Early creatinine dynamics for stratifying acute kidney injury trajectories in patients with systemic lupus...

Patients with systemic lupus erythematosus (SLE) exhibit heterogeneous renal courses after acute kidney injury (AKI). This study applied latent class mixed modeling to identify AKI trajectory phenotypes in SLE, developed a risk-stratification model using early post-AKI data, and explored whether hydroxychloroquine (HCQ) use is associated with AKI trajectory class membership.

This multicenter retrospective study used MIMIC-IV for model development and internal assessment and eICU, NWICU, and local cohorts for exploratory external assessment. Adult SLE patients with AKI were included. The primary model was a race-free, no-imbalance-correction LASSO logistic regression model. Performance was assessed with AUC, Brier score, calibration intercept, and calibration slope. Bootstrap optimism correction was applied. A non-overlap sensitivity analysis examined the influence of structural predictor-outcome overlap. HCQ was evaluated using multivariable logistic regression and propensity score matching.

Among 279 MIMIC patients, three AKI trajectories were identified (progressive 9.3%, recovery 19.4%, stable 71.3%). The primary race-free LASSO model achieved an apparent AUC of 0.761 (optimism-corrected: 0.706) and a Brier score of 0.086 (corrected: 0.092). When assessed against a non-overlapping post-48-hour renal endpoint, discrimination diminished substantially (AUC 0.593). Exploratory external assessments were event-limited: the main SLE external discrimination subsets contained 6 events in eICU, 3 events in NWICU, and 1 event in the local cohort; therefore, these estimates were considered descriptive rather than definitive validation. HCQ showed an exploratory association not interpretable as causal.

This study provides an exploratory risk-stratification framework for early AKI trajectory patterns in SLE. The apparent discrimination was substantially attenuated after removing predictor-outcome overlap and adjusting for optimism. External assessments were event-limited and should be interpreted as exploratory transportability assessments rather than definitive evidence of generalizability.