Isaka Yoshitaka, Takabatake Yoshitsugu, Takahashi Atsushi, Saitoh Tatsuya, Yoshimori Tamotsu
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Nephrol Dial Transplant. 2016 Jun;31(6):890-6. doi: 10.1093/ndt/gfv024. Epub 2015 Mar 31.
Classically, urate nephropathy has been postulated to cause kidney disease by depositing intraluminal crystal in the collecting duct. Recently, molecular mechanisms of inflammasome have been investigated. Urate-induced inflammasome pathway is comprised of urate crystal uptake into intracellular lysosomes and subsequent lysosomal rupture with mitochondrial reactive oxygen species (ROS) production, which activates the NLRP3 inflammasome. Against the lysosomal rupture and mitochondrial ROS production, autophagy acts to protect proximal tubular cells by isolating them from expanding the inflammation. In addition, increased cellular urate, directly or indirectly via xanthine oxidase-induced oxidative stress, may be associated with inflammasome. In addition to the traditional therapy against hyperuricemia, management of urate-induced inflammasome or augmentation of autophagy may offer the new effective therapies.
传统上，人们认为尿酸肾病是通过在集合管内沉积管腔内晶体而导致肾脏疾病。最近，人们对炎性小体的分子机制进行了研究。尿酸诱导的炎性小体途径包括尿酸晶体被细胞内溶酶体摄取，随后溶酶体破裂并产生活性氧（ROS），从而激活NLRP3炎性小体。针对溶酶体破裂和线粒体ROS的产生，自噬通过将近端肾小管细胞与不断扩大的炎症隔离开来，起到保护作用。此外，细胞内尿酸增加，直接或通过黄嘌呤氧化酶诱导的氧化应激间接增加，可能与炎性小体有关。除了针对高尿酸血症的传统治疗方法外，对尿酸诱导的炎性小体进行管理或增强自噬可能会提供新的有效治疗方法。
