Predictors of long-term renal survival and mortality in patients with proliferative and membranous lupus nephritis

Objective Lupus nephritis (LN) is a major mortality risk factor in patients with systemic lupus erythematosus (SLE). We investigated the predictors of end-stage renal disease (ESRD) and mortality in patients with LN. Methods We enrolled 599 Korean patients with biopsy-proven proliferative or membranous LN from a prospective cohort of 1497 patients with SLE. Baseline demographics, serology, histology, disease activity, and organ damage were collected and assessed. Regression models were used to evaluate predictors of renal survival and mortality. Results We followed a total of 599 patients with proliferative LN (class III or IV/±V, N = 509) or membranous LN (class V, N = 90). Among these patients, 42 patients (7.0%) progressed to ESRD and 31 (5.2%) died. In a multivariate logistic regression analysis, antiphospholipid antibody positivity (OR 3.18, p = .023), higher activity and chronicity indices at biopsy (OR 1.14, p = .034; OR 1.33, p = .042), and sustained high disease activity (extra-renal adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2K] ≥ 3, OR 4.33, p = .019) significantly influenced progression to ESRD after adjusting for age at LN diagnosis, gender, disease duration, and hypertension. While the 6-month renal response after induction treatment showed no association with ESRD risk, the 12-month treatment response demonstrated a significant association ( p < .001). Renal survival was poorer in patients with an activity index ≥6 and in those with a chronicity index ≥4 ( p = .013 and p = .002, respectively). Patients who developed ESRD had significantly worse overall survival than those who did not ( p = .028). Higher adjusted mean SLEDAI-2K (hazard ratio [HR] 1.43, p < .0001) and higher extra-renal adjusted mean SLEDAI-2K (HR 1.83, p < .0001) were significantly associated with increased overall mortality. Conclusions Our study indicates that antiphospholipid antibodies, higher histologic activity and chronicity indices, and sustained high disease activity beyond renal items were independently associated with progression to ESRD. Mortality was increased among patients with ESRD and those with persistent high disease activity. These findings emphasize the need for stringent disease activity control and support clinicopathologic stratification to identify patients at high risk of adverse long-term renal outcomes.