Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma

Introduction: In current studies, treatment of tuberous sclerosis complex (TSC)–related renal angiomyolipoma (RAML) was initiated only after clinical progression or the onset of symptoms, rather than at an earlier stage in the disease process. However, the previous case report indicated that early m...

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Main Authors: Shuo Dun, Lin Wan, Yang-Yang Wang, Qian Lu, Qi Zhang, Qiu-Hong Wang, Jia Wang, Hai-Qing Zhao, Li-Ping Zou
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925001640
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author Shuo Dun
Lin Wan
Yang-Yang Wang
Qian Lu
Qi Zhang
Qiu-Hong Wang
Jia Wang
Hai-Qing Zhao
Li-Ping Zou
author_facet Shuo Dun
Lin Wan
Yang-Yang Wang
Qian Lu
Qi Zhang
Qiu-Hong Wang
Jia Wang
Hai-Qing Zhao
Li-Ping Zou
author_sort Shuo Dun
collection DOAJ
description Introduction: In current studies, treatment of tuberous sclerosis complex (TSC)–related renal angiomyolipoma (RAML) was initiated only after clinical progression or the onset of symptoms, rather than at an earlier stage in the disease process. However, the previous case report indicated that early mammalian target of rapamycin (mTOR) inhibition in patients with TSC might prevent the development of TSC lesions. We performed this nested case-control study to evaluate whether prophylactic sirolimus initiation in early infancy prevented TSC-related RAML (TSC-RAML). Methods: A nested case-control study design was used, based on the Efficacy and Safety of Sirolimus in Pediatric Patients With Tuberous Sclerosis (ESOSIPT) study cohort. Children with TSC initiating sirolimus at age ≤ 3 months and without RAML at baseline comprised the case group (treatment group). Propensity score matching (1:3) was used to select the control group from the first visit patients who were aged > 3 months without mTOR inhibitor exposure. The incidence of RAML was compared via Kaplan-Meier method with log-rank testing. Results: Twenty-seven eligible children entered the study as a case group, and 81 patients who had not used mTOR inhibitors were matched. The log-rank test showed that the incidence of RAML between the 2 groups was statistically significant (P = 0.047). Short-term adverse events (AEs) were reported in 55.6% (15/27) of early-treated infants, predominantly grade 1 or 2 according to the common terminology criteria for AEs. Conclusion: The use of sirolimus in early infancy might have had potential benefits in preventing TSC-RAML, and the short-term AEs were usually mild or moderate.
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spelling doaj-art-3f2bf8cb4f3f45c89890b6d51336ac272025-08-20T02:33:35ZengElsevierKidney International Reports2468-02492025-06-011061960197010.1016/j.ekir.2025.03.021Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal AngiomyolipomaShuo Dun0Lin Wan1Yang-Yang Wang2Qian Lu3Qi Zhang4Qiu-Hong Wang5Jia Wang6Hai-Qing Zhao7Li-Ping Zou8Senior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, ChinaSenior Department of Pediatrics, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, China; Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing, China; State Key Laboratory of Kidney Diseases, Beijing, China; Correspondence: Li-Ping Zou, Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.Introduction: In current studies, treatment of tuberous sclerosis complex (TSC)–related renal angiomyolipoma (RAML) was initiated only after clinical progression or the onset of symptoms, rather than at an earlier stage in the disease process. However, the previous case report indicated that early mammalian target of rapamycin (mTOR) inhibition in patients with TSC might prevent the development of TSC lesions. We performed this nested case-control study to evaluate whether prophylactic sirolimus initiation in early infancy prevented TSC-related RAML (TSC-RAML). Methods: A nested case-control study design was used, based on the Efficacy and Safety of Sirolimus in Pediatric Patients With Tuberous Sclerosis (ESOSIPT) study cohort. Children with TSC initiating sirolimus at age ≤ 3 months and without RAML at baseline comprised the case group (treatment group). Propensity score matching (1:3) was used to select the control group from the first visit patients who were aged > 3 months without mTOR inhibitor exposure. The incidence of RAML was compared via Kaplan-Meier method with log-rank testing. Results: Twenty-seven eligible children entered the study as a case group, and 81 patients who had not used mTOR inhibitors were matched. The log-rank test showed that the incidence of RAML between the 2 groups was statistically significant (P = 0.047). Short-term adverse events (AEs) were reported in 55.6% (15/27) of early-treated infants, predominantly grade 1 or 2 according to the common terminology criteria for AEs. Conclusion: The use of sirolimus in early infancy might have had potential benefits in preventing TSC-RAML, and the short-term AEs were usually mild or moderate.http://www.sciencedirect.com/science/article/pii/S2468024925001640angiomyolipomamTOR inhibitorpreventionsirolimustuberous sclerosis
spellingShingle Shuo Dun
Lin Wan
Yang-Yang Wang
Qian Lu
Qi Zhang
Qiu-Hong Wang
Jia Wang
Hai-Qing Zhao
Li-Ping Zou
Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
Kidney International Reports
angiomyolipoma
mTOR inhibitor
prevention
sirolimus
tuberous sclerosis
title Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
title_full Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
title_fullStr Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
title_full_unstemmed Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
title_short Nested Case-Control Study of Intervention in Early Infancy to Prevent Tuberous Sclerosis Complex–Associated Renal Angiomyolipoma
title_sort nested case control study of intervention in early infancy to prevent tuberous sclerosis complex associated renal angiomyolipoma
topic angiomyolipoma
mTOR inhibitor
prevention
sirolimus
tuberous sclerosis
url http://www.sciencedirect.com/science/article/pii/S2468024925001640
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