Abstract Background Renal angiomyolipomas (AMLs) drive substantial morbidity in tuberous sclerosis complex (TSC) through hemorrhage and repeated invasive procedures. While mTOR inhibitors (mTORi) reduce AML volume, long-term real-world data on clinically meaningful bleeding and procedure outcomes remain limited, particularly in cohorts enriched for high-risk imaging phenotypes. Methods We conducted a multicenter observational study (2004–2020) in three French tertiary centers. Among 103 included patients, the 96 with TSC constituted the primary analysis set. We assessed AML-related hemorrhage and selective arterial embolization (SAE). For patients initiating mTORi, follow-up was split into pre- and post-initiation periods and incidence rate ratios (IRR) were estimated using Poisson regression with patient-time offsets and patient-clustered robust standard errors; GEE Poisson and negative binomial models were used as sensitivity analyses. Results Total follow-up was 694.3 patient-years. Thirty-nine patients (40.6%) initiated an mTORi (everolimus 94.9%). Hemorrhage rates decreased from 0.061 to 0.007 events per patient-year after mTORi initiation (IRR 0.11; 95% CI 0.02–0.62), and SAE rates decreased from 0.197 to 0.020 sessions per patient-year (IRR 0.10; 95% CI 0.04–0.29). Therapeutic inertia remained substantial: among 57 never-treated patients, high-risk imaging features and active complications were frequent at last assessment. Conclusion In this long-term real-world cohort of TSC-associated renal AMLs, mTOR inhibitor initiation was associated with markedly lower rates of AML hemorrhage and SAE. Despite these benefits, many high-risk patients remained untreated in routine care, supporting earlier nephrology referral, systematic risk stratification, and timely treatment initiation to reduce preventable AML-related morbidity.
Gemander et al. (2026) studied this question.