Plasma Galactose-Deficient IgA1 and C3 and CKD Progression in IgA Nephropathy
Plasma Galactose-Deficient IgA1 and C3 and CKD Progression in IgA Nephropathy
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血浆半乳糖缺乏 IgA1 和 C3 以及 IgA 肾病的 CKD 进展
DOI：
10.2215/cjn.13711118
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发表时间：
2019-10-07
影响因子：
9.8
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Chen, Pei;Yu, Guizhen;Zhang, Hong
背景和目的循环中半乳糖缺乏的 IgA1 增加以及随后的补体激活在 IgA 肾病的病理生理学中都发挥着重要作用。然而，它们与疾病严重程度和进展的关系仍不清楚。 设计、设置、参与者和测量 我们在北京大学第一医院开展的一项活检证实的 IgA 肾病队列研究中对 1210 名参与者进行了评估。在活检时测量半乳糖缺陷型 IgA1 和补体成分 C3 的血浆浓度。我们使用 Cox 比例风险模型和限制三次样条测试了半乳糖缺乏型 IgA1 和半乳糖缺乏型 IgA1/C3 比率与 CKD 进展事件（定义为 ESKD 或 eGFR 下降 50%）之间的关联。结果 经过 43 个月的中位随访（四分位距，24-76 个月），172 名（14%）参与者达到了 CKD 进展事件。半乳糖缺乏的 IgA1 水平与 CKD 进展事件的关联显示出非线性关系。血浆半乳糖缺乏型 IgA1 水平越高，CKD 进展事件的风险就越大，但当半乳糖缺乏型 IgA1>325 U/ml 时，CKD 进展事件的风险会达到平台期，而 CKD 进展事件的风险随着半乳糖缺乏型 IgA1/C3 比率的升高而单调增加。调整传统危险因素（人口统计学、eGFR、蛋白尿、高血压、牛津病理评分和皮质类固醇/免疫抑制治疗）后，较高水平的半乳糖缺乏型 IgA1/C3 比率与 CKD 进展事件独立相关（根据自然对数转换[半乳糖缺乏型 IgA1/C3]，风险比为 2.03；95% 置信区间 [95% CI]， 1.25至3.29；P=0.004)。参考半乳糖缺乏型 IgA1/C3 比率的第一个四分位数，第二个四分位数的风险比为 1.71（95% CI，1.01 至 2.89），第三个四分位数的风险比为 1.55（95% CI，0.91 至 2.63），第三个四分位数的风险比为 2.17（95% CI，1.33 至 3.56）。结论 在 IgA 肾病中，血浆半乳糖缺乏的 IgA1/C3 比率与 CKD 进展事件相关，与临床和活检特征无关。
Background and objectives Increased circulating galactose-deficient IgA1 and subsequently complement activation both play important roles in the pathophysiology of IgA nephropathy. However, their relationship to disease severity and progression remains unclear.Design, setting, participants, & measurements We assessed 1210 participants in a cohort study of biopsy-proven IgA nephropathy at Peking University First Hospital. Plasma concentrations of galactose-deficient IgA1 and complement component C3 were measured at the time of biopsy. We tested associations of galactose-deficient IgA1 and galactose-deficient IgA1/C3 ratio with CKD progression event, defined as ESKD or 50% decline in eGFR, using Cox proportional hazards models and restricted cubic splines.Results After a median follow-up of 43 months (interquartile range, 24-76 months), 172 (14%) participants reached the CKD progression event. The association of galactose-deficient IgA1 levels and CKD progression event showed a nonlinear relationship. The risk of CKD progression events was greater with higher plasma galactose-deficient IgA1 levels but reached a plateau when galactose-deficient IgA1>325 U/ml, whereas the risk of CKD progression events monotonically increased with higher galactose-deficient IgA1/C3 ratio. After adjustment for traditional risk factors (demographics, eGFR, proteinuria, hypertension, Oxford pathologic score, and corticosteroids/immunosuppressive therapy), higher levels of galactose-deficient IgA1/C3 ratio were independently associated with CKD progression event (per natural log-transformed [galactose-deficient IgA1/C3], hazard ratio, 2.03; 95% confidence interval [95% CI], 1.25 to 3.29; P=0.004). In reference to the first quartile of the galactose-deficient IgA1/C3 ratio, hazard ratios were 1.71 (95% CI, 1.01 to 2.89) for the second quartile, 1.55 (95% CI, 0.91 to 2.63) for the third quartile, and 2.17 (95% CI, 1.33 to 3.56) for the fourth quartile.Conclusions In IgA nephropathy, plasma galactose-deficient IgA1/C3 ratio was associated with CKD progression event independent of clinical and biopsy characteristics.