Molecular genetic analysis of various types of complications in patients with long-term dialysis therapy

本研究的目的是调查遗传多态性与透析患者各种类型并发症的相关性，并探索治疗这些疾病的新分子靶点。目前，新泻县约有4，500名患者正在接受血液透析治疗，其中血液透析20年或以上的患者比例超过8.5%。是这个国家最高的此外，在日本，长期血液透析30年以上的患者中，有15.5%在本县，因此，我们收集了新泻县长期血液透析患者的详细临床资料和基因组DNA，分析了炎症细胞因子、脂质代谢、钙代谢、血管活性肽等基因的多个遗传多态性。我们对他们进行随访，以确定他们的生存率，并记录任何透析相关的并发症，特别是透析相关的淀粉样变性，骨/关节并发症，心血管事件，以及尿毒症性瘙痒症。我们已经报道了数百例血液透析患者的各种基因多态性与透析相关的淀粉样变性和心血管并发症的发生有关。).此外，我们在大量（N = 2，400）维持性血液透析患者中研究了重度尿毒症性瘙痒的风险因素，发现重度尿毒症性瘙痒与不良结局独立相关，即使在调整这些患者的其他显著临床风险因素后也是如此（Narita I，et al. Kidney Int，2006）。我们还报告了一项长期血液透析治疗患者的前瞻性研究（Ajiro J等人，Clin J Am Soc Nephrol，2007）

The aim of this study was to investigate the association of genetic polymorphisms and various types of complications in dialysis patients and to explore new molecular targets for these disorders.About 4,500 patients are currently receiving hemodialysis therapy in Niigata prefecture, and, the proportion of the patients, who have been hemodialysed for 20 years or more, is more than 8.5%, which is the highest in this country. Moreover, 15.5% of cases under long-term hemodialysis for more than 30 years in this country are in our prefecture.We have collected detailed clinical data and genomic DNA of long-term hemodialysis patients in Niigata prefecture and analyzed multiple genetic polymorphisms, including genes for inflammatory cytokines, lipid metabolism, calcium metabolism, and vasoactive peptides. We are following them up in order to determine their survival, and to record any dialysis associated complications particularly dialysis-associated amyloidosis, complications of bone / joint, and cardiovascular events, as well as uremic pruritus.We have reported that various genetic polymorphisms are associated with the onset of dialysis-associated amyloidosis and cardiovascular complications in hundreds patients with hemodialysis. ). Moreover, we have investigated the risk factors for severe uremic pruritus in a large-population (N = 2,400) of patients under maintenance hemodialysis and found that severe uremic pruritus was independently associated with poor outcome even after adjusting for other significant clinical risk factors in these patients (Narita I, et al. Kidney Int, 2006). We also have reported a prospective study of patients with long-term hemodialysis treatment (Ajiro J, et al. Clin J Am Soc Nephrol, 2007)