Antimalarial exposure and renal histopathologic findings in lupus nephritis

Abstract Objectives This study aimed to evaluate the association between antimalarial exposure and renal histopathologic findings at kidney biopsy in patients with lupus nephritis (LN). Methods This study was conducted within the University of Toronto Lupus Clinic cohort. To ensure adequate assessment of antimalarial exposure, patients were included if they underwent a kidney biopsy at least three months after clinic entry. The kidney biopsy served as the index time point (baseline) for the analysis and corresponded to the clinic visit immediately preceding the biopsy. Antimalarial exposure was defined as use during ≥ 2 consecutive clinic visits prior to biopsy. Sensitivity analyses evaluated longer durations of continuous antimalarial exposure (≥6 months and ≥1 year). Histopathologic outcomes included proliferative versus non-proliferative LN class, NIH activity index (AI), NIH chronicity index (CI), and interstitial fibrosis and tubular atrophy (IFTA) score. Associations were evaluated using logistic and linear regression models adjusted for demographic, clinical, and treatment covariates. Results The study included 165 patients with biopsy-proven LN (median age 35.3 years; 84.2% female; median disease duration 6.2 years), of whom 50.3% were on antimalarial therapy at baseline. In the adjusted multivariable analyses, antimalarial exposure was not associated with detectable differences in proliferative LN, NIH AI, NIH CI, or IFTA score. Sensitivity analyses requiring ≥6 months and ≥1 year of continuous antimalarial exposure yielded similar findings. Conclusions Antimalarial exposure was not associated with detectable differences in renal histopathologic findings at biopsy. These findings should be interpreted within the limitations of the study design and sample size.