Circulating complement factor H-related protein 5 levels contribute to development and progression of IgA nephropathy
Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved..
IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility. Here we compared circulating levels of FHR-5 in 1126 patients with IgAN and regular follow-up with those of 153 unrelated healthy individuals to explore the relationship of FHR-5 levels with IgAN development and progression. Circulating FHR-5 levels were significantly elevated in patients with IgAN compared to healthy individuals (median 4.55 [interquartile range 3.58 to 5.85] μg/ml vs 3.19 [interquartile range 2.55 to 3.92] μg/ml). Higher circulating FHR-5 levels were associated with a lower estimated glomerular filtration rate, hypertension, and severe Oxford-T and Oxford-C scores. High FHR-5 levels were independently and significantly associated with a risk of developing either a 30% decline in the estimated glomerular filtration rate or end-stage renal disease (hazard ratio, per standard deviation increment of natural square root transformed FHR-5 of 1.226; 95% confidence interval: 1.106-1.359). Thus, the circulating FHR-5 level is an independent risk factor for IgAN progression.
| Errataetall: |
CommentIn: Kidney Int. 2018 Jul;94(1):16-18. - PMID 29933843 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:94 |
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| Enthalten in: |
Kidney international - 94(2018), 1 vom: 14. Juli, Seite 150-158 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhu, Li [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.08.2019 Date Revised 08.04.2022 published: Print-Electronic CommentIn: Kidney Int. 2018 Jul;94(1):16-18. - PMID 29933843 Citation Status MEDLINE |
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| doi: |
10.1016/j.kint.2018.02.023 |
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| Förderinstitution / Projekttitel: |
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NLM284060607 |
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| 500 | |a CommentIn: Kidney Int. 2018 Jul;94(1):16-18. - PMID 29933843 | ||
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| 520 | |a Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility. Here we compared circulating levels of FHR-5 in 1126 patients with IgAN and regular follow-up with those of 153 unrelated healthy individuals to explore the relationship of FHR-5 levels with IgAN development and progression. Circulating FHR-5 levels were significantly elevated in patients with IgAN compared to healthy individuals (median 4.55 [interquartile range 3.58 to 5.85] μg/ml vs 3.19 [interquartile range 2.55 to 3.92] μg/ml). Higher circulating FHR-5 levels were associated with a lower estimated glomerular filtration rate, hypertension, and severe Oxford-T and Oxford-C scores. High FHR-5 levels were independently and significantly associated with a risk of developing either a 30% decline in the estimated glomerular filtration rate or end-stage renal disease (hazard ratio, per standard deviation increment of natural square root transformed FHR-5 of 1.226; 95% confidence interval: 1.106-1.359). Thus, the circulating FHR-5 level is an independent risk factor for IgAN progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IgA nephropathy | |
| 650 | 4 | |a IgAN progression | |
| 650 | 4 | |a complement factor H–related protein 5 | |
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| 650 | 7 | |a CFHR5 protein, human |2 NLM | |
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| 700 | 1 | |a Guo, Wei-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Su-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Li-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Ji-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Medjeral-Thomas, Nicholas R |e verfasserin |4 aut | |
| 700 | 1 | |a Lomax-Browne, Hannah J |e verfasserin |4 aut | |
| 700 | 1 | |a Pickering, Matthew C |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
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