Trajectories of long-term eGFR and proteinuria in lupus nephritis: a real-world biopsy-proven cohort study

The long-term trajectories of estimated glomerular filtration rate (eGFR) and their relation to early proteinuria trajectories in biopsy-proven lupus nephritis (LN) are unclear. We aimed to identify eGFR trajectories and examine their association with 24-hour urine protein (24hUP) trajectories.

In this retrospective single-centre cohort, 215 adults with class III/IV (±V) LN were followed from the date of their initial renal biopsy. eGFR and 24hUP trajectories were modelled using latent class trajectory models, and associations with clinical and pathologic features were assessed. Multinomial logistic regression was used to identify baseline predictors of trajectory membership.

Three eGFR trajectories were identified: stable (87.9%), late-decline (7.0%) and persistent-decline (5.1%). Persistent-decline patients had a higher chronicity index (p<0.01) and baseline serum creatinine (p=0.03), and a higher chronicity index independently predicted persistent-decline (OR 1.64; 95% CI 1.24 to 2.18). The late-decline group had higher baseline eGFR (p=0.03) and more frequent proteinuric flares (91% vs 25% for stable, p<0.01). Three 24hUP trajectories were identified: low-decreasing (81.5%), high-decreasing (11.4%) and high-increasing (7.1%). eGFR late/persistent-decline trajectories were associated with high-decreasing/increasing 24hUP trajectories (p<0.001). Notably, 48% of patients with declining eGFR achieved complete proteinuria response within 12 months, and 38% met criteria for complete renal response, despite long-term eGFR deterioration.

Distinct long-term trajectories of eGFR and proteinuria exist in LN. Short-term responses in eGFR and proteinuria may not reliably predict long-term renal outcomes, highlighting the need for more robust biomarkers to improve risk stratification and management in LN.