Does Baseline Nephrotic Range Proteinuria Determine the Long-term Outcomes of Membranous Lupus Nephritis Patients?

Management strategies for membranous lupus nephritis (MLN) are generally based on the severity of proteinuria. However, long-term outcomes comparing subnephrotic and nephrotic range proteinuria remain understudied. We explored whether baseline proteinuria level, subnephrotic or nephrotic, impacts long-term outcomes. We conducted a retrospective study identifying patients with biopsy-proven MLN. Patients were categorized based on baseline proteinuria: subnephrotic (<3.5 g/day) or nephrotic (≥3.5 g/day). Long-term outcomes, including an adverse composite outcome (end-stage kidney disease, sustained ≥30 % decline in eGFR, or death) and LN flares, were analyzed. Time-to-event outcomes were assessed using Kaplan-Meier curves, and associations were evaluated using Cox regression. 88 patients were included, with 49 (55.7 %) in the subnephrotic group (median 1.5 g/day) and 39 (44.3 %) in the nephrotic group (median 4.7 g/day). At baseline, the subnephrotic group had a longer time to LN onset, less frequent hyperlipidemia, higher serum albumin, less diffuse podocyte effacement, and less frequent cyclophosphamide treatment. No significant differences were noted in kidney function, urine sediment abnormalities, or histopathology. 38 patients (43.2 %) experienced the adverse composite outcome, with no difference between groups (40.8 % in the subnephrotic group vs. 46.2 % in the nephrotic group, p = 0.78]. Flares occurred in 35 patients (39.8 %), with no difference between groups (38.8 % in the subnephrotic group vs. 41.0 % in the nephrotic group, p = 1.00). No significant differences in renal disease characteristics or long-term outcomes were found between MLN patients with nephrotic and subnephrotic baseline proteinuria. These findings challenge current practices, suggesting a need for more individualized immunosuppressive treatment in MLN.