Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA.
Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA.
Nat Rev Nephrol. 2016 Jan;12(1):27-36. doi: 10.1038/nrneph.2015.172. Epub 2015 Nov 10.
Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis-associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1-associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants.
在非糖尿病、轻度至中度高血压且蛋白尿水平低或无蛋白尿的个体中,常发生与疾病无关的过程,并伴有慢性肾病:新近有非洲血统的个体存在原发性肾小球硬化症,而在其他情况下,由于高血压和血管疾病危险因素导致的小动脉性肾硬化症会引起肾小球缺血。不幸的是,肾脏病学家经常不加区分地将“高血压性肾硬化症”这一诊断应用于这两种情况下的患者,这意味着高血压是导致其肾脏疾病的原因。尽管与载脂蛋白 L1 基因 (APOL1) 变异相关的肾病通常会导致继发性高血压,但它们属于局灶节段性肾小球硬化症的范畴,并非由系统性高血压引起。由于可进行针对 APOL1 变异和其他肾小球硬化症相关基因变异的基因检测,并能提供疾病发病机制的精确定义,我们认为现在应该摒弃“高血压性肾硬化症”这一术语,代之以基于基因的(例如,与 APOL1 相关的)肾小球硬化症或小动脉性肾硬化症。精准医学将是提高该领域诊断准确性的关键。区分这些不同的疾病有可能消除与 APOL1 肾脏风险变异相关的原发性肾小球硬化症。