A/L B Vasanth Rao Vikram Rao, Tan Sean Hong, Candasamy Mayuren, Bhattamisra Subrat Kumar
School of Postgraduate Studies, International Medical University, No 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
School of Pharmacy, International Medical University, No 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
Diabetes Metab Syndr. 2019 Jan-Feb;13(1):754-762. doi: 10.1016/j.dsx.2018.11.054. Epub 2018 Nov 30.
Diabetic nephropathy (DN) is a major cause of end-stage renal disease and affects a large number of individuals with diabetes. However, the development of specific treatments for DN has not yet been identified. Hence, this review is concisely designed to understand the molecular pathways leading to DN in order to develop suitable therapeutic strategies. Extensive literature search have been carried in regard with the pathogenesis and pathophysiology of DN, drug targets and updates on clinical trials, the consequences associated with DN and the potential biomarkers for diagnosis and prediction of DN are discussed in this review. DN is characterised by microalbuminuria and macroalbuminuria, and morphological changes such as glomerular thickening, interstitial fibrosis, formation of nodular glomerulosclerosis and decreased endothelial cell fenestration. Besides, the involvement of renin-angiotensin-aldosterone system, inflammation and genetic factors are the key pathways in the progression of DN. In regard with drug development drugs targeted to epidermal growth factor, inflammatory cytokines, ACTH receptor and TGFβ1 receptors are in pipeline for clinical trials whereas, several drugs have also failed in phase III and phase IV of clinical trials due to lack of efficacy and severe adverse effect. The research on DN is limited with respect to its pathogenesis and drug development. Thus, a more detailed understanding of the pathogenesis of DN is very essential to progress in the drug development process.
糖尿病肾病（DN）是终末期肾病的主要病因，影响着大量糖尿病患者。然而，尚未确定针对DN的特异性治疗方法。因此，本综述旨在简要了解导致DN的分子途径，以制定合适的治疗策略。针对DN的发病机制和病理生理学、药物靶点以及临床试验进展进行了广泛的文献检索，本综述还讨论了与DN相关的后果以及用于诊断和预测DN的潜在生物标志物。DN的特征为微量白蛋白尿和大量白蛋白尿，以及形态学改变，如肾小球增厚、间质纤维化、结节性肾小球硬化形成和内皮细胞窗孔减少。此外，肾素-血管紧张素-醛固酮系统、炎症和遗传因素的参与是DN进展的关键途径。在药物研发方面，针对表皮生长因子、炎性细胞因子、促肾上腺皮质激素受体和转化生长因子β1受体的药物正处于临床试验阶段，然而，由于缺乏疗效和严重不良反应，几种药物在临床试验的III期和IV期也失败了。关于DN的发病机制和药物研发的研究有限。因此，更详细地了解DN的发病机制对于药物研发进程的推进非常重要。
