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

To investigate the clinical characteristics, renal pathology treatment responses, and renal outcomes of patients with lupus nephritis (LN) with different levels of baseline proteinuria.

A total of 239 patients with biopsy-proven LN were stratified by baseline 24-h urine protein (UPro) levels (<1 g/24 h vs ≥1 g/24 h) and disease onset status (incident vs relapsing). Renal treatment responses were measured by overall renal response, 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% estimated glomerular filtration rate (eGFR) decline by 156 weeks.

Among the 239 patients with LN, 42 (17.6%) had UPro <1 g/24 h, and 197 (82.4%) had UPro ≥1 g/24 h; 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 with the UPro ≥1 group. Both groups exhibited similar overall renal response 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 with those with high-grade proteinuria. Glomerulosclerosis independently predicted long-term renal deterioration in relapsing but not incident LN.

Low-grade proteinuria (UPro <1g/24h) does not 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 noninvasive biomarkers for risk assessment.