Researchers conducted an observational study of 239 patients with biopsy‑proven lupus nephritis (mean age, 33.4-35.6 years; approximately 90% women) at a hospital in China between January 2017 and July 2022 to investigate the clinical characteristics, renal pathology, treatment responses, and renal outcomes across different baseline proteinuria levels.
• Demographics, clinical indicators, and laboratory results — including 24-hour urine protein quantification — were collected at biopsy, and patients were followed up regularly with treatment-related data (serum creatinine levels, proteinuria levels, and induction therapy regimens) recorded at each visit.
• Analysis stratified patients by baseline 24-hour urine protein levels (< 1 g/24 h vs ≥ 1 g/24 h) and disease onset status (incident vs relapsing lupus nephritis).
• Outcome measures included overall response, complete response, and primary efficacy renal response at weeks 26 and 52, with follow-ups extending up to 156 weeks.

TAKEAWAY:

• At baseline, 17.6% of patients had proteinuria levels < 1 g/24 h, and 82.4% had ≥ 1 g/24 h; those with lower proteinuria levels showed lower global (P = .022) and renal disease activity (P = .002) than those with higher proteinuria levels; however, chronicity indices were similar between groups.
• Overall treatment response rates at weeks 26 and 52 were similar between the low- and high-proteinuria groups.
• Over up to 156 weeks of follow-up, 25 patients experienced a 30% or greater renal function decline, and baseline proteinuria did not predict decline, whereas total glomerulosclerosis independently predicted a 30% decline.
• In this cohort, 51% had incident disease and 49% had relapsing disease, with comparable renal function and baseline proteinuria levels; glomerulosclerosis independently predicted 30% and 40% declines in estimated glomerular filtration rate in patients with relapsing lupus nephritis but not in those with incident disease, and patients with relapsing disease with baseline proteinuria levels < 1 g/24 h had better treatment responses.

IN PRACTICE:

“Although patients with low baseline proteinuria have milder disease phenotypes, their treatment response and long-term renal outcomes are not superior to those of patients with higher proteinuria under current therapeutic strategies,” the authors wrote. “In relapsing [lupus nephritis], low baseline proteinuria linked to better treatment response, while glomerulosclerosis predicted decline. These findings highlight the need for early biopsy, individualized therapy, and dynamic monitoring, with noninvasive biomarkers aiding risk stratification.”

SOURCE:

The study was led by Yiwei Shen, MS, and Jingyi Peng, Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. It was published online on November 28, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The relatively small sample size in the low-proteinuria group may have affected the generalizability of these findings. As a retrospective study, data collection relied on existing medical records, and treatment regimen heterogeneity may have introduced confounding factors. The 3-year follow-up duration may be insufficient to capture long-term outcomes such as progression to chronic kidney disease or death. 

DISCLOSURES:

The study was supported by grants from the Basic-Clinical Collaborative Innovation Project from Shanghai Immune Therapy Institute, the National Natural Science Foundation of China, Science and Technology Innovation Action Plan medicine innovation fund by Science and Technology Commission of Shanghai Municipality, and other sources. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.