Bianchi S, Bigazzi R, Campese V M
Unità Operativa Nefrologia, Spedali Riuniti, Livorno, Italy.
Kidney Int. 2006 Dec;70(12):2116-23. doi: 10.1038/sj.ki.5001854. Epub 2006 Oct 11.
Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25 mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g creatinine (P<0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r=0.76, P<0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r=0.42, P<0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2), respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2), P<0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment, P<0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.
实验证据表明醛固酮会导致进行性肾病。血管紧张素转换酶抑制剂和血管紧张素1型受体拮抗剂可抑制肾素-血管紧张素系统，但它们并不能有效降低血浆醛固酮水平。因此，给予醛固酮受体拮抗剂可能会提供额外的肾脏保护作用。在本项前瞻性随机开放标签研究中，我们评估了螺内酯（25毫克/天，共1年）对83例已接受血管紧张素转换酶抑制剂和/或血管紧张素1型受体拮抗剂治疗的慢性肾病患者蛋白尿和估计肾小球滤过率的影响。82例患者仅接受血管紧张素转换酶抑制剂和/或血管紧张素1型受体拮抗剂治疗并作为对照。治疗1年后，接受螺内酯治疗的患者蛋白尿从2.1±0.08降至0.89±0.06克/克肌酐（P<0.001），而对照患者的蛋白尿没有变化。基线醛固酮水平与蛋白尿显著相关（r=0.76，P<0.0001），并可预测螺内酯治疗后蛋白尿的降低程度（r=0.42，P<0.0002）。接受螺内酯治疗的患者和对照患者的基线估计肾小球滤过率相似（分别为62.4±2.4和62.2±2.1毫升/分钟/1.73平方米）。使用螺内酯治疗1个月后，接受螺内酯治疗的患者估计肾小球滤过率的下降幅度大于对照患者。然而，到1年末，接受螺内酯治疗的患者估计肾小球滤过率相对于基线的每月下降率低于对照患者（0.323±0.044对0.474±0.037毫升/分钟/1.73平方米，P<0.01）。螺内酯导致血清钾水平显著升高（从基线时的4.2±0.04升至治疗12个月后的5.0±0.05毫当量/升，P<0.001）。总之，本研究表明螺内酯可能会降低慢性肾病患者的蛋白尿并延缓肾脏病变进展。
