Repeat kidney biopsy unmasks the transition from active inflammation to irreversible damage in lupus nephritis: longitudinal outcomes from a single-center cohort in Egypt.

BACKGROUND: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus, and repeat kidney biopsy has a potential value in monitoring disease progression and impact on treatment adjustments. METHODS: We retrospectively analyzed 81 Egyptian LN patients who underwent two kidney biopsies at the Urology and Nephrology Center, Mansoura University, between January 2011 and April 2024. Indications included persistent proteinuria, active urinary sediment, or unexplained renal impairment. Demographic, clinical, laboratory, histological, and treatment data were collected. Pathology was assessed using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, activity and chronicity indices, and outcomes were analyzed by Cox regression. RESULTS: At repeat biopsy, pathological transitions occurred in 48%. The transition toward more severe disease categories was frequent and included: Class I/II to III/IV: 7 of 10 patients, Class III to IV: 6 of 11 patients, Class III/IV + V to IV: all 3 patients, Class IV to VI: 5 of 49 patients, Class V to III/IV/VI: 6 of 8 patients. The activity index decreased (median 12→7, P < .001), while chronicity increased (2→4, P < .001). Treatment escalation was needed in 53.1% of patients. Over a median follow-up of 5.4 years, 56.8% progressed to kidney failure. Serum creatinine at both biopsies independently predicted kidney failure (Hazard ratio [HR] 1.24, P = .007; HR 1.22, P < .001). Shorter biopsy intervals were protective (HR 0.97, P < .001). At the second biopsy, chronicity index, glomerulosclerosis, and cellular crescents independently predicted kidney failure. CONCLUSION: Repeat biopsy is of pivotal importance in LN, unmasking critical histological transitions and shifts towards chronicity that can guide essential therapy changes and improve prognostication beyond clinical assessment alone.