Real-world management of tuberous sclerosis complex-associated renal angiomyolipomas: the impact of mTOR inhibitors

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.