Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis
BackgroundComplement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterione...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.836155/full |
| _version_ | 1819158856057487360 |
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| author | Xuejing Chen Yu Wang Xiaojuan Yu Suxia Wang Suxia Wang Minghui Zhao Minghui Zhao |
| author_facet | Xuejing Chen Yu Wang Xiaojuan Yu Suxia Wang Suxia Wang Minghui Zhao Minghui Zhao |
| author_sort | Xuejing Chen |
| collection | DOAJ |
| description | BackgroundComplement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.MethodsPatients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.ResultsFifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24–138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR (r = 0.341, p = 0.013), sclerotic/ischemic glomerular lesions (r = –0.364, p = 0.008) and PTC density (r = 0.426, p = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition (r = –0.174, p = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen (r = 0.330, p = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.ConclusionOur findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis. |
| first_indexed | 2024-12-22T16:31:18Z |
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| id | doaj.art-136f4823b8154667b3d5a6df96447c48 |
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| language | English |
| last_indexed | 2024-12-22T16:31:18Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-136f4823b8154667b3d5a6df96447c482022-12-21T18:20:02ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-03-01910.3389/fmed.2022.836155836155Potential Involvement of Complement Activation in Kidney Vascular Lesions of ArterionephrosclerosisXuejing Chen0Yu Wang1Xiaojuan Yu2Suxia Wang3Suxia Wang4Minghui Zhao5Minghui Zhao6Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People’s Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People’s Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People’s Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People’s Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, ChinaLaboratory of Electron Microscopy, Pathological Centre, Peking University First Hospital, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, National Health and Family Planning Commission of the People’s Republic of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Beijing, ChinaPeking-Tsinghua Center for Life Sciences, Beijing, ChinaBackgroundComplement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.MethodsPatients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.ResultsFifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24–138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR (r = 0.341, p = 0.013), sclerotic/ischemic glomerular lesions (r = –0.364, p = 0.008) and PTC density (r = 0.426, p = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition (r = –0.174, p = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen (r = 0.330, p = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.ConclusionOur findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis.https://www.frontiersin.org/articles/10.3389/fmed.2022.836155/fullcomplementarterionephrosclerosishypertensionbenign nephrosclerosisC3d |
| spellingShingle | Xuejing Chen Yu Wang Xiaojuan Yu Suxia Wang Suxia Wang Minghui Zhao Minghui Zhao Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis Frontiers in Medicine complement arterionephrosclerosis hypertension benign nephrosclerosis C3d |
| title | Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis |
| title_full | Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis |
| title_fullStr | Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis |
| title_full_unstemmed | Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis |
| title_short | Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis |
| title_sort | potential involvement of complement activation in kidney vascular lesions of arterionephrosclerosis |
| topic | complement arterionephrosclerosis hypertension benign nephrosclerosis C3d |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.836155/full |
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