#3157 Renal involvement and functional impact in the pediatric age of a cohort of patients with tuberous sclerosis complex (TSC) and contiguous gene syndrome (CGS)

Abstract Background and Aims TSC is a rare multisystem genetic disorder (1:6,000), autosomal dominant, due to mutations in TSC1(Cr9)/TSC2(Cr16), predisposing to tumor development by deregulation of the mTOR pathway. Premature deterioration of glomerular filtration rate (GFR) in adults (40%, without hemorrhages due to angiomyolipomas-AML-/interventions), suggesting the presence of intrinsic kidney disease. Cysts, associated or not with SGC (joint TSC2/PKD1 genes deletion), AML, arterial hypertension or the risk of nephrolithiasis (ketogenic diet or carbonic anhydrase inhibitors) are the other parameters to control. Our aim is to determine renal involvement and GFR affectation in a pediatric cohort of TSC and/or CGS followed in our service in the last decade (2013–2023). Method Retrospective observational study of 116 patients (66 males, 50 females) diagnosed and/or in follow-up for TSC (111 patients/95.68%) or CGS (5 patients/4.32%) between 2013-2023. Patients with known renal damage unrelated to TSC/CGS were excluded. Data were collected on diagnosis/disease progression, ultrasound, abdominal MRI, serum and urinary tests, mTORi or other treatment and their responses after a variable follow-up period. Results Mean age 13.39 years (SD 6.228). Kidney involvement 54.9% (67): AML 41.8% (mean 10.33 mm/SD 14.64), cysts 29.5% (mean 12.39 mm/SD 17.23. Patterns: multicystic 11.5%, polycystic 3.3%, cortical cystic 4.1%, cortical microcystic 9.8% and focal cystic 0.8%), 3 tumors of other type (1 hamartoma, 1 PEComa and 1 exophytic renal mass). HBP 4.1% (80% grade I/20% high BP), proteinuria 4.1% (median Pr/Cr 0.63mg/mg [0.28–59.32]. Median Alb/Cr 32.9 mg/mmol [6.1–75.1]. Only 2 CGS presented elevated B2 microglobulin) and 2 patients, both. Those who presented HBP and/or proteinuria were treated with ARB/ACE inhibitors and 2 of them with amlodipine. Only 1 patient with CGS presented CKD (stage IV) with the rest of the cohort having normal eGFR. 3 patients presented prelithiasis (1 hypocitraturia/microlithiasis ultrasound and 2 lithogenic risks: hypercalciuria/hypocitraturia and hypercalciuria/hyperuricosuria) in the context of ketogenic diet or topiramate use. 64% were taking mTORi (3 for renal indication/AML >30mm). 1 patient presented hemorrhage treated with embolization. There was a statistically significant correlation (P = 0.02) of renal implications with GCS, as well as between mTORi and control of AML/cyst size (P = 0.03). Conclusion GFR impairment was exceptional, only in one patient with GCS, and LMA and renal cysts were the predominant conditions (41.8%/29.5%). early recognition (by MRI) and management of renal impairment, avoiding surgery and promoting the use of mTORi if indicated, are the fundamental factors for preserving renal function in these patients.