Cattran Daniel C, Floege Jürgen, Coppo Rosanna
University Health Network, Toronto, Ontario, Canada.
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
Kidney Int Rep. 2023 Sep 22;8(12):2515-2528. doi: 10.1016/j.ekir.2023.09.020. eCollection 2023 Dec.
The highly variable rate of decline in kidney function in patients with immunoglobulin A nephropathy (IgAN) provides a major clinical challenge. Predicting which patients will progress to kidney failure, and how quickly, is difficult. Multiple novel therapies are likely to be approved in the short-term, but clinicians lack the tools to identify patients most likely to benefit from specific treatments at the right time. Noninvasive and validated markers for selecting at-risk patients and longitudinal monitoring are urgently needed. This review summarizes what is known about demographic, clinical, and histopathologic prognostic markers in the clinician's toolkit, including the International IgAN Prediction Tool. We also briefly review what is known on these topics in children and adolescents with IgAN. Although helpful, currently used markers leave clinicians heavily reliant on histologic features from the diagnostic kidney biopsy and standard clinical data to guide treatment choice, and very few noninvasive markers reflect treatment efficacy over time. Novel prognostic and predictive markers are under clinical investigation, with considerable progress being made in markers of complement activation. Other areas of research are the interplay between gut microbiota and galactose-deficient IgA1 expression; microRNAs; imaging; artificial intelligence; and markers of fibrosis. Given the rate of therapeutic advancement, the remaining gaps in biomarker research need to be addressed. We finish by describing our route to clinical utility of predictive and prognostic markers in IgAN. This route will provide us with the chance to improve IgAN prognosis by using robust, clinically practical markers to inform patient care.
免疫球蛋白A肾病（IgAN）患者肾功能下降的速率高度可变，这带来了重大的临床挑战。预测哪些患者会进展至肾衰竭以及进展速度有多快是困难的。短期内可能会批准多种新型疗法，但临床医生缺乏在合适时间识别最可能从特定治疗中获益的患者的工具。迫切需要用于选择高危患者和进行纵向监测的非侵入性且经过验证的标志物。本综述总结了临床医生工具包中有关人口统计学、临床和组织病理学预后标志物的已知信息，包括国际IgAN预测工具。我们还简要回顾了IgAN儿童和青少年在这些主题上的已知情况。尽管目前使用的标志物有一定帮助，但临床医生仍严重依赖诊断性肾活检的组织学特征和标准临床数据来指导治疗选择，而且很少有非侵入性标志物能反映随时间变化的治疗效果。新型预后和预测标志物正在进行临床研究，补体激活标志物方面取得了相当大的进展。其他研究领域包括肠道微生物群与半乳糖缺乏型IgA1表达之间的相互作用；微小RNA；影像学；人工智能；以及纤维化标志物。鉴于治疗进展的速度，生物标志物研究中剩余的差距需要得到解决。我们通过描述IgAN中预测和预后标志物的临床应用途径来结束本文。这条途径将为我们提供机会，通过使用可靠的、临床实用的标志物来指导患者护理，从而改善IgAN的预后。
