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Updated: Aug 7, 2025

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Association between glomerular mTORC1 activation and crescents formation in lupus nephritis patients
Ying Ding1, Zhong-Qiu Luan2, Zhao-Min Mao3
1Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, PR China; Department of Nephrology, Peking University International Hospital, Beijing 102206, PR China; Institute of Nephrology, Peking University, Beijing 100034, PR China; Key laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, PR China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, PR China.
Objective:
This study aims to explore the association between glomerular mammalian target of rapamycin complex 1 (mTORC1) pathway activation and crescents' degree in lupus nephritis (LN) patients.
Methods:
A total of 159 biopsy-proven LN patients were enrolled in this retrospective study. The clinical and pathological data of them were collected at the time of renal biopsy. mTORC1 pathway activation was measured by immunohistochemistry, expressed by the mean optical density (MOD) of p-RPS6 (ser235/236), and multiplexed immunofluorescence. The association of mTORC1 pathway activation with clinico-pathological features especially renal crescentic lesions, and the composite outcomes in LN patients was further analyzed.
Results:
mTORC1 pathway activation could be detected in the crescentic lesions and was positively correlated with the percentage of crescents (r = 0.479, P < 0.001) in LN patients. Subgroup analysis showed mTORC1 pathway was more activated in patients with cellular or fibrocellular crescentic lesions (P < 0.001), but not fibrous crescentic lesions (P = 0.270). The optimal cutoff value of the MOD of p-RPS6 (ser235/236) was 0.0111299 for predicting the presence of cellular-fibrocellular crescents in >7.39% of the glomeruli by the receiver operating characteristic curve. Cox regression survival analysis showed that mTORC1 pathway activation was an independent risk factor for the worse outcome (defined by composite endpoints of death, end-stage renal disease and a decrease of >30% in eGFR from baseline).
Conclusion:
Activation of mTORC1 pathway was closely associated with the cellular-fibrocellular crescentic lesions and could be a prognostic marker in LN patients.
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