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Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a

Chuanchuan Sun1,2,3, Li Wan4, Hui Gao5

  • 1Department of Nephrology, Peking University International Hospital, Beijing, China.

Frontiers in Pharmacology
|August 13, 2026
PubMed
Abstract

Insights

Intrarenal mTORC1 activation may predict response to sirolimus in autoimmune kidney diseases. Higher mTORC1 staining correlated with improved renal function, suggesting a precision medicine approach for these conditions.

Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • The mechanistic target of rapamycin (mTORC1) pathway is implicated in the pathogenesis of autoimmune kidney diseases.
  • Intrarenal mTORC1 activation may serve as a biomarker to predict response to sirolimus therapy.

Purpose of the Study:

  • To investigate whether intrarenal mTORC1 activation can identify patients with autoimmune kidney diseases who are likely to benefit from sirolimus treatment.
  • To evaluate sirolimus efficacy across different autoimmune kidney disease diagnoses based on mTORC1 activation levels.

Main Methods:

  • Prospective screening of eight patients with active autoimmune kidney disease using immunohistochemistry on renal biopsy to assess mTORC1 activation.
  • Five patients with positive mTORC1 staining (moderate to high) received sirolimus treatment.
  • Monitoring of renal function, proteinuria, and treatment tolerance over a mean follow-up of 25 months.

Main Results:

  • Four out of five patients receiving sirolimus showed improved or stable renal function.
  • A strong correlation was observed between higher mTORC1 staining intensity and positive treatment response.
  • Proteinuria decreased significantly in most responders, and sirolimus was generally well-tolerated.

Conclusions:

  • Intrarenal mTORC1 activation levels may guide the selection of patients with autoimmune kidney diseases for sirolimus therapy.
  • This biomarker-guided approach shows promise as a precision medicine strategy for managing autoimmune kidney diseases.
  • Further research is warranted to validate these findings in larger patient cohorts.
Keywords:
autoimmune associated kidney diseasesmTORC1observational studiesprecision therapysirolimus

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