Rethinking hypertensive kidney disease: arterionephrosclerosis as a genetic, metabolic, and inflammatory disorder.
Rethinking hypertensive kidney disease: arterionephrosclerosis as a genetic, metabolic, and inflammatory disorder.
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DOI：
10.1097/mnh.0b013e3283600f8c
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发表时间：
2013-05
影响因子：
3.2
通讯作者：
Kopp JB
中科院分区：
文献类型：
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作者：
Kopp JB
高血压是美国约30%的终末期肾病病例的归因原因，但良性高血压是否是慢性肾病的原因一直存在争议。非恶性高血压引起的慢性肾脏疾病的组织学表现为肾动脉硬化，病理表现为小叶间动脉的终末分支，以及肾小球硬化。APOL1编码区变异体的鉴定为这一争论开辟了新的视角。这些变异仅限于最近的非洲裔人群，与临床诊断的动脉肾硬化症密切相关，特别是当有中度或高度蛋白尿或进展到更高级的肾功能障碍时。然而，并非所有进展为终末期肾病的高血压非裔美国人都有两种APOL1风险变异，欧洲和亚洲血统的个体也表现出动脉肾硬化。此外，我们不了解APOL1在肾微循环中引发病理的机制。APOL1肾病包括疾病谱（可能具有不同的内源性表型），包括局灶节段性肾小球硬化、塌陷性肾小球病和动脉肾硬化。术语高血压肾病和高血压肾硬化已经失去了它们的用处。现在可能是时候使用已建立的病因学中性术语动脉肾硬化症来考虑这是否是一种疾病而不是病理描述，并确定各种临床相关因素（包括衰老、肥胖、高脂血症、吸烟、慢性炎症和氧化应激）的因果作用。
Hypertension is the attributed cause of approximately 30% of end-stage kidney disease cases in the United States, but there has been controversy as to whether benign hypertension is a cause of chronic kidney disease. The histology of chronic kidney disease attributed to nonmalignant hypertension is arterionephrosclerosis, with pathology in the terminal branches of the interlobular arteries, together with global glomerulosclerosis. The identification of coding region variants in APOL1, encoding apolipoprotein L1, has opened a new perspective on this debate. These variants are restricted to populations of recent African descent and are strongly associated with clinically diagnosed arterionephrosclerosis, particularly when there is moderate-grade or high-grade proteinuria or progression to more advanced levels of kidney dysfunction. Nevertheless, not all African Americans with hypertension who progress to end-stage kidney disease have two APOL1 risk variants, and individuals of European and Asian descent also manifest arterionephrosclerosis. Further, we do not understand the mechanisms by which APOL1 initiates pathology in the renal microcirculation. APOL1 nephropathy comprises a disease spectrum (perhaps with distinct endophenotypes), including focal segmental glomerulosclerosis, collapsing glomerulopathy, and arterionephrosclerosis. The terms hypertensive kidney disease and hypertensive nephrosclerosis have outlived their usefulness. It may be time to use the established, etiologically neutral term, arterionephrosclerosis, to consider whether this is a disease rather than a pathologic description, and to determine the causal role of various clinical correlates including aging, obesity, hyperlipidemia, smoking, chronic inflammation, and oxidative stress.