Ravid M, Brosh D, Levi Z, Bar-Dayan Y, Ravid D, Rachmani R
Tel-Aviv University and Meir Hospital, Kfar-Sava, Israel.
Ann Intern Med. 1998 Jun 15;128(12 Pt 1):982-8. doi: 10.7326/0003-4819-128-12_part_1-199806150-00004.
Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes.
To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes.
Randomized, double-blind, placebo-controlled trial with 6-year follow-up.
Eight outpatient clinics coordinated by a department of medicine in a university hospital.
156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion < or = 30 mg/24 h).
Enalapril, 10 mg/d, or placebo.
Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1c values.
Enalapril therapy decreased albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal (< 107 mm Hg) in all patients.
Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.
血管紧张素转换酶（ACE）抑制剂可减缓糖尿病微量白蛋白尿患者肾功能的衰退。然而，关于使用ACE抑制剂预防2型糖尿病血压正常、尿白蛋白正常患者肾功能减退的数据尚不存在。
评估长期使用ACE抑制剂对2型糖尿病患者肾功能和蛋白尿的影响。
随机、双盲、安慰剂对照试验，随访6年。
由大学医院的一个内科协调的8个门诊诊所。
156例40岁后诊断为2型糖尿病的患者，其基线平均血压低于107 mmHg且有蛋白尿（白蛋白排泄量≤30 mg/24 h）。
依那普利，10 mg/d，或安慰剂。
24小时蛋白尿程度、肌酐清除率、血压和糖化血红蛋白值。
依那普利治疗2年后，白蛋白排泄量从平均±标准差11.6±7 mg/24 h降至9.7±6 mg/24 h。随后在6年时逐渐升至15.8±8 mg/24 h。在安慰剂组，6年时白蛋白排泄量从10.8±8 mg/24 h增至26.5±10 mg/24 h（依那普利组与安慰剂组相比，P = 0.001）。79名安慰剂接受者中有15名（19%）转变为微量白蛋白尿，77名依那普利接受者中有5名（6.5%）转变为微量白蛋白尿。依那普利治疗使微量白蛋白尿发生的绝对风险降低了12.5%（95%CI，2%至23%；P = 0.042）。6年后，依那普利接受者的肌酐清除率从1.78±0.13 mL/s降至1.63±0.12 mL/s（平均每年降低0.025 mL/s），安慰剂接受者的肌酐清除率从1.81±0.15 mL/s降至1.57±0.17 mL/s（平均每年降低0.04 mL/s）（P = 0.040）。两组糖化血红蛋白值均有适度下降。所有患者的平均血压均保持正常（<107 mmHg）。
依那普利减缓了血压正常、尿白蛋白正常的2型糖尿病患者肾功能的衰退，并降低了蛋白尿程度。需要进一步研究以确定这种治疗是否能预防显性肾病的发生。
