FOCAL, DIFFUSE, AND MEMBRANOUS LESIONS IN LUPUS NEPHRITIS: PROGNOSTIC IMPLICATIONS FOR RENAL OUTCOMES

O038 / #692 Topic: AS15 - Lupus Nephritis-Clinical ABSTRACT CONCURRENT SESSION 06: LUPUS NEPHRITIS – CLINICAL OUTCOMES, PREDICTION AND THERAPY 23-05-2025 1:40 PM - 2:40 PM Background/Purpose Lupus nephritis (LN) is major cause of morbidity in systemic lupus erythematosus, with histological classes potentially influencing clinical outcomes. We aimed to assess the predictive value of LN classes to inform prognosis and management. Methods We included patients with LN from Mayo Clinic between 1992 and 2023. Earliest kidney biopsy was index date. Patients were followed until July 2023, death, or loss follow-up. A nephropathologist (SS) reclassified LN classes using histological findings from light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM). Biopsies were categorized based on presence of mesangial, focal, diffuse, or membranous components. If a biopsy has more than one component, it was included in each of them. Focal and diffuse were mutually exclusive. Outcomes included proteinuria <500 mg/day and complete renal response (CRR) (proteinuria <500 mg/day and stabilization of glomerular filtration rate ± 20%) within 1 year, development of end-stage kidney disease (ESKD) and death. Stratified multivariable Cox proportional hazards regression models, adjusted for sex and age, were used to assess associations. Statistical significance defined p-values <0.05. Results Among 307 patients (median age: 34 years; 75% female; median follow-up: 11 years), 98.4% of biopsies had a mesangial component, 27% had a focal, 38.4% had a diffuse, and 49.5% had a membranous component. At 1 year, 47.5% of patients achieved proteinuria <500 mg/day, 43.4% CRR. The Table shows performance of components in predicting outcomes. Biopsies with focal component were significantly associated with higher rates of achieving proteinuria <500 mg/day (HR 1.74 [95% CI, 1.21–2.50]) and CRR (HR 1.82 [95% CI, 1.24–2.66]). A diffuse component was not significantly associated with either proteinuria <500 mg/day (HR 0.98 [95% CI, 0.69–1.40]) or CRR (HR 1.00 [95% CI, 0.69–1.44]), though confidence intervals suggest near-significant association with achieving proteinuria <500 mg/day. A membranous component was associated with lower likelihood of achieving proteinuria <500 mg/day (HR 0.64 [95% CI, 0.45–0.90]) and CRR (HR 0.59 [95% CI, 0.41–0.84]). Cumulative incidence curves for CRR are in (Figure 1). During follow-up, 33 patients died (10.7%), 60 developed ESKD (19.5%). No components were associated with mortality. Membranous component was associated with lower risk of ESKD (HR 0.58 [95% CI, 0.35–0.90]), while focal (HR 0.65 [95% CI, 0.35–1.23]) and diffuse (HR 1.65 [95% CI, 0.98–2.77]) were not predictive, though diffuse component trended toward significance. Cumulative incidence curves for ESKD are in (Figure 2). Table. Hazard ratios of outcomes for variables. Figure 1. Kaplan Meier curves for Complete renal response (CRR) for focal and membranous component. Patients with focal component in the biopsy are more likely to experience CRR, whereas patients with membranous component are less likely. Red line: Having the mentioned component (Focal or membranous), Black: Not having the mentioned component (Focal or membranous). Figure 2. Kaplan Meier curves for end stage kidney disease (ESKD) for diffuse and membranous component. Diffuse component in the biopsy is not predicting ESKD, whereas membranous component tends to be protective for developing ESKD. Red line: Having the mentioned component (Diffuse or membranous), Black: Not having the mentioned component (Diffuse or membranous). Conclusions Mesangial components are present in nearly all biopsies. Focal components are associated with better short-term renal outcomes, including higher rates of CRR. Membranous components predict both a lower likelihood of CRR and a reduced risk of developing ESKD. Consequently, patients with mixed lesions may take longer to achieve CRR compared to those with pure proliferative GN. Our study also demonstrates patients with focal lesions have better prognosis than those with diffuse. These underscore the importance of detailed histological analysis in LN biopsies to guide prognosis and therapeutic.