Jim Belinda, Santos Jolina, Spath Fuad, Cijiang He John
Division of Nephrology, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine Bronx, NY 10461, USA.
Curr Diabetes Rev. 2012 Sep;8(5):317-28. doi: 10.2174/157339912802083478.
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Searching for the perfect biomarker of DN has become the holy grail of nephrology since the burden of this disease is untenable. The only feasible way to tackle this health care crisis is by prevention and treatment in a mechanistically rational approach. Therefore, the discovery of a specific, reliable diagnostic and prognostic biomarker for DN is imperative. Part of the difficulty in finding such a marker is the complex pathogenesis of DN; it is clearly multifactorial and involves multiple genes, proteins, metabolic pathways, and environmental factors. In this review, we will discuss the latest findings in the use of genetic, protein, and metabolic markers of DN. Particular attention will be paid to the urinary biomarker as a noninvasive method to detect either morphological or biochemical changes in DN. Urinary protein and mRNA studies have focused on either the glomerular (podocyte-specific) or tubular components (matrix or injury-related) of the nephron. The virtues and pitfalls of using the podocyte as a biomarker will be discussed. The systems biology approach of biomarker discovery in the studies of genomics, transcriptomics, proteomics, and metabolomics will be explored. Despite significant numbers of new biomarkers described, most studies are limited by either their small sample size or their cross-sectional nature, so that the ability to predict future and severity of DN is lacking. In order to successfully search for the ideal, validated biomarker, we need to conduct large, prospective, multi-center trials enlisting both Type 1 and Type II diabetic patients with and without nephropathy for at least two decades.
糖尿病肾病（DN）是终末期肾病的主要病因。由于这种疾病的负担难以承受，寻找完美的DN生物标志物已成为肾脏病学的圣杯。应对这一医疗危机的唯一可行方法是以机械合理的方式进行预防和治疗。因此，发现一种针对DN的特异性、可靠的诊断和预后生物标志物势在必行。寻找此类标志物的部分困难在于DN复杂的发病机制；它显然是多因素的，涉及多个基因、蛋白质、代谢途径和环境因素。在本综述中，我们将讨论DN遗传、蛋白质和代谢标志物使用方面的最新发现。将特别关注尿生物标志物作为检测DN形态或生化变化的非侵入性方法。尿蛋白和mRNA研究主要集中在肾单位的肾小球（足细胞特异性）或肾小管成分（基质或损伤相关）上。将讨论使用足细胞作为生物标志物的优点和缺陷。将探索在基因组学、转录组学、蛋白质组学和代谢组学研究中发现生物标志物的系统生物学方法。尽管描述了大量新的生物标志物，但大多数研究都受到样本量小或横断面性质的限制，因此缺乏预测DN未来发展和严重程度的能力。为了成功寻找理想的、经过验证的生物标志物，我们需要开展大型、前瞻性、多中心试验，纳入1型和2型糖尿病肾病患者及非肾病患者，至少持续二十年。
