Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Kidney Blood Press Res. 2014;39(5):450-89. doi: 10.1159/000368458. Epub 2014 Nov 30.
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD.
慢性肾脏病（CKD）是一个全球性的公共卫生问题，影响着来自所有种族和民族群体的数百万人。截至2013年底，超过30万日本患者接受维持性透析治疗（JSDT）。在日本，终末期肾病（ESKD）的主要病因是慢性肾小球肾炎（尤其是IgA肾病）、2型糖尿病肾病和高血压性肾硬化。高血压是推动CKD进展为ESKD的主要因素。由于IgA肾病发病机制的许多特征仍不清楚，目前尚无特异性治疗方法。然而，世界各地的研究人员的努力已逐渐阐明了IgA肾病发病机制和治疗的不同方面。如今，日本约一半的糖尿病患者接受治疗。2型糖尿病肾病是日本近40%糖尿病患者发生的主要长期微血管并发症之一。糖尿病肾病的发病机制涉及遗传和环境因素。然而，在糖尿病肾病患者中，与该疾病起始和进展相关的候选基因仍不清楚。关于环境因素，持续性高血糖、活性氧、全身和/或肾小球高血压、血脂异常和补体的毒性被认为起重要作用。本综述的第一部分涵盖IgA肾病和2型糖尿病肾病的发病机制，并将患者的临床病理结果与我们对ddY和KKA-y小鼠模型（分别为IgA肾病和糖尿病肾病的自发动物模型）的研究相结合。在日本，主要的肾脏替代治疗（RRT）是腹膜透析（PD）和血液透析（HD）。本综述的第二部分重点关注PD和HD。基于我们从患者以及动物模型中获得的研究结果，我们讨论了PD和HD患者的管理策略。
