Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ; and the Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN.
Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ; and the Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN.
Adv Chronic Kidney Dis. 2018 Mar;25(2):192-201. doi: 10.1053/j.ackd.2017.11.004.
Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of diabetic kidney disease (DKD), additional biomarkers are needed, especially for the early stages of the disease when both albuminuria and estimated glomerular filtration rate may still be in the normal range and are less helpful for identifying those at risk of progression. Traditional biomarker studies for early DKD are challenging because of a lack of good early clinical end points, and most rely on changes in existing imprecise biomarkers to assess the value of new biomarkers. There are well-characterized changes in kidney structure, however, that are highly correlated with kidney function, always precede the clinical findings of DKD and, at preclinical stages, predict DKD progression. These structural parameters may thus serve as clinically useful end points for identifying new biomarkers of early DKD. In addition, investigators are analyzing tissue transcriptomic data to identify pathways involved in early DKD which may have associated candidate biomarkers measurable in blood or urine, and differentially expressed microRNAs and epigenetic modifications in kidney tissue are beginning to yield important observations which may be useful in identifying new clinically useful biomarkers. This review examines the emerging literature on the use of kidney tissue in biomarker discovery in DKD.
虽然估算肾小球滤过率和白蛋白尿是糖尿病肾病（DKD）的既定生物标志物，但仍需要其他生物标志物，特别是在疾病的早期阶段，此时白蛋白尿和估算肾小球滤过率可能仍在正常范围内，对识别有进展风险的患者帮助不大。由于缺乏良好的早期临床终点，传统的 DKD 早期生物标志物研究具有挑战性，并且大多数研究都依赖于现有不精确生物标志物的变化来评估新生物标志物的价值。然而，肾脏结构存在特征性变化，这些变化与肾功能高度相关，总是先于 DKD 的临床发现，并且在临床前阶段预测 DKD 进展。因此，这些结构参数可以作为识别早期 DKD 新生物标志物的临床有用终点。此外，研究人员正在分析组织转录组数据，以识别早期 DKD 中涉及的途径，这些途径可能具有可在血液或尿液中测量的相关候选生物标志物，并且在肾脏组织中差异表达的 microRNAs 和表观遗传修饰开始产生可能有助于识别新的临床有用生物标志物的重要观察结果。本文综述了在 DKD 中使用肾脏组织进行生物标志物发现的新兴文献。
