School of Medicine, University of Liverpool, Liverpool, UK.
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Pediatr Nephrol. 2021 Oct;36(10):3033-3044. doi: 10.1007/s00467-021-05107-7. Epub 2021 May 15.
Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N).
The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity.
A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values.
One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-β-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity.
Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.
肾炎是 IgA 血管炎（IgAV，过敏性紫癜）的一种公认并发症，占所有慢性肾脏病（CKD）5 期的 1-2%。更好地了解 IgAV 肾炎（IgAV-N）可能会减少不可逆的损伤。
本研究旨在进行全面的系统文献回顾，以确定 IgAV-N 患儿中有希望的临床和临床前尿液生物标志物，这些标志物可以预测肾炎的存在，并/或确定其严重程度。
使用四个搜索引擎和一个预先设定的搜索词策略进行系统文献回顾。有希望的生物标志物根据临床或临床前以及预测肾炎存在或确定其严重程度的能力进行分类。结果用统计学意义（p < 0.05）和曲线下面积（AUC）值来描述。
共确定了 121 项研究，其中 13 项符合纳入标准。共纳入 2446 名儿科患者：健康对照组（n = 761）、IgAV-N 患儿（n = 1236）和无肾炎的 IgAV 患儿（IgAV-noN，n = 449）。男性占 51%，中位年龄为 7.9 岁。24 小时蛋白量和尿蛋白/肌酐比值这两个临床标志物被认为可以评估肾炎的严重程度（AUC < 0.8）。尿白蛋白浓度（Malb）表现良好（AUC 0.81-0.98）。预测肾炎存在最有希望的临床前尿液生物标志物如下：肾损伤分子-1（KIM-1）（AUC 0.93）、单核细胞趋化蛋白-1（MCP-1）（AUC 0.83）、N-乙酰-β-氨基葡萄糖苷酶（NAG）（0.76-0.96）和血管紧张素原（AGT）（AUC 不可用）。尿 KIM-1、MCP-1 和 NAG 似乎与疾病严重程度相关。
需要进行纵向研究，以评估临床前生物标志物是否能增强 IgAV-N 的标准治疗。
