Low‐Grade Proteinuria Does Not Predict Favorable Outcomes in Lupus Nephritis: A Longitudinal Cohort Study

Objective To investigate the clinical characteristics, renal pathology treatment responses, and renal outcomes of lupus nephritis (LN) patients with different levels of baseline proteinuria. Methods A total of 239 biopsy‐proven LN patients were stratified by baseline proteinuria (UPro) levels (<1g/24h vs. ≥1g/24h) and disease onset status (incident vs. relapsing). Renal treatment responses were measured by overall response (OR), complete response, and primary efficacy renal response at weeks 26 and 52. Cox proportional hazards regression and Kaplan‐Meier analyses were used to assess predictors of time to first 30% and 40% eGFR decline by 156 weeks. Results Among the 239 LN patients, 42 (17.6%) had UPro <1g/24h, and 197 (82.4%) had UPro ≥1g/24h; 122 (51.0%) had incident LN and 117 (49.0%) had relapsing LN. The UPro <1 group had a lower incidence of urinary sediments, a higher frequency of Class V, and a lower renal pathology activity index, but similar chronicity index compared to the UPro ≥1 group. Both groups exhibited similar OR rates at weeks 26 and 52. Patients with low‐grade proteinuria had equivalent risk probabilities for experiencing a 30% or 40% decline in eGFR over 156 weeks compared to those with high‐grade proteinuria. Glomerulosclerosis independently predict long‐term renal deterioration in relapsing, but not incident LN. Conclusion Low‐grade proteinuria (UPro <1g/24h) doesn't confer better renal outcomes or treatment response in LN. Glomerulosclerosis predicts renal function decline in relapsing LN. These results underscore the importance of early biopsy, personalized therapy, and close monitoring, supported by non‐invasive biomarkers for risk assessment.