Abstract: SA-PO0112
A Case of Tuberous Sclerosis Complex with a TSC1 Variant Leading to ESKD at a Young Age
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Kotani, Mina, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Sugioka, Sayaka, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Shinya, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
- Yanagita, Motoko, Kyoto Daigaku, Kyoto, Kyoto Prefecture, Japan
Introduction
Tuberous sclerosis complex (TSC) is a hereditary multisystem disorder caused by pathogenic variants in the TSC1 or TSC2 genes, with manifestations including epilepsy, hypopigmented macules, and pulmonary and renal lesions. Although kidney manifestations commonly include angiomyolipomas, renal cysts, and renal cell carcinoma, progression to end-stage kidney disease (ESKD) at a young age is rare. We report a case of TSC with a TSC1 mutation that led to ESKD at a young age.
Case Description
A 27-year-old man with no prior medical or family history of kidney disease was found during routine health screening to have severe kidney dysfunction, renal masses, multiple kidney microcysts, and multiple pulmonary nodules. Laboratory tests showed a serum creatinine level of 6.2 mg/dL and a urine protein-to-creatinine ratio of 1.2 g/gCr. Kidney biopsy revealed that 53% of glomeruli were globally sclerosed with prominent periglomerular fibrosis. Tubular atrophy and irregular tubular dilation, epithelial multilayering and detachment, interstitial fibrosis, and lymphocyte-predominant inflammatory infiltration were observed. The pulmonary nodules were diagnosed as multifocal micronodular pneumocyte hyperplasia. Genetic testing identified a heterozygous nonsense variant in the TSC1 gene, leading to a diagnosis of TSC.
Discussion
This case is notable for the development of ESKD at a young age in the setting of a TSC1 mutation, which has rarely been reported. TSC functions as a negative regulator of mTOR signaling and suppresses cellular proliferation. Prominent deposition of phosphorylated S6 ribosomal protein, a downstream marker of mTOR activation, was observed in the affected tubulointerstitial areas, suggesting a link between TSC mutations and kidney dysfunction. When characteristic tubular lesions, including tubular atrophy, irregular dilation, epithelial multilayering, and epithelial detachment, are observed in the presence of multi-organ involvement, tuberous sclerosis complex should be considered, and genetic testing is warranted.