Mehdi Uzma F, Adams-Huet Beverley, Raskin Philip, Vega Gloria L, Toto Robert D
University of Texas Southwestern Medical Center, 5939 Harry Hines Boulevard, Dallas, TX 75930, USA.
J Am Soc Nephrol. 2009 Dec;20(12):2641-50. doi: 10.1681/ASN.2009070737. Epub 2009 Nov 19.
Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio > or =300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, -51.0%, -11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, -37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial.
在糖尿病肾病动物模型中，醛固酮可独立于血管紧张素II促进肾小球和肾小管硬化。大多数关于在基于抑制血管紧张素转换酶（ACE）的治疗方案中添加血管紧张素受体阻滞剂或盐皮质激素受体拮抗剂的肾脏保护益处的人体研究，使用的ACE抑制剂剂量相对较低。此外，这些研究并未确定抗蛋白尿作用是否独立于血压降低。我们对81例患有糖尿病、高血压和蛋白尿（尿白蛋白与肌酐比值≥300mg/g）的患者进行了一项双盲、安慰剂对照试验，所有患者均接受赖诺普利（每日一次80mg）治疗。我们将患者随机分配至安慰剂组、氯沙坦组（每日100mg）或螺内酯组（每日25mg），治疗48周。在基线、24周和48周时，我们获取了血液和尿液中的白蛋白、尿素、肌酐、电解质、糖化血红蛋白以及动态血压。与安慰剂组相比，分配至螺内酯组的患者尿白蛋白与肌酐比值降低了34.0%（95%CI，-51.0%，-11.2%，P = 0.007），分配至氯沙坦组的患者降低了16.8%（95%CI，-37.3%，+10.5%，P = 0.20）。各组之间的诊室血压和动态血压、肌酐清除率、钠和蛋白质摄入量以及血糖控制并无差异。添加螺内酯或氯沙坦后，血清钾水平显著升高。总之，在包括最大程度ACE抑制的治疗方案中添加螺内酯而非氯沙坦，在糖尿病肾病中可提供更大的肾脏保护作用，尽管对血压的影响相似。这些结果支持开展一项长期、大规模的肾衰竭结局试验的必要性。
