1 - Central Lisbon University Hospital Centre, Paediatric Nephrology Unit, Lisbon, Portugal
2 - Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal, Pediatric Unit, Almada, Portugal
3 - NOVA Medical School / Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal
4 - Central Lisbon University Hospital Centre, Pediatric Unit, Neurocutaneous Outpatient Clinic, Lisbon, Portugal
5 - Central Lisbon University Hospital Centre, Paediatric Neurology Unit, Lisbon, Portugal
6 - Central Lisbon University Hospital Centre, Pediatric Unit, Primary Deficiencies Unit, Lisbon, Portugal
- 56th Annual Meeting of the European Society for Paediatric Nephrology, 24-26/9/2024, Valência, Espanha, Poster
- Resumo publicado em: Pediatr Nephrol 2024;39(Suppl 1):S344.
Abstract:
Aims/Purpose: Tuberous sclerosis complex (TSC) is a genetic disorder where anomalous activity of the mammalian target of rapamycin leads to multiple organic features, including the kidneys. The most frequent renal manifestations are angiomyolipomas (AML), for which the mammalian target of rapamycin inhibitors (mTORi) has been a paradigm shifting therapeutic. Our aim was to analyze renal outcomes of patients with TSC with and without mTORi therapy.
Methods: Retrospective cohort study enrolling patients (children and adults) with TSC followed in a level III hospital, between 2016 and 2024. Sociodemographic, clinical and laboratorial data were analyzed. Baseline and last follow-up estimated glomerular filtration rate (eGFR) and CKD stage (based on eGFR) was compared between patients with and without mTORi therapy. AML's largest dimension was analyzed in patients under mTORi therapy (pre and post therapy).
Results: 46 patients were included, 30 (65.2%) were male. Mean age was 18.2 years (IQR 10.2-24.0) and mean time of follow-up was 6.1 years (IQR 1.2-11.9). Eleven (23.9%) patients had prenatal diagnosis. Regarding genetics, TSC2 mutation was present in 20 (68.9%) patients, TSC1 in 9 (19.6%) and TSC2/PKD in 3 (6.5%). Of all, 19 (41.3%) were submitted to mTORi (18 everolimus, 1 sirolimus) for a mean time of 30.2 months (IQR 25.9-57.8). At baseline follow-up, 8 patients had CKD stage ≥ 2 (KDIGO) and mean eGFR was similar between groups (mTORi 131 vs no mTORi 124 mL/min/1.73 m2, p=0.368). No patient was under dialysis. At last follow-up, mean eGFR remained without differences between groups (mTORi 129 vs no mTORi 132 mL/min/1.73 m2, p=0.961), and 8 (17.4%) patients with CKD (based on eGFR), where 1 (2.2%) patient showed CKD stage improvement and 3 (6.5%) revealing progression. Regarding other renal manifestations, 30 (65.2%) presented multiple kidney cysts, 26 (56.5%) had AML and 3 (6.5%) had polycystic kidney disease. Those with AML, 11 (23.9%) were under mTORi and 8 (17.4%) showed AML reduction: ≥ 50% reduction in 2 (4.4%), 30-49% reduction in 2 (4.4%) and ≤ 30% reduction in 7 (15.2%). Two patients under mTORi therapy revealed AML dimension increase between evaluations.
Conclusion: Therapy mTORi appeared to be effective and safe in reducing AML secondary to TSC, in line with recent evidence. Possible effect of mTORi in CKD progression shall be further investigated in long-term follow-up.
Keywords: angiomyolipomas, mammalian target of rapamycin inhibitors, tuberous sclerosis complex