Extra-renal disease patterns in lupus nephritis: clinical and serological activity confers increased risk of renal flares and damage accrual
Konstantinos Drougkas, Spyridon Katechis, Myrto Nikoloudaki, Myrto Kostopoulou, Christina Tsalapaki, Sofia Flouda, Maria Pappa, Marija Bakula, Ivan Padjen, Pinelopi Konstantopoulou, George Moustakas, Aggelos Banos, Dimitrios Vassilopoulos, George Bertsias, Paraskevi V Voulgari, Dimitrios T Boumpas, Antonis FanouriakisAbstract
Objective
To explore patterns of extra-renal disease activity following renal response in lupus nephritis (LN) and evaluate their association with renal flares and organ damage accrual.
Methods
Multicenter retrospective cohort study of patients with biopsy-proven LN who achieved renal response. Latent class analysis (LCA) was applied to identify patterns of extra-renal activity. Associations with adverse outcomes were examined using Cox proportional hazards models.
Results
A total of 168 patients were included. Over a median follow-up of 4.0 years, 92.3% of patients exhibited extra-renal activity at least once. Serological activity (anti-dsDNA positivity and/or hypocomplementemia) was the most frequent active domain, followed by mucocutaneous and musculoskeletal involvement. Clinically significant extra-renal flares occurred in 37.5% of patients. Higher non-renal SLEDAI-2K scores were independently associated with increased risk of subsequent renal flares (aHR 1.18, 95% CI 1.07–1.30) and damage accrual (aHR 1.23, 95% CI 1.13–1.35), while BILAG-A extra-renal flares were strongly associated with damage accrual (aHR 10.56, 95% CI 4.63–24.06). LCA identified three classes of extra-renal activity: (1) mucocutaneous/musculoskeletal, (2) combined serological–clinical activity, and (3) predominant hypocomplementemia. Only the combined phenotype was independently associated with renal flares (aHR 2.66, 95% CI 1.34–5.30) and damage accrual (aHR 2.37, 95% CI 1.07–5.25). In exploratory analyses stratified by anti-dsDNA status, clinical extra-renal activity was associated with adverse outcomes among anti-dsDNA positive visits.
Conclusions
Extra-renal activity in LN following renal response is common. Anti-dsDNA positivity is the main factor associated with adverse outcomes, while concomitant clinical extra-renal activity may further increase risk among serologically active patients.