Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis
Abstract Background Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disr...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-021-02700-x |
| _version_ | 1798034352040312832 |
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| author | Ning An Chen Yang Hong-Luan Wu Yun Guo Xi-Jie Huang Tong-Sheng Huang Zhi-Hong Wu Jing Xue Rui-Hong Chen Zhi-Hang Li Qing-Jun Pan Hua-Feng Liu |
| author_facet | Ning An Chen Yang Hong-Luan Wu Yun Guo Xi-Jie Huang Tong-Sheng Huang Zhi-Hong Wu Jing Xue Rui-Hong Chen Zhi-Hang Li Qing-Jun Pan Hua-Feng Liu |
| author_sort | Ning An |
| collection | DOAJ |
| description | Abstract Background Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. Method HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. Results As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. Conclusion HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion. |
| first_indexed | 2024-04-11T20:43:06Z |
| format | Article |
| id | doaj.art-faab48701f13457e91f347b486d0dfff |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T20:43:06Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-faab48701f13457e91f347b486d0dfff2022-12-22T04:04:09ZengBMCArthritis Research & Therapy1478-63622022-01-0124111510.1186/s13075-021-02700-xHydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritisNing An0Chen Yang1Hong-Luan Wu2Yun Guo3Xi-Jie Huang4Tong-Sheng Huang5Zhi-Hong Wu6Jing Xue7Rui-Hong Chen8Zhi-Hang Li9Qing-Jun Pan10Hua-Feng Liu11Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityKey Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical UniversityAbstract Background Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. Method HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. Results As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. Conclusion HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.https://doi.org/10.1186/s13075-021-02700-xHydroxychloroquineLupus nephritisProteinuriaTubular epithelial cellsAcute kidney injuryRepair |
| spellingShingle | Ning An Chen Yang Hong-Luan Wu Yun Guo Xi-Jie Huang Tong-Sheng Huang Zhi-Hong Wu Jing Xue Rui-Hong Chen Zhi-Hang Li Qing-Jun Pan Hua-Feng Liu Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis Arthritis Research & Therapy Hydroxychloroquine Lupus nephritis Proteinuria Tubular epithelial cells Acute kidney injury Repair |
| title | Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| title_full | Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| title_fullStr | Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| title_full_unstemmed | Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| title_short | Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| title_sort | hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis |
| topic | Hydroxychloroquine Lupus nephritis Proteinuria Tubular epithelial cells Acute kidney injury Repair |
| url | https://doi.org/10.1186/s13075-021-02700-x |
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