Bauer J H
The Medical Service, Harry S. Truman Memorial Veterans' Hospital and the Department of Internal Medicine University of Missouri, Columbia 65212, USA.
J Hypertens Suppl. 1998 Oct;16(5):S17-24.
In animal models of hypertension, the resistance state of the preglomerular (afferent) and postglomerular (efferent) capillary arterioles may determine whether a particular form of antihypertensive therapy will spare the kidney from hemodynamic-mediated glomerular injury. In experimental models of renal disease with impaired autoregulation, control of systemic blood pressure is a prerequisite for normalizing glomerular capillary hydraulic pressure.
In humans, effective blood pressure control reverses renal hemodynamic abnormalities in hypertensive patients, reduces microalbuminuria in essential hypertensive, nondiabetic, and diabetic renal diseases, and attenuates but does not prevent the progression of nondiabetic and diabetic renal disease. Although some researchers have concluded that angiotensin converting enzyme inhibitors are the renal protective drugs of choice, these pronouncements are not based on clinical trials correlating specific drug-mediated changes in albumin or protein excretion with the longitudinal assessment of glomerular filtration rate (GFR), permitting derivation of a slope-defining change in GFR, and/or the longitudinal assessment of renal structure (i.e. renal biopsy). Definitive clinical trials have not been reported. It is important to recognize that an elevated serum creatinine is a powerful predictor of mortality and that, in most patients, death is caused by a cardiovascular or cerebrovascular event, rather than by renal failure.
Because morbidity and mortality of essential hypertension and nondiabetic or diabetic renal disease is related primarily to cardiovascular or cerebrovascular events, the antihypertensive 'drugs of choice' should be those that reduce these risks, prevent or regress target-organ damage, and optimize treatment of concomitant diseases.
在高血压动物模型中,肾小球前(入球)和肾小球后(出球)毛细血管小动脉的阻力状态可能决定某种特定形式的抗高血压治疗是否能使肾脏免受血流动力学介导的肾小球损伤。在肾自动调节受损的肾脏疾病实验模型中,控制全身血压是使肾小球毛细血管液压正常化的前提条件。
在人类中,有效的血压控制可逆转高血压患者的肾脏血流动力学异常,减少原发性高血压、非糖尿病和糖尿病肾病患者的微量白蛋白尿,并减缓但不能阻止非糖尿病和糖尿病肾病的进展。尽管一些研究人员得出结论认为血管紧张素转换酶抑制剂是首选的肾脏保护药物,但这些结论并非基于将白蛋白或蛋白质排泄的特定药物介导变化与肾小球滤过率(GFR)的纵向评估相关联的临床试验,从而无法得出GFR斜率定义变化,和/或肾脏结构的纵向评估(即肾活检)。尚未报道确定性的临床试验。重要的是要认识到血清肌酐升高是死亡率的有力预测指标,并且在大多数患者中,死亡是由心血管或脑血管事件引起的,而非肾衰竭。
由于原发性高血压以及非糖尿病或糖尿病肾病的发病率和死亡率主要与心血管或脑血管事件相关,因此抗高血压“首选药物”应是那些能降低这些风险、预防或逆转靶器官损害并优化伴发疾病治疗的药物。