Background

C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G.

Methods

Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood.

Results

DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m² at last follow-up.

Conclusions

We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics.

Graphical abstract

中文翻译：

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长期随访，包括对儿科 C3 肾小球病队列的广泛补体分析

背景

C3 肾小球病 (C3G) 是一种罕见的肾脏疾病，其特征在于补体 C3 的主要肾小球沉积。C3G可细分为致密沉积病（DDD）和C3肾小球肾炎（C3GN）。本研究描述了对 29 名患有 C3G 的荷兰儿童进行广泛补体分析的长期随访。

方法

包括 1992 年至 2014 年间诊断的 29 名 C3G 患者（19 名 DDD，10 名 C3GN）。在就诊时和随访期间收集临床和实验室检查结果。专门的检测用于检测补体基因中的罕见变异，并测量血液中补体导向的自身抗体和生物标志物。

结果

DDD 患者的估计肾小球滤过率 (eGFR) 较低。在 20 名患者中检测到 C3 肾炎因子 (C3NeFs)，尽管进行了免疫抑制治疗，但随着时间的推移仍可检测到。就诊时，84% 的患者检测到低血清 C3 水平。随访期间，约 50% 的患者均为 C3NeF 阳性，C3 水平仍较低。线性混合模型分析表明，与 DDD 患者相比，C3GN 患者具有更高的可溶性 C5b-9 (sC5b-9) 和更低的备解素水平。中位随访时间为 52 个月，在最后一次随访中只有 6 名 eGFR 低于 90 ml/min/1.73 m ^{2的患者观察到总体良性结果。}

结论

我们广泛描述了临床和实验室发现，包括专门儿科 C3G 队列的补充特征。结果相对良性，持续的低 C3 与 C3NeF 的存在相关，C3GN 与较高的 sC5b-9 和较低的备解素水平相关。需要进行前瞻性研究以进一步阐明 C3G 的致病机制，并通过补体疗法指导个性化医疗。

图形概要