Low-Grade Proteinuria Not Tied to Improved Renal Outcomes in Lupus Nephritis

In new research on patients with lupus nephritis, low-grade proteinuria does not predict improved renal outcomes or treatment responses, while glomerulosclerosis predicts renal function decline in patients who relapse.1

Study investigator Nan Shen, MD, PhD, a distinguished professor of medicine at Shanghai JiaoTong University, and colleagues, aimed to “investigate the clinical characteristics, renal pathology treatment responses, and renal outcomes of lupus nephritis (LN) patients with different levels of baseline proteinuria.”1

A previous 12-month study identified proteinuria as the strongest predictor of long-term renal outcomes in lupus nephritis compared with serum creatinine or urinary red blood cells.2 However, whether patients with low-grade proteinuria at baseline experience better clinical or histologic outcomes over time has remained unclear.

In lupus nephritis research, a 30%-40% decline in eGFR over several years is often used as a surrogate endpoint for long-term kidney function deterioration, allowing investigators to quantify clinically meaningful loss of renal function within a shorter follow-up period. In contrast, glomerulosclerosis represents a biopsy-based chronicity marker reflecting structural scarring present at baseline. Analyzing functional decline, eGFR loss, and structural damage associated with glomerulosclerosis can help clarify whether baseline proteinuria levels or chronicity features predict long-term renal outcomes.1

In this longitudinal cohort study, investigators aimed to understand the association between proteinuria levels at baseline and clinical characteristics, renal pathology treatment responses, and renal outcomes of patients with lupus nephritis. The analysis incorporated chronicity markers such as glomerulosclerosis to identify predictors of long-term decline.1

Shen and colleagues stratified patients by baseline proteinuria levels: low-grade (<1 g/24 h) and high-grade (≥1 g/24 h), in addition to disease onset status, incident or relapsing. At weeks 26 and 52, renal treatment responses were assessed by overall, complete, and primary efficacy renal response. By 156 weeks, investigators used Cox proportional hazards regression and Kaplan–Meier analyses to evaluate predictors of time to the first 30% and 40% eGFR decline as surrogate endpoints of long-term kidney disease progression.¹

The study included 239 patients with biopsy-proven lupus nephritis. Of these, 17.6% of participants had low-grade proteinuria levels (n = 42), and 82.4% had high-grade (n = 197). Additionally, investigators identified 51% of patients with incident lupus nephritis, and 49% had relapsing.1

Upon analysis, investigators noted a decreased incidence of urinary sediments, an increased frequency of class V, and a decreased renal pathology activity index in the <1 group compared to the ≥1 group. These groups exhibited similar chronicity index, as well as similar overall remission rates at week 26 and 52.1

At 156 weeks, investigators were able to observe an equivalent risk of 30% or 40% eGFR decline in patients with low-grade proteinuria compared with those with high-grade proteinuria. Investigators also evaluated renal pathology features. According to their findings, glomerulosclerosis independently predicted long-term renal deterioration in relapsing but not incident lupus nephritis.1

“These results underscore the importance of early biopsy, personalized therapy, and close monitoring, supported by non-invasive biomarkers for risk assessment,” concluded investigators.1 

References

1. Shen Y, Peng J, Dai D, et al. Low‐Grade Proteinuria Does Not Predict Favorable Outcomes in Lupus Nephritis: A Longitudinal Cohort Study. Arthritis & Rheumatology. Published online November 28, 2025. doi:https://doi.org/10.1002/art.70009

2. Dall’Era M, Cisternas MG, Smilek DE, et al. Predictors of Long-Term Renal Outcome in Lupus Nephritis Trials: Lessons Learned from the Euro-Lupus Nephritis Cohort. Arthritis & Rheumatology. 2015;67(5):1305-1313. doi:https://doi.org/10.1002/art.39026