Sato Atsuhisa, Hayashi Koichi, Naruse Mitsuhide, Saruta Takao
Department of Internal Medicine, Mito Red Cross Hospital, Mito city, Ibaraki, Japan.
Hypertension. 2003 Jan;41(1):64-8. doi: 10.1161/01.hyp.0000044937.95080.e9.
It has been reported that continuous ACE inhibitor therapy does not necessarily produce a maintained decrease in plasma aldosterone levels, which may remain high or increase eventually during long-term use (aldosterone escape). We have examined the role of aldosterone escape in 45 patients with type 2 diabetes and early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment, there was a 40% reduction in average urinary albumin excretion, although urinary albumin excretion in patients with aldosterone escape (18 patients) was significantly higher than that in patients without escape (27 patients). In the 18 patients with escape, spironolactone (25 mg/d) was added to ACE inhibitor treatment in 13. After a 24-week study period, urinary albumin excretion and left ventricular mass index were significantly reduced without blood pressure change. In conclusion, the present study demonstrates that aldosterone escape is observed in 40% of patients with type 2 diabetes with early nephropathy despite the use of ACE inhibitors. Our study suggests the possibility that aldosterone blockade may represent optimal therapy for patients with early diabetic nephropathy who show aldosterone escape during ACE inhibitor treatment and who no longer show maximal antiproteinuric effects of ACE inhibition. Additional, larger, prospectively randomized, double-blind studies will be needed before adaptation of this strategy.
据报道，持续使用血管紧张素转换酶（ACE）抑制剂治疗不一定会使血浆醛固酮水平持续降低，在长期使用过程中，血浆醛固酮水平可能会保持在较高水平或最终升高（醛固酮逃逸）。我们研究了醛固酮逃逸在45例2型糖尿病合并早期肾病患者中的作用，这些患者接受了40周的ACE抑制剂治疗。治疗后，平均尿白蛋白排泄量降低了40%，尽管存在醛固酮逃逸的患者（18例）的尿白蛋白排泄量显著高于无醛固酮逃逸的患者（27例）。在18例有醛固酮逃逸的患者中，13例在ACE抑制剂治疗基础上加用了螺内酯（25mg/d）。经过24周的研究期，尿白蛋白排泄量和左心室质量指数显著降低，而血压无变化。总之，本研究表明，尽管使用了ACE抑制剂，但在40%的2型糖尿病合并早期肾病患者中仍观察到醛固酮逃逸现象。我们的研究提示，对于在ACE抑制剂治疗期间出现醛固酮逃逸且不再表现出ACE抑制最大抗蛋白尿作用的早期糖尿病肾病患者，醛固酮阻断可能是最佳治疗方法。在采用这一策略之前，还需要进行更多更大规模的前瞻性随机双盲研究。
