Thomas Merlin C, Atkins Robert C
Danielle Alberti Memorial Centre for Diabetic Complications, Wynn Domain, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Drugs. 2006;66(17):2213-34. doi: 10.2165/00003495-200666170-00005.
The current pandemic of diabetes mellitus will inevitably be followed by an epidemic of chronic kidney disease. It is anticipated that 25-40% of patients with type 1 diabetes and 5-40% of patients with type 2 diabetes will ultimately develop diabetic kidney disease. The control of blood pressure represents a key component for the prevention and management of diabetic nephropathy. There is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes. Hypertension is closely linked to insulin resistance as part of the 'metabolic syndrome'. Diabetic nephropathy may lead to hypertension through direct actions on renal sodium handling, vascular compliance and vasomotor function. Recent clinical trials also support the utility of blood pressure reduction in the prevention of diabetic kidney disease. In patients with normoalbuminuria, transition to microalbuminuria can be prevented by blood pressure reduction. This action appears to be significant regardless of whether patients have elevated blood pressure or not. The efficacy of ACE inhibition appears to be greater than that achieved by other agents with a similar degree of blood pressure reduction; although large observational studies suggest the risk of microalbuminuria may be reduced by blood pressure reduction, regardless of modality. In patients with established microalbuminuria, ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) consistently reduce the risk of progression from microalbuminuria to macroalbuminuria, over and above their antihypertensive actions. The clinical utility of combining these strategies remains to be established. In patients with overt nephropathy, blood pressure reduction is associated with reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. In addition to actions on systemic blood pressure, it is now clear that ACE inhibitors and ARBs also reduce proteinuria in patients with diabetes. This anti-proteinuric activity is distinct from other antihypertensive agents and diuretics. Although there is a clear physiological rationale for blockade of the renin angiotensin system, which is strongly supported by clinical studies, to achieve the optimal lowering of blood pressure, particularly in the setting of established diabetic renal disease, a number of different antihypertensive agents will always be needed. In the end, the choice of agents should be individualised to achieve the maximal tolerated reduction in blood pressure and albuminuria. Ultimately, no matter how it is achieved, so long as it is achieved, renal risk can be reduced by agents that lower blood pressure and albuminuria.
当前的糖尿病大流行之后，不可避免地会出现慢性肾脏病的流行。预计1型糖尿病患者中有25%-40%以及2型糖尿病患者中有5%-40%最终会发展为糖尿病肾病。血压控制是糖尿病肾病预防和管理的关键组成部分。糖尿病中的高血压与糖尿病的不良结局之间存在很强的流行病学关联。高血压与作为“代谢综合征”一部分的胰岛素抵抗密切相关。糖尿病肾病可通过对肾脏钠处理、血管顺应性和血管舒缩功能的直接作用导致高血压。近期的临床试验也支持降低血压在预防糖尿病肾病方面的效用。在正常白蛋白尿患者中，降低血压可预防向微量白蛋白尿的转变。无论患者血压是否升高，这一作用似乎都很显著。血管紧张素转换酶（ACE）抑制剂的疗效似乎大于其他降压程度相似的药物；尽管大型观察性研究表明，无论采用何种方式，降低血压都可能降低微量白蛋白尿的风险。在已确诊微量白蛋白尿的患者中，ACE抑制剂和血管紧张素受体拮抗剂（血管紧张素受体阻滞剂[ARBs]）除了具有降压作用外，还能持续降低从微量白蛋白尿进展为大量白蛋白尿的风险。联合这些策略的临床效用仍有待确定。在显性肾病患者中，降低血压与尿白蛋白排泄减少相关，随后肾功能损害或终末期肾病的风险降低。除了对全身血压的作用外，现在很清楚ACE抑制剂和ARBs还能降低糖尿病患者的蛋白尿。这种抗蛋白尿活性不同于其他降压药物和利尿剂。尽管阻断肾素血管紧张素系统有明确的生理学依据，且得到临床研究的有力支持，但要实现血压的最佳降低，尤其是在已确诊的糖尿病肾病情况下，始终需要多种不同的降压药物。最后，药物的选择应个体化，以实现血压和蛋白尿的最大耐受降低。最终，无论如何实现，只要能实现，降低血压和蛋白尿的药物就能降低肾脏风险。
