Schjoedt K J, Astrup A S, Persson F, Frandsen E, Boomsma F, Rossing K, Tarnow L, Rossing P, Parving H-H
Steno Diabetes Center, Gentofte, Denmark.
Diabetologia. 2009 Jan;52(1):46-9. doi: 10.1007/s00125-008-1184-8. Epub 2008 Oct 31.
AIMS/HYPOTHESIS: The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy.
At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy completed this double-masked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Allocation was concealed by sequentially numbered opaque sealed envelopes. UAER, 24 h ambulatory blood pressure (ABP) and estimated GFR were determined at baseline and after each treatment period.
All 49 patients completed all three treatment periods. Baseline values were: UAER (geometric mean [95% CI]) 362 (240-545) mg/24 h, 24 h ABP (mean [SD]) 142 (14)/74 (8) mmHg and estimated GFR 75 (29) ml min(-1) 1.73 m(-2). Reductions in UAER from baseline were 63%, 71% and 70%, respectively, with the increasing doses of lisinopril (p < 0.001). Compared with lisinopril 20 mg there was a further reduction in UAER of 23% with lisinopril 40 mg and 19% with 60 mg, p < 0.05. ABP was reduced from baseline by 10/5, 13/7 and 12/7 mmHg (p < 0.001 vs baseline, p < 0.05 for diastolic ABP 20 vs 40 mg, otherwise NS between doses). The difference in UAER between 20 and 40 mg lisinopril was significant after adjustment for changes in ABP (p < 0.01). Two patients were excluded from the study because of an increase in plasma creatinine and one because of high BP; otherwise the study medication was well tolerated with few, mild, dose-independent adverse effects.
CONCLUSIONS/INTERPRETATION: Lisinopril 40 mg once daily is generally safe and offers additional reductions in BP and UAER in comparison with the currently recommended dose of 20 mg. Lisinopril 60 mg offers no further beneficial effect.
ClinicalTrials.gov NCT00118976.
目的/假设：本研究旨在评估超大量赖诺普利对1型糖尿病肾病患者的最佳肾脏保护作用，以尿白蛋白排泄率（UAER）的短期变化为指标。
在斯滕诺糖尿病中心，49例1型糖尿病肾病患者完成了这项双盲随机交叉试验，试验包括初始洗脱期，随后是三个各持续2个月的治疗期，所有患者除服用缓释速尿外，还随机接受每日一次20、40和60mg赖诺普利治疗。通过按顺序编号的不透明密封信封进行随机分组。在基线期和每个治疗期结束后测定UAER、24小时动态血压（ABP）和估算肾小球滤过率（GFR）。
49例患者均完成了三个治疗期。基线值为：UAER（几何均数[95%CI]）362（240 - 545）mg/24小时，24小时ABP（均数[标准差]）142（14）/74（8）mmHg，估算GFR 75（29）ml·min⁻¹·1.73m⁻²。随着赖诺普利剂量增加，UAER较基线分别降低63%、71%和70%（p < 0.001）。与20mg赖诺普利相比，40mg赖诺普利使UAER进一步降低23%，60mg使UAER进一步降低19%，p < 0.05。ABP较基线分别降低10/5、13/7和12/7 mmHg（与基线相比p < 0.001，舒张压ABP 20mg与
