Remuzzi Giuseppe, Perico Norberto, Macia Manuel, Ruggenenti Piero
Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Italy.
Kidney Int Suppl. 2005 Dec(99):S57-65. doi: 10.1111/j.1523-1755.2005.09911.x.
The renin-angiotensin-aldosterone system (RAAS) is a well known regulator of blood pressure (BP) and determinant of target-organ damage. It controls fluid and electrolyte balance through coordinated effects on the heart, blood vessels, and Kidneys. Angiotensin II (AII) is the main effector of the RAAS and exerts its vasoconstrictor effect predominantly on the postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and the ultrafiltration of plasma proteins, effects that may contribute to the onset and progression of chronic renal damage. AII may also directly contribute to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. Interventions that inhibit the activity of the RAAS are renoprotective and may slow or even halt the progression of chronic nephropathies. ACE inhibitors and angiotensin II receptor antagonists can be used in combination to maximize RAAS inhibition and more effectively reduce proteinuria and GFR decline in diabetic and nondiabetic renal disease. Recent evidence suggests that add-on therapy with an aldosterone antagonist may further increase renoprotection, but may also enhance the risk hyperkalemia. Maximized RAAS inhibition, combined with intensified blood pressure control (and metabolic control in diabetics) and amelioration of dyslipidemia in a multimodal approach including lifestyle modifications (Remission Clinic), may achieve remission of proteinuria and renal function stabilization in a substantial proportion of patients with proteinuric renal disease. Ongoing studies will tell whether novel drugs inhibiting the RAAS, such as the renin inhibitors or the vasopeptidase inhibitors, may offer additional benefits to those who do not respond, or only partially respond, to this multimodal regimen.
肾素-血管紧张素-醛固酮系统（RAAS）是一种广为人知的血压调节因子和靶器官损伤的决定因素。它通过对心脏、血管和肾脏的协同作用来控制体液和电解质平衡。血管紧张素II（AII）是RAAS的主要效应物，其血管收缩作用主要作用于肾小球后小动脉，从而增加肾小球液压和血浆蛋白超滤，这些作用可能有助于慢性肾损伤的发生和发展。AII还可能通过维持细胞生长、炎症和纤维化直接促进肾损伤的加速。抑制RAAS活性的干预措施具有肾脏保护作用，可能会减缓甚至阻止慢性肾病的进展。血管紧张素转换酶抑制剂和血管紧张素II受体拮抗剂可以联合使用，以最大限度地抑制RAAS，并更有效地降低糖尿病和非糖尿病肾病患者的蛋白尿和肾小球滤过率下降。最近的证据表明，加用醛固酮拮抗剂可能会进一步增强肾脏保护作用，但也可能增加高钾血症的风险。通过包括生活方式改变（缓解诊所）在内的多模式方法，最大限度地抑制RAAS，结合强化血压控制（以及糖尿病患者的代谢控制）和改善血脂异常，可能会使相当一部分蛋白尿肾病患者实现蛋白尿缓解和肾功能稳定。正在进行的研究将揭示，抑制RAAS的新型药物，如肾素抑制剂或血管肽酶抑制剂，是否能为那些对这种多模式治疗方案无反应或仅部分反应的患者带来额外益处。
