期刊
KIDNEY INTERNATIONAL
卷 94, 期 1, 页码 150-158出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2018.02.023
关键词
IgA nephropathy; complement factor H; related protein 5; IgAN progression
资金
- National Science Foundation of China [81670638, 81470945]
- Beijing New-Star Plan of Science and Technology [Z161100004916167]
- Capital of Clinical Characteristics and the Applied Research Fund [Z141107002514037]
- Natural Science Foundation for Innovation Research Group of China [81621092]
- National Key Research and Development Program of China [2016YFC0904102]
- Training Program of the Major Research Plan of the National Natural Science Foundation of China [91642120]
- Wellcome Trust [WT082291MA]
- Kidney Research UK PhD clinical research fellowship [TF14/2015]
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] mg/ml vs 3.19 [interquartile range 2.55 to 3.92] mg/ml). Higher circulating FHR-5 levels were associated with a lower estimated glomerular filtration rate, hypertension, and severe OxfordT 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.
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