期刊
KIDNEY INTERNATIONAL
卷 92, 期 4, 页码 942-952出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2017.03.043
关键词
complement; glomerular disease; IgA nephropathy
资金
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare National Health Service Trust and Imperial College London
- NIHR Clinical Research Network
- Medical Research Council [MR/K01353X/1]
- Wellcome Trust Senior Fellow in Clinical Science [WT082291MA]
- Kidney Research UK PhD Clinical Research Fellowship
- Wellcome Trust
- Medical Research Council
- European Union
- National Institute for Health Research-funded BioResource
- Clinical Research Facility
- Biomedical Research Centre based at Guy's and St Thomas' National Health Service Foundation Trust in partnership
- King's College London
- MRC [MR/K01353X/2, MR/K01353X/1] Funding Source: UKRI
- Kidney Research UK [TF14/2015] Funding Source: researchfish
- Medical Research Council [MR/K01353X/1, MR/K01353X/2] Funding Source: researchfish
- National Institute for Health Research [ACF-2014-21-015] Funding Source: researchfish
IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation. From a large cohort of patients, we demonstrated that plasma FHR-1 and the FHR-1/fH ratio were elevated in IgAN and associated with progressive disease. Plasma FHR-1 negatively correlated with eGFR but remained elevated in patients with IgAN with normal eGFR. Serum FHR5 was slightly elevated in IgAN but did not correlate with eGFR. Neither FHR5 levels nor the FHR-5/fH ratio was associated with progressive disease. However, higher serum FHR-5 levels were associated with a lack of response to immunosuppression, the presence of endocapillary hypercellularity, and histology scores of disease severity (the Oxford Classification MEST score). Thus, FHR-1 and FHR-5 have a role in IgAN disease progression.
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