Attainment of early targets does not ensure a complete response at 12 months in lupus nephritis, especially in nephrotic-range proteinuria

OBJECTIVE: EULAR recommends early proteinuria reduction targets in lupus nephritis (LN) (≥25% at 3 months and ≥50% at 6 months). We examined the predictive value of these targets for achieving complete renal response (CRR) at 12 months, a surrogate for favorable long-term outcomes. METHODS: We examined data from a cohort study of patients with biopsy-proven LN. Regression models were applied to identify independent associations with 12-month CRR. Performance metrics for EULAR 3- and 6-month targets were calculated for the whole cohort, and for patients with nephrotic or subnephrotic baseline proteinuria. RESULTS: 132 patients with biopsy-proven LN were included; 92 (69.7%) achieved CRR at 12 months. Attainment of EULAR-proposed 3- and 6-month targets was independently associated with 12-month CRR (OR 7.38, 95% CI 2.84-20.4 at 3 months; OR 10.6, 95% CI 3.74-32.4 at 6 months). Higher baseline proteinuria levels were inversely associated with CRR in both models (OR 0.77 and 0.75 per 1 g increase, respectively). Both targets had high sensitivity (86-89%) but moderate specificity (40-45%), while negative likelihood ratios (0.27-0.31) suggested that failure to achieve these early targets meaningfully reduced the probability of subsequent 12-month CRR. In patients with nephrotic range proteinuria, both targets showed lower specificity (0.30 and 0.17), suggesting limited ability to predict 12-month CRR. CONCLUSIONS: Failure to achieve the EULAR 3- and 6-month proteinuria targets serves as a warning sign for suboptimal response at 12 months. In patients with baseline nephrotic range proteinuria attainment of early response has limited predictive value for 12-month CRR.