Hollenberg N K, Raij L
Department of Medicine, Harvard Medical School, Boston, Mass.
Arch Intern Med. 1993 Nov 8;153(21):2426-35.
The role of hypertension in the pathogenesis of renal damage is a subject of both historical interest and current investigation. Because of the difficulty associated with studying the pathophysiologic role of glomerular injury in systemic hypertension, experimental models have provided much of the data in this field. The mechanisms leading to glomerular injury are complex and not fully elucidated. Mesangial and endothelial cell injury are thought to be important pathophysiologic mechanisms in the renal injury associated with hypertension. One hypothesis suggests that glomerular hypertension (ie, a hemodynamic event) is the primary pathogenetic mechanism, but another supports the notion that glomerular hypertrophy (ie, abnormal growth-related events) contributes to injury. The intrarenal renin-angiotensin system may play an important pathogenetic role in end-stage renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to arrest the progression of renal injury in animal models. Although the clinical database is incomplete, the findings of anecdotal reports and short-term studies suggest that ACE inhibition may preserve renal function in patients with scleroderma renal crisis, reduce proteinuria in patients with diabetic nephropathy, and normalize renal hemodynamics in patients with a variety of renal diseases. The beneficial effects of ACE inhibition may be due to both hemodynamic (eg, reduction in glomerular capillary and intraglomerular pressures) and nonhemodynamic (eg, potassium-sparing and reduction in mesangial proliferation) mechanisms. The precise role of ACE inhibitors in the prevention of renal damage awaits the results of ongoing long-term, double-blind clinical studies. Nevertheless, ACE inhibition may be an appropriate therapeutic alternative in the hypertensive patient whose renal injury is progressing despite aggressive antihypertensive therapy.
高血压在肾损伤发病机制中的作用既是一个具有历史研究价值的课题，也是当前的研究热点。由于研究系统性高血压中肾小球损伤的病理生理作用存在困难，实验模型为该领域提供了大量数据。导致肾小球损伤的机制复杂且尚未完全阐明。系膜细胞和内皮细胞损伤被认为是与高血压相关的肾损伤重要病理生理机制。一种假说认为肾小球高压（即一种血流动力学事件）是主要的发病机制，但另一种假说则支持肾小球肥大（即与异常生长相关的事件）导致损伤这一观点。肾内肾素 - 血管紧张素系统可能在终末期肾病中发挥重要的发病作用。在动物模型中，血管紧张素转换酶（ACE）抑制已被证明可阻止肾损伤进展。尽管临床数据库尚不完整，但轶事报道和短期研究结果表明，ACE抑制可能在硬皮病肾危象患者中保留肾功能，在糖尿病肾病患者中减少蛋白尿，并使各种肾病患者的肾血流动力学恢复正常。ACE抑制的有益作用可能归因于血流动力学（如降低肾小球毛细血管和球内压力）和非血流动力学（如保钾和减少系膜细胞增殖）机制。ACE抑制剂在预防肾损伤的确切作用有待正在进行的长期双盲临床研究结果。然而，对于尽管积极进行抗高血压治疗但肾损伤仍在进展的高血压患者，ACE抑制可能是一种合适的治疗选择。
