One-third of patients with lupus nephritis classified as complete responders continue to accrue progressive renal damage despite resolution of proteinuria

Abstract

Objective Treatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of proteinuria. Using estimated glomerular filtration rate (EGFR) trajectories, we characterised early chronic kidney disease in LN and examined whether certain patients continue to accrue renal damage despite proteinuric response. Methods We conducted a single-centre study of patients diagnosed with their first episode of biopsy-proven class III, IV, and/or V LN (n=37). For each patient, EGFR trajectory was graphed over 5 years following renal biopsy. Participants were divided into those with progressive EGFR loss (EGFR slope <500 mg/g) were compared between EGFR trajectory groups. Results Overall, 30% (n=11) of participants accrued progressive EGFR loss despite standard of care therapy over the first 5 years following renal biopsy. There were no significant differences in baseline renal biopsy features, medication regimens or comorbidities between EGFR trajectory groups. Resolution of proteinuria at 1 year did not differentiate between groups: 6 of 18 (33%) of complete responders continued to accrue renal damage compared with 5 of 17 (29%) of non-responders. Response status could not be assigned for two participants in the stable EGFR group due to missing clinical information at 1 year. Conclusions We identified an understudied category of patients with LN who accrue progressive renal damage despite apparent response to standard of care therapy. Better definitions and biomarkers of response are needed to improve renal outcomes and trial design.